physiology ....final material .... urinary system

8/3/2019 physiology ....final material .... Urinary System

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Urinary system

Introduction

GF

Tubular reabsorption Tubular secretion

Urine excretion & plasma clearance


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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


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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


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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


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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


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


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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


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Podocyte

foot process

Filtration

slit

Basement

membrane

Capillarypore

Endothelialcell

Lumen of glomerularcapillary

Lumen ofBowmans capsule


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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


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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


14/76Table 13-1, p. 412


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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


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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


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Vasoconstriction(decreases blood flowinto the glomerulus)

Afferent arteriole

Glomerulus

Efferent arteriole

Glomerularcapillaryblood pressure

Net filtrationpressure

GFR


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Afferent arteriole

Glomerulus

Efferent arteriole

Glomerularcapillaryblood pressure

Net filtrationpressure

GFR

Vasodilation(increases blood flowinto the glomerulus)

Short-term Arterial blood Long-term


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


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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)


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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


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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


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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


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Fig. 13-10, p. 416

Lumen Tubular cell Interstitial fluid


Diffusion

Na+channel

Active transport

BasolateralNa+ K+ ATPasecarrier

Lateral space Diffusion


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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


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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


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Fig. 13-12, p. 420


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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


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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 /


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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


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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/


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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


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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


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Table 13-3, p. 424


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Cl reabsorption

Passively absorbed down theelectrical gradient which is createdby active Na reabsorption

-


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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


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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


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Fig. 13-13, p. 421

Glomerulus

Bowmans

capsule

Beginning ofproximal

tubule


Na+ (active)

H2O (osmosis)

Na+ (active)

H2O (osmosis)

Passive diffusion

of urea down itsconcentration gradient

44 mloffiltrate

125 mloffiltrate

End ofproximaltubule

= Urea molecules


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wastes

Waste products are not reabsorbedbecause the permeability of thetubules to these products is almost

zero :

-phenol

-creatinine

-other toxics


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Tubular secretion

Supplemental mechanisms that hastenelimination of substances from the body

1- hydrogen:- important for acid-base balance

- secreted by proximal, distal, &

collecting tubules


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2- potassium:

-actively reabsorbed in proximal

tubules

-actively secreted in distal &

collecting tubules

-when plasma [K] increases,

secretion is adjusted to eliminate Kout


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-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


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-control of K secretion:

increased [K]plasma stimulation of

adrenal cortex increase

aldosterone increase in K

secretion & Na reabsorption


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Fig. 13-14, p. 423

Lumen Tubular cellPeritubularcapillaryInterstitial fluid

K+channel

Activetransport

Diffusion

Diffusion


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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


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Plasma clearance

Plasma clearance of any substance is

the volume of plasma completelycleared of that substance by thekidneys per minute


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-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


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Fig. 13-16a, p. 426

Glomerulus

Tubule


Inurine

For a substance filtered and not reabsorbed

or secreted, such as inulin, all of the filteredplasma is cleared of the substance.


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-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


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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.


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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.


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- 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)


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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


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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


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Fig. 13-17, p. 427

Cortex

All values in milliosmols (mosm)/liter.

U i i t d i th f 100 1200


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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


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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


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Fig. 13-19a, p. 430

Bowmans capsule

Proximal tubule

Distal tubule

Cortex

Medulla

Long loopof Henle

Collectingtubule


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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


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Fig. 13-19b, p. 431Step 1

St 2 t f l i l filt t


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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


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Fig. 13-19c, p. 431Step 2

Todistaltubule

Fromproximaltubule


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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


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Fig. 13-19d, p. 430Step 3


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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


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Step4 Step5

Fromproximaltubule

todistaltubule


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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


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Fig. 13-19g, p. 431Step 6 and on

proximaltubule

distaltubule


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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


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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


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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


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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


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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


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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

physiology ....final material .... urinary system

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