lecture notes on renal physiology for mbbs

7/23/2019 Lecture Notes on Renal Physiology for MBBS

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Lecture notes on RenalLecture notes on Renal

Physiology for MBBSPhysiology for MBBS

Dr.Abubakkar Siddique

Version:03Version:03


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Compiled by Dr.Abubakkar Siddique


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Renal Functions and Anatomy


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Urinary System

Homeostasis

Cells

Body systems

maintain

homeostasis

Homeostasis is

essential forsurvival of cells

Cells make up

body systems


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Summary of Kidney unctions!hey contribute to homeostasis.

!hey control electrolyte and "ater balance of the #C$ plusurinary output.

%f the #C has an e&cess of "ater or electrolytes$ the kidneyseliminate the e&cess. %f there is a deficiency of these substances$

the kidneys can reduce the loss of these from the body.

'ther functions of the kidneys include( maintainin) the proper osmolarity of body fluids maintainin) proper plasma volume

helpin) to maintain proper acid*base balance e&cretin) "astes of body metabolism e&cretin) many forei)n compounds producin) erythropoietin and renin convertin) vitamin D to an active form


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Kidney is bean shapedstructure

Measures 12 X6 X3 cm

Weight 120 170 gramin adult male and 115 155

gram in adult female

Kidney is cntained in fibrus capsule

Kidney lies retrperitneal! in the para"ertebralgutter! n the psterir abdminal #all

$t e%tends frm 12th thracic "ertebra t 3rd lumbar

"ertebra

&he 't Kidney is slightly l#er


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Kidney (arenchyma 1)5 2 cm

*uter crte%1cm +,ntain -lmerular and cn"luted

tubules.$nner medulla

/rmed f 1 pyramids #hich are cnical shaped#ith its base t#ards crticmedullary unctin

#ith its ape% prects in minr calyces as papillae*n the tip f each papilla are 10 t 25 small penings

that represent the distal ends f the cllecting ducts+f ellini.)

&he crte% may e%tend bet#een pyramids frmingclumns f ertini

Medullary rays are striated elements #hich radiatesfrm the pyramids +4trait segments f nephrn.


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Nephron:functional

unit of the

kidney


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&he ephrnephrn is the functinal unit f the idney

ach idney cntains nearly millin ephrns&he first part f the ephrn is the

-lmerulus +renal crpuscle.#hich lies mainly in therenal crte%! fll#ed by

pr%imal cn"luted tubule #hich als lies mainly inthe renal crte%)

&his is fll#ed by a lp f 8enle#hich is partly inthe crte% and partly e%tends deep int the medulla

&his is fll#ed by the distal cn"luted tubule#hichlies in the renal crte%)

,llecting duct #hich lies partly in the crte% andpartly in the medulla)


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Renal Blood Flow


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ld supply f the idney

'enal arteriesarise frm the 9rtappsite the

inter"ertebral disc :umbar 1 2

&he renal artery enters the hillar regin and usually

di"ides t frm an anterir and a psterir branch!

then they di"ide t frm interlbar arteries! &henarcuate arteries! &hen interlbular arteries #hich

penetrate the crte% and frm afferent arterile

9fferent arterile in"aginate the #man;s capsule

and frm -lmerular tuft #hich is mdifiedcapillaries structure thrugh #hich -/' is frmed


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CorticalandJuxtamedullaryNephronSegments


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/rm the glmerulus;s efferent arterile emerges

fferent arterile f the uter and middle crtical

glmeruli get d#n bet#een tubules #here theydi"ide int capillary net#r called peritubular

capillaries

fferent arterile f the inner crtical glmeruli

penetrate deeply int Medullary pyramids frming

"asa rectasharing in the cunter current e%change

system

'enal "enus system and lymphatic fll# samepatterns f arteries

Kidney recei"e sympathetic and parasympathetic

supply frm ,eliac ple%us


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Blood Supply to the Kidneys

Figure 26.5a, b


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Blood Supply to the Kidneys

Figure 26.5c, d


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Renal blood flow (RBF) is huge relative tothe mass of the kidneysabout ! "#min$

or %&' of the resting cardiac outputonsidering that the volume of eachkidney is less than !*& cm+$ this meansthat each kidney is perfused with overthree times its total volume every minute

All of this blood is delivered to the corte,A small fraction of the cortical blood flow is

then directed to the medulla


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-he significance of the .uantitative differences

between cortical and medullary blood flow isthat the high blood flow in the corticalperitubular capillaries maintains the interstitialenvironment of the cortical renal tubules very

close in composition to that of blood plasmathroughout the body

/n contrast$ the low blood flow in the medulla

permits an interstitial environment that is .uitedifferent from blood plasma


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F"01$ R2S/S-A32$ A34 B"004

5R2SS6R2 /3 -72 K/4328S

-he basic e.uation for blood flow through any organ

is as follows9

+ , -/ 0

where

:;;is organ blood flow$


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-he high RBF is accounted for by low totalrenal vascular resistance

-he resistance is low because there areso many pathways in parallel$ that is$ somany glomeruli and their associated

vessels-he resistances of the afferent andefferent arterioles are about e.ual in most

circumstances and account for most of thetotal renal vascular resistance

Arteriolar resistancesare variable andare the sites of regulation


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Arteriolar resistances are variable and are

the sites of regulation

A change in the afferent arteriole orefferent arteriole resistance produces the

same effect on RBF because these

vessels are in series1hen the two resistances both change in

the same direction $ their effects on RBF

are additive1hen they change in different directions

one resistance increasing and the other

decreasingthe changes offset each other

-h l l filt t t i t i i i


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-he glomerular filtrate contains most inorganic ionsand low;molecular;weight organic solutes in virtuallythe same concentrations as in the plasma /t alsocontains small plasma peptides and a very limited

amount of albumin Filtered fluid must pass through a three;layeredglomerular filtration barrier

!he first layer$ the endothelial cells of the capillaries$

is perforated by many large fenestrae (=windows>)$like a slice of Swiss cheese$ which occupy about !&'of the endothelial surface area -hey are freelypermeable to everything in the blood e,cept cells andplatelets

!he middle layer$ the capillary basement membrane$is a gel;like acellular meshwork of glycoproteins andproteoglycans$ with a structure like a kitchen sponge

!h thi d l i t f ith li l ll 1 d t ) th t


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!he third layerconsists of epithelial cells 1podocytes)thatsurround the capillaries and rest on the basement membrane-he podocytes have an unusual octopus like structure

Small =fingers$> called pedicels (or foot processes)$ e,tend from

each arm of the podocyte and are embedded in the basementmembrane

5edicels from a given podocyte interdigitate with the pedicelsfrom ad?acent podocytes Spaces between ad?acent pedicelsconstitute the path through which the filtrate$ once it has passedthrough the endothelial cells and basement membrane$ travelsto enter Bowman@s space

-he foot processes are coated by a thick layer of e,tracellularmaterial$ which partially occludes the slits 2,tremely thin

processes called slit diaphra)msbridge the slits between thepedicels

Slit diaphra)msare widened versions of the tight ?unctionsand adhering ?unctions that link all contiguous epithelial cellstogether and are like miniature ladders -he pedicels form the

sides of the ladder$ and the slit diaphragms are the rungs


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BAS/ R23A" 5R02SS2S


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ive rocesses of Urinary Systemive rocesses of Urinary System

0elated by equation(0elated by equation(

# , * 0 2 S# , * 0 2 S

345 6 / day filtered$ 7889 reabsorbed$345 6 / day filtered$ 7889 reabsorbed$

3.: 6/day e&creted3.: 6/day e&creted

3.3. iltration$iltration$

;.;. 0eabsorption$0eabsorption$

icturition

-h b i f h h l l


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-hree basic processes of the nephrons are glomerular

filtration$ tubular reabsorption$ and tubular secretion

lomerular filtration is the first process A protein;free plasma is

filtered from the lomerulus into the Bowman@s capsule Bloodcells are not normally filtered 3ormally about %& ' of the plasmais filtered lomerular filtrate is produced at the rate of !%* ml perminute (!& liters per day)

By tubular reabsorption$ filtered substances move from the insideof the tubular part of the 3ephron into the blood of the peritubularcapillaries -he reabsorption rates of most substances are veryhigh

-ubular secretion is a selective process by which substances from

the peritubular capillaries enter the lumen of the 3ephron tubule

-he &' of the plasma not filtered passes into the efferent arterioleand through the peritubular capillaries

6rine e,cretion results from these three processes


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?lomerular

capillaries

#fferent

arteriole

eritubular

capillaries

Venous

blood

Urine!ubule 1from pro&imal

tubule to collectin) duct@

Bo"mans

capsule

iltrate

path"ay

Blood

path"ay

?lomerularfiltration

!ubularreabsorption

!ubularsecretion


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3@ iltration3@ iltration, >ovement of fluid from blood to lumen of ephron., >ovement of fluid from blood to lumen of ephron.

'nce in lumen consider it outside body'nce in lumen consider it outside body

Composition of filtrateComposition of filtrate


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lomerular Filtration

Fluid filtered from the lomerulus intoBowman@s capsule passes through +

layers9 the lomerular capillary wall

the basement membrane

ollagen

lycoproteins; negative charge

the inner layer of Bowman@s capsule5odocytes

Filtration slits


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1hat 4rives FiltrationC

7ow does fluid move from the plasmaacross the lomerular membrane intoBowman@s capsuleC

3o active transport mechanisms3o local energy e,penditure

Simple passive physical forces accomplish

filtration; Filtration occurs throughout the length of

the capillaries


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Forces involved in Filtration

lomerular capillary blood pressure

(favors filtration)

5lasma;colloid osmotic pressure (opposes

filtration)

Bowman@s capsule hydrostatic pressure

(opposes filtration)


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lomerular apillary Blood

5ressure

Fluid pressure e,erted by the blood within the

lomerular capillaries

lomerular capillary pressure is significantly

higher than other capillary blood pressures -his is due to the larger diameter of the afferent

arteriole compared with the efferent arteriole

Blood pressure does not fall along the length of

this capillary$ which pushes fluid out of the

lomerulus into Bowman@s capsule (pressure build;up in glom ap D **mm7g)


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5ressure opposing filtration

5lasma;colloid oncotic pressure; caused

by the une.ual distribution of plasma

proteins across the glomerular membrane (D+&mm7g)

Bowman@s capsule hydrostatic pressure;

the pressure e,erted by the fluid in this

initial part of the tubule; tends to push fluidout of Bowman@s capsule (D!*mm7g)


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3et Filtration 5ressure

Force favoring filtration (glomerular

capillary blood pressure of ** mm7g)

minus forces opposing filtration (plasma

colloid osmotic pressure of +& mm7g EBowman@s capsule pressure of !* mm7g)

** G (+& H !*) !& mm7g


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?0?0,, ?lomerular iltration 0ate?lomerular iltration 0ate

Describes filtration efficiency( Amount of fluid filtered perDescribes filtration efficiency( Amount of fluid filtered perunit of timeunit of time

Average !R " #$0 L%day&Average !R " #$0 L%day&

!iltration 'oefficient is influenced by!iltration 'oefficient is influenced by et filtration pressureet filtration pressure Available surface area of ?lomerular capillariesAvailable surface area of ?lomerular capillaries

?0 is closely re)ulated to remain constant?0 is closely re)ulated to remain constantover ran)e of B 145 * 345 mm H)@over ran)e of B 145 * 345 mm H)@


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lomerular Filtration Rate

4epends on -he net filtration pressure 7ow much glomerular surface area is available for

penetration

7ow permeable the glomerular membrane is

?0 , Kf& net filtration pressure

1here (Kf) filtration coefficient (a product ofthe above two glomerular properties)

; Roughly !%* ml#min in males


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Filtration Fraction

-he 5ercentage of Renal 5lasma Flow

that is Filtered

FF FR#R5F

Roughly %&'


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Regulation of FRRegulation of FR

Several mechanisms provideSeveral mechanisms provideclose control of ?0Eclose control of ?0E

iltration ressure 1B@iltration ressure 1B@

Hydrostatic$ colloidHydrostatic$ colloid

0esistance in afferent0esistance in afferent

vs. efferent arteriolesvs. efferent arterioles !ubulo)lomerular feedback!ubulo)lomerular feedback

F? ApparatusF? Apparatus

Hormones and ASHormones and AS

An)iotensin %%An)iotensin %%

1vasoconstrictor@1vasoconstrictor@rosta)landinsrosta)landins

1vasodilator@1vasodilator@


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Iechanisms to Regulate FR

Autore)ulation(prevent spontaneous

changes in FR) /nvolves >yo)enicand !ubulo)lomerular

feedback mechanisms

#&trinsic sympathetic control(long;term

regulation of arterial B5) Iediated by the sympathetic nervous system an override autoregulatory mechanisms


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Auto regulation

!;Myogenic mechanism

Response to changes in pressure within

the nephron@s vascular component

Arterioles contract inherently in responseto the stretch accompanying J pressure

essel automatically constricts$ which

helps limit blood flow into glomerulus

despite increased systemic pressure

0pposite reaction occurs when smooth

muscles sense a drop in pressure


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/mportance of Autoregulation of

FR

Iyogenic and -ubuloglomerular feedback

mechanisms work in tandem to auto regulate

FR within a IA5 range of &;!& mm7g

Autoregulation greatly blunts the direct effect

that changes in arterial pressure might

otherwise have on FR and preserves water

and solute homeostasis and allows wastee,cretion to carry on as usual


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Clinical %mportance ofClinical %mportance of

?0 and Clearance?0 and Clearance

?0?0is indicator for overall kidney functionis indicator for overall kidney function

ClearanceClearanceL non;invasive way to measure FRL non;invasive way to measure FR

%nulin 1research use@%nulin 1research use@

either secreted nor reabsorbedeither secreted nor reabsorbed

Creatinine 1clinically useful@Creatinine 1clinically useful@

/f a substance is filtered and reabsorbed but not/f a substance is filtered and reabsorbed but not

secretedsecreted clearance rate M FRclearance rate M FR

/f a substance is filtered and secreted but not/f a substance is filtered and secreted but not

reabsorbedreabsorbed clearance rate N FRclearance rate N FR


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=@ #&cretion , Urine 'utput=@ #&cretion , Urine 'utput

#&cretion of e&cess ions$ H#&cretion of e&cess ions$ H;;'$ to&ins$ Gforei)n'$ to&ins$ Gforei)n

molecules Gnitro)enous "aste 1Hmolecules Gnitro)enous "aste 1H==22 $ urea@$ urea@

Depends on iltration$ 0eabsorption$ SecretionDepends on iltration$ 0eabsorption$ Secretion

# , 0 2 S# , 0 2 S

Direct measurement of $ 0$ S impossibleDirect measurement of $ 0$ S impossible

infer from comparison of blood I urinalysisinfer from comparison of blood I urinalysis

or any substance(or any substance( 10enal@ Clearance10enal@ Clearance,,plasma volume completely cleared of thatplasma volume completely cleared of thatsubstance per minutesubstance per minute !ypically e&pressed as ml/min!ypically e&pressed as ml/min

A t l ti


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Autoregulation

2-Tubuloglomerular feedback

Ou,taglomerular apparatus the combination of tubular and vascular cells where

the tubule passes through the angle formed by the

afferent and efferent arterioles as they ?oin the

lomerulus

Smooth muscle cells within the afferent arteriole

form granular cells

SpecialiPed tubular cells in this region known asmacula;densa sense changes in salt level of

tubular fluid

! b l l l db k! b l l l db k


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!ubulo)lomerular eedback!ubulo)lomerular eedback

As ?0As ?0 $ flo" throu)h DC!$ flo" throu)h DC!

>acula densa cells(>acula densa cells(releaserelease

paracrines1A!@paracrines1A!@

Ju&ta)lomerularJu&ta)lomerularcells1?ranular cells@cells1?ranular cells@1smooth muscle fibers from1smooth muscle fibers from

afferent arteriole@afferent arteriole@( contract( contract

!hus ?0!hus ?0


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2 t i i S th ti t l


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2,trinsic Sympathetic ontrol

FR can be changed purposefully$ even when IA5

is within the autoregulatory range

FR is reduced by the baroreceptor refle, response

to a fall in blood pressure (the S3S causes

vasoconstriction in most arterioles as acompensatory mechanism to J -5R)

Afferent arterioles innervated with sympathetic

vasoconstrictor fibers much more than are the

efferent aa

Q FR causes Q urine output$ conserving some water

and salt$ helping to restore plasma volume to normal


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Baroreceptor

0efle&

%nfluence on the?0 in

6on)*term

0e)ulation of

Arterial Blood

ressure


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;@ !ubular 0eabsorption;@ !ubular 0eabsorption 1889 of filtrate@1889 of filtrate@

ActiveActive

3a3aHHtransporttransport

((Recall Antiports andRecall Antiports and

Symports)Symports)assiveassive (think(think

concentration andconcentration and

osmotic gradients)osmotic gradients)

aracellulararacellularegureaegurea!ranscytosis!ranscytosis

5roteins5roteins


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A-5ase on Basolateral membrane of 5-


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A-5ase on Basolateral membrane of 5-


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"60S2 7andling in 5-

6nder most circumstances$ it would bedeleterious to lose glucose in the urine$

particularly in conditions of prolonged fasting

-hus$ the kidneys normally reabsorb all of theglucose that is filtered

-hi i l t ki l f th


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-his involves taking up glucose from the

tubular lumen along with sodium via a

sodium*dependent )lucose symporter1S?6U!@across the apical membrane of

pro,imal convoluted tubule epithelial cells

Followed by its e,it across the basolateralmembrane into the interstitium via a )lucose

transporter 1?6U!@$a uniporter


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SaturationSaturationof 0enal !ransportof 0enal !ransport

Same < characteristics asSame < characteristics as

discussed indiscussed in (ediated(ediated

trans)orttrans)ort

!ransport ma&imum!ransport ma&imum

determined bydetermined by

SaturationSaturation 0enal0enal!hreshold!hreshold

SpecificitySpecificity

CompetitionCompetition

Saturation , >a&imum rate of transport 1tm@

5R0-2/3S E 525-/42S


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5R0-2/3S E 525-/42S

in 5-

Although the glomerular filtrate is protein free$ itis not truly free of all protein it ?ust has a totalprotein content much lower than plasma

5eptides and smaller proteins (eg$ angiotensin$

insulin)3ormally all of these proteins and peptides arereabsorbed completely$ although not in theconventional way

-hey are enPymatically degraded into theirconstituent amino acids$ which are then returnedto the blood

For the larger proteins the initial step in recovery is


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For the larger proteins$ the initial step in recovery isendocytosis at the apical membrane -his energy;re.uiring process is triggered by the binding of filtered

protein molecules to specific receptors on the apicalmembrane

-he rate of endocytosis is increased in proportion tothe concentration of protein in the glomerular filtrateuntil a ma,imal rate of vesicle formation$ and thus the

-m for protein uptake$ is reached-he pinched;off intracellular vesicles resulting fromendocytosis merge with lysosomes$ whose enPymesdegrade the protein to low;molecular;weight

fragments$ mainly individual amino acids-hese end products then e,it the cells across thebasolateral membrane into the interstitial fluid$ fromwhich they gain entry to the peritubular capillaries

ery small peptides such as angiotensin //


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ery small peptides$ such as angiotensin //$

are cataboliPed into amino acids or di;

peptides and tri;peptides within the pro,imaltubular lumen by peptidases located on the

apical surface of the plasma membrane

-hese products are then reabsorbed by the

same transporters that normally reabsorb

filtered amino acids


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M d ll t ti di t


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Medullary concentration gradient

Active transport of 3a$ K$ l etc out of ascendinglimb (especially thick limb) of loop of 7enle to the

medullary interstitium

Active transport of ions from collecting duct to

medullary interstitium

5assive diffusion of urea from medullary collecting

ducts into the medullary interstitium

4iffusion of less amounts of water from medullarytubules into medullary interstitium


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D%S!A6 C''6U!#D !UBU6#

-he distal tubule continues to reabsorb sodium and


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chloride$

-he ma?or luminal entry step being via the aCl

symporter-his transporter differs significantly from the 3aGKG%l symporter in the thick ascending limb and issensitive to different drugs

-he 3al symporter is blocked by the thia*idediuretics

Sodium channels also permit sodium entry in thedistal convoluted tubule

"ike the ascending limb of the loop of 7enle$ thedistal tubule is not permeable to water$ so that itfurther dilutes the already somewhat dilute fluidentering it from the thick ascending limb


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0""2-/3 46- S8S-2I


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/n the collecting ducts$ there is a division of

labor among several different cell typesReabsorption of sodium and water is

associated with rincipal cells

Reabsorption of chloride occurs partially viaparacellular pathways

Active reabsorption is also associated with

another class of collecting duct cells$ the%ntercalated cells


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-he 5rincipal cells


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-he 5rincipal cellsReabsorb sodium$ the luminal entry step being

via #pithelial Sodium Channels(23a)-he activity of 23a in colon and kidney is

modulated bythe Aldosterone

/t can be blocked byeither !riamtereneorAmiloridewhich are used medically to serve

as diuretics

/n the kidney it is inhibited byAtrial atriureticpeptideis a powerful vasodilator$ and a protein

hormone secreted by heart atrial muscle cells


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5rincipal cells in the collecting ducts are also


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5rincipal cells in the collecting ducts are alsothe crucial players in reabsorbing water

-he water permeability of the principal cells inthe collecting duct systemboth the corticaland medullary portionsis sub?ect tophysiological control by circulatingAntidiuretic hormone 1ADH$ asopressin)

-he inner medullary collecting duct has alimited water permeability even in the absence

of A47$ but the outer medullary and corticalregions have almost no water permeabilitywithout A47


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4epending on levels of A47$ water permeability formost of the collecting duct system can vary from very


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most of the collecting duct system can vary from verylow to very highLhen "ater permeability is very lo" 1absence ofADH@$the hypo;osmotic fluid entering the collectingduct system from the distal convoluted tubule remainshypo;osmotic as it flows along the ducts 1hen thisfluid reaches the medullary portion of the collectingducts$ there is now a huge osmotic gradient favoringreabsorption$ which occurs to some e,tent -hat is$although there is little cortical water reabsorptionwithout A47$ there is still a limited medullaryabsorption because of the enormous osmotic gradient

As so much water is not reabsorbed in the corte,$most of the water entering the medullary collectingduct flows on to the ureter -he result is the e,cretionof a large volume of very hypo;osmotic (dilute) urine$or water diuresis


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Lhen the collectin) duct systems "ater permeability ishi h 1Hi h ADH@


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very hi)h 1Hi)h ADH@As the hypo;osmotic fluid entering the collecting duct systemfrom the distal convoluted tubule flows through the cortical

collecting ducts$ most of the water is rapidly reabsorbed -his isbecause of the large difference in osmolality between the hypo;osmotic luminal fluid and the isosmotic (%* m0sm#kg)interstitial fluid of the corte,/n essence$ the cortical collecting duct is reabsorbing the largevolume of water that did not accompany solute reabsorption inthe ascending limbs of 7enle@s loop and distal convolutedtubule0nce the osmolality of the luminal fluid approaches that of thecortical interstitial fluid$ the cortical collecting duct thenreabsorbs appro,imately e.ual proportions of solute (mainly

sodium chloride) and water-he result is that the tubular fluid$ which leaves the corticalcollecting duct to enter the medullary collecting duct$ isisosmotic with cortical plasma$ but its volume is greatly reducedcompared with the amount entering from the distal tubule

/n the medullary collecting duct solute


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/n the medullary collecting duct$ solutereabsorption continues$ but in the presence of

A47 water reabsorption is proportionally evengreater -his is because the A47 has signaled

much of the medullary collecting duct

epithelium to have high water permeability$ andthe medullary interstitium is hyper;osmoticrelative to normal plasma

-herefore$ the tubular fluid becomes more andmore hyper;osmotic$ and reduced in volume


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Formation of a 4ilute 6rineFormation of a 4ilute 6rine


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4ecrease water reabsorption

ontinue electrolyte reabsorptionMechanism:Decreased ADH release and reduced water

permeability in distal and collecting tubules

Formation of a oncentrated 6rineFormation of a oncentrated 6rine

/ncrease water reabsorptionontinue electrolyte reabsorption

Mechanism:

Increased ADH release which increases water permeability in

distal and collecting tubulesHigh osmolarity o renal medulla!ountercurrent low o tubular luid

Urea recyclin)


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"hic# ascending

limb, D!" $

cortical collectingduct is

impermeable to

urea.

%rea is permeablethrough medullary

collecting duct

&permeability is

enhanced by ADH'.

%rea mo(e out rom

medullary !", and

enters into thin limbs o

loop o Henle


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+, A))aratus


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F.?

AA0A!US


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ranular cells (also called

? t l l ll )


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?u,taglomerular cells)

Act as intrarenal baroreceptors-hey act entirely within the kidney Although granular

cells acting as intrarenal baroreceptors do not send

signals centrally

-hese intrarenal baroreceptors sense renal afferentarteriolar pressure

/f low response by releasing Renin

the activity of the granular cells is affected both bydirect sensing of pressure in the renal arterioles and

by pressures sensed by neural baroreceptors

elsewhere in the body vis sympathetic neves

-he Iacula 4ensa cells


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-he Iacula 4ensa cells

-he macula densa cells at the end of the thickascending limb have aK;Cl symporters

that rapidly take up 3a$ l$ and K when FR$

and hence$ 3al delivery is high

Sodium also enters the macula densa cells via

a aH antiporter.Since the action of this

antiporter causes the cells to lose a hydrogen

ion for every sodium ion entering$ this

increases intracellular p7

A combination of cellular volume change$ increasedintra cellular chloride and higher intracellular p7


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intra;cellular chloride$ and higher intracellular p7initiates intracellular signaling processes that leadto the release of A!from the basolateral surfaceof the cells in close pro,imity to the glomerularmesangial cells

-his A-5 stimulates uriner)ic ;receptorsonthe mesangial cells and afferent arteriolar smooth

muscle cells5% receptor stimulation increases calcium in thesecells and promotes contraction

ontraction of mesangial cellsdecreases the

effective filtration area$ which decreases FRontraction of the afferent arteriolar smooth musclecellsincreases afferent resistance and decreasesRBF and FR

/n addition$ it is the increased calcium in the

ff t t i l ll th t d R i


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afferent arteriolar cells that reduces Renin

secretion

-he A-5 may also be metaboliPed to

Adenosine$ which can stimulate Adenosine

receptorsthat produce the same result as the

5% receptors

7igh salt content in the thick ascending limb of


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a given nephron generates signals that reduce

glomerular blood flow and reduce filtration inthat nephron$ thus blunting (but not eliminating)

the increase in sodium e,cretion initiated by

other processes in conditions (eg$ volume

e,pansion) in which the appropriate overall

response is increased sodium e,cretion

-he same signals that reduce filtration also

reduce the secretion of renin


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ontrol of Renin secretion


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-hree primary mechanisms regulate renin secretion

irst$ renal sympathetic nerve activity activates T!;adrenergic

receptors on granular cells of the afferent arteriole to stimulaterenin secretion

Second$the granular cells also act as intrarenal baroreceptors$responding to changes in pressure within the afferent arteriole$

which$ e,cept in cases of renal artery stenosis$ is a reflection ofchanges in arterial blood pressure 4eformation of the granularcells alters renin secretion9 when pressure falls$ reninproduction increases

!hird$macula densa cells in the thick ascending limb sense the

delivery of tubular sodium chloride$ leading to the release ofchemical transmitters that alter renin secretion from thegranular cells9 when sodium chloride delivery increases$ reninproduction decreases


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Regulation of Sodium and 1ater

2,cretion

-he kidneys work in partnership with thecardiovascular system -ogether they ensure


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that

(!) -here is enough blood volume to fill thevascular tree$

(%) 2nough pressure to drive blood flow

through peripheral tissues(+) -he blood$ and therefore the cells through;

out the body$ has the proper osmolality

All the regulatory mechanisms that controlsodium and water e,cretion e,ist for the

purpose of meeting these three goals


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ariations in 0enal blood flo" 10B) and?lomerular filtration rate 1?0@are

ma?or means of regulating sodium

e,cretion

S04/6I 2UR2-/039 -72

AR4/0AS6"AR 0332-/03


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AR4/0AS6"AR 0332-/03


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ostly transepithelial transport>ostly transepithelial transport (analogous to(analogous to

reabsorption).reabsorption).Depends mostly on active membraneDepends mostly on active membrane

transport systemstransport systems

rovides mechanism for rapid removal ofrovides mechanism for rapid removal of

substancessubstances 1most important for H1most important for H22$ K$ K22$ forei)n or)anic ions$ forei)n or)anic ionsand dru)s such as penicillin etc.@and dru)s such as penicillin etc.@

:. >icturition:. >icturition


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Spinal cord inte)ration( ;Spinal cord inte)ration( ;

simultaneous efferentsimultaneous efferentsi)nalssi)nals

%n infant Just simple spinal%n infant Just simple spinal

refle&refle&

6ater( learned refle& under6ater( learned refle& underconscious control fromconscious control fromhi)her brain centershi)her brain centers

arious subconscious factorsarious subconscious factors

affect refle&affect refle&


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lecture notes on renal physiology for mbbs

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