2012 4-16 renal physiology
TRANSCRIPT
Renal Physiology
Xiaohong Xia
夏晓红
Department of Physiology
Hebei Medical University
E-mail xiaunmchotmailcom)
About this Chapter
bull Anatomy of the excretory system
bull How the kidney is organized
bull How the nephron works to filter blood
recycle secrete and excrete
bull How filtration is regulated
bull Urination reflex
Kidney Function
1 Regulation of water and inorganic ions
balance
2 Excretion of metabolic waste products
3 Removing of foreign chemicals
by producingexcreting urine
to maintain the internal homeostasis
of the body
Kidney Function
4 Secretion of hormones
a Erythropoietin (EPO --- is produced by
interstitial cells in peritubular capillary)
which controls erythrocyte production
b Renin ( is produced by juxtaglomerular cell)
which controls formation of angiotensin
c 125-dihydroxyvitamin D3
which influences calcium balance
Outline
bull 1048715 Functional Anatomy of Kidneys and Renal
Circulation
bull 1048715 Glomerular Filtration
bull 1048715 Tubular Processing of Urine Formation
bull 1048715 Urine Concentration and Dilution
bull 1048715 Regulation of Water and Sodium Excretion
bull 1048715 Renal Clearance
bull 1048715 Urine Volume and Micturition
SECTION 1
Functional Anatomy of Kidneys and
Renal Circulation
Urinary system
paired kidneys
paired ureters
a bladder
a urethra
The kidney renal cortex
renal medulla
renal pelvis
Anatomical Characteristics of the Kidney
1 Nephrons functional unit of kidneys
(1) Consist of nephron
bull Nephron is the basic smallest functional unit
of kidney
bull Nephron consists of renal corpuscle and renal
tubule
bull Each kidney is composed of about 1 million
microscopic functional unit
Anatomical Characteristics of the Kidney
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
About this Chapter
bull Anatomy of the excretory system
bull How the kidney is organized
bull How the nephron works to filter blood
recycle secrete and excrete
bull How filtration is regulated
bull Urination reflex
Kidney Function
1 Regulation of water and inorganic ions
balance
2 Excretion of metabolic waste products
3 Removing of foreign chemicals
by producingexcreting urine
to maintain the internal homeostasis
of the body
Kidney Function
4 Secretion of hormones
a Erythropoietin (EPO --- is produced by
interstitial cells in peritubular capillary)
which controls erythrocyte production
b Renin ( is produced by juxtaglomerular cell)
which controls formation of angiotensin
c 125-dihydroxyvitamin D3
which influences calcium balance
Outline
bull 1048715 Functional Anatomy of Kidneys and Renal
Circulation
bull 1048715 Glomerular Filtration
bull 1048715 Tubular Processing of Urine Formation
bull 1048715 Urine Concentration and Dilution
bull 1048715 Regulation of Water and Sodium Excretion
bull 1048715 Renal Clearance
bull 1048715 Urine Volume and Micturition
SECTION 1
Functional Anatomy of Kidneys and
Renal Circulation
Urinary system
paired kidneys
paired ureters
a bladder
a urethra
The kidney renal cortex
renal medulla
renal pelvis
Anatomical Characteristics of the Kidney
1 Nephrons functional unit of kidneys
(1) Consist of nephron
bull Nephron is the basic smallest functional unit
of kidney
bull Nephron consists of renal corpuscle and renal
tubule
bull Each kidney is composed of about 1 million
microscopic functional unit
Anatomical Characteristics of the Kidney
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Kidney Function
1 Regulation of water and inorganic ions
balance
2 Excretion of metabolic waste products
3 Removing of foreign chemicals
by producingexcreting urine
to maintain the internal homeostasis
of the body
Kidney Function
4 Secretion of hormones
a Erythropoietin (EPO --- is produced by
interstitial cells in peritubular capillary)
which controls erythrocyte production
b Renin ( is produced by juxtaglomerular cell)
which controls formation of angiotensin
c 125-dihydroxyvitamin D3
which influences calcium balance
Outline
bull 1048715 Functional Anatomy of Kidneys and Renal
Circulation
bull 1048715 Glomerular Filtration
bull 1048715 Tubular Processing of Urine Formation
bull 1048715 Urine Concentration and Dilution
bull 1048715 Regulation of Water and Sodium Excretion
bull 1048715 Renal Clearance
bull 1048715 Urine Volume and Micturition
SECTION 1
Functional Anatomy of Kidneys and
Renal Circulation
Urinary system
paired kidneys
paired ureters
a bladder
a urethra
The kidney renal cortex
renal medulla
renal pelvis
Anatomical Characteristics of the Kidney
1 Nephrons functional unit of kidneys
(1) Consist of nephron
bull Nephron is the basic smallest functional unit
of kidney
bull Nephron consists of renal corpuscle and renal
tubule
bull Each kidney is composed of about 1 million
microscopic functional unit
Anatomical Characteristics of the Kidney
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Kidney Function
4 Secretion of hormones
a Erythropoietin (EPO --- is produced by
interstitial cells in peritubular capillary)
which controls erythrocyte production
b Renin ( is produced by juxtaglomerular cell)
which controls formation of angiotensin
c 125-dihydroxyvitamin D3
which influences calcium balance
Outline
bull 1048715 Functional Anatomy of Kidneys and Renal
Circulation
bull 1048715 Glomerular Filtration
bull 1048715 Tubular Processing of Urine Formation
bull 1048715 Urine Concentration and Dilution
bull 1048715 Regulation of Water and Sodium Excretion
bull 1048715 Renal Clearance
bull 1048715 Urine Volume and Micturition
SECTION 1
Functional Anatomy of Kidneys and
Renal Circulation
Urinary system
paired kidneys
paired ureters
a bladder
a urethra
The kidney renal cortex
renal medulla
renal pelvis
Anatomical Characteristics of the Kidney
1 Nephrons functional unit of kidneys
(1) Consist of nephron
bull Nephron is the basic smallest functional unit
of kidney
bull Nephron consists of renal corpuscle and renal
tubule
bull Each kidney is composed of about 1 million
microscopic functional unit
Anatomical Characteristics of the Kidney
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Outline
bull 1048715 Functional Anatomy of Kidneys and Renal
Circulation
bull 1048715 Glomerular Filtration
bull 1048715 Tubular Processing of Urine Formation
bull 1048715 Urine Concentration and Dilution
bull 1048715 Regulation of Water and Sodium Excretion
bull 1048715 Renal Clearance
bull 1048715 Urine Volume and Micturition
SECTION 1
Functional Anatomy of Kidneys and
Renal Circulation
Urinary system
paired kidneys
paired ureters
a bladder
a urethra
The kidney renal cortex
renal medulla
renal pelvis
Anatomical Characteristics of the Kidney
1 Nephrons functional unit of kidneys
(1) Consist of nephron
bull Nephron is the basic smallest functional unit
of kidney
bull Nephron consists of renal corpuscle and renal
tubule
bull Each kidney is composed of about 1 million
microscopic functional unit
Anatomical Characteristics of the Kidney
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
SECTION 1
Functional Anatomy of Kidneys and
Renal Circulation
Urinary system
paired kidneys
paired ureters
a bladder
a urethra
The kidney renal cortex
renal medulla
renal pelvis
Anatomical Characteristics of the Kidney
1 Nephrons functional unit of kidneys
(1) Consist of nephron
bull Nephron is the basic smallest functional unit
of kidney
bull Nephron consists of renal corpuscle and renal
tubule
bull Each kidney is composed of about 1 million
microscopic functional unit
Anatomical Characteristics of the Kidney
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
The kidney renal cortex
renal medulla
renal pelvis
Anatomical Characteristics of the Kidney
1 Nephrons functional unit of kidneys
(1) Consist of nephron
bull Nephron is the basic smallest functional unit
of kidney
bull Nephron consists of renal corpuscle and renal
tubule
bull Each kidney is composed of about 1 million
microscopic functional unit
Anatomical Characteristics of the Kidney
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
1 Nephrons functional unit of kidneys
(1) Consist of nephron
bull Nephron is the basic smallest functional unit
of kidney
bull Nephron consists of renal corpuscle and renal
tubule
bull Each kidney is composed of about 1 million
microscopic functional unit
Anatomical Characteristics of the Kidney
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Consist of Nephron
Nephron
renal corpuscle
glomerulus
Bowmanrsquos capsule
renal tubule
proximal tubule
thin segment
distal tubule
proximal convoluted tubule
thick descending limb
thin descending limb
thin ascending limb
thick ascending limb
distal convoluted tubule
loop of Henley
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Anatomical Characteristics of the Kidney
Functional unit -nephron
Corpuscle
Bowmanrsquos capsule
Glomerulus capillaries
Tubule
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Two Types of Nephron
bull Cortical nephrons
bull ~85 of all nephrons
bull Located in the cortex
bull Juxtamedullary nephrons
bull Closer to renal medulla
bull Loops of Henle extend deep into renal pyramids
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
AA = EA
1
AA gt EA
2
Diameter of AA
Diameter of EA
To form Vasa recta To form Peritubular capillary EA
Poor Rich Sympathetic
nerve innervation
Almost no High Concentration of renin
10
Concentrate and dilute
urine
90
Reabsorption and secretion
Ratio
Function
Longer into inner part of
cortex
Short next to outer cortex Loop of Henle
Big Small Glomerulus
Inner part of the cortex
next to the medulla
Outer part of the cortex Location
Juxtamedullary nephron Cortical nephron
AA = afferent glomerular arteriole
EA = efferent glomerular arteriole
Tab 8-1 Differences between a cortical and a Juxtamedullary nephron
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Cortical and Juxtamedullary Nephrons
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
2 Collecting duct
Function As same as distal tubular
3 Juxaglomerular apparatus (JGA)
macula densa --- in initial portion of DCT
Function sense change of volume and NaCl
concentration of tubular fluid and transfer
information to JGC
mesangial cell
juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function secrete renin
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Juxaglomerular apparatus
JA locate in cortical nephron consist of juxtaglomerular
cell mesangial cell and macula densa
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Tubulo-glomerular Feedback
bull Macula densa can detects Na+ K+ and Cl-
of tubular fluid and then sent some
information to glomerule regulation
releasing of renin and glomerular filtration
rate This process is called Tubulo-
glomerullar feedback
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Renal circulation
1Characteristics of renal blood circulation
bull Huge volumes blood
1200mlmin15 ndash 14 of the cardiac output
bull Distribution
Cortex 94 outer medulla 5 - 6 inner medulla lt1
bull Two capillary beds
Renal arteryrarrinterlobar arteries rarrarcuate arteries rarrafferent arterioles rarrglomerular capillaries rarrefferent arteriole rarrperitubular capillaries rarrarcuate vein rarrinterlobar vein rarrrenal vein
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Renal circulation
bull Glomerular capillaries
Higher pressure benefit for filtration
bull Peritubular capillaries
Lower pressure benefit for reabsorption
bull Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Renal circulation
Glomerular
capillary
cortex
medulla
Peritubular
capillary
vasa recta
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Regulation of renal blood flow
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg renal
blood flow (RBF) is relatively constant in denervated isolated
or intact kidney
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation myogenic theory of
autoregulation
Physiological significance
To maintain a relatively constant glomerular filtration rate
(GFR)
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Autoregulation of renal blood flow
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Neural regulation
Renal efferent nerve from brain to kidney
bull Renal sympathetic nerve
Renal afferent nerve from kidney to brain
bull Renal afferent nerve fiber can be stimulated
mechanical and chemical factors
renorenal reflex
One side renal efferent nerve activity can effect other side renal nerve activity
Activity of sympathetic nerves is low but can increase during hemorrhage stress and exercise
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Hormonal regulation
Vasoconstriction
bull Angiotensin II
bull Epinephrine
bull Norepinephrine
Vasodilation
bull Prostaglandin
bull nitrous oxide
bull Bradykinin
RBF
RBF
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Basic processes for urine formation
Glomerular filtration
Most substances in blood except for protein and cells are
freely filtrated into Bowmans space
Reabsorption
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries)
Secretion
Some substances (waste products etc) are secreted from
peritubular capillaries or tubular cell interior into tubules
Amount Excreted = Amount filtered ndash Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Three basic processes of the formation of urine
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Basic processes for urine formation
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Section 2 Glomerular Filtration
Only water and small solutes can be filtrated----selective
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Except for proteins the composition of glomerular filtrates is
same as that of plasma
1 Composition of the glomerular filtrates
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
2 Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanrsquos
space
Composition three layers
bull Capillary endothelium ---
fenestrations(70-90nm)
bull Basement membrane ---
meshwork
bull Epithelial cells (podocyte) -
--slit pores
Figure 2610a b
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Showing the filtration membran To be filtered a substance must pass
through 1 the pores between the endothelial cells of the glomerullar capillary
2 an cellular basement membrane and 3 the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanrsquos capsule
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Selective permeability of filtration
membrane
Structure Characteristics
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Selective permeability of filtration
membrane
Size selection
impermeable to substances
with molecule weight (MW)
more than 69 000 or EMR 42 nm (albumin)
Charge selection
Repel negative charged substances
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Filtrate Composition bull Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
bull Neutral solutes
bull Solutes smaller than 180 nanometers in radius are freely filtered
bull Solutes greater than 360 nanometers do not
bull Solutes between 180 and 360 nm are filtered to various degrees
bull Serum albumin is anionic and has a 355 nm radius only ~7 g is filtered per day (out of ~70 kgday passing through glomeruli)
bull In a number of glomerular diseases the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation resulting in proteinuria (ie increased filtration of serum proteins that are mostly negatively charged)
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Glomerular filtration rate (GFR)
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate
(Normally is 125mlmin)
bull Filtration fraction (FF)
The ratio of GFR and renal plasma flow
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Factors affecting glomerular filtration
bull Effective filtration pressure (EFP)
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries
bull EFP is promotion of filtration
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Formation and calculate of EPF
Formation of EPF depends on three pressures
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
bull Calculate of EPF
EFP = Pcap ndash (Pcol + Picap)
bull Part of afferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (30 + 15) = 10
bull Part of efferent arterial
EFP = Pcap ndash (Pcol + Picap) = 55 ndash (40 + 15) = 0
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Effective filtraton pressure
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Filtration Coefficient ( Kf )
bull Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive Kf =KtimesS
bull GFR is dependent on the filtration coefficient
as well as on the net filtration pressure
GFR=Ptimes Kf
bull The surface area the permeability of the
glomerular membrane can affect Kf
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
What kind of factors can affect filtration rate
1Effective filtration pressure
2Glomerular capillary pressure
3Plasma colloid osmotic pressure
4Intracapsular pressure
5Renal plasma flow
6Kf =KtimesS Kf filtration coefficient
K permeability coefficient
S surface area the permeability
Factors Affecting Glomerular Filtration
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Regulation of Glomerular Filtration
bull If the GFR is too high needed substances cannot be reabsorbed quickly enough and are lost in the urine
bull If the GFR is too low - everything is reabsorbed including wastes that are normally disposed of
bull Control of GFR normally result from adjusting glomerular capillary blood pressure
bull Three mechanisms control the GFR
bull Renal autoregulation (intrinsic system)
bull Neural controls
bull Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Autoregulation of GFR bull Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
bull Two mechanisms are in operation for autoregulation
bull Myogenic mechanism
bull Tubuloglomerular feedback
bull Myogenic mechanism
bull Arterial pressure rises afferent arteriole stretches
bull Vascular smooth muscles contract
bull Arteriole resistance offsets pressure increase RBF (amp hence GFR) remain constant
bull Tubuloglomerular feed back mechanism for autoregulation
bull Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
bull Increased GFR (amp RBF) triggers release of vasoactive signals
bull Constricts afferent arteriole leading to a decreased GFR (amp RBF)
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Extrinsic Controls
bull When the sympathetic nervous system is at rest
bull Renal blood vessels are maximally dilated
bull Autoregulation mechanisms prevail
bull Under stress
bull Norepinephrine is released by the sympathetic nervous system
bull Epinephrine is released by the adrenal medulla
bull Afferent arterioles constrict and filtration is inhibited
bull The sympathetic nervous system also stimulates the renin-angiotensin mechanism
bull A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Renin-Angiotensin Mechanism
bull Renin release is triggered by
bull Reduced stretch of the granular JG cells
bull Stimulation of the JG cells by activated macula densa cells
bull Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves
bull Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II
bull Angiotensin II
bull Causes mean arterial pressure to rise
bull Stimulates the adrenal cortex to release aldosterone
bull As a result both systemic and glomerular hydrostatic pressure rise
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Figure 2510
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Other Factors Affecting Glomerular Filtration
bull Prostaglandins (PGE2 and PGI2)
bull Vasodilators produced in response to sympathetic stimulation and angiotensin II
bull Are thought to prevent renal damage when peripheral resistance is increased
bull Nitric oxide ndash vasodilator produced by the vascular endothelium
bull Adenosine ndash vasoconstrictor of renal vasculature
bull Endothelin ndash a powerful vasoconstrictor secreted by tubule cells
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Control of Kf bull Mesangial cells have contractile properties influence
capillary filtration by closing some of the capillaries ndash
effects surface area
bull Podocytes change size of filtration slits
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Glomerular filtration
bull Tubular reabsorption of
the substance from the
tubular fluid into blood
bull Tubular secretion of the
substance from the blood
into the tubular fluid
bull Mass Balance
bull Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Process of Urine Formation
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Tubular Secretion
bull Essentially reabsorption in reverse where
substances move from peritubular capillaries or
tubule cells into filtrate
bull Tubular secretion is important for
bull Disposing of substances not already in the filtrate
bull Eliminating undesirable substances such as urea and
uric acid
bull Ridding the body of excess potassium ions
bull Controlling blood pH
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Tubular reabsorption and secretion
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
SECTION 3 Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption
quantitatively large
More than 99 volume of filtered fluid are reabsorbed
(gt 178L)
selective
100 glucose 99 sodium and chloride 85
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
(1) Type of transportation in renal tubule and
colllecting duct
bull Reabsorption and secretion are divided two types
bull Passive reabsorption (needless energy)
Diffusion osmosis facilitated diffusion
bull Active reabsorption (need energy)
bull Saldium pump (Na+-K+ ATPase) proton pump (H+-ATPase) calcium pump (Ca2+-ATPase)
bull Cotransport (coupled transport)
One transportor can transport two or more substances
bull Symport transport like Na+ and glucose Na+ and amine acids
Antiport transport like Na+-H+ and Na+-K+
bull Secondary active transport like H+ secretion
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Na+ active transport in PT epithelium
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Passway of transport
Apical membrane tight juction brush border
basolateral membrane
bull Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
bull Paracellular transport
Water Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Fig8-23 The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Location of reabsorption
Proximal tubule
Brush border can increase the area of
reabsorption
Henles loop
Distal tubule
Collecting duct
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
(2) Reabsorption and secretion in different part of
renal tubule
bull Proximal tubule (PT)
67 Na+ Cl- K+ and water 85 HCO3- and 100
glucose and amine acids are reabsorption
secretion H+
23 Transcellular pathway
13 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule)
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
1 Na+Cl- and water reabsorption
Na+ and Cl- reabsorption
bull About 65 - 70 in proximal tubule 10 in
distal tubule 20 loop of Henle
bull Valume of filtration 500gday
Valume of excretion 3 ndash 5g99 are
reabsorption
bull Front part of PT Na+ reabsorption with HCO3-
Glucose and Amine acids
Behind part of PT Na+ reabsorption with Cl-
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Cl- reabsorption
Passive reabsorption with Na+
bull water reabsorption
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Water passive reabsorption
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
K+ reabsorption
Most of in PT (70)20 in loop of Henle
Active reabsorption
Ca2+ reabsorption
70 in PT 20 in loop of Henle 9 in DCT
20 is transcellular pathway
80 is paracellular transport
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
HCO -3 reabsorption and H+ secretion
bull About 80 in PT 15 in ascending thick limb 5 in
DCT and CD
bull H2CO3 CO2 + H2O CO2 is easy reabsorption
bull HCO3ndash reabsorption is priority than Cl-
H+ secretion
bull CO2 + H2O H2CO3 HCO3ndash+ H
+
bull H+ secretion into lumen
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Glucose and amino acid reabsorption
Glucose reabsorption 99 glucose are reabsorption no glucose in urine
bull Location
early part of PT
bull Type of reabsorption
secondary active transport
bull Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter glucose can first
be detected in the urine this value is called the renal
glucose threshold
9-101 mmolL (160-180mgdl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules
Amino acid reabsorption
Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Co-transport of amino acids via Na+ symport mechanism
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Loop of Henle
Ascending thick limb of loop of Henle
Na+ Cl- and K+ cotransport
Transportation rate Na+ 2Cl- K+
Distal tubule and collecting duct
Principal cell Reabsorption Na+ water and
secretion K+
Intercalated cell Secretion H+
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull 12 Na+ Cl- and water are reabsorbed in distal tubule and collecting duct
bull Water reabsorption depends on whether lack of
water of body ADH (discuss later)
bull Na+ and K+ reabsorption Aldosteron (discuss later)
bull K+ secretion Na+ - K+ - ATPase
bull H+ secretion Na+ -H+ antiport transport
bull NH3 secretion Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine Na+ reabsorption into blood
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull DCT performs final adjustment of urine
bull Active secretion or absorption
bull Absorption of Na+ and Cl-
bull Secretion of K+ and H+ based on blood pH
bull Water is regulated by ADH (vasopressin)
bull Na+ K+ regulated by aldosterone
Secretion at the DCT
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Co-transport of amino acids via Na+ symport mechanism
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Proximal tubule
Reabsorption Secretion
67 of filtered Na+ actively
reabsorbed not subject to control
Cl- follows passively
All filtered glucose and amino acids
reabsorbed by secondary active
transport not subject to control
65 of filtered H2O osmotically
reabsorbed not subject to control
Almost all filtered K+ reabsorbed
not subject to control
Variable H+ secretion
depending on acid-base
status of body
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by
Aldosterone
Cl- follows passively
Variable H2O reabsorption
controlled by vasopressin (ADH)
Variable H+ secretion
depending on acid-base
status of body
Variable K+ secretion
controlled by aldosterone
Table 8-2 Summary of transport across PT DT and collecting duct
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Urinary Concentration and Dilution
bull Hypertonic urine
Lack of water in body can forms concentrated urine
(1200 mOsmL)
bull Hypotonic urine
More water in body can forms dilute urine (50 mOsmL)
bull Isotonic urineInjury of renal function
bull Urinary dilution
The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water
bull Urinary concentration
The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
formation of dilute and concentrated urine
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Control of Urine Volume and Concentration
bull Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption
bull Precise control allowed via facultative water reabsorption
bull Osmolality
bull The number of solute particles dissolved in 1L of water
bull Reflects the solutionrsquos ability to cause osmosis
bull Body fluids are measured in milliosmols (mOsm)
bull The kidneys keep the solute load of body fluids constant at about 300 mOsm
bull This is accomplished by the countercurrent mechanism
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine
Lack of water ADH water reabsorption
in DCT and CD concentrated urine
Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid
Role of countercurrent exchanger
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Urinary concentrating environment
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Basic structure
ldquoUrdquotype of loop of Henle
Vasa rectarsquos cliper type (发卡样排列)
Collecting duct from cortex to medulla
bull Basic function
Different permeability of solutes and water in
DCT CD and loop of Henle
bull Osmotic gradient exit from cortex to medulla
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Tab8-2 Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability to
water
Permeability to
Na+
Permeability to
urea
Thick ascending
limb
Almost not Active transport of
Na+ Secondary
active Transport of Cl-
Almost not
Thin ascending
limb Almost not Yes Moderate
Thin descending
limb
Yes Almost not Almost not
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of K+
K+-Na+ exchange Almost not
Collecting
duct Permeable
Under ADH
action
Yes Cortex and outer
Medulla almost not
Inner medulla Yes
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
Formation of osmotic gradient is related to
physiological characters of each part of renal tubule
Outer medulla
Water are permeated in descending thin limb but not NaCl
and urea
NaCl and urea are permeated in ascending thin limb but
not water
NaCl is active reabsorbed in ascending thick limb but not
Urea and water
Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Inner medulla
bull High concentration urea exit in tubular fluid
bull Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
bull NaCl is not permeated in descending thin limb
bull NaCl is permeated in ascending thin limb
bull Urea recycling
bull Urea is permeated in ascending thin limb part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again
bull Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Countercurrent Mechanism
bull Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
bull The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Countercurrent exchange Countercurrent exchange is a common process in
the vascular system Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta and solutes and water
are Exchanged between these capillary blood vessels
Countercurrent multiplication Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Loop of Henle Countercurrent Multiplication
bull Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid
bull Maintains the osmotic gradient
bull Delivers blood to the cells in the area
bull The descending loop relatively impermeable to solutes highly permeable to water
bull The ascending loop permeable to solutes impermeable to water
bull Collecting ducts in the deep medullary regions are permeable to urea
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Medullary osmotic gradient
bull H2OECFvasa recta vessels
Countercurrent Multiplier and Exchange
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Formation of Concentrated Urine
bull ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis
bull This equalizes the osmolality of the filtrate and the interstitial fluid
bull In the presence of ADH 99 of the water in filtrate is reabsorbed
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Formation of Dilute Urine
bull Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted
bull Dilute urine is created by allowing this filtrate to continue into the renal pelvis
bull Collecting ducts remain impermeable to water no further water reabsorption occurs
bull Sodium and selected ions can be removed by active and passive mechanisms
bull Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Mechanism of ADH (Vasopressin) Action
Formation of Water Pores
bull ADH-dependent water reabsorption is called facultative
water reabsorption
Figure 20-6 The mechanism of action of vasopressin
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Water Balance Reflex
Regulators of Vasopressin Release
Figure 20-7 Factors affecting vasopressin release
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
bull Way of regulation for urine formation
Filtration Reabsorption and Secretion
bull Autoregulation
bull Solute concentration of tubular fluid
Osmotic diuresis -- diabaticmannitol
bull Glomerulotubular balance
Regulation of Urine Formation in the Kidney
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Nervous regulation
Role of Renal Sympathetic Nerve
Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Renin-Angiotension-Aldosterone System
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Regulation by ADH
bull Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality
bull Dehydration or excess
salt intake
bull Produces sensation
of thirst
bull Stimulates H20
reabsorption from
urine
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
The change of crystal osmotic
pressure
Effective stimuli
The change of effective blood
volume
The regulation of ADH secretion
Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Source of ADH
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Figure 2615a b
Effects of ADH on the DCT and Collecting Ducts
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Regulation of ADH release over hydration
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Regulation of release hypertonicity
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Atrial Natriuretic Peptide Activity
Increase GFR reducing water reabsorption
Decrease the osmotic gradient of renal medulla and promotes Na+ excretion
Acting directly on collecting ducts to inhibit Na+ and water reabsorption promotes Na+ and water excretion in the urine by the kidney
Inhibition renin release and decrease angiotensin II and aldosterone promotes Na+ excretion
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Endothelin (ET)
Constriction blood vessels decrease GFR
Nitic Oxide (NO)
Dilation blood vessels increase GFR
Epinephrine (EP) Norepinephrine (NE)
promote Na+ and water reabsorption
Prostaglandin E2 I2
Dilation blood vessels excretion Na+ and water
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
A Summary of Renal Function
Figure 2616a
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
1 Concept
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2 Calculate
concentration of it in urine timesurine volume
C =
concentration of it in plasma
Renal clearance
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Renal Clearance
RC = UVP
RC = renal clearance rate
U = concentration (mgml) of the substance in urine
V = flow rate of urine formation (mlmin)
P = concentration of the same substance in plasma
bull Renal clearance tests are used to
bull Determine the GFR
bull Detect glomerular damage
bull Follow the progress of diagnosed renal disease
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Theoretical significance of clearance
31 Measure GFR
bull A substance---freely filtered non reabsorbed
non secreted--its renal clearance = GFR
bull Clearance of inulin or creatinine can be used to
estimate GFR
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
32 Calculate RPF and RBF
A substance--freely filtered non reabsorbed secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
33 Estimate of tubular handling for a substance
If the clearance of substancegt125mlmin
---it must be secreted
If it lt125mlmin --- it must be reabsorbed
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Physical Characteristics of Urine
Color and transparency
bull Clear pale to deep yellow (due to urochrome)
bull Concentrated urine has a deeper yellow color
bull Drugs vitamin supplements and diet can change the color of urine
bull Cloudy urine may indicate infection of the urinary tract
pH
bull Slightly acidic (pH 6) with a range of 45 to 80
bull Diet can alter pH
Specific gravity
bull Ranges from 1001 to 1035
bull Is dependent on solute concentration
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Chemical Composition of Urine
bull Urine is 95 water and 5 solutes
bull Nitrogenous wastes include urea uric acid and
creatinine
bull Other normal solutes include
bull Sodium potassium phosphate and sulfate ions
bull Calcium magnesium and bicarbonate ions
bull Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Urine Volume and Micturition
1 Urine volume
Normal volume 10~20Lday
Obligatory urine volume ~400mlday
Minimum needed to excrete metabolic wastes of
waste products in body
Oliguria--- urine volume lt 400mlday
Anuria---urine volume lt 100mlday
Accumulation of waste products in body
Polyuria--- urine volume gt 2500mlday long time
Abnormal urine volume Losing water and electrolytes
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Micturition
Functions of ureters and bladder
Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle
Urine is stored in bladder and intermittently ejected during urination or micturition
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Micturition
bull Micturition is process of emptying the urinary bladder
bull Two steps are involved
bull (1) bladder is filled progressively until its pressure rises
bull above a threshold level (400~500ml)
bull (2) a nervous reflex called micturition reflex occurs that empties bladder
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Micturition
bull Pressure-Volume curve of the bladder has
a characteristic shape
bull There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Pressure-volume graph for normal human
bladder
100 200 300 400
025
050
075
100
125
1st desire
to empty
bladder
Discomfort Sense of
urgency
Volume (ml)
Pre
ss
ure
(k
Pa
)
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Micturition (Voiding or Urination)
bull Bladder can hold 250 - 400ml
bull Greater volumes stretch bladder walls initiates micturation reflex
bull Spinal reflex
bull Parasympathetic stimulation causes bladder to contract
bull Internal sphincter opens
bull External sphincter relaxes due to inhibition
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Innervation of bladder
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Urination Micturation reflex
Figure 19-18 The micturition reflex
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Micturition (Voiding or Urination)
Figure 2520a b
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Review Questions
Explain concepts
1Glomerular filtration rate
2 Effective filtration pressure
3 Filtration fraction
4Renal glucose threshold
5Osmotic diuresis
6Renal clearance
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Review Questions
1 What are the functions of the kidneys
2 Describe autoregulation of renal plasma flow
3 What are three basic processes for urine formation
4 Describe the forces affecting glomerular filtration
5 Describe the factors affecting GFR
6 What is the mechanism of sodium reabsorption in the proximal tubules
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria
Review Questions
7 What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption
8 What is the mechanism of formation of
concentrated and diluted urine
9 After drinking large amount of water what does
the amount of urine change Why
10 Why a patient with diabetes has glucosuria and
polyuria