-
8/3/2019 physiology ....final material .... Urinary System
1/76
Urinary system
Introduction
GF
Tubular reabsorption Tubular secretion
Urine excretion & plasma clearance
-
8/3/2019 physiology ....final material .... Urinary System
2/76
functions
1- maintaining ECF stability volume &compsoition
2- main route for eliminating potentially
toxic wastes & foreign compounds from
the body
3- acid-base balance
4- producing erythropoiten
5- producing renin which triggers a chainreaction important in salt conservation
by kidneys
6- converting vitamin D into its active
form
-
8/3/2019 physiology ....final material .... Urinary System
3/76
Kidneys: urine forming organs, bean-shaped, located in the back of the
abdominal wall Renal pelvis: central collecting cavity
that leads to the ureter which is a
smooth muscle walled duct Urinary bladder: smooth muscle
walled sac that stores urine
Urethra: straight and short infemale, long and curving course inmales passing through the prostate
gland and the penis
-
8/3/2019 physiology ....final material .... Urinary System
4/76
Nephron: the functional unit, 2 million inboth kidneys: a- medullary b- cortical
vascular components of the nephron :
1- Glomerulus : ball like tuft of capillaries
2-afferent arteriole to the glomerulus
3-efferent arteriole out of the glomerulus
4-peritubular capillaries then venules
-
8/3/2019 physiology ....final material .... Urinary System
5/76
-
8/3/2019 physiology ....final material .... Urinary System
6/76
Tubular components of the nephron:-hallow fluid filled tube, single layer ofepithelium1-Bowman's capsule around the
glomerulus2-proximal tubule convoluted3-loop of Henle: u-shaped, dips into the
medulla:a-descending b-ascendingpasses between the afferent & efferentarterioles
4-distal tubule: lies in the cortex5-collecting duct: 8 nephrons drain in one
duct
-
8/3/2019 physiology ....final material .... Urinary System
7/76Fig. 13-2, p. 408
Proximal tubule Distaltubule Collecting
duct
Bowmanscapsule
Glomerulus
CortexMedulla
Loop ofHenle
To renalpelvisOverview of Functions of Parts of a Nephron
Peritubularcapillaries
Vein
Artery
Afferentarteriole
Efferent
arteriole
Juxtaglomerularapparatus
-
8/3/2019 physiology ....final material .... Urinary System
8/76
-
8/3/2019 physiology ....final material .... Urinary System
9/76
Glomerular filtration Plasma free from protein filters in b. capsule 20% of plasma that enters the glomerulus is filtered 125mL of glomerular filtrate is formed each minute (
180L/day) kidneys filter the entire plasma volume 65 times/day Glom. Membrane:
a-wall of glom. Capillaries is 100x more permeableb-basement membrane: acellular gelatinous layerc-inner layer of B. capsule is made of podocytes which areoctopus like cells between filtration slits
-
8/3/2019 physiology ....final material .... Urinary System
10/76Fig. 13-5c, p. 410
Podocyte
foot process
Filtration
slit
Basement
membrane
Capillarypore
Endothelialcell
Lumen of glomerularcapillary
Lumen ofBowmans capsule
-
8/3/2019 physiology ....final material .... Urinary System
11/76Fig. 13-4, p. 409
Afferentarteriole
Efferentarteriole
80% of the plasmathat enters theglomerulus isnot filteredand leaves throughthe efferent arteriole.
Glomerulus
Bowmanscapsule
20% of the
plasma thatenters theglomerulusis filtered.
Kidneytubule(entirelength,uncoiled)
Urine excretion
(eliminatedfrom the body)
To venous system(conservedfor the body)
Peritubularcapillary
GF
TR
TS
-
8/3/2019 physiology ....final material .... Urinary System
12/76
-
8/3/2019 physiology ....final material .... Urinary System
13/76
Forces involved in GF
Like forces starling capillary circulation with 2 exceptions:a- permeability is much higherb- filtration occurs through out the whole glomerulus capillary
1- glomerulus blood pressure ~55mmHg larger than any other
capillary because the afferent arteriole are wide and theefferent are narrow2-plasma colloid osmotic pressure ~30mmHg, opposes
filtration3-Bomans capsule hydrostatic pressure ~15mmHg exerted by
the fluid in the initial part of the tubule, opposes filtration
-
8/3/2019 physiology ....final material .... Urinary System
14/76Table 13-1, p. 412
-
8/3/2019 physiology ....final material .... Urinary System
15/76
GFR
Net filtrating pr. = 55- (30+15)= 10mmHg Changes in GFR occurs mainly due to changes in
the glom. capillary pr. By the sympathetic effectmainly on the afferent arteriole not the efferentone
decreased BP carotid & aorticbaroreceptors increase symp.vasoconstriction afferent spasm decrease bl.Flow decrease glom. Cap. Pr. decrease GFR
decrease urine
conserve body fluid & salts
increase BP
-
8/3/2019 physiology ....final material .... Urinary System
16/76
GFR
increased BP carotid & aortic baroreceptorsdecrease symp. vasodilatation afferentdilatation increase bl. Flow increase glom.Cap. Pr. increase GFR increase urine
decrease body fluid decrease BP
-
8/3/2019 physiology ....final material .... Urinary System
17/76Fig. 13-8a, p. 413
Vasoconstriction(decreases blood flowinto the glomerulus)
Afferent arteriole
Glomerulus
Efferent arteriole
Glomerularcapillaryblood pressure
Net filtrationpressure
GFR
-
8/3/2019 physiology ....final material .... Urinary System
18/76Fig. 13-8b, p. 413
Afferent arteriole
Glomerulus
Efferent arteriole
Glomerularcapillaryblood pressure
Net filtrationpressure
GFR
Vasodilation(increases blood flowinto the glomerulus)
Short-term Arterial blood Long-term
-
8/3/2019 physiology ....final material .... Urinary System
19/76Fig. 13-7, p. 413
Short termadjustmentfor
Arterial bloodpressure
Long termadjustment for
Arterialbloodpressure
Detection by aorticarch and carotid sinusbaroreceptors
Cardiacoutput
Totalperipheralresistance
Sympathetic activity
Generalizedarteriolar vasoconstriction
Afferent arteriolarvasoconstriction
Glomerular capillaryblood pressure
GFR
Urine volume
Conservation of fluid and salt
Arterial blood pressure
-
8/3/2019 physiology ....final material .... Urinary System
20/76
22-25% of the cardiac output goesto the kidneys ( 1140mL/min) and
Htc. accounts for 45% so the kidneyreceives 625mL plasma/min and20% of those are filtrated
(125mL)(GFR)
-
8/3/2019 physiology ....final material .... Urinary System
21/76
Tubular reabsorption
Tremendously & highly selective & has ahigh reabsorptive capacity for neededmaterials
Little capacity for wastes & no capacity for
toxics 125mL/min GFR 124 ml is reabsorbed
(99% H2O, 100% glucose, 99.5% salts) Steps of transepithelial transport:
1-luminal membrane 2-cytosol3-basolateral mem. 4-interstitial5-capillary wall
-
8/3/2019 physiology ....final material .... Urinary System
22/76
-
8/3/2019 physiology ....final material .... Urinary System
23/76
Passive transport and active transport :active if one step is active
-glucose, AA, organic nutrients, Na, PO4
Na reabsorption: Na-K pump at basolateralmembrane is essential for Nareabsorption(99.5%):
-67% in proximal tubules
-25% in loop of henle
-8% in collecting & distal tubules
-in proximal tubules Na reabsorption helps inglucose, AA, H2O, Cl, and urea reabsorption.
+ -3
-
8/3/2019 physiology ....final material .... Urinary System
24/76
in the ascending limb of the loop of henle Nareabsorption along with Cl play a critical role inproducing urine of varying concentration andvolume
Theres no Na reabsorption in the descendinglimb of loop of henle
In the distal & collecting tubules Na reabsorptionis variable & subject to hormonal control, and itplays a role in regulating ECF volume and linkswith K & H secretion
Na is firstly absorbed by the Na-K pump in thebasolateral wall then from the lumen in cells bypassive transport
Na reabsorption
-
8/3/2019 physiology ....final material .... Urinary System
25/76
Fig. 13-10, p. 416
Lumen Tubular cell Interstitial fluid
Peritubularcapillary
Diffusion
Na+channel
Active transport
BasolateralNa+ K+ ATPasecarrier
Lateral space Diffusion
-
8/3/2019 physiology ....final material .... Urinary System
26/76
Glucose reabsorption
Proximal tubules with glucose cotransportand AA almost 100%, then by facilitatedpassive transport in the basolateral wall, Na-
glucose carriers as well as Na-AA arespecific
-those carriers has a maximum transportcapacity called tubular maximum (Tm)
-any quantity beyond Tm will escape intourine
-filtered load= plasma con. x GFR
for glucose= 100mg/100mL x 125mL/min
-
8/3/2019 physiology ....final material .... Urinary System
27/76
Glucose reabsorption
-Tm for glucose averages 375mg/min
-the plasma con. Of glucose at whichglucose reaches its Tm is called renal
threshold (300mg/100mL)-if glucose plasma con. Increases itwill leave the filtrate
-if glucose plasma con. decreases itwill be completely reabsorbed
-kidneys do not regulate glucose andAA
-
8/3/2019 physiology ....final material .... Urinary System
28/76
Fig. 13-12, p. 420
-
8/3/2019 physiology ....final material .... Urinary System
29/76
Phosphate & calcium reabsorption
Both are actively absorbed and regulatedby the kidneys
The renal threshold for both of thesesubstances equals to their plasma con.
-the tubules will reabsorb the samenormal plasma con. And any excess that isingested will be spilled out in the urinerestoring the normal plasma con.
- PO4 & Ca renal threshold can beregulated by the parathyroid hormonedepending on the body needs
-3 +2
-
8/3/2019 physiology ....final material .... Urinary System
30/76
aldosterone
Aldosterone stimulates Na reabsorption in the distaland collecting tubules
-if Na con. In plasma is high no regulation Na out
-if Na con. In plasma is low aldosterone release
more reabsorption conserve Na Renin-angeotensin-aldosterone system (RAAS):
-renin is secreted from the juxtaglomerulusapparatus which activates the angiotensin in the
plasma into angiotensin I-angiotensin I under the effect of ACE in thepulmonary circulation is converted to angiotensin IIwhich stimulates aldosterone release
NaCl / ECF volume /
-
8/3/2019 physiology ....final material .... Urinary System
31/76
Fig. 13-11, p. 417
Arterial blood pressure
Liver Kidney LungsAdrenalcortex
Kidney
H2Oconserved
Na+ (and CI)osmotically holdmore H2O in ECF
Na+ (and CI)conserved
Na+ reabsorptionby kidney tubules( CI
reabsorptionfollows passively)
Vasopressin Thirst Arteriolarvasoconstriction
H2O reabsorption
by kidney tubulesFluid intake
Renin
Angiotensin-converting
enzyme
Angiotensinogen Angiotensin I Angiotensin II Aldosterone
-
8/3/2019 physiology ....final material .... Urinary System
32/76
aldosterone effects:-promotes insertion of new Na channels intothe luminal membrane
-additional Na-K carriers in the basolateralmembrane-these effects are seen in the distal &collecting tubules
When Na load, ECF/plasma volume, and BPare above normal renin release isinhibited no aldosterone Na portion inthe distal tubules and the collecting ducts isexcerted
8% is not a small amount considering thefact that per day plasma will be filtered 65times so 20g of salt is lost per day
Na+/ ECF volume/
-
8/3/2019 physiology ....final material .... Urinary System
33/76
Fig. 13-15, p. 423
Na+/ ECF volume/arterial pressure
Renin
Angiotensin I
Angiotensin IIPlasma K+
Aldosterone
Tubular K+ secretion Tubular Na+ reabsorption
Urinary K+ excretion Urinary Na+ excretion
-
8/3/2019 physiology ....final material .... Urinary System
34/76
ANP(atrial natriuretic peptide)
ANP is released from the atria whenthe heart is stretched by expansionof the ECF volume as a result of Na &
H2O retention
-increased BP ANP release inhibitNa reabsorption more Na & H2O
are released into the urine less ECFvolume decrease BP
-
8/3/2019 physiology ....final material .... Urinary System
35/76
Table 13-3, p. 424
-
8/3/2019 physiology ....final material .... Urinary System
36/76
Cl reabsorption
Passively absorbed down theelectrical gradient which is createdby active Na reabsorption
-
-
8/3/2019 physiology ....final material .... Urinary System
37/76
H2O reabsorption
Passive by osmosis following Nareabsorption
- 65% (117L/day) by the end of
the proximal tubules
- 15% of filtered H2O is obligatorily
reabsorbed from loop of henle
- 20% remaining is reabsorbed in distal
tubules
Hormonal regulation:
-water channels in the aquaporins part
is regulated by vasopressin
-
8/3/2019 physiology ....final material .... Urinary System
38/76
Urea reabsorption
Passive linked to active Nareabsorption
In the proximal tubules [urea] isincreased three time because of Na &H2O reabsorption
Urea is passively absorbed but it
does not have good permeability
only 50% of urea is reabsorbed
-
8/3/2019 physiology ....final material .... Urinary System
39/76
Fig. 13-13, p. 421
Glomerulus
Bowmans
capsule
Beginning ofproximal
tubule
Peritubularcapillary
Na+ (active)
H2O (osmosis)
Na+ (active)
H2O (osmosis)
Passive diffusion
of urea down itsconcentration gradient
44 mloffiltrate
125 mloffiltrate
End ofproximaltubule
= Urea molecules
-
8/3/2019 physiology ....final material .... Urinary System
40/76
wastes
Waste products are not reabsorbedbecause the permeability of thetubules to these products is almost
zero :
-phenol
-creatinine
-other toxics
-
8/3/2019 physiology ....final material .... Urinary System
41/76
Tubular secretion
Supplemental mechanisms that hastenelimination of substances from the body
1- hydrogen:- important for acid-base balance
- secreted by proximal, distal, &
collecting tubules
-
8/3/2019 physiology ....final material .... Urinary System
42/76
2- potassium:
-actively reabsorbed in proximal
tubules
-actively secreted in distal &
collecting tubules
-when plasma [K] increases,
secretion is adjusted to eliminate Kout
-
8/3/2019 physiology ....final material .... Urinary System
43/76
-mechanism of secretion:
coupled with Na-K pump which
reduces [K]interstitial plasma Kleaves peritubular capillary the
pump get K inside the tubular cells
which has many K channels tohelp K to get out to the tubular
lumin passively
-K channels in the proximal tubules
are located at the basolateral side
-
8/3/2019 physiology ....final material .... Urinary System
44/76
-control of K secretion:
increased [K]plasma stimulation of
adrenal cortex increase
aldosterone increase in K
secretion & Na reabsorption
-
8/3/2019 physiology ....final material .... Urinary System
45/76
Fig. 13-14, p. 423
Lumen Tubular cellPeritubularcapillaryInterstitial fluid
K+channel
Activetransport
Diffusion
Diffusion
-
8/3/2019 physiology ....final material .... Urinary System
46/76
3- organic anions & cations:
-two types of carriers one for
anions & the other for cations:
-prostaglandins
-food additives-histamine & nor-epinephrine
-environmental pollutants
(pesticides), drugs
-
8/3/2019 physiology ....final material .... Urinary System
47/76
-
8/3/2019 physiology ....final material .... Urinary System
48/76
Plasma clearance
Plasma clearance of any substance is
the volume of plasma completelycleared of that substance by thekidneys per minute
-
8/3/2019 physiology ....final material .... Urinary System
49/76
-a substance (X) that is filtered but notreabsorbed or secreted has a plasma
clearance= GFR 125mL/min of plasma is filtered
containing an amount of X, this
amount of X is left behind andis excreted with urine thus each
minute 125mL of plasma will be
cleared from X example inulinproduced chemically
-
8/3/2019 physiology ....final material .... Urinary System
50/76
Fig. 13-16a, p. 426
Glomerulus
Tubule
Peritubularcapillary
Inurine
For a substance filtered and not reabsorbed
or secreted, such as inulin, all of the filteredplasma is cleared of the substance.
-
8/3/2019 physiology ....final material .... Urinary System
51/76
-a substance (Y) is filtered andreabsorbed but not secreted has aplasma clearance that is less than
GFR
examples:
a- glucose pl. cl. = 0
b- urea pl. cl. =62.5mL/min
-
8/3/2019 physiology ....final material .... Urinary System
52/76
Fig. 13-16b, p. 426
For a substance filtered,
not secreted, and completelyreabsorbed, such as glucose,none of the filtered plasmais cleared of the substance.
-
8/3/2019 physiology ....final material .... Urinary System
53/76
Fig. 13-16c, p. 426
For a substance filtered,not secreted, and partiallyreabsorbed, such as urea, onlya portion of the filtered plasma
is cleared of the substance.
-
8/3/2019 physiology ....final material .... Urinary System
54/76
- a substance (Z) is filtered and secretedbut not reabsorbed has a plasmaclearance that is larger than GFR
H+ is an example which is cleared by
the following rates: 125mL/min by
filtration & 25mL/min by secretion so it
has a pl. cl =150mL/min
paraaminohippuric acid (PAH), 20% of
this chemical is filtered, and the
remaining 80% will be secreted so it a
has a pl. cl =plasma flow rate (625mL/min)
-
8/3/2019 physiology ....final material .... Urinary System
55/76
Fig. 13-16d, p. 426
For a substance filtered and secretedbut not reabsorbed, such as hydrogenion, all of the filtered plasma iscleared of the substance, and theperitubular plasma from which the
substance is secreted is also cleared.
Urine e cretion of ar ing
-
8/3/2019 physiology ....final material .... Urinary System
56/76
Urine excretion of varyingconcentrations
Interstitial fluid of the medulla build upa large osmotic gradient
The concentration of fluid progressivelyincreases from the cortex downthrough the depth of the medulla up to
1200mOsmole/L
Medulla
-
8/3/2019 physiology ....final material .... Urinary System
57/76
Fig. 13-17, p. 427
Cortex
All values in milliosmols (mosm)/liter.
U i i t d i th f 100 1200
-
8/3/2019 physiology ....final material .... Urinary System
58/76
Urine is excreted in the range of 100-1200mOsmole/L depending on body fluid status:
1- ideally 1mL/min, isotonic
2- overhydration up to 25mL/min,
hypotonic, 100mOsmole/L
3-dehydration 0.3mL/min
hypertonic, up to 1200mOsm/L
1, 2, 3 represent the medullary countercurrent
system
Countercurrent multiplication
-
8/3/2019 physiology ....final material .... Urinary System
59/76
Countercurrent multiplication(c.c.m)
In the proximal tubules, 65% reabsorbed(water & salts) so solvent & solute are equallyabsorbed, so the tonicity will remain isotonic
In the loop of henle:
1-descending limb: -high water permeability
-no sodium reabsorption2-ascending limb: -actively reabsorbed NaCl
-impermeable for water
Glomerulus
-
8/3/2019 physiology ....final material .... Urinary System
60/76
Fig. 13-19a, p. 430
Bowmans capsule
Proximal tubule
Distal tubule
Cortex
Medulla
Long loopof Henle
Collectingtubule
-
8/3/2019 physiology ....final material .... Urinary System
61/76
Mechanism of c.c.m
Initial scene: interstitial fluid is 300mOsm/L
Step1: -NaCl actively pumped from
ascending with the force of
200mOsm/L dif.
-water will be reabsorbed from the
descending to equilibrate with the
outside until both have 400mOsm/L
-
8/3/2019 physiology ....final material .... Urinary System
62/76
Fig. 13-19b, p. 431Step 1
St 2 t f l i l filt t
-
8/3/2019 physiology ....final material .... Urinary System
63/76
Step2: -movement of luminal filtrate so
from ascending 200mOsm/L fluid
to the distal tubules, &300mOsm/L fluid from proximal
tubules gets in the descending
limb & in between 400mOsm/L is
moved around the tip
-
8/3/2019 physiology ....final material .... Urinary System
64/76
Fig. 13-19c, p. 431Step 2
Todistaltubule
Fromproximaltubule
-
8/3/2019 physiology ....final material .... Urinary System
65/76
Step3: -ascending limb pumps NaCl
while water is reabsorbedfrom the descending limb until
200mOsm/L dif. Is established
between the ascending, the
interstitial fluid & the
descending
-
8/3/2019 physiology ....final material .... Urinary System
66/76
Fig. 13-19d, p. 430Step 3
-
8/3/2019 physiology ....final material .... Urinary System
67/76
Step4: -movement of filtrate will
again disrupt the 200mOsm/Lgradient at the horizontal level
Step5: -active NaCl pump in the
ascending limb with water
diffusion in the descending one-the 200mOsm/L is reestablished
-
8/3/2019 physiology ....final material .... Urinary System
68/76
Step4 Step5
Fromproximaltubule
todistaltubule
-
8/3/2019 physiology ....final material .... Urinary System
69/76
Step6: -filtrate movement again will changethe gradient so that it will lead to a
progressive increment in the
tonicity of the fluid in the
descending limb & decrement in the
ascending one
Fromproximal
To
-
8/3/2019 physiology ....final material .... Urinary System
70/76
Fig. 13-19g, p. 431Step 6 and on
proximaltubule
distaltubule
-
8/3/2019 physiology ....final material .... Urinary System
71/76
Vasopressin effects
180L/day is filtered, 65% is reabsorbedin the prox. tubules, 15% is reabsorbedin the L.H, & the remaining 20% is
reabsorbed in the distal tubules~36L/day
This 36L filtrate is very hypotonic(100mOsm/L), whereas the interstitialfluid is isotonic in the cortex and up to1200mOsm/L in the collecting ducts
through the medulla
-
8/3/2019 physiology ....final material .... Urinary System
72/76
Vasopressin will make the distal & collectingducts permeable to water
Vasopressin is produced in the hypothalamus,stored in the posterior pituitary gland, &stimulated by hypertonicity of the ECF
Vasopressin binds receptors in the distal &collecting tubules activates cAMP promotesinsertion of aquaporins in the luminal
membrane
Vasopressin effects
-
8/3/2019 physiology ....final material .... Urinary System
73/76
The previous process is reversible bydecreasing vasopressin
Maximum effect of vasopressin:
-everyday 600 mOsm of waste is
produced, this should be dissolved
in water, the normal ability of thekidneys to concentrate a sln. is
1200mOsm/L, so these 600mOsm
will be dissolved in 0.5L
Vasopressin effects
-
8/3/2019 physiology ....final material .... Urinary System
74/76
Vasopressin effects
-these 0.5L of urine is the minimum volumeof urine that is required to excrete dailywaste (obligatory water loss)
-if there is no vasopressin, the distal &collecting tubules are impermeable towater, so 20% of filtrate cannot be
reabsorbed completely, so 25mL/min willbe excreted & the fluid will be hypotonic
Fromproximal
Filtrate has concentrationof 100 mosm/liter as itenters distal and
-
8/3/2019 physiology ....final material .... Urinary System
75/76
Fig. 13-20a, p. 433
tubule enters distal andcollecting tubules
In thefaceof awaterdeficit
Collectingtubule
Loop ofHenle
Medulla
Cortex
Distal tubule
Concentration ofurine may be up
to 1,200 mosm/literas it leavescollecting tubule
= permeability to H2Oincreased by vasopressin
= passive diffusion ofH2O
= active transport of NaCl
= portions of tubuleimpermeable to H2O
*
Fromproximaltubule
Filtrate has concentrationf 100 /lit it
-
8/3/2019 physiology ....final material .... Urinary System
76/76
tubule of 100 mosm/liter as itenters distal andcollecting tubules
In thefaceof awaterexcess
Collectingtubule
Loop ofHenle
Medulla
Cortex
Distal tubule
Concentration ofurine may be as lowas 100 mosm/literas it leavescollecting tubule
= passive diffusion ofO
= portions of tubuleimpermeable to H O