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Wang Guoqing

Department of Physiology,

Medical School, Soochow University,

Suzhou 215123, ChinaE-mail:[email protected]

Tel:0512-62096158; 13506212030

Chapter 8Formation and Excretion of Urine

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Chapter outline

I. Functional renal anatomy

II. Renal blood flow

III. Glomerular filtration

IV. Transport in the renal tubule and collecting duct

V. Urinary concentration and dilution

VI. Regulation of urine formation

VII. Clearance

VIII.Renal regulation of acid-base balance

IX. Micturition

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Respiratory system ( )Large intestine ( )

Skin ( )

Kidney ( )**

Excretion pathway

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Excretory Approach

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Urinary System

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General principles

Kidney Functions**

Kidneys regulate water and electrolyte levels.

Kidneys regulate acid-base balance.

Kidneys excrete metabolic waste products and foreign

substances.

Hormones produced are angiotensin ,1, 25-

dihydroxyvitamin D3, aldosterone and

erythropoietin(EPO).

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Body water homeostasis (balance)

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I. Functional renal anatomy

The nephron is the basic subunit of the kidney. It iscomposed of two components: the glomerulus and therenal tubule.

Renal arterioles lead to glomerular capillary tufts, which

are the site of blood filtration. Bowmans capsule receives this filtrate, which is modified

as it passes along the kidney tubules.

A single kidney is divided into four major sequential

sections:Proximal tubule, loop of Henle, distal tubule, and collectingduct, each with unique characteristics.

Capillaries surround kidney tubules enabling exchangebetween blood and tubular fluid.

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1.Basic kidney structure

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Renal Tubules

2. Nephron structure

Nephron is composed of two components: the glomerulus and the renal tubule.

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Nephron structure

Nephron is composed of two components:

the glomerulus and the renal tubule.

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Nephrons can reach to

renal medulla

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Cortical nephron The nephrons have their glomeruli located in theouter and middle portion of the renal cortex arecalled cortical nephrons.

Juxtamedullary nephron

The nephrons have glomeruli that lie deep in therenal cortex near the medulla and have long

loops of Henle that are deep into the medullaare called juxtamedullary nephron.

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Cortical Nephron Juxtamedullary Nephron

85% 15%

A

A

U

N

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3. Glomerulus

Called Capillary Tufts

Under the Electronic

Microscope

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Glomerulus

Blood In

Blood Out

Relationship visualized as a fist(Glomerulus,in) and a balloon(Bowman`s capsule, out)

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juxtaglomerular apparatus

The juxtaglomerular apparatus consists ofthe juxtaglomerular cells, the macula

densa and the extraglomerular mesangial.

juxtaglomerular cell

The juxtaglomerular cells are specializedmyoepithelial cells in the media of afferentarteriole close to the glomerulus.

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Juxtaglomerular apparatus JG cells can secrete Renin.

JG cells serve as baroreceptor in afferent arteriole.

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4. Glomerular filtration membrane

porous

he epithelial cellsof Bowman`scapsule called

Space

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Glomerular filtration membrane

The barrier between the capillary bloodand the fluid inside the Bowmen's capsule

is called glomerular filtration membrane.

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Glomerular filtration membrane

Pores

Glomerular filtration membrane isimpermeable to blood cell and plasmaprotein.

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5. Renal tubule

The renal tubule is divided intofour sections: proximal tubule,loop of Henle, distal tubuleandcollecting duct.

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Nephron

Collectingduct

Glomerulus

Bowman capsule

renalcorpuscle

renal tubule

proximaltubule

henle loop

distal tubule

proximalconvoluted

tubule

distalconvoluted

tubule

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II. Renal blood flow (RBF)Renal blood flow distribution

95%

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Renal blood flow (RBF)

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Renal blood flow distribution

1 A d ill t k

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1. A second capillary networks

called the peritubular capillaries

a first capillarynetwork

a second capillarynetwork

These capillaries surround specific

segments of the tubule, and theyreturn water and substancesreabsorbed by the tubule to thegeneral circulation, as well as deliverneeded nutrients to the tubule.

P it b l ill i

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Peritubular capillariesUnder the electronic microscope

Higher plasma colloid osmotic pressure in the peritubularcapillaries is in favor of tubular reabsorption.

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2. vasa recta

3 Ch i i f l bl d fl **

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3. Characteristics of renal blood flow**

Large blood flow400 ml/min100g

Maldistribution of blood flow

renal papilla (1%) renal medulla (5%)renal cortex (94%)

Primary and secondary capillary networks

glomerular capillary network (primary network)

(between afferent glomerular arteriole and efferent glomerular arteriole,

high blood pressurein favour of glomerular filtration)

peritubular capillary network (secondary network)

(made by branch of efferent glomerular arteriole, low blood pressure, in

favour of tubular reabsorption)

Autoregulation of renal blood flow Tubuloglomerular feedback

Nervous and humoral regulation

Renal blood volume

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4. Determinants and regulation of RBF

RBF is determined by systemic arterial bloodpressure and renal vascular resistance (renalsympathetic vasoconstrictor nerve control).

RBF demonstrates autoregulation. Autoregulation involves afferent not efferent

arterioles.

Autoregulation is explained either by themyogenic hypothesis or tubuloglomerularfeedback.

A t l ti f RBF d GFR

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Autoregulation of RBF and GFR

Systemic Arterial Pressure (mm Hg)80 150

Glomerular Filtration Rate

Renal Blood Flow (RBF)

Ren

alBloodFlow

orGlomerular

Filtration

Rate

The kidney maintains a constant blood flow (autoregulation) andglomerular filtration rate over the physiological range of systemicarterial pressure.

Autoregulation means simply regulation of blood flow bythe tissue itself. Whenever on excessive amount of blood

flows through a tissue., the local vasculture constricts anddecreases the blood flow forward to normal.

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Autoregulation of RBF and GFR

Mechanism of autoregulation

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Mechanism of autoregulationTwo hypotheses describe autoregulation:

myogenic and tubuloglomerular feedback.

1.The myogenic hypothesis: When systemic arterial pressure

increases RBF, the afferent arterioles are stretched. This stretchstimulates them to contract increasing their resistance and maintaininga constant RBF. If RBF decreased, then the opposite would occur.

2. Tubuloglomerular feedbackinvolves an interaction between thedistal tubules and the afferent arterioles. The beginning portion of the

distal tubule passes close to the afferent arteriole, and together theyform a specialized structure called thejuxtaglomerular apparatus.Specialized epithelial cells in this portion of the distal tubule, calledmacula densa cells, sense the amount of NaCl (sodium chloride) in thetubular fluid. With an increase in RBF there will be an increase in GFR,

an increase in filtration, and an increase in the amount of NaCl passingby the macula densa cells. In response to this increased NaCl, a yetunidentified substance is released that causes afferent arteriolarconstriction. This constriction reduces RBF, GFR, and the amount ofNaCl delivered to the macula densa cells. If RBF were to decrease, then

the opposite would occur.

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Tubuloglomerular feedback

NaCl

NaCl

5 N i ti f kid

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5. Nerve innervation of kidney

Renal sympathetic vasoconstrictor nerve

control the smooth muscle of afferent glomerular arterioleand efferent glomerular arteriole, renal tubule andjuxtaglomerular cell. Vasoconstriction and RBF regulation Increased reabsorption of Na+ Cl-, etc., in the renal

tubular epithelial cell control juxtaglomerular cell to release renin

Kidney have no vagus nerve fibers innervation

Renal afferent nerve fibers act on mechanical andchemical stimulation toward central nervous system.

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,,.

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Process of urine formation

Three steps:Glomerular filtration

Renal tubule/collecting duct

reabsorptionRenal tubule/collecting ductsecretion and excretion

Material transport of renaltubule/collecting duct

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III. Glomerular filtration

Glomerular filtration rate (GFR)

Effective filtration pressure (EFP)

Factors affecting glomerular filtration rate

Regulation of GFR

Interaction between renal blood flow (RBF)and GFR

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Basic renal terminology * Glomerular filtration rate (GFR) is the amount of fluid

moving into Bowmans capsule per unit time (min). Renal blood flow (RBF) is the amount of blood flowing

through the kidney per unit of time (min). Filtration is the process by which substances enter

Bowmans capsule.

Reabsorption is the process by which substances movefrom inside to outside the tubule.

Secretion is the process by which substances move fromoutside to inside the tubule.

Excretion refers to substances that pass from the kidneyinto the bladder.

it is the ability of the kidney to selectively move specificsubstances into and out of the tubule in a very controlledand coordinated manner that makes normal kidneyfunction so critical to life.

E l i f

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Explanation for some terms

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Glomerular filtration*Filtration is the process by which substances enter

Bowmans capsule.

Glomerular filtration rate, GFR* ( )

It is the amount of fluid moving into Bowmans capsule per

unit time (min).

glomerular filtration fraction, GFF* ( )

The glomerular filtration fraction is the filtration rate aspercentage of the total renal plasma flow that passes

through both kidneys.

1. Glomerular filtration rate (GFR)

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2. Factors affecting glomerular filtration rate

Effective filtration pressure

Filtration coefficient Kf

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(1) Glomerular effective filtration pressure

The effective filtration pressure of glomerulus

represents the sum of the hydrostatic andcolloid osmotic forces that either favor or

oppose filtration across the glomerular

capillaries.

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Effective

filtration pressure Glomerular

capillary pressure Plasma colloid

osmotic pressure

intracapsular

pressure

Formula*:

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(2) Filtration coefficient Kf

Under the effective filtration pressure (EFP) driving

force, liquid volume passing through filtration

membranes per unit time.

Two determinants ofKf

filtration membranes area (s)

permeability coefficient of filtration membranes (K)Kf = k s

St t f filt ti b

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Structure of filtration membrane

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3. Factors affecting glomerular filtration**

Change of effective filtration pressure

Change of filtration coefficient

GFR KfS PGCGCPBC

GFR: glomerular filtration rate S: glomerular filtration membrane area

Kf : permeability coefficient PGC: glomerular capillary pressure

GC: plasma colloid osmotic pressure PBC: hydrostatic pressure in bowman

Changes in renal blood flow

EFP

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GFR is determined by the balance of forces acting across thefiltration membrane. The forces that drive fluid out of theglomerulus are the capillary blood pressure (PGC) and theosmotic pressure (BC) of the fluid in Bowmans capsule. The

forces driving fluid into the glomerulus are the hydrostatic

pressure (PBC) of the fluid in Bowmans capsule and theosmotic pressure (GC) of the blood within the glomerulus.The difference between these four forces determines the netfiltration pressure, which is approximately 15 mm Hg.

Net filtration pressure* = (PGC+BC) (PBC+GC)= (55+0) (15+25) = 15 mm Hg

BCis zero. Explanation

Filtration coefficient(Kf), a factor reflects permeability of

filtration membrane.

Determinants and regulation of GFR and RBF

N t filtr ti n pr ssur

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Net filtration pressure

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4. Regulation of GFR Changes in systemic arterial pressure, the radius of the

renal arterioles, and the filtration coefficient normallyregulate GFR.1. If systemic arterial pressure increases, then the pressurein the glomerular capillaries will increase and GFR willincrease. The opposite will happen if systemic arterialpressure decreases.2. Renal arteriolar resistance. (see next illustration)3. Filtration coefficientThe filtration coefficient can bealtered by the contractile activity of an additional set ofcells located among the podocytes. These cells are calledmesangial cells. These cells can be stimulated to contract,and when this occurs they decrease the area available forfiltration and thus decrease the filtration coefficient andGFR.4. Clinic diseases:

Starvation / Burn GFR,Renal Stones GFR

5 Interaction between RBF and GFR

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5. Interaction between RBF and GFRAs discussed above, an increase in efferentarteriolar resistance produces opposite effects on

RBF and GFR. RBF decreases and GFR increases.Under normal situations, blood leaving theglomerular capillary bed is at a higher osmoticpressure (GC) than the blood entering because of

the fluid lost as ultrafiltrate. This rise in GC is notsufficient to significantly limit GFR.

However, with a large increase in efferent resistance,RBF is reduced enabling GC to increase to such anextent that GFR is reduced. Therefore, GFR does notincrease as much as expected with an increase inefferent arteriolar resistance because of therelationship between GFR, RBF, and GC.

R l i f GFR i h diff

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Regulation of GFR with differentarteriolar diameters

PGCPGC

PGC

Decreased Afferent

Arteriolar Diameter GFR Glomerular Capillary

GFR

Decreased Efferent

Arteriolar Diameter

Changes in arteriolar resistance before (afferent) and after (efferent) theglomerular capillary bed have different effects on capillary hydrostatic

pressure (PGC) and therefore on glomerular filtration rate (GFR).

Effects of different arteriolar

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Effects of different arteriolarresistance on GFR


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Nervous and humoral regulation of RBF and GFR

Nervous regulation Renal sympathetic nerve:

Hypovolemia, noxious stimulation or agitation, etc.sympatheticnervous activity afferent glomerular arteriolecontraction

RBF and GFRHypervolaemiasympathetic nervous activity afferent

glomerular arteriole dilatation RBF and GFR .

Humoral regulation

epinephrine, norepinephrine, vasopressin, angiotensin

Renal vasoconstriction decreases RBF.

prostaglandin, NO, ANP, bradykinin, endothelin

Renal vasodilatation increases RBF.

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Summarization

PLEASE TAKE DOWN

Summary

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Summary Urine formation starts with the filtration of plasma in

the kidney. Glomerular filtration is favored by the high hydrostatic

pressure of the blood in the glomerular capillaries and

is opposed by the hydrostatic pressure in the urinary

space of Bowmans capsule and by the glomerular

capillary colloid osmotic pressure.

Glomerular filtration is rather nonselective; proteins

are mostly retained in the plasma by the glomerularbarrier, but all low-molecular-weight substances are

freely filtered.

Key terms: GFR, EFP, FF, Autoregulation

IV. Transport in the renal tubule

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1. Overview of tubule properties Permeability properties of the luminal and basolateral

membranes of the epithelial cells lining renal tubules aredifferent, enabling directional movement of salt and

water. Proximal tubule reabsorbs isotonically a constant 60%

of the GFR.

Loop of Henle reabsorbs more salt than water.

Distal tubule continues to reabsorb more salt than water. Permeability of the collecting duct to salt and water is

hormonally controlled by antidiuretic hormone (ADH)and aldosterone. [dilute urine / concentrated urine]

IV. ransport n the renal tubuleand collecting duct

R b ti d ti i th l

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Reabsorption and secretion in the renaltubule and collecting duct

Transport

Renal tubular reabsorption* ( )

Tubular reabsorption denotes the transport of substancesfrom the tubular fluid through the tubular epithelium into

peritubular capillary blood.

Secretion of the renal tubule and collecting duct

(

Product made by epithelial cells itself or blood

substance are transported into renal tubular lumen.

Definition

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Transport patterns

assive transportdiffusion, permeation, facilitate diffusion, solvent

daggling

Active transport

sodium pump, hydrogen pump, calcium pump (symportor antiport)

Transport pathway:

Paracellular pathway transcellular pathway

2. Reabsorption of the renal tubule and

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pcollecting duct

Proximal tubule reabsorbs 67%of the filtered Na+, Cl-

and H2O

Proximal tubule is the only site for glucose reabsorption

Loop of Henle reabsorbs 20% of the filtered Na+ and Cl-

The luminal cell membrane of the thick ascending limb

contains a Na+-k+-2Cl- cotransporter

The distal tubule and collecting duct reabsorb 12% of thefiltered Na+ and Cl-

General situation

Renal tubule reabsorption of

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Renal tubule reabsorption of

salt and water

3 Proximal tubule reabsorption of

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3. Proximal tubule reabsorption ofsalt and water

NaCl reabsorption is dependent upon the coordinated

action of the Na-K-ATPase on basolateral membrane

of the epithelial cell and several facilitated transport

systems on the luminal membrane of the epithelial cell.

Water reabsorption follows and is dependent upon Na

ion reabsorption.

Water reabsorption is assisted by the elevated

osmolarity of the peritubular capillary blood.

Proximal tubule reabsorption of salt

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and water

The major mechanisms by which molecules move across the epitheliumof the proximal tubule are diagramed in this figure.

ATP

Na+

Na+

K+Na+

Glucose & amino acids

H+

Water

Luminal membraneBasal lateralmembrane

Proximal Tubular Cell

BLOOD

TUBULARFLUID

Cell 1

Cell 2

P i l b l b i f N

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Proximal tubule reabsorption of Na+

Proximal tubule reabsorption

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of salt and water

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4. Proximal tubule reabsorption of

glucose and amino acids

Reabsorption of glucose and amino acids iscoupled to the reabsorption of Na ions.

Glucose reabsorption is overwhelmed whenblood glucose is very high (diabetes).

[daiebi:ti:z, -ti:s]


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of glucose


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of glucose

Relationship between plasma glucosed fil i f l

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and filtration rate of glucose

Relationship between plasma glucose

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and reabsorption rate of glucose

Relationship between Plasma Glucosed E ti R t f Gl

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and Excretion Rate of Glucose

renal glucose threshold*When the plasma glucose concentration increasesup to a value about 180 to 200 mg per deciliter,glucose can first be detected in the urine, this valueis called the renal glucose threshold.

Summary about Glucose

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Summary about Glucose

Graph Questions

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Graph Questions

5. Proximal tubule reabsorption

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pof bicarbonate ions

Bicarbonate reabsorption requires Na-

dependent H ion secretion.

Bicarbonate reabsorption occurs

indirectly through the formation of CO2

and H2

O.


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TUBULAR

FLUID

BLOO

D

Na+

H+ +HCO3-

H2CO3

CO2 + H2OH2O + CO2

H2CO3

HCO3- + H+

CACA

Na+ + HCO3-

Reabsorption of bicarbonate ions in proximal tubule requires the formationand breakdown of carbonic acid (H2CO3) within the tubular fluid and epithelialcells. The enzyme carbonic anhydrase (CA) is essential for this process tooccur.

Some diuretics work by inhibiting the carbonic anhydrase enzyme.

Proximal tubule reabsorptionof bicarbonate ions

Proximal tubule reabsorptionf bi b t i

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of bicarbonate ions

6. Loop of Henle reabsorption of

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6. Loop of Henle reabsorption ofsalt and water

Descending limb of the loop of Henle is

permeable to water but not to salt.

Ascending limb of the loop of Henle is

permeable to salt, because of a Na-K-Cl ion

tritransporter, but not to water.

Reabsorption of water from the descending limb

results from the reabsorption of salt by thetritransporter in the ascending limb.

Loop of Henle reabsorption ofsalt and water

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salt and water

Ascending limb of the loop of Henle: a Na-K-Cl ion

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tritransporter for reabsorption of salt

Blood

Na+-2Cl--K+

tritransporter

TubularLumenFluid

Place is the ascending limb of the loop of Henle

CELL

Tubule epithelial Cell

C t t lti li ti

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Counter-current multiplication

An osmotic gradient is established in the interstitialspace surrounding the loop of Henle that increases

from the top to the bottom of the loop.

The action of the tritransporter of the epithelial cells

of the ascending limb, the water permeability of the

descending limb, and the shape of the loop

contribute to the development of this osmotic

gradient.

The process by which this occurs is called counter-

current multiplication.

Counter current dissipation

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Counter-current dissipation

Counter-current exchange

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g

Counter-current multiplication

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A B

C D

300

300

300

300

300

300

300

300

300

300

300

300

Water

Reabsorption

Na-K-Cl

Reabsorption

400400

400

400

400

400400

400

400

400

200200

200

200

200

Equilibrium State

300

300

400

400

400

400

400

400

400

200

200

400

400

400

Equilibrium State

350

350

350

500

500

350

350

350

500

500

150

150150

150

300

300

Increasing

Osmotic GradientThe shape and permeability properties of the loop of Henle enable an osmotic gradient to be established

within the kidney. Diagrams A through D show in a step-wise manner how the gradient is established.

pAssuming that initially all fluid within theloop has the same osmolarity (panel A) thetritransporter will reabsorb Na, K, and Clfrom the tubular fluid creating an osmotic

gradient of 200 mOsm between the interstitialspace and the tubular fluid. The ascendinglimb is not permeable to water so watercannot follow. The descending limb is notpermeable to salt so it cannot enter from theinterstitial space. However, the descendinglimb is permeable to water so water isreabsorbed into the interstitial space. A newsteady state is established (panel B). At this

point new fluid enters from the proximaltubule displacing the fluid within the loop.This disrupts the steady state (panelC).Through the reabsorption of salt by theascending limb and water by the descendinglimb, a new steady state is established (panelD). Notice that an osmotic gradient is beingestablished in the interstitial space from thetop to the bottom of the loop. It is the result

of the loop structure and the differentpermeabilities of the two limbs of the loop.Fluid leaving the ascending limb is hypotoniccompared to the fluid entering because moresalt than water is reabsorbed. We will see ina later section that the interstitial osmoticgradient is critical for water reabsorption.

Counter-current exchangeof vasa recta

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of vasa recta

7. Distal tubule reabsorption oflt d t

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salt and water

More salt than water is reabsorbed.

Na and Cl ions reabsorbed together.

The distal tubule retains some of the properties ofthe ascending limb of the loop of Henle in that it is

not very permeable to water and reabsorbs Na andCl ions. The reabsorption of Na and Cl ions occursthrough a co-transport carrier protein on theluminal side of the epithelial cell that combines the

movement of one Na and Cl ion into the cell. Thisreabsorption is driven by the Na ion concentrationgradient established by the Na-K-ATPase on thebasal lateral side of the epithelial cell.

Distal tubule reabsorption of

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BloodTubularFluid

Lumen

psalt and water




Symporter

8. Collecting duct reabsorptionf lt d t

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of salt and water

The permeability of the collecting duct to Naions and water is variable.

Antidiuretic hormone (ADH or Vasopressin,

VP) increases the permeability of thecollecting duct to water.

Aldosterone increases the reabsorption of Na

ions by the collecting duct.

Collecting duct reabsorption

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Epithelial Cell of the Collecting Duct

TubularLumenFluid

Blood

Epithelial Cell of the Collecting Duct

of Na+

Effect of antidiuretic hormone (ADH) on thepermeability of the collecting duct to water

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permeability of the collecting duct to waterADH release

Concentrated Urine

EpithelialCellofthe

Collecting

Duct

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Antidiuretic Hormone(ADH i VP)

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(ADH or vasopressin, VP)

Mechanism of ADH or VP in thell ti d t f t b ti

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collecting duct for water reabsorption

Antidiuretic hormone, also known as vasopressin, a posterior pituitaryhormone, increases the number of aquaporin channels in the membraneof the epithelial cells increasing water reabsorption. In the presence ofADH, water can leave the collecting duct in response to the osmotic

gradient.

Relationship between plasmaosmolarit and plasma asopressin

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osmolarity and plasma vasopressin

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9. Collecting duct secretion of Kd H i

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and H ions The collecting duct secretes both K and H ions.

K and H ion secretion is sensitive to aldosterone.

K ions are secreted through channels located in theluminal membrane of specialized epithelial cells of thecollecting duct called principle cells. This secretion isdown a concentration gradient established by the Na-K-ATPase located on the basolateral membrane. In thepresence of aldosterone, more channels are opened andsecretion is increased.

Specialized cells of the collecting duct, called intercalatedcells, are responsible for H ion secretion. This secretion isdue to an active transport process that moves H ions fromthe inside of epithelial cell to the tubular fluid. The activity

of this transporter is increased by aldosterone.

Collecting duct secretion of Kand H ions

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and H ions

Cl-

TubularLumen

Fluid

Blood

principle cell

Channels

aldosterone+

intercalated cell

Epithelium of the Collecting Duct


aldosterone+

10. NH3secretion is related to H+and HCO3

-

t t

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transport

60% of NH3 secretion

from glutaminate (

), 40%from glycine

( )

secretion promotes

secretion and

reabsorption, in favor

of renal acids excretion

and alkaline

reabsorption.

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NH3NH3

NH4

V. Urinary concentration

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and dilution

Urinary dilution

Urinary concentration

The loops of Henle are countercurrentmultipliers

The vasa recta are countercurrent exchangers

Urea plays a special role in the concentratingmechanism

1. Overview

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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.

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.

Urinary concentration and dilution2

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2. Definition

Plasma osmotic pressure (POP) 300 mmol/L300mOsm/kg H2O

Urine osmotic pressure POP, hypertonic urine

Concentrated urine, 1200 mmol/L Urine osmotic pressure POP, hypotonic urine

Diluted urine, 50 mmol/L

Urine osmotic pressure =POP, isosthenuria

Urinary concentration and dilution of kidneyis damaged.

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3. Mechanism of urinary concentration and dilution

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3. Mechanism of urinary concentration and dilution

Uinary dilution

Na+Cl-

ADH

Na+


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4

Forming mechanisms of hypertonicity in the medulla

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Countercurrent multiplication of Henle's loop

Countercurrent exchange of vasa recta

Counter-current theory

U

vasa recta

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Countercurrent multiplication Countercurrent multiplication is the

process where by a small gradient

established at any level of the loop ofHenle is increased (multiplied) into a much

larger gradient along the axis of the loop.

Countercurrent multiplicationof Henle's loop

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:

NaClNaCl

NaCl

urea recycling

NaCl

NaClurea

Countercurrent exchange of vasa recta

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NaCl

Process of urinary concentration and dilution

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VI. Regulation of urine formation

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VI.Regulation of urine formation

Autoregulation of urinary formation

Glomerulotubular banlance

Effect of renal sympathetic nerve

Effect of antidiuretic hormone

Renin-angiotensin-aldosterone system

Effect of atrial natriuretic peptide

1. Regulatory patterns and Significance

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g y p g

Regulatory patterns:

Autoregulation ( )

Nervous regulation ( )

Humoral regulation ( )

Significance

Maintenance of internal environmenthomeostasis.

2. Autoregulation in kidney

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g y osmotic diuresis

Solute concentration of renal tubular fluid Mannitol ( ) clinic use

Different from water diuresis *

Glomerulotubular balance

One of the most basic mechanisms for controlling

tubular reabsorption is the intrinsic ability of the tubules

to increase their reabsorption rate in response toincreased tubular inflow. This phenomenon is referred to

as glomerular-tubular balance.

The volume of urine increases when water intake

exceeds body needs, it is resulted from suppression ofADH secretion.

3. Nervous regulation

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Renal sympathetic nerve

receptor activation contracts afferent and efferentglomerular arteriole inducing decreased RBF and GFR .

receptor activation increases proximal convoluted tubule

reabsorbing Na+ and othersolutes;

receptor activation promotes juxtaglomerular cellreleasing renin;

Homeostasis of Na+and water maintained.

Renal sympathetic nerve involved in reflex:

cardiopulmonary receptor reflex; Kidney Kidney reflex.

4. Humoral regulation

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Renin-angiotensin-aldosterone system RAAS

- - Renal kallikrein-kinin system ( - )

Atrial natriuretic peptide ANP

Endothelin ET

Nitric oxide NO

Vasopressin VP

Antidiuretic hormone ADH

Catecholamine, CA

Prostaglandin, PG ( )

Renalregulation of salt andt b l

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water balance

Sensing alterations in salt balance Salt balance, principally NaCl concentration, is

assessed by monitoring osmolarity.

Salt levels are changed by adjusting waterreabsorption through the action of antidiuretichormone (ADH).

ADH* increases the number of open aquaporinchannels in the collecting duct therebyincreasing water reabsorption.

Renal regulation of salt andwater balance

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Cells shrink

[NaCl]o

Signal to

water balance

Sensing alterations in waterbalance

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balance

Water balance is assessed by monitoring bloodvolume through changes in blood pressure.

Water levels are changed by adjusting saltreabsorption through the renin-angiotensin- -aldosterone system.

Increased sympathetic nerve stimulation directlyincreases renal secretion of renin.

Decreased distal tubule Na-load directly stimulatesrenal renin secretion.

Increased volume stimulates the secretion of atrialnatriuretic peptide form the atria.

Sensing alterations in waterbalance

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a ance

Sensing alterations in water balance

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g

Renin-Angiotensin- -Aldosteronesystem (R-A-A-S)

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system (R A A S).

Increased sympathetic nerve stimulation directly increasesrenal secretion of renin.

+

Angiotensin- also directly stimulates Na+

reabsorption by cells of the proximal tubule.

-

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Effects of ANP on kidney

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Dilatation of afferent glomerular arteriole increases GFR and

Na+ in tubular fluid;

Inhibiting Na+ channel on the collecting duct epithelium with

help of cGMP decreases Na+ and waterreabsorption at the

collecting duct;

Inhibiting renin release reduces ANG and aldosterone

secretion, then indirectly inhibits Na+ reabsorption

Inhibiting ADH secretion induces kidney water drain

increasingly.

Sensing alterations in water balance

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Renal regulation of salt and water balanceRelationship of osmolarity and volume

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p y

5. Reflex response to dehydration*D h d ti lt f i b l b t t

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Dehydration initiates reflexes to conserve bothsalt and water .

Dehydration reduces blood pressure , which

reduces GFR and RBF independent of otherfactors.

Baroreceptor-regulated increased sympathetic

nerve activity activates the renin-angiotensin- -aldosterone system and decreases GFR and RBF.

Osmoreceptors stimulate the release of ADH.

Sense of thirst is stimulated.

Dehydration results from an imbalance between waterintake and water loss

Reflex response to dehydration *

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With sweating (running) induced dehydrationwater volumeand

osmolarityblood pressureGFR,RBFwater and salt excretion

Blood pressurebaroreceptormediated reflex responsesympathetic nerve activityR-A-A-Swater and salt

reabsorptiondiminish dehydration

Sympathetic nerve activityafferent arteriolar constriction

GFR,RBF diminish dehydration

Blood pressureGFR and the distal tubule Na loadThe distal

tubular epithelial cells stimulatereninR-A-A-S

Extracellular osmolarityADH releasewater reabsorption

Water volumeand osmolaritythirst occursdrink water

Na+

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RSSA

RSSA

Na+

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VII. Renal clearanceResearch method of kidney function

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Research method of kidney function

Renal clearance **

The volume of plasma per unit time

needed to supply its quantity of substanceexcreted in the urine per unit time.

Clearance*

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Clearance used to measure GFR and RBF Clearance is based on the principle of

conservation of mass.

Clearance is the volume of blood per unit of timethat had all of a particular substance removed bythe kidney.

The clearance formula is Cx= (VU [X]U) / [X]p The clearance of substances with specific

properties enables one to determine GFR and RBF.

Clearance for use

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1 g/mL Glomerular Capillary Efferent Arteriole

Afferent Arteriole

125 mL/min

125 g/min

Proximal Tubule

1 mL/min

125 g/mL

125 g/min

Bowman`sCapsule

PeritubularCapillary

Urine

This figure illustrates the principle ofclearance and how it can be used todetermine glomerular filtration rate.

Clearance = GFR

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Creatinine, that is normally present in the bloodand is not reabsorbed and minimally secreted

by the kidney. By measuring urine flow rate and

the concentration of creatinine in the blood andurine, the GFR can be calculated. Because of

the characteristics of creatinine, you can say

that the clearance of creatinine is the GFR. The clearance equation: Cx= (VU[X]U) / [X]p

Urea clearance

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Glucose clearance

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Penicillin clearance

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Clearance for use

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The clearance equation can also be used tocalculate renal plasma flow(RPF) if asubstance with an additional property is used.This additional property is that all of it needs tobe removed from the blood by the kidneythrough a combination offiltration and secretion.

Para-aminohippuric acid (PAH) clearance

equals the RPF. RBF= RPF/ (1 - Hct). (hematocrit, Hct)

Significance of renal clearance

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Estimate renal function; Determine glomerular filtration rate (GFR )

Determine renal blood flow (RBF)

Presume renal tubular transport effect

Free-water clearance

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Efferent arteriole

Afferent arterioleDistal convoluted tubule

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Bowmancapsule

Glomerulus

micropuncture

VIII. Renal regulation of acid-basebalance

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balance

General considerations Metabolism of food generates acid.

Acid in the body is in two forms: fixed and

volatile. Kidneys remove excess fixed acid; lungs

remove excess volatile acid.

Acidemia is excess H ions in the blood;alkalemia is excess bicarbonate ions in theblood.

Normal Blood pH Value 7 35 7 45

Renal regulation of acid-basebalance

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Normal Blood pH Value 7.35 7.45

CO2 + H2O H2CO3 H+ + HCO3

-, H+ is volatile acid

Increasing ventilation will blow off more CO2 driving the reactionto the left and lowering the H+ concentration.

Decreasing ventilation will allow CO2 to accumulate driving thereaction to the right and increasing the H+ concentration.

Other acids named fixed acids. (such as sulfuric and phosphoricacids ).

Kidneys role (keeps appropriate level of bicarbonate ions /excretes the fixed acids produced by the body / secreteshydrogen ions).

Lungs role (ventilation controls CO2 adjusting [H+

] ). When the blood contains excess H ions the condition is called

acidemia (acidosis ). Diarrhea

When the blood contains excess bicarbonate ion, the conditionis called alkalemia (alkalosis). Vomiting

Renal regulation of acid-base balance

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Renal production of bicarbonate ions

The kidney produces bicarbonate through the

formation of titratable acid. The kidney produces bicarbonate through the

metabolism of glutamine.


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Formation of titratable acid in the proximal tubule is one way by which the kidneygenerates new bicarbonate ions in response to acidemia. The H+ ion secreted bythe epithelium is excreted as NaH2PO4 (titratable acid) leaving a bicarbonate ionbehind.

Na+

Na++NaHPO4-

Na2

HPO4

H+ H++ NaHPO4-

NaH2PO4

Urine

Renal TubularEpithelial Cell

TUBULA

RFLUID

(Disodium salts)

(Monosodium salts)Carbonic acid

(H2CO3)

HCO3- + H-

BLOOD

H+

Glutamine NH3 NH3+H+


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(New HCO3- )

TubularLumen Fluid

Blood


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Renal secretion of H ionsTubularLumen

BloodEpithelium of the Collecting Duct

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H ion secretion in the collecting duct leads to acidification of the urine.

Collecting duct H ion secretion is stimulated by aldosterone.

Cl-

LumenFluid

principle cell

Channels

aldosterone+

intercalated cell


aldosterone+

Pump

[H+]=4 10-8 M

pH=7.4

[H+]=3 10-5 M

pH=4.5

Renal compensation foralkalemia

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When the blood contains excess base, the kidneyexcretes bicarbonate and does not generateadditional bicarbonate. Increase bicarbonateexcretion occurs because there are insufficient H

ions to be secreted by the proximal tubules toreabsorb all the filtered bicarbonate. The excessbicarbonate is excreted. Also, the low level of Hions means that filtered sulfuric and phosphoric

acids will not be titrated and so no additionalbicarbonate will be generated. In these ways, thekidney attempts to lower the blood bicarbonateconcentration compensating for the alkalemia.

Renal compensation for alkalemia

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Renal compensation foracidemia

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When the blood contains excess H ions, the kidneyexcretes H ions and generates additional bicarbonate. Inthe presence of excess H ions, there are plenty of H ions toreabsorb all the filtered bicarbonate. In addition, the filtered

fixed acid will be titrated generating additional bicarbonateions. Also, the excess H ions stimulate the metabolism ofglutamine by the kidney and the production of even morebicarbonate. Finally, the collecting duct increases itssecretion of H ions. The combined effects of complete

bicarbonate reabsorption , new bicarbonate generation,and the secretion of H ions helps the body compensate forthe acidosis.

Renal compensation for acidemia

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concentration

Relationship Between plasma K IonConcentration and Acid-base Status

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Increase in plasma K+ levels can leadto acidemia.

Increase in plasma H+ levels can leadto hyperkalemia.

Plasma K+ levels can compromise theability of the kidney to regulate H+excretion.

A relationship exists between the K andthe H ion levels of the blood

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[ K+]o(hyperkalemia) [ K+] into cellsH+ leaves cells toblood for countering K+ into the cell [plasma H+]acidemia.

In an opposite manner, [ K+]o(hypokalemia) alkalemia.

[plasma H+](acidemia)K+ leave cells into blood[ plasma K+](hyperkalemia).

In an opposite manner, [plasma H+](alkalemia) hypokalemia.

Plasma K+ levels at the time of onset of either acidemia oralkalemia affect the ability of the kidney to compensate forthe acid-base disturbance.

Renal handling of calcium andphosphate

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Renal handing of calcium

All segments of the nephron reabsorb calcium except thedescending limb of the loop of Henle.

Calcium moves from the tubular fluid into the epithelialcells by passive diffusion down a concentration gradient.

On the basal lateral side of the cells, it leaves either inexchange for Na ions or by means of an ATP-requiringcalcium efflux pump.

Reabsorption is influenced by parathyroid hormone (PTH)

and calcium levels. An increase in plasma calcium levels reduces Ca++

reabsorption , while an increase in PTH results in anincrease in Ca++ reabsorption.

Renal handling of calcium andphosphate

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Renal Handling of Phosphate

Phosphate is reabsobed in the proximal tubule coupledwith sodium reabsorption.

Phosphate reabsorption exhibits saturation. The maximum capacity of this reabsorptive system is close

to the amount of phosphate normally filtered.

Parathyroid hormone (PTH) inhibits renal phosphate

reabsorption. PTH lowers the transport maximum of theNa-phosphate co-transporter, reducing phosphatereabsorption and increasing phosphate excretion.

IX. MicturitionUrinary excretion

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Urinary excretion is the renal important

function for maintaining normal metabolismand homeostasis of internal environment inthe human body.

Urinary excretion

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Volume and Pressure Relationship Curve in the Bladder

Volume (mL)

Pressureinthe

Bladder(cmH2O

)

Bladder

Contractive Wave

Urinary excretion

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PressureintheB

ladder(cmH2O

)

Volume (mL)

Volume and Pressure Relationship Curve in the Bladder

Reflex of urinary excretion

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Reflex of urinary excretion

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Clinic Problem is related to Reflex of Urinary excretion

Summarization

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Summarization

PLEASE TAKE DOWN

Summary on renal physiology

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Consideration after class

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1. Please describe the uropoietic elementary process .2. What are the influential factors of glomerular filtration

3. Please describe main position , patterns and mechanism of

Na+ reabsorption.

4. Please describe physiological function and secretion

regulation of ADH.

5. Please describe physiological function and secretion

regulation of aldosterone.

6. What is the mechanism of water diuresis

Guide of Reference

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1. . . . : , 2000.

2. , , . . : , 2000.

3. , , . . : , 2001.

4. , . . , 1991.

5. . . , 2002.

6. . . , : , 2005.

7. Berne RM, Levy MN, Koeppen BM, Stanton BA. Physiology, 5th ed, St Louis:

Mosby, 2004.

8. Guyton AC, Hall JE. TEXTBOOK OF MEDICAL PHYSIOLOGY, 10th ed,

Philadelphia: W.B. Saunders Co, 2000.

9. Charles Seidel. BASIC CONCEPTS IN PHYSIOLOGY: a students survival guide

(Great for Course Prep and USMLE), Houston: McGraw-Hill Co Inc, 2002.

10. Koeppen BM, Stanton BA. Renal physiology, 3rd ed, Health Scicece Asia: Elsevier

Science, 2002.

Navigation for Web Address

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1.http://clem.mscd.edu/~raoa/bio2320/uriphys/

2.http://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htm

3.http://www.cat.cc.md.us/~dhargrov/ppp/urinary/

4.http://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htm

5.http://sciences.aum.edu/bi/B12100/cadams/urinary.htm

6.http://www.yiyee.com/mdinter/zhyfenke-mnk.htm

7.http://www.zgxl.net/sljk/imgbody/mnxt.htm
http://clem.mscd.edu/~raoa/bio2320/uriphys/http://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htmhttp://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/http://www.cat.cc.md.us/~dhargrov/ppp/urinary/http://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htmhttp://sciences.aum.edu/bi/B12100/cadams/urinary.htmhttp://sciences.aum.edu/bi/B12100/cadams/urinary.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.zgxl.net/sljk/imgbody/mnxt.htmhttp://www.zgxl.net/sljk/imgbody/mnxt.htmhttp://www.zgxl.net/sljk/imgbody/mnxt.htmhttp://www.zgxl.net/sljk/imgbody/mnxt.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://sciences.aum.edu/bi/B12100/cadams/urinary.htmhttp://sciences.aum.edu/bi/B12100/cadams/urinary.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/http://www.cat.cc.md.us/~dhargrov/ppp/urinary/http://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htmhttp://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htmhttp://clem.mscd.edu/~raoa/bio2320/uriphys/

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Formation and excretion ofUrine

Question

Answer

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urinary 3

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