UrinarySystem

Content

FunctionsoftheUrinarySystem
RenalAnatomy
BloodSupplytotheKidneys
Nephrons
GlomerularFiltrationRate(GFR)
ExtrinsicControls
ReninAngiotensinMechanism
Reabsorption:SecondaryActiveTransport
TubularSecretion
UrineFormation
AtrialNatriureticPeptide(ANP)Activity
ControlofUrineVolume
LoopofHenle:CountercurrentMultiplication
Renal&CreatinineClearance

FunctionsoftheUrinarySystem

FiltersWasteProductsfromBlood
Excretionofwaterandsodiumchloride
(NaCl)isregulatedinconjunctionwith
cardiovascular,endocrine,&central
nervoussystem

Theurinarysystemeliminatesin
theurinedifferentwasteproducts
suchasammoniaandurea
(bothformedwhenaminoacids
arebrokendown),uricacid
(formedwhennucleicacidsare
brokendown),creatinine(from
muscles),endproductsof
hemoglobinmetabolism,
hormonemetabolites,and
foreignsubstances(e.g.,drugs,
pesticides,&otherchemicals
ingestedinthefood)

Thebloodisfilteredbythe
kidneythrough3processes
calledfiltration,reabsorption,
andsecretion.Thewastesleave
thebodyasurine.

ConservesValuableNutrients
Theurinarysystemensuresglucose,amino

acidsandothervaluablenutrientsarenotlost
fromtheurine
RegulatesIonLevelsinthePlasma
Theurinarysystemregulatesion(electrolyte)
levelsintheplasmabyregulatingtheamount

ofsodium,potassium,chlorideandotherions
lostintheurine.
RegulatesBloodpH
TheurinarysystemregulatesbloodpHby
regulatingthenumberofH+andbicarbonate
ions(HCO3)lostintheurine.

Thekidneysworkinconcertwithlungs
toregulatethepHinanarrowlimitsof
bufferswithinbodyfluids.

RegulatesBloodVolume
Theurinarysystemregulatesblood
volumeby:
 1)releasingrenin,a
hormonethatafteraseries
ofreactionseventually
restrictssaltandwaterloss
atthekidneys.

2)adjustingthevolumeof
waterlostintheurine

RegulatesRBCProduction

Ifoxygenlevelsinthebloodarelow,the
kidneysreleaseerythropoietin,a
hormonethatstimulatesthe
hemocytoblasts(stemcellsinthebone
marrow)toincreaseredbloodcell
formation.HavingmoreRBCsallows
thebloodtotransportmoreoxygen.
StoresUrine

Thebladderstorestheurineuntilitis
convenienttoexcreteit.
ExcretesUrine

Theurethratransportsurinefrom
theurinarybladdertotheoutside
ofthebody.

Producesandsecreteshormones:

Reninactivatesthereninangiotensin
aldosteronesystem,thusregulating
bloodpressure&Na+,K+balance
Prostaglandins/kininsbradykinin=
vasoactive,leadingtomodulationof
renalbloodflow&alongwith
angiotensinIIaffectthesystemicblood
flow
Erythropoietinstimulatesredblood
cellformationbybonemarrow

RenalAnatomy

Thefunctionalunitsofthekidneysarecalled
nephrons.Eachkidneyismadeupofmillionsof
nephrons.

Eachnephronismadeupofthefollowing:

Glomerulus
BowmansCapsule
GlomerularCapillaries
ProximalConvolutedTubule(PCT)
LoopofHenle
DistalConvolutedTubule(DCT)
CollectingDuct

Clickhereforananimationthatreviewsthe
microanatomyofthekidney.

TwoTypesofNephrons:

Corticalnephrons

~85%ofallnephrons
Arelocatedinthecortex

Juxtamedullarynephrons,

Arecloser(juxta=nextto)therenal
medulla
TheloopsofHenleextenddeepinto
therenalpyramids

BloodSupplytotheKidneys

Bloodtravelsfromtheafferentarterioletoaballofcapillariesinthenephroncalledaglomerulus
Bloodleavesthenephronviatheefferentarteriole
Bloodtravelsfromefferentarterioletotheperitubularcapillariesandvasarecta
FiltrateComposition

Glomerularfiltrateisproducedfrombloodplasma
Thefiltratemustpassthrough:
Poresbetweenendothelialcellsoftheglomerularcapillary
BasementmembraneAcellulargelatinousmembranemadeofcollagenandglycoprotein
Filtrationslitsformedbypodocytes
Filtrateissimilartoplasmaintermsofconcentrationsofsaltsandoforganicmolecules(e.g.,glucose,aminoacids)exceptitisessentiallyproteinfree
Glomerularfiltrationbarrierrestrictsthefiltrationofmoleculesonthebasisofsizeandelectricalcharge
Neutralsolutes:
Solutessmallerthan180nanometersinradiusarefreelyfiltered
Solutesgreaterthan360nanometersarenot
Solutesbetween180and360nmarefilteredtovariousdegrees
Serumalbuminisanionicandhasa355nmradius,only~7gisfilteredperday(outof~70kg/daypassingthroughglomeruli)
Inanumberofglomerulardiseases,thenegativechargeonvariousbarriersforfiltrationislostduetoimmunologicdamageandinflammation,resultingin
proteinuria(i.e.increasedfiltrationofserumproteinsthataremostlynegativelycharged).


Theprinciplesoffluiddynamicsthataccountfortissuefluidinthecapillarybedsapplytotheglomerulusaswell
FiltrationisdrivenbyStarlingforcesacrosstheglomerularcapillaries.Changesintheseforcesandinrenalplasmaflowaltertheglomerularfiltrationrate(GFR)
Theglomerulusismoreefficientthanothercapillarybedsbecause:
Itsfiltrationmembraneissignificantlymorepermeable
Glomerularbloodpressureishigher
Ithasahighernetfiltrationpressure
Plasmaproteinsarenotfilteredandareusedtomaintainoncotic(colloidosmotic)pressureoftheblood

ForcesInvolvedinGlomerularFiltration

NetFiltrationPressure(NFP)Thisisthe
pressureresponsibleforfiltrateformation
NFPequalstheglomerularhydrostatic
pressure(HPg)minustheoncoticpressureof
glomerularblood(OPg)pluscapsular
hydrostaticpressure(HPc)

NFP=HPg(OPg+HPc)

NFP=55(30+15)=10

GlomerularFiltrationRate(GFR)

Thetotalamountoffiltrateformedperminutebythekidneys

Filtrationratefactors:
Totalsurfaceareaavailableforfiltrationandmembranepermeability(filtrationcoefficient=Kf)
Netfiltrationpressure(NFP)
GFR=KfxNFP
GFRisdirectlyproportionaltotheNFP
ChangesinGFRnormallyresultfromchangesinglomerularcapillarybloodpressure

KidneysReceive2025%ofCO

AtNFPof10mmHG
Filtrationfraction:~20%oftheplasmathatenterstheglomerulusisfiltered
Males=180Lofglomerularfiltrateperday125ml/min
Females=160Lperday115ml/min
For125ml/min,renalplasmaflow=625ml/min
55%ofbloodisplasma,sobloodflow=1140ml/min
1140=22%of5liters
Requiredforadjustmentsandpurification,nottosupplykidneytissue

RegulationofGlomerularFiltration
RegulationofGlomerularFiltration
IftheGFRistoohigh,neededsubstancescannotbereabsorbedquicklyenoughandarelostintheurine
IftheGFRistooloweverythingisreabsorbed,includingwastesthatarenormallydisposedof
ControlofGFRnormallyresultfromadjustingglomerularcapillarybloodpressure
3mechanismscontroltheGFR
Renalautoregulation(intrinsicsystem)
Neuralcontrols
Hormonalmechanism(thereninangiotensinsystem)

AutoregulationofGFR

Undernormalconditions(MAP=80180mmHg)renalautoregulationmaintainsanearlyconstantglomerularfiltrationrate
2mechanismsareinoperationforautoregulation:
Myogenicmechanism
Arterialpressurerises,afferentarteriolestretches
Vascularsmoothmusclescontract
ArterioleresistanceoffsetspressureincreaseRBF(&henceGFR)remainconstant.
Tubuloglomerularfeedbackmechanismforautoregulation:
Feedbackloopconsistsofaflowrate(increasedNaCl)sensingmechanisminmaculadensaofjuxtaglomerularapparatus(JGA)
IncreasedGFR(&RBF)triggersreleaseofvasoactivesignals
ConstrictsafferentarterioleleadingtoadecreasedGFR(&RBF)

ExtrinsicControls

Whenthesympatheticnervoussystemisatrest:
Renalbloodvesselsaremaximallydilated
Autoregulationmechanismsprevail
Understress:
Norepinephrineisreleasedbythesympatheticnervoussystem
Epinephrineisreleasedbytheadrenalmedulla
Afferentarteriolesconstrictandfiltrationisinhibited
Thesympatheticnervoussystemalsostimulatesthereninangiotensinmechanism
AdropinfiltrationpressurestimulatestheJuxtaglomerularapparatus(JGA)toreleasereninanderythropoietin

ReninAngiotensinMechanism

Reninreleaseistriggeredby:

ReducedstretchofthegranularJGcells
StimulationoftheJGcellsbyactivatedmaculadensacells
DirectstimulationoftheJGcellsviab1adrenergicreceptorsbyrenalnerves
ReninactsonangiotensinogentoreleaseangiotensinIwhichisconvertedtoangiotensinII
AngiotensinII
Causesmeanarterialpressuretorise
Stimulatestheadrenalcortextoreleasealdosterone
Asaresult,bothsystemicandglomerularhydrostaticpressurerise
OtherFactorsAffectingGlomerularFiltration

Prostaglandins(PGE2andPGI2)
VasodilatorsproducedinresponsetosympatheticstimulationandangiotensinII
Arethoughttopreventrenaldamagewhenperipheralresistanceisincreased
Nitricoxidevasodilatorproducedbythevascularendothelium
Adenosinevasoconstrictorofrenalvasculature
Endothelinapowerfulvasoconstrictorsecretedbytubulecells

ControlofKf

Mesangialcellshavecontractileproperties,influencecapillaryfiltrationbyclosingsomeofthecapillarieseffectssurfacearea
Podocyteschangesizeoffiltrationslits

ProcessofUrineFormation

Urineformationdependson3processes:

1.Glomerularfiltration
2.Tubularreabsorptionofthesubstancefromthetubularfluidintoblood
3.Tubularsecretionofthesubstancefromthebloodintothetubularfluid

Clickhereforananimationthatdescribesindetailtheprocessofurineformation.

AmountExcretedinUrine=AmountFilteredthroughglomeruliintorenalproximaltubuleMINUSamountreabsorbedintocapillariesPLUSamount
secretedintothetubules
1.ReabsorptionandSecretion

Accomplishedvia
diffusion
osmosis
activeandfacilitatedtransport
Carrierproteinshaveatransportmaximum(Tm)whichdeterminesrenalthresholdforreabsorptionofsubstancesintubularfluid
Atransportmaximum(Tm):
Reflectsthenumberofcarriersintherenaltubulesavailable
Existsfornearlyeverysubstancethatisactivelyreabsorbed
Whenthecarriersaresaturated,excessofthatsubstanceisexcreted

Reabsorption:SecondaryActiveTransport

Na+linkedactivetransport
Cotransport
Glucose
Ions
Aminoacids
Proximaltubule,keysite

NonReabsorbedSubstances

Substancesarenotreabsorbedifthey:
Lackcarriers
Arenotlipidsoluble
Aretoolargetopassthroughmembranepores
Urea,creatine,anduricacidarethemostimportantnonreabsorbedsubstances

SodiumReabsorption:

Sodiumreabsorptionisalmostalwaysby
activetransportviaaNa+K+ATPasepump
Sodiumreabsorptionprovidestheenergyand
themeansforreabsorbingmostothersolutes
Waterbyosmosis
Organicnutrientsandselectedcations
bysecondary(coupled)activetransport

2.TubularSecretion

Essentiallyreabsorptioninreverse,wheresubstancesmovefromperitubularcapillariesortubulecellsintofiltrate
Tubularsecretionisimportantfor:
Disposingofsubstancesnotalreadyinthefiltrate
Eliminatingundesirablesubstancessuchasureaanduricacid
Riddingthebodyofexcesspotassiumions
ControllingbloodpH

ReabsorptionandSecretionatthePCT

Glomerularfiltrationproducesfluidsimilartoplasmawithoutproteins
ThePCTreabsorbs6070%ofthefiltrateproduced
Sodium,allnutrients,cations,anions,andwater
Ureaandlipidsolublesolutes
Smallproteins
H+secretionalsooccursinthePCT

ReabsorptionandSecretionattheDCT

DCTperformsfinaladjustmentofurine

Activesecretionorabsorption
AbsorptionofNa+andCl
SecretionofK+andH+basedonbodypH
WaterisregulatedbyADH(vasopressin)
Na+,K+regulatedbyaldosterone

AtrialNatriureticPeptide(ANP)Activity

ANPreducesbloodNa+which:
Decreasesbloodvolume
Lowersbloodpressure
ANPlowersbloodNa+by:

ActingdirectlyonmedullaryductstoinhibitNa+reabsorption
CounteractingtheeffectsofangiotensinII
AntagonistictoaldosteroneandangiotensinII.
PromotesNa+andH20excretionintheurinebythekidney.
IndirectlystimulatinganincreaseinGFRreducingwaterreabsorption

RegulationbyADH

Releasedbyposteriorpituitarywhen
osmoreceptorsdetectanincreaseinplasma
osmolality.
Dehydrationorexcesssaltintake:
Producessensationofthirst.
StimulatesH20reabsorptionfromurine.

ClickhereforananimationonthereleaseofADHin
responsetodecreasedbloodvolume.

Theanimationisfollowedbypracticequestions.
Theanimationisfollowedbypracticequestions.

ControlofUrineVolume

Urinevolumeandosmoticconcentrationareregulatedbycontrollingwaterreabsorption
Precisecontrolallowedviafacultativewaterreabsorption

RegulationofUrineConcentrationandVolume

Osmolality
Thenumberofsoluteparticlesdissolvedin1Lofwater
Reflectsthesolutionsabilitytocauseosmosis
Bodyfluidsaremeasuredinmilliosmols(mOsm)
Thekidneyskeepthesoluteloadofbodyfluidsconstantatabout300mOsm
Thisisaccomplishedbythecountercurrentmechanism

CountercurrentMechanism

InteractionbetweentheflowoffiltratethroughtheloopofHenle(countercurrentmultiplier)andtheflowofbloodthroughthevasarectabloodvessels
(countercurrentexchanger)
ThesoluteconcentrationintheloopofHenlerangesfrom300mOsmto1200mOsm
VasaRectapreventslossofmedullaryosmoticgradientequilibrateswiththeinterstitialfluid
Maintainstheosmoticgradient
Deliversbloodtothecellsinthearea

LoopofHenle:CountercurrentMultiplication

Thedescendingloop:relativelyimpermeabletosolutes,highlypermeabletowater
Theascendingloop:permeabletosolutes,impermeabletowater
Collectingductsinthedeepmedullaryregionsarepermeabletourea
WaterReabsorptioninDescendingLoopofHenle

Countercurrentmultiplierandexchange
Medullaryosmoticgradient
H2OECFvasarectavessels

FormationofDiluteUrine

Filtrateisdilutedintheascendingloopof
Henleiftheantidiuretichormone(ADH)or
vasopressinisnotsecreted
Diluteurineiscreatedbyallowingthisfiltrate
tocontinueintotherenalpelvis
Collectingductsremainimpermeabletowater
nofurtherwaterreabsorptionoccurs
Sodiumandselectedionscanberemovedby
activeandpassivemechanisms
Urineosmolalitycanbeaslowas50mOsm
(onesixththatofplasma)

FormationofConcentratedUrine

Antidiuretichormone(ADH)inhibitsdiuresis
Thisequalizestheosmolalityofthefiltrateand
theinterstitialfluid
InthepresenceofADH,99%ofthewaterin
filtrateisreabsorbed
ADHdependentwaterreabsorptioniscalled
facultativewaterreabsorption
 ADHisthesignaltoproduceconcentrated
urine
Thekidneysabilitytoresponddependsupon
thehighmedullaryosmoticgradient

RenalClearance

Thevolumeofplasmathatisclearedofaparticularsubstanceinagiventime:

RC=UV/P

RC=renalclearancerate
U=concentration(mg/ml)ofthesubstanceinurine
V=flowrateofurineformation(ml/min)
P=concentrationofthesamesubstanceinplasma

Renalclearancetestsareusedto:

DeterminetheGFR

GFR=concentrationinurineXvolumeofurineperunitoftime
Plasmaconcentration

Detectglomerulardamage
Followtheprogressofdiagnosedrenaldisease

CreatinineClearance

Creatinineclearanceistheamountofcreatineintheurine,dividedbytheconcentrationinthebloodplasma,overtime.
Glomerularfiltrationratecanbecalculatedbymeasuringanychemicalthathasasteadylevelintheblood,andisfilteredbutneitheractivelyabsorbedorexcreted
bythekidneys.
Creatinineisusedbecauseitfulfillstheserequirements(thoughnotperfectly),anditisproducednaturallybythebody.
Theresultofthistestisanimportantgaugeusedinassessingexcretoryfunctionofthekidneys.Forexamplegradingofchronicrenalinsufficiencyanddosageof
drugsthatareprimarilyexcretedviaurinearebasedonGFR
Othermethodsinvolveconstantinfusionsofinulinoranothercompound,tomaintainasteadystateintheblood.

PhysicalCharacteristicsofUrine

ColorandTransparency
Clear,paletodeepyellow(duetourochrome)
Concentratedurinehasadeeperyellowcolor
Drugs,vitaminsupplements,anddietcanchangethecolorofurine
Cloudyurinemayindicateinfectionoftheurinarytract
pH
Slightlyacidic(pH6)witharangeof4.5to8.0
DietcanalterpH
SpecificGravity
Rangesfrom1.001to1.035
Isdependentonsoluteconcentration

ChemicalCompositionofUrine

Urineis95%waterand5%solutes
Nitrogenouswastesincludeurea,uricacid,andcreatinine
Othernormalsolutesinclude:
Sodium,potassium,phosphate,andsulfateions
Calcium,magnesium,andbicarbonateions
Abnormallyhighconcentrationsofanyurinaryconstituentsmayindicatepathology

Micturition

Fromthekidneysurineflowsdowntheureterstothebladderpropelledbyperistalticcontractionofsmoothmuscle.Thebladderisaballoonlikebagof
smoothmuscle=detrussormuscle,contractionofwhichemptiesbladderduringmicturition.
PressureVolumecurveofthebladderhasacharacteristicshape.
Thereisalongflatsegmentastheinitialincrementsofurineenterthebladderandthenasuddensharpriseasthemicturitionreflexistriggered.
Bladdercanhold250400ml
Greatervolumesstretchbladderwallsinitiatesmicturationreflex:
Spinalreflex

Parasympatheticstimulationcausesbladdertocontract
Internalsphincteropens
Externalsphincterrelaxesduetoinhibition

Clickhereforananimationonmicturition.Theanimationisfollowedbypracticequestions.

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This material is based upon work supported by the Nursing, Allied Health and Other Health-related Educational
Grant Program, a grant program funded with proceeds of the States Tobacco Lawsuit Settlement and administered
by the Texas Higher Education Coordinating Board.