Physiology, Lecture 6, Urinary System

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    Urinary systemUrinary system

    IntroductionIntroduction

    GFGF

    Tubular reabsorptionTubular reabsorption Tubular secretionTubular secretion

    Urine excretion & plasma clearanceUrine excretion & plasma clearance

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    functionsfunctions11-- maintaining ECF stabilitymaintaining ECF stability volume &volume &

    compsoitioncompsoition

    22-- main route for eliminating potentiallymain route for eliminating potentially

    toxic wastes & foreign compounds fromtoxic wastes & foreign compounds from

    the bodythe body

    33-- acidacid--base balancebase balance

    44-- producing erythropoitenproducing erythropoiten

    55-- producing renin which triggers a chainproducing renin which triggers a chainreaction important in salt conservationreaction important in salt conservation

    by kidneysby kidneys

    66-- converting vitamin D into its activeconverting vitamin D into its active

    formform

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    Kidneys: urine forming organs, beanKidneys: urine forming organs, bean--shaped, located in the back of theshaped, located in the back of theabdominal wallabdominal wall

    Renal pelvis: central collecting cavityRenal pelvis: central collecting cavitythat leads to the ureter which is athat leads to the ureter which is a

    smooth muscle walled ductsmooth muscle walled duct Urinary bladder: smooth muscleUrinary bladder: smooth muscle

    walled sac that stores urinewalled sac that stores urine

    Urethra: straight and short inUrethra: straight and short infemale, long and curving course infemale, long and curving course inmales passing through the prostatemales passing through the prostate

    gland and the penisgland and the penis

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    Nephron: the functional unit, 2 million inNephron: the functional unit, 2 million inboth kidneys: aboth kidneys: a-- medullary bmedullary b-- corticalcortical

    vascular components of the nephron :vascular components of the nephron :

    11-- Glomerulus : ball like tuft of capillariesGlomerulus : ball like tuft of capillaries

    22--afferent arteriole to the glomerulusafferent arteriole to the glomerulus

    33--efferent arteriole out of the glomerulusefferent arteriole out of the glomerulus

    44--peritubular capillaries then venulesperitubular capillaries then venules

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    Tubular components of the nephron:Tubular components of the nephron:

    --hallow fluid filled tube, single layer ofhallow fluid filled tube, single layer ofepitheliumepithelium

    11--Bowman's capsule around theBowman's capsule around the

    glomerulusglomerulus

    22--proximal tubule convolutedproximal tubule convoluted

    33--loop of Henle: uloop of Henle: u--shaped, dips into theshaped, dips into the

    medulla:medulla:

    aa--ascending bascending b--descendingdescending

    passes between the afferent & efferentpasses between the afferent & efferentarteriolesarterioles

    44--distal tubule: lies in the cortexdistal tubule: lies in the cortex

    55--collecting duct: 8 nephrons drain in onecollecting duct: 8 nephrons drain in one

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    Fig. 13-2, p. 408

    Proximal tubule Distal

    tubule Collecting

    duct

    Bowmans

    capsule

    Glomerulus

    Cortex

    Medulla

    Loop of

    Henle

    To renalpelvisOverview of Functions of Parts of a Nephron

    Peritubular

    capillaries

    Vein

    Artery

    Afferent

    arteriole

    Efferentarteriole

    Juxtaglomerular

    apparatus

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    GlomerularfiltrationGlomerularfiltration Plasma free from protein filters in b. capsulePlasma free from protein filters in b. capsule 20% of plasma that enters the glomerulus is filtered20% of plasma that enters the glomerulus is filtered 125mL of glomerular filtrate is formed each minute (125mL of glomerular filtrate is formed each minute (

    180L/day)180L/day) kidneys filter the entire plasma volume 65 times/daykidneys filter the entire plasma volume 65 times/day Glom. Membrane:Glom. Membrane:

    aa--wall of glom. Capillaries is 100x more permeablewall of glom. Capillaries is 100x more permeablebb--basement membrane: acellular gelatinous layerbasement membrane: acellular gelatinous layercc--inner layer ofB. capsule is made of podocytes which areinner layer ofB. capsule is made of podocytes which areoctopus like cells between filtration slitsoctopus like cells between filtration slits

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    Fig. 13-5c, p. 410

    Podocyte

    foot process

    Filtration

    slit

    Basement

    membrane

    Capillary

    pore

    Endothelial

    cell

    Lumen of glomerular

    capillary

    Lumen of

    Bowmans capsule

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    Fig. 13-4, p. 409

    Afferent

    arteriole

    Efferent

    arteriole

    80% of the plasma

    that enters theglomerulus is

    not filtered

    and leaves through

    the efferent arteriole.

    Glomerulus

    Bowmans

    capsule

    20% of the

    plasma that

    enters the

    glomerulus

    is filtered.

    Kidney

    tubule

    (entire

    length,

    uncoiled)

    Urine excretion

    (eliminatedfrom the body)

    To venous system

    (conserved

    for the body)

    Peritubular

    capillary

    GF

    TR

    TS

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    Fig. 13-5a, p. 410

    Afferent arteriole Efferent arteriole

    Glomerulus

    Bowmans

    capsule

    Lumen of

    Bowmans

    capsule

    Outer layer of

    Bowmans capsule

    Inner layer

    of Bowmans capsule

    (podocytes)

    Proximal convoluted tubule

    Lumen of

    glomerular

    capillary

    Endothelial

    cell

    Basement

    membrane

    Podocyte

    foot process

    (see

    nextslide)

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    Forces involved in GFForces involved in GF

    Like forces starling capillary circulation with 2 exceptions:Like forces starling capillary circulation with 2 exceptions:aa-- permeability is much higherpermeability is much higherbb-- filtration occurs through out the whole glomerulus capillaryfiltration occurs through out the whole glomerulus capillary

    11-- glomerulus blood pressure ~55mmHg larger than any otherglomerulus blood pressure ~55mmHg larger than any othercapillary because the afferent arteriole are wide and thecapillary because the afferent arteriole are wide and theefferent are narrowefferent are narrow

    22--plasma colloid osmotic pressure ~30mmHg, opposesplasma colloid osmotic pressure ~30mmHg, opposesfiltrationfiltration

    33--Bomans capsule hydrostatic pressure ~15mmHg exerted byBomans capsule hydrostatic pressure ~15mmHg exerted bythe fluid in the initial part of the tubule, opposes filtrationthe fluid in the initial part of the tubule, opposes filtration

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    Table 13-1, p. 412

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    GFRGFR

    Net filtrating pr. = 55Net filtrating pr. = 55-- (30+15)= 10mmHg(30+15)= 10mmHg

    Changes in GFR occurs mainly due to changes inChanges in GFR occurs mainly due to changes inthe glom. capillary pr. By the sympathetic effectthe glom. capillary pr. By the sympathetic effectmainly on the afferent arteriole not the efferentmainly on the afferent arteriole not the efferent

    oneone decreased BPdecreased BP carotid & aortic baroreceptorscarotid & aortic baroreceptorsincrease symp.increase symp. vasoconstrictionvasoconstriction afferentafferentspasmspasm decrease bl. Flowdecrease bl. Flow decrease glom. Cap.decrease glom. Cap.Pr.Pr. decrease GFRdecrease GFR decrease urinedecrease urine conserveconserve

    body fluid & saltsbody fluid & salts

    increaseBP

    increaseBP

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    GFRGFR

    increased BPincreased BP carotid & aortic baroreceptorscarotid & aortic baroreceptorsdecrease symp.decrease symp. vasodilatationvasodilatation afferentafferentdilatationdilatation increase bl. Flowincrease bl. Flow increase glom. Cap.increase glom. Cap.P

    r.P

    r.

    increase GFRincrease GFR

    increase urineincrease urine

    decrease bodydecrease bodyfluidfluid decrease BPdecrease BP

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    Fig. 13-8a, p. 413

    Vasoconstriction

    (decreases blood flow

    into the glomerulus)

    Afferent arteriole

    Glomerulus

    Efferent arteriole

    Glomerular

    capillary

    blood pressure

    Net filtration

    pressure

    GFR

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    Fig. 13-8b, p. 413

    Afferent arteriole

    Glomerulus

    Efferent arteriole

    Glomerular

    capillary

    blood pressure

    Net filtration

    pressure

    GFR

    Vasodilation

    (increases blood flow

    into the glomerulus)

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    Fig. 13-7, p. 413

    Short-termadjustmentfor

    Arterial bloodpressure

    Long-term

    adjustment for

    Arterialbloodpressure

    Detection by aorticarch and carotid sinusbaroreceptors

    Cardiac

    output

    Total

    peripheral

    resistance

    Sympathetic activity

    Generalized

    arteriolar vasoconstriction

    Afferent arteriolarvasoconstriction

    Glomerular capillary

    blood pressure

    GFR

    Urine volume

    Conservation of fluid and salt

    Arterial blood pressure

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    2222--25% of the cardiac output goes25% of the cardiac output goesto the kidneys ( 1140mL/min) andto the kidneys ( 1140mL/min) andHtc. accounts for 45% so the kidneyHtc. accounts for 45% so the kidneyreceives 625mL plasma/min andreceives 625mL plasma/min and20% of those are filtrated20% of those are filtrated

    (125mL)(125mL)(GFR)(GFR)

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    Tubular reabsorptionTubular reabsorption

    Tremendously & highly selective & has aTremendously & highly selective & has ahigh reabsorptive capacity for neededhigh reabsorptive capacity for neededmaterialsmaterials

    Little capacity for wastes & no capacity forLittle capacity for wastes & no capacity fortoxicstoxics

    125mL/min GFR125mL/min GFR 124 ml is reabsorbed124 ml is reabsorbed(99% H(99% H22O, 100% glucose, 99.5% salts)O, 100% glucose, 99.5% salts)

    Steps of transepithelial transport:Steps of transepithelial transport:

    11--luminal membrane 2luminal membrane 2--cytosolcytosol33--basolateral mem. 4basolateral mem. 4--interstitialinterstitial55--capillary wallcapillary wall

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    Passive transport and active transport :Passive transport and active transport :active if one step is activeactive if one step is active

    --glucose, AA, organic nutrients, Na, POglucose, AA, organic nutrients, Na, PO44

    Na reabsorption: NaNa reabsorption: Na--K pump at basolateralK pump at basolateral

    membrane is essential forN

    amembrane is essential forN

    areabsorption(99.5%):reabsorption(99.5%):

    --67% in proximal tubules67% in proximal tubules

    --25% in loop of henle25% in loop of henle

    --8% in collecting & distal tubules8% in collecting & distal tubules

    --in proximal tubules Na reabsorption helps inin proximal tubules Na reabsorption helps inglucose, AA, Hglucose, AA, H22O, Cl, and urea reabsorption.O, Cl, and urea reabsorption.

    + -3

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    in the ascending limb of the loop of henle Nain the ascending limb of the loop of henle Nareabsorption along with Cl play a critical role inreabsorption along with Cl play a critical role inproducing urine of varying concentration andproducing urine of varying concentration andvolumevolume

    Theres noN

    a reabsorption in the descendingTheres noN

    a reabsorption in the descendinglimb of loop of henlelimb of loop of henle In the distal & collecting tubules Na reabsorptionIn the distal & collecting tubules Na reabsorption

    is variable & subject to hormonal control, and itis variable & subject to hormonal control, and itplays a role in regulating ECF volume and linksplays a role in regulating ECF volume and linkswith K & H secretionwith K & H secretion

    Na is firstly absorbed by the NaNa is firstly absorbed by the Na--K pump in theK pump in thebasolateral wall then from the lumen in cells bybasolateral wall then from the lumen in cells bypassive transportpassive transport

    Na reabsorptionNa reabsorption

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    Fig. 13-10, p. 416

    Lumen Tubular cell Interstitial fluid

    Peritubular

    capillary

    Diffusion

    Na+

    channelActive transport

    Basolateral

    Na+ K+ ATPase

    carrier

    Lateral space Diffusion

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    Glucose reabsorptionGlucose reabsorption

    Proximal tubules with glucose cotransportProximal tubules with glucose cotransportand AA almost 100%, then by facilitatedand AA almost 100%, then by facilitatedpassive transport in the basolateral wall, Napassive transport in the basolateral wall, Na--

    glucose carriers as well as Naglucose carriers as well as Na--AA areAA arespecificspecific

    --those carriers has a maximum transportthose carriers has a maximum transportcapacity called tubular maximum (Tcapacity called tubular maximum (Tmm))

    --any quantity beyond Tany quantity beyond Tmm will escape intowill escape intourineurine

    --filtered load= plasma con. x GFRfiltered load= plasma con. x GFR

    for glucose= 100mg/100mL x 125mL/min =for glucose= 100mg/100mL x 125mL/min =

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    Glucose reabsorptionGlucose reabsorption

    --TTmm for glucose averages 375mg/minfor glucose averages 375mg/min

    --the plasma con. Of glucose at whichthe plasma con. Of glucose at whichglucose reaches its Tm is called renalglucose reaches its Tm is called renalthreshold (300mg/100mL)threshold (300mg/100mL)

    --if glucose plasma con. Increasesif glucose plasma con. Increases ititwill leave the filtratewill leave the filtrate

    --if glucose plasma con. decreasesif glucose plasma con. decreases ititwill be completely reabsorbedwill be completely reabsorbed

    --kidneys do not regulate glucose andkidneys do not regulate glucose andAAAA

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    Fig. 13-12, p. 420

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    Phosphate & calcium reabsorptionPhosphate & calcium reabsorption

    Both are actively absorbed and regulatedBoth are actively absorbed and regulatedby the kidneysby the kidneys

    The renal threshold for both of theseThe renal threshold for both of thesesubstances equals to their plasma con.substances equals to their plasma con.--the tubules will reabsorb the samethe tubules will reabsorb the samenormal plasma con. And any excess that isnormal plasma con. And any excess that isingested will be spilled out in the urineingested will be spilled out in the urinerestoring the normal plasma con.restoring the normal plasma con.

    -- POPO44 & Ca renal threshold can be& Ca renal threshold can beregulated by the parathyroid hormoneregulated by the parathyroid hormonedepending on the body needsdepending on the body needs

    -3 +2

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    aldosteronealdosterone

    Aldosterone stimulates Na reabsorption in the distalAldosterone stimulates Na reabsorption in the distaland collecting tubulesand collecting tubules

    --ifNa con. In plasma is highifNa con. In plasma is high no regulationno regulation Na outNa out

    --ifNa con. In plasma is lowifNa con. In plasma is low aldosterone releasealdosterone releasemore reabsorptionmore reabsorption conserve Naconserve Na

    ReninRenin--angeotensinangeotensin--aldosterone system (RAAS):aldosterone system (RAAS):

    --renin is secreted from the juxtaglomerulusrenin is secreted from the juxtaglomerulusapparatus which activates the angiotensin in theapparatus which activates the angiotensin in the

    plasma into angiotensin Iplasma into angiotensin I--angiotensin I under the effect of ACE in theangiotensin I under the effect of ACE in thepulmonary circulation is converted to angiotensin IIpulmonary circulation is converted to angiotensin IIwhich stimulates aldosterone releasewhich stimulates aldosterone release

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    Fig. 13-11, p. 417

    NaCl / ECF volume /

    Arterial blood pressure

    Liver Kidney LungsAdrenal

    cortexKidney

    H2O

    conserved

    Na+ (and CI)osmotically holdmore H2O in ECF

    Na+ (and CI)

    conserved

    Na+ reabsorption

    by kidney tubules

    ( CI

    reabsorption

    follows passively)

    Vasopressin Thirst Arteriolarvasoconstriction

    H2O reabsorption

    by kidney tubulesFluid intake

    Renin

    Angiotensin-

    convertingenzyme

    Angiotensinogen Angiotensin I Angiotensin II Aldosterone

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    aldosterone effects:aldosterone effects:--promotes insertion of new Na channels intopromotes insertion of new Na channels into

    the luminal membranethe luminal membrane--additional Naadditional Na--K carriers in the basolateralK carriers in the basolateralmembranemembrane

    --these effects are seen in the distal &these effects are seen in the distal &collecting tubulescollecting tubules

    When Na load, ECF/plasma volume, and BPWhen Na load, ECF/plasma volume, and BPare above normalare above normal renin release is inhibitedrenin release is inhibitedno aldosteroneno aldosterone Na portion in the distalNa portion in the distaltubules and the collecting ducts is excertedtubules and the collecting ducts is excerted

    8% is not a small amount considering the8% is not a small amount considering thefact that per day plasma will be filtered 65fact that per day plasma will be filtered 65times so 20g of salt is lost per daytimes so 20g of salt is lost per day

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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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    ANPANP

    (atrial natriuretic peptide)(atrial natriuretic peptide)

    ANP is released from the atria whenANP is released from the atria whenthe heart is stretched by expansionthe heart is stretched by expansionof the ECF volume as a result ofNa &of the ECF volume as a result ofNa &HH22O retentionO retention

    --increased BPincreased BP ANP releaseANP release inhibitinhibitNa reabsorptionNa reabsorption more Na & Hmore Na & H22O areO are

    released into the urinereleased into the urine less ECFless ECFvolumevolume decrease BPdecrease BP

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    Table 13-3, p. 424

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    Cl reabsorptionCl reabsorption

    Passively absorbed down thePassively absorbed down theelectrical gradient which is createdelectrical gradient which is createdby active Na reabsorptionby active Na reabsorption

    -

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    H22O reabsorptionO reabsorption Passive by osmosis following NaPassive by osmosis following Na

    reabsorptionreabsorption

    -- 65% (117L/day) by the end of65% (117L/day) by the end of

    the proximal tubulesthe proximal tubules-- 15% of filtered H2O is obligatorily15% of filtered H2O is obligatorily

    reabsorbed from loop of henlereabsorbed from loop of henle

    -- 20% remaining is reabsorbed in distal20% remaining is reabsorbed in distal

    tubulestubules

    Hormonal regulation:Hormonal regulation:

    --water channels in the aquaporins partwater channels in the aquaporins part

    is regulated by vasopressinis regulated by vasopressin

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    Urea reabsorptionUrea reabsorption

    Passive linked to active NaPassive linked to active Nareabsorptionreabsorption

    In the proximal tubules [urea] isIn the proximal tubules [urea] isincreased three time because ofNa &increased three time because ofNa &HH22O reabsorptionO reabsorption

    Urea is passively absorbed but itUrea is passively absorbed but itdoes not have good permeabilitydoes not have good permeability

    only 50% of urea is reabsorbedonly 50% of urea is reabsorbed

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    Fig. 13-13, p. 421

    Glomerulus

    Bowmanscapsule

    Beginning of

    proximaltubule

    Peritubular

    capillary

    Na+ (active)

    H2O (osmosis)

    Na+ (active)

    H2O (osmosis)

    Passive diffusion

    of urea down itsconcentration gradient

    44 ml

    of

    filtrate

    125 ml

    of

    filtrate

    End of

    proximal

    tubule

    = Urea molecules

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    wasteswastes

    Waste products are not reabsorbedWaste products are not reabsorbedbecause the permeability of thebecause the permeability of thetubules to these products is almosttubules to these products is almostzero :zero :

    --phenolphenol

    --creatininecreatinine

    --other toxicsother toxics

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    Tubular secretionTubular secretion

    Supplemental mechanisms that hastenSupplemental mechanisms that hastenelimination of substances from the bodyelimination of substances from the body

    11-- hydrogen:hydrogen:

    -- important for acidimportant for acid--base balancebase balance

    -- secreted by proximal, distal, &secreted by proximal, distal, &

    collecting tubulescollecting tubules

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    22-- potassium:potassium:

    --actively reabsorbed in proximalactively reabsorbed in proximal

    tubulestubules

    --actively secreted in distal &actively secreted in distal &

    collecting tubulescollecting tubules

    --when plasma [K] increases,when plasma [K] increases,

    secretion is adjusted to eliminate Ksecretion is adjusted to eliminate Koutout

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    --mechanism of secretion:mechanism of secretion:

    coupled with Nacoupled with Na--K pump whichK pump which

    reduces [K]reduces [K]interstitialinterstitial plasma Kplasma K

    leaves peritubular capillaryleaves peritubular capillary thethe

    pump get K inside the tubular cellspump get K inside the tubular cells

    which has many K channels towhich has many K channels tohelp K to get out to the tubularhelp K to get out to the tubular

    lumin passivelylumin passively

    --K channels in the proximal tubulesK channels in the proximal tubules

    are located at the basolateral sideare located at the basolateral side

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    --control ofK secretion:control ofK secretion:

    increased [K]increased [K]plasmaplasma stimulation ofstimulation of

    adrenal cortexadrenal cortex increaseincrease

    aldosteronealdosterone increase in Kincrease in K

    secretion &Na reabsorptionsecretion &Na reabsorption

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    Fig. 13-14, p. 423

    Lumen Tubular cellPeritubularcapillaryInterstitial fluid

    K+

    channel

    Active

    transport

    Diffusion

    Diffusion

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    33-- organic anions & cations:organic anions & cations:

    --two types of carriers one fortwo types of carriers one foranions & the other for cations:anions & the other for cations:

    --prostaglandinsprostaglandins

    --food additivesfood additives--histamine & norhistamine & nor--epinephrineepinephrine

    --environmental pollutantsenvironmental pollutants

    (pesticides), drugs(pesticides), drugs

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    urine excretionurine excretion

    125mL/min is filtered, 124mL/min is125mL/min is filtered, 124mL/min isreabsorbed, so 1mL/min is excretedreabsorbed, so 1mL/min is excreted

    If125mL/min is filtered, and weIf

    125mL/min is filtered, and wehave a slightly reduced reabsorptionhave a slightly reduced reabsorption

    (123mL/min) then urine excretion is(123mL/min) then urine excretion isdoubled (2mL/min)doubled (2mL/min)

    By excreting substances in the urine,By excreting substances in the urine,kidneys clear the plasma flowingkidneys clear the plasma flowingthrough them of these substancesthrough them of these substances

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    Plasma clearancePlasma clearance

    Plasma clearance of any substance isPlasma clearance of any substance is

    the volume of plasma completelythe volume of plasma completelycleared of that substance by thecleared of that substance by thekidneys per minutekidneys per minute

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    --a substance (X) that is filtered but nota substance (X) that is filtered but notreabsorbed or secreted has a plasmareabsorbed or secreted has a plasma

    clearance= GFRclearance= GFR 125mL/min of plasma is filtered125mL/min of plasma is filtered

    containing an amount of X, thiscontaining an amount of X, this

    amount of X is left behind andamount of X is left behind andis excreted with urine thus eachis excreted with urine thus each

    minute 125mL of plasma will beminute 125mL of plasma will be

    cleared from Xcleared from X exampleexample inulininulinproduced chemicallyproduced chemically

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    Fig. 13-16a, p. 426

    Glomerulus

    Tubule

    Peritubular

    capillary

    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 anda substance (Y) is filtered andreabsorbed but not secreted has areabsorbed but not secreted has aplasma clearance that is less thanplasma clearance that is less thanGFRGFR

    examples:examples:

    aa-- glucose pl. cl. = 0glucose pl. cl. = 0

    bb-- urea pl. cl. =62.5mL/minurea 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 plasma

    is cleared of the substance.

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    Fig. 13-16c, p. 426

    For a substance filtered,

    not secreted, and partially

    reabsorbed, such as urea, only

    a portion of the filtered plasma

    is cleared of the substance.

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    -- a substance (Z) is filtered and secreteda substance (Z) is filtered and secretedbut not reabsorbed has a plasmabut not reabsorbed has a plasma

    clearance that is larger than GFRclearance that is larger than GFR H+ is an example which is cleared byH+ is an example which is cleared by

    the following rates: 125mL/min bythe following rates: 125mL/min by

    filtration & 25mL/min by secretion so itfiltration & 25mL/min by secretion so ithas a pl. cl =150mL/minhas a pl. cl =150mL/min

    paraaminohippuric acid (PAH), 20% ofparaaminohippuric acid (PAH), 20% of

    this chemical is filtered, and thethis chemical is filtered, and the

    remaining 80% will be secreted so it aremaining 80% will be secreted so it a

    has a pl. cl =plasma flow ratehas a pl. cl =plasma flow rate (625mL/min)(625mL/min)

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    Fig. 13-16d, p. 426

    For a substance filtered and secreted

    but not reabsorbed, such as hydrogen

    ion, all of the filtered plasma is

    cleared of the substance, and the

    peritubular plasma from which the

    substance is secreted is also cleared.

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    Urine excretion ofvaryingUrine excretion ofvarying

    concentrationsconcentrations

    Interstitial fluid of the medulla build upInterstitial fluid of the medulla build upa large osmotic gradienta large osmotic gradient

    The concentration of fluid progressivelyThe concentration of fluid progressivelyincreases from the cortex downincreases from the cortex downthrough the depth of the medulla up tothrough the depth of the medulla up to

    1200mOsmole/L1200mOsmole/L

    M d ll

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    Fig. 13-17, p. 427

    Medulla

    Cortex

    All values in milliosmols (mosm)/liter.

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    Urine is excreted in the range of100Urine is excreted in the range of100--12001200mOsmole/L depending on body fluid status:mOsmole/L depending on body fluid status:

    11-- ideallyideally 1mL/min, isotonic1mL/min, isotonic22-- overhydrationoverhydration up to 25mL/min,up to 25mL/min,

    hypotonic, 100mhypotonic, 100mOOsmole/Lsmole/L

    33--dehydrationdehydration

    0.3mL/min0.3mL/minhypertonic, up to 1200mOsm/Lhypertonic, up to 1200mOsm/L

    1, 2, 3 represent the medullary countercurrent1, 2, 3 represent the medullary countercurrent

    systemsystem

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    Countercurrent multiplicationCountercurrent multiplication

    (c.c.m)(c.c.m)

    In the proximal tubules, 65% reabsorbedIn the proximal tubules, 65% reabsorbed(water & salts) so solvent & solute are equally(water & salts) so solvent & solute are equallyabsorbed, so the tonicity will remain isotonicabsorbed, so the tonicity will remain isotonic

    In the loop of henle:In the loop of henle:

    11--descending limb:descending limb: --high water permeabilityhigh water permeability

    --no sodium reabsorptionno sodium reabsorption22--ascending limb:ascending limb: --actively reabsorbed NaClactively reabsorbed NaCl

    --impermeable for waterimpermeable for water

    Gl l

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    Fig. 13-19a, p. 430

    Glomerulus

    Bowmans capsule

    Proximal tubule

    Distal tubule

    Cortex

    Medulla

    Long loop

    of Henle

    Collecting

    tubule

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    Mechanism ofc.c.mMechanism ofc.c.m

    Initial scene: interstitial fluid is 300mOsm/LInitial scene: interstitial fluid is 300mOsm/L

    Step1:Step1: --NaCl actively pumped fromNaCl actively pumped from

    ascending with the force ofascending with the force of

    200mOsm/L dif.200mOsm/L dif.

    --water will be reabsorbed from thewater will be reabsorbed from the

    descending to equilibrate with thedescending to equilibrate with the

    outside until both have 400mOsm/Loutside until both have 400mOsm/L

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

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    Step2:Step2: --movement of luminal filtrate somovement of luminal filtrate so

    from ascending 200mOsm/L fluidfrom ascending 200mOsm/L fluid

    to the distal tubules, &to the distal tubules, &

    300mOsm/L fluid from proximal300mOsm/L fluid from proximal

    tubules gets in the descendingtubules gets in the descending

    limb & in between 400mOsm/L islimb & in between 400mOsm/L is

    moved around the tipmoved around the tip

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

    To

    distal

    tubule

    From

    proximal

    tubule

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    Step3:Step3: --ascending limb pumps NaClascending limb pumps NaCl

    while water is reabsorbedwhile water is reabsorbed

    from the descending limb untilfrom the descending limb until

    200mOsm/L dif. Is established200mOsm/L dif. Is established

    between the ascending, thebetween the ascending, the

    interstitial fluid & theinterstitial fluid & the

    descendingdescending

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    Step4:Step4: --movement of filtrate willmovement of filtrate will

    again disrupt the 200mOsm/Lagain disrupt the 200mOsm/L

    gradient at the horizontal levelgradient at the horizontal level

    Step5:Step5: --active NaCl pump in theactive NaCl pump in the

    ascending limb with waterascending limb with water

    diffusion in the descending onediffusion in the descending one--the 200mOsm/L is reestablishedthe 200mOsm/L is reestablished

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    Step4 Step5Step4 Step5

    From

    proximal

    tubule

    to

    distal

    tubule

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    Step6:Step6: --filtrate movement again will changefiltrate movement again will changethe gradient so that it will lead to athe gradient so that it will lead to a

    progressive increment in theprogressive increment in the

    tonicity of the fluid in thetonicity of the fluid in thedescending limb & decrement in thedescending limb & decrement in the

    ascending oneascending one

    From

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

    From

    proximal

    tubule

    To

    distal

    tubule

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    Vasopressin effectsVasopressin effects

    180L/day is filtered, 65% is reabsorbed180L/day is filtered, 65% is reabsorbedin the prox. tubules, 15% is reabsorbedin the prox. tubules, 15% is reabsorbedin the L.H, & the remaining 20% isin the L.H, & the remaining 20% is

    reabsorbed in the distal tubulesreabsorbed in the distal tubules~36L/day~36L/day

    This 36L filtrate is very hypotonicThis 36L filtrate is very hypotonic(100mOsm/L), whereas the interstitial(100mOsm/L), whereas the interstitialfluid is isotonic in the cortex and up tofluid is isotonic in the cortex and up to1200mOsm/L in the collecting ducts1200mOsm/L in the collecting ducts

    through the medullathrough the medulla

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    Vasopressin will make the distal & collectingVasopressin will make the distal & collectingducts permeable to waterducts permeable to water

    Vasopressin is produced in the hypothalamus,Vasopressin is produced in the hypothalamus,stored in the posterior pituitary gland, &stored in the posterior pituitary gland, &stimulated by hypertonicity of the ECFstimulated by hypertonicity of the ECF

    Vasopressin binds receptors in the distal &Vasopressin binds receptors in the distal &collecting tubulescollecting tubules activates cAMPactivates cAMP promotespromotesinsertion of aquaporins in the luminalinsertion of aquaporins in the luminal

    membranemembrane

    Vasopressin effectsVasopressin effects

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    The previous process is reversible byThe previous process is reversible bydecreasing vasopressindecreasing vasopressin

    Maximum effect of vasopressin:Maximum effect of vasopressin:

    --everyday 600 mOsm of waste iseveryday 600 mOsm of waste is

    produced, this should be dissolvedproduced, this should be dissolved

    in water, the normal ability of thein water, the normal ability of thekidneys to concentrate a sln. iskidneys to concentrate a sln. is

    1200mOsm/L, so these 600mOsm1200mOsm/L, so these 600mOsm

    will be dissolved in 0.5Lwill be dissolved in 0.5L

    Vasopressin effectsVasopressin effects

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    Vasopressin effectsVasopressin effects

    --these 0.5L of urine is the minimum volumethese 0.5L of urine is the minimum volumeof urine that is required to excrete dailyof urine that is required to excrete dailywaste (obligatory water loss)waste (obligatory water loss)

    --if there is no vasopressin, the distal &if there is no vasopressin, the distal &collecting tubules are impermeable tocollecting tubules are impermeable towater, so 20% of filtrate cannot bewater, so 20% of filtrate cannot be

    reabsorbed completely, so 25mL/min willreabsorbed completely, so 25mL/min willbe excreted & the fluid will be hypotonicbe excreted & the fluid will be hypotonic

    From Filtrate has concentration

    of 100 mosm/liter as it

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    Fig. 13-20a, p. 433

    proximal

    tubule

    of 100 mosm/liter as it

    enters distal and

    collecting tubules

    In the

    face

    of a

    water

    deficit

    Collecting

    tubule

    Loop of

    HenleMedulla

    Cortex

    Distal tubule

    Concentration of

    urine may be up

    to 1,200 mosm/literas it leaves

    collecting tubule

    = permeability to H2O

    increased by vasopressin

    = passive diffusion of

    H2O

    = active transport of NaCl

    = portions of tubule

    impermeable to H2O

    *

    From

    proximal Filt t h t ti

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    proximal

    tubuleFiltrate has concentration

    of 100 mosm/liter as it

    enters distal and

    collecting tubules

    In the

    face

    of a

    water

    excess

    Collecting

    tubule

    Loop of

    HenleMedulla

    Cortex

    Distal tubule

    Concentration of

    urine may be as low

    as 100 mosm/liter

    as it leaves

    collecting tubule

    = passive diffusion of

    H2O

    = portions of tubule

    impermeable to H2O