RENALPHYSIOLOGYPhysiologyUnit4

RenalFunctions

• PrimaryFunctionistoregulatethechemistryofplasmathroughurineformation• AdditionalFunctions

• Regulateconcentrationofwasteproducts

• Regulatemineralbalance• Regulatesbodywaterbalance• Regulatebloodpressure(MAP)• RegulateplasmapH• Produceandsecretehormones

RenalTubularMembraneTransport

1. Filtration• Bloodtorenaltubules

• Outofyourblood• Nonspecific/BulkFlow

2. Reabsorption• Renaltubulestoblood

• Intoyourblood

3. Secretion• Bloodtorenaltubules

• Outofyourblood• Highlyspecific

4. Excretion• Urine

GlomerularFiltrationRate(GFR)FiltrationofPlasma

• GFR =Volumeoffiltrateproducedbybothkidneysperminute• GFR rates

• 115ml/mininwomen(166L/day)• 125ml/mininmen(180L/day)

• 7.5L/hour• 🤔about45gallons/day

• Entireplasmavolume(3L)isfilteredover60timesaday!

• FactorsthatdetermineGFR• Permeabilityofthefilter- fixed• Surfaceareaforfiltration- fixed• Netfiltrationpressure(NFP)**canberegulated**

RenalCorpuscleTheFilter

• Renalcorpuscleisthefilter• Thepermeabilityofthefilterdeterminedbythesizeofporeandelectricalcharge• Ultrafiltrationistheresultofaporesizethatis0.01microns• Electricalcharge

• Negativelychargedsurfaceofpodocytespreventsmovementofproteins

• Filtrateisprotein-freeandacellular

RenalCorpuscleTheFilter

• Starlingforcesintheglomerulusfavorfiltration• NFP =16mmHg• HigherthanperipheralNFP of10mmHg

• Ultrafiltrationisdrivenbyahighhydrostaticpressureintheglomerulus thatiscreatedbythedifferencesinthediameteroftheafferentandefferentarteriole• Thehighhydrostaticpressureforcessmallmoleculesthroughthefilterintothenephron• Water,urea,uricacid,creatinine,aminoacids,minerals(ions)

RenalNetFiltrationPressure

• NFP isafactorthatdeterminesGFR• NFP issubjecttophysiologicalcontrol• Regulationoftheafferent andefferent arterioles• Causechangesinvesseldiameter• Vasoconstriction/VasodilationcanchangeNFP• ↑NFP =↑GFR• ↓NFP =↓GFR

Nephrons

• CorticalNephrons• LOH extendsjustslightlyintotherenalmedulla

• Peritubularcapillariesreceiveproductsofreabsorption

• Primaryfunctionisreabsorption

• JuxtamedullaryNephrons• LOH extendsdeepintotherenalmedulla

• VasarectafollowtheLOH andreceiveH20fromcollectingducts

• Primaryfunctioniswaterreclamation

Na+ ReabsorptionCorticalNephrons

• ThemajorityofreabsorptionoccursatthePCT• TheNa+/K+/ATPasepumpestablishesandmaintainsalow[Na+]insidethetubularcells• ThemovementofNa+ isusedtomoveothermoleculesoutofthelumenofthetubeandintothetubularcells• Cotransport/Countertransport• H+,glucose,aminoacids

tube➜ blooddrivenbytheNa+/K+/ATPasepump

Mineral Balance

GlucoseReabsorptionCorticalNephrons

• AverageBloodSugarLevel• Theamountofglucoseinplasma• 125mg/dL• Rangeis100mg/dL (fasting)– 140mg/dL (2hourspost-meal)

• RenalThresholdofGlucose(RTG)Concentration• 125mgofglucoseperdeciliteroffiltrateinPCT• Thresholdoffilteredglucoseis>180mg/dL• IfRTG isexceeded,theresultisglucosuria (glucoseintheurine)

• Causesdehydration(calledosmoticdiuresis)• Usuallycausedbydiabetesmellitus…..HOW??

• CarrierMediatedTransportofGlucoseCanBecomeSaturatedRate• Glucosereabsorptionhappensintheproximalconvolutedtubules• SGLT-1/SGLT-2transportersarefoundontheapicaloftherenaltubularcells• Thetransportmaximumofglucoseis325mg/min(thisisarate)

1dL=100mL

100%ofglucosefiltered

100%ofglucose

reabsorbed

Mineral Balance

GlucoseReabsorption

ProximalConvolutedTubule

Apicalsurface Basolateralsurface

MineralBalance

H2OReabsorptionCorticalNephrons

• About65%ofH2OisreabsorbedatthePCT• TheNa+/K+/ATPasepumpestablishesandmaintainsalow[Na+]insidethetubularcells• ThemovementofNa+ isusedtomoveH2O outofthelumenofthetubeandintothetubularcells• Watercontinuestochasethesaltintotheperitubularcapillaries

Water Balance

JuxtamedullaryNephronsWater Balance

RegulationofWaterBalance

• Amountofoffiltrateproduced• 180L/day• 180Lofwatermovedoutofyourbloodtoformfiltrate

• 99%ofwaterisreabsorbed• Averageurineoutput• 1.8L/day

• Obligatorywaterloss• 0.5L/day

Howdoyougetwatertomovebackintoyour

blood?

Water Balance

AntidiureticHormone(ADH)Theregulationofwaterbalance

• ADH istheprimaryregulatorofbodywaterbalance• ADH isreleasedfromtheposteriorpituitary• ADH causestheinsertionofaquaporins inthecollectingducts• Withoutaquaporins,theCDisimpermeabletoH2O

Water Balance

AntidiureticHormone(ADH)Theregulationofwaterbalance

• ThestimulusforsecretionofADHisplasmaosmolarity• Monitoredbyosmoreceptors inthehypothalamus

• Plasmaosmolarity belowthreshold• Osmoreceptors arenotactivated• ADH secretionissuppressed

• Plasmaosmolarity abovethreshold• Osmoreceptors stimulateneuronstosecreteADH

• AnotherstimulusforsecretionofADH isadecreaseinbloodvolume

Water Balance

CountercurrentMultiplierSystemJuxtamedullaryLoopofHenleandVasaRecta

• Descendinglimb– ImpermeabletoNaCl– PermeabletoH2O

• Ascendinglimb– PermeabletoNaCl– ImpermeabletoH2O

– CreatesahyperosmoticgradientintheIFofthemedullaofthekidney– HyperosmoticgradientpromotesH2Oreclamationfromfiltrate– H2OmovesfromtheCDthroughaquaporins intotheVasaRecta

Water Balance

RegulationofBloodPressure

• OneofthefunctionsofthekidneysistoregulateBP• RegulatingBP- regulatesMAP

• ThekidneysregulateBPisbyadjustingbloodvolume• BloodvolumeisadjustedbyreabsorptionandexcretionofNa+ attheDCT

Howdoyougetwatertomovetoadjustblood

volume?

BloodPressure

WaterChasestheSaltThereabsorption/excretionofNa+ willadjustBP

ReabsorptionofNa+ willincreasebloodpressure

• ↑Na+ reabsorption• ↑H2Oreabsorption• ↑bloodvolume• ↑bloodpressure

• AresponsetodecreasedBP

ExcretionofNa+ willdecreasebloodpressure

• ↓Na+ reabsorption• ↓H2Oreabsorption• ↓bloodvolume• ↓bloodpressure

• AresponsetoincreasedBP

BloodPressure

SensoryReceptorsProvidesensoryfeedbacktoregulateBP

• MaculaDensa• PatchofcellsintheDCT wheretheALOH meetstheDCT• Chemoreceptors• Sensitivetoadropin[Na+]

• Juxtaglomerular(JG)Cells• Secretorycellssurroundtheafferentarteriole(secreteanenzyme)• Baroreceptors• SensitivetoadropinBP

BloodPressure

RegulationofBloodPressureRAAS - Renin-AngiotensinAldosteroneSystem

• ActivationofRAAS increasesBP• Renin (angiotensinogenase)• CleavesAngiotensinogentoAngiotensinI

• AngiotensinI isconvertedtoAngiotensinIIbyACE• ACE:angiotensinconvertingenzyme

• AngiotensinII• Strongvasoconstrictor(increasesBP)• StimulatesAldosteroneproduction

• Aldosterone• Increasesbloodvolume(increasesBP)

↑ BloodPressure

1. Causesvasoconstriction(angiotensinII)

2. Increasesbloodvolume(aldosterone)

WhatwouldanACEinhibitordotoBP?

RegulationofBloodPressureRenin(RAAS)

• Renin isanenzymethatconvertsangiotensinogentoangiotensinI(inplasma)• ReninissecretedbyJGcellsinresponseto:• DecreaseinNFP• DetectedbyJGcells

• Decreased[Na+]inDCT• Detectedbythemaculadensa

• Sympatheticactivation

↑ BloodPressure

RegulationofBloodPressureAngiotensinII(RAAS)

• Angiotensinogen• Producedbytheliver• Reninconvertsto AngiotensinI• Inplasma

• AngiotensinI• ACEconvertstoAngiotensinII• Inthelungs

• Pulmonaryendothelialcells• Producedinthelungstopreventpulmonaryvasoconstriction

• Alsobecausethehalflifeis16seconds

• AngiotensinII• Causesvasoconstriction

• IncreasesBP• StimulatessecretionofAldosterone• IncreasesBP

• Stimulatesthirst• IncreasesBP

• StimulatestheproductionofADH fromtheposteriorpituitary• IncreasesBP

↑ BloodPressure

RegulationofBloodPressureAldosterone(RAAS)

RegionofAdrenalCortex

HormonesReleased

Example

ZonaGlomerulosa

MineralCorticoids

Aldosterone

ZonaFasciculata

Glucocorticoids Cortisol

ZonaReticularis

Androgens DHEA

↑ BloodPressure

AldosteronestimulatesNa+ reabsorptionintheDCT andCD

RegulationofBloodPressureAldosterone(RAAS)

• StimuliforAldosterone:• Serumpotassiumlevels• Increasedplasma[K+]

• AngiotensinII• Acidosis• IncreasedACTH• Stretchreceptorsintheatria• Responsetodecreasedstretch

↑ BloodPressure

RegulationofBloodPressureAldosterone(RAAS)

• Na+ reabsorption• 90%reabsorbedinPCT

• WithoutAldosterone• TotalNa+ reabsorptionis98%• 8%Na+ reabsorbedinDCT• 2%Na+ excretedinurine

• WithAldosterone• TotalNa+ reabsorptionis100%• K+ isexcreted

↑ BloodPressure

RegulationofBloodPressureAtrialNatriureticPeptide(ANP)

• AtrialNatriureticPeptide(ANP)• Producedbyatrialmyocardialcells

• StimulusforANP:• Atrialstretch- highbloodvolume• Increasedsympatheticactivation• Vasoconstriction• Exercise

• TheResponsetoANP• ReducesNa+ reabsorptionintheDCT andCD• Causesnatriuresis• IncreasesrenalNa+ excretion

• Causesdiuresis• Decreasesbloodvolume• Decreasessecretionofrenin• DecreasesTPR

• vasodilation

↓ BloodPressure

RegulationofBloodPressureAtrialNatriureticPeptide(ANP)

• Vasodilatesafferentarteriole• DecreasesGFR• ↓Na+ reabsorption

• DecreasesNa+ permeabilityintheDCT andCD• ↓Na+ reabsorption

• Inhibitsaldosteronesecretion• ↓Na+ reabsorption

↓ BloodPressure

RegulationofAcid-BaseBalance

• KidneysmaintainplasmapH• Acidisproducedbycellularmetabolism

• H+ productionincreases• Increasedmetabolism• Dietaryintakeofacidicfoods

• RenalregulationofpH• 100%reabsorptionoffilteredHCO3

-

• Usinghydrogenphosphateasanadditionalbuffer

• AdditionofnewHCO3-

• ExcretionofNH4

• DailyH+production• 100mmol/day

• Un-bufferedurine• Excreting1-2Lofurineonlyeliminates1mmol/dayofH+

• Doesnotmatchtheproductionofacid

• Bufferedurine• HCO3

- istheprimarybufferinurine

Acid/BaseBalance

RegulationofAcid-BaseBalance100%ReabsorptionofHCO3

-

• 100%reabsorptionoffilteredHCO3

-

• PCT ,LOH,corticalCD• Thebicarbonatethatisfilteredactsasabuffertoaccepthydrogenions

• Renaltubularcellshavecarbonicanhydrase• HCO3

- productionmatchesHCO3-

excretion• Resultsin100%reabsorption• Thisreactionisongoing

Acid/BaseBalance

RegulationofAcid-BaseBalanceAdditionofNewHCO3

-

• Increasedmetabolismproducesmoreacid∴morebufferisneeded• Filteredhydrogenphosphateisusedasanadditionalbufferinurine• Bicarbonatereactionintherenaltubularcells:• NewHCO3

- isproduced• SecretionofH+

• HPO42- combineswithH+ toform

H2PO4-

• Dihydrogenphosphateisexcreted

Acid/BaseBalance

RegulationofAcid-BaseBalanceAdditionofNewHCO3

- AND ExcretionofNH4

Acid/BaseBalance

• Renalammoniagenesis (PCT)• RenalNH4

+ excretionisderivedfromintrarenalproduction• notfromNH4

+filtration• Renalmetabolismofglutamineproduces:• HCO3

-

• AdditionofnewHCO3-

• NH4+

• Excreted• PromotesH+ excretion