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
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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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