21 renal physiology new - mt. sac · •100 mmol/day •un-buffered urine •excreting 1-2l of...
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RENALPHYSIOLOGYPhysiologyUnit4
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RenalFunctions
• PrimaryFunctionistoregulatethechemistryofplasmathroughurineformation• AdditionalFunctions
• Regulateconcentrationofwasteproducts
• Regulatemineralbalance• Regulatesbodywaterbalance• Regulatebloodpressure(MAP)• RegulateplasmapH• Produceandsecretehormones
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RenalTubularMembraneTransport
1. Filtration• Bloodtorenaltubules
• Outofyourblood• Nonspecific/BulkFlow
2. Reabsorption• Renaltubulestoblood
• Intoyourblood
3. Secretion• Bloodtorenaltubules
• Outofyourblood• Highlyspecific
4. Excretion• Urine
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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**
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RenalCorpuscleTheFilter
• Renalcorpuscleisthefilter• Thepermeabilityofthefilterdeterminedbythesizeofporeandelectricalcharge• Ultrafiltrationistheresultofaporesizethatis0.01microns• Electricalcharge
• Negativelychargedsurfaceofpodocytespreventsmovementofproteins
• Filtrateisprotein-freeandacellular
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RenalCorpuscleTheFilter
• Starlingforcesintheglomerulusfavorfiltration• NFP =16mmHg• HigherthanperipheralNFP of10mmHg
• Ultrafiltrationisdrivenbyahighhydrostaticpressureintheglomerulus thatiscreatedbythedifferencesinthediameteroftheafferentandefferentarteriole• Thehighhydrostaticpressureforcessmallmoleculesthroughthefilterintothenephron• Water,urea,uricacid,creatinine,aminoacids,minerals(ions)
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RenalNetFiltrationPressure
• NFP isafactorthatdeterminesGFR• NFP issubjecttophysiologicalcontrol• Regulationoftheafferent andefferent arterioles• Causechangesinvesseldiameter• Vasoconstriction/VasodilationcanchangeNFP• ↑NFP =↑GFR• ↓NFP =↓GFR
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Nephrons
• CorticalNephrons• LOH extendsjustslightlyintotherenalmedulla
• Peritubularcapillariesreceiveproductsofreabsorption
• Primaryfunctionisreabsorption
• JuxtamedullaryNephrons• LOH extendsdeepintotherenalmedulla
• VasarectafollowtheLOH andreceiveH20fromcollectingducts
• Primaryfunctioniswaterreclamation
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Na+ ReabsorptionCorticalNephrons
• ThemajorityofreabsorptionoccursatthePCT• TheNa+/K+/ATPasepumpestablishesandmaintainsalow[Na+]insidethetubularcells• ThemovementofNa+ isusedtomoveothermoleculesoutofthelumenofthetubeandintothetubularcells• Cotransport/Countertransport• H+,glucose,aminoacids
tube➜ blooddrivenbytheNa+/K+/ATPasepump
Mineral Balance
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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
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GlucoseReabsorption
ProximalConvolutedTubule
Apicalsurface Basolateralsurface
MineralBalance
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H2OReabsorptionCorticalNephrons
• About65%ofH2OisreabsorbedatthePCT• TheNa+/K+/ATPasepumpestablishesandmaintainsalow[Na+]insidethetubularcells• ThemovementofNa+ isusedtomoveH2O outofthelumenofthetubeandintothetubularcells• Watercontinuestochasethesaltintotheperitubularcapillaries
Water Balance
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JuxtamedullaryNephronsWater Balance
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RegulationofWaterBalance
• Amountofoffiltrateproduced• 180L/day• 180Lofwatermovedoutofyourbloodtoformfiltrate
• 99%ofwaterisreabsorbed• Averageurineoutput• 1.8L/day
• Obligatorywaterloss• 0.5L/day
Howdoyougetwatertomovebackintoyour
blood?
Water Balance
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AntidiureticHormone(ADH)Theregulationofwaterbalance
• ADH istheprimaryregulatorofbodywaterbalance• ADH isreleasedfromtheposteriorpituitary• ADH causestheinsertionofaquaporins inthecollectingducts• Withoutaquaporins,theCDisimpermeabletoH2O
Water Balance
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AntidiureticHormone(ADH)Theregulationofwaterbalance
• ThestimulusforsecretionofADHisplasmaosmolarity• Monitoredbyosmoreceptors inthehypothalamus
• Plasmaosmolarity belowthreshold• Osmoreceptors arenotactivated• ADH secretionissuppressed
• Plasmaosmolarity abovethreshold• Osmoreceptors stimulateneuronstosecreteADH
• AnotherstimulusforsecretionofADH isadecreaseinbloodvolume
Water Balance
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CountercurrentMultiplierSystemJuxtamedullaryLoopofHenleandVasaRecta
• Descendinglimb– ImpermeabletoNaCl– PermeabletoH2O
• Ascendinglimb– PermeabletoNaCl– ImpermeabletoH2O
– CreatesahyperosmoticgradientintheIFofthemedullaofthekidney– HyperosmoticgradientpromotesH2Oreclamationfromfiltrate– H2OmovesfromtheCDthroughaquaporins intotheVasaRecta
Water Balance
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RegulationofBloodPressure
• OneofthefunctionsofthekidneysistoregulateBP• RegulatingBP- regulatesMAP
• ThekidneysregulateBPisbyadjustingbloodvolume• BloodvolumeisadjustedbyreabsorptionandexcretionofNa+ attheDCT
Howdoyougetwatertomovetoadjustblood
volume?
BloodPressure
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WaterChasestheSaltThereabsorption/excretionofNa+ willadjustBP
ReabsorptionofNa+ willincreasebloodpressure
• ↑Na+ reabsorption• ↑H2Oreabsorption• ↑bloodvolume• ↑bloodpressure
• AresponsetodecreasedBP
ExcretionofNa+ willdecreasebloodpressure
• ↓Na+ reabsorption• ↓H2Oreabsorption• ↓bloodvolume• ↓bloodpressure
• AresponsetoincreasedBP
BloodPressure
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SensoryReceptorsProvidesensoryfeedbacktoregulateBP
• MaculaDensa• PatchofcellsintheDCT wheretheALOH meetstheDCT• Chemoreceptors• Sensitivetoadropin[Na+]
• Juxtaglomerular(JG)Cells• Secretorycellssurroundtheafferentarteriole(secreteanenzyme)• Baroreceptors• SensitivetoadropinBP
BloodPressure
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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?
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RegulationofBloodPressureRenin(RAAS)
• Renin isanenzymethatconvertsangiotensinogentoangiotensinI(inplasma)• ReninissecretedbyJGcellsinresponseto:• DecreaseinNFP• DetectedbyJGcells
• Decreased[Na+]inDCT• Detectedbythemaculadensa
• Sympatheticactivation
↑ BloodPressure
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RegulationofBloodPressureAngiotensinII(RAAS)
• Angiotensinogen• Producedbytheliver• Reninconvertsto AngiotensinI• Inplasma
• AngiotensinI• ACEconvertstoAngiotensinII• Inthelungs
• Pulmonaryendothelialcells• Producedinthelungstopreventpulmonaryvasoconstriction
• Alsobecausethehalflifeis16seconds
• AngiotensinII• Causesvasoconstriction
• IncreasesBP• StimulatessecretionofAldosterone• IncreasesBP
• Stimulatesthirst• IncreasesBP
• StimulatestheproductionofADH fromtheposteriorpituitary• IncreasesBP
↑ BloodPressure
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RegulationofBloodPressureAldosterone(RAAS)
RegionofAdrenalCortex
HormonesReleased
Example
ZonaGlomerulosa
MineralCorticoids
Aldosterone
ZonaFasciculata
Glucocorticoids Cortisol
ZonaReticularis
Androgens DHEA
↑ BloodPressure
AldosteronestimulatesNa+ reabsorptionintheDCT andCD
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RegulationofBloodPressureAldosterone(RAAS)
• StimuliforAldosterone:• Serumpotassiumlevels• Increasedplasma[K+]
• AngiotensinII• Acidosis• IncreasedACTH• Stretchreceptorsintheatria• Responsetodecreasedstretch
↑ BloodPressure
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RegulationofBloodPressureAldosterone(RAAS)
• Na+ reabsorption• 90%reabsorbedinPCT
• WithoutAldosterone• TotalNa+ reabsorptionis98%• 8%Na+ reabsorbedinDCT• 2%Na+ excretedinurine
• WithAldosterone• TotalNa+ reabsorptionis100%• K+ isexcreted
↑ BloodPressure
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RegulationofBloodPressureAtrialNatriureticPeptide(ANP)
• AtrialNatriureticPeptide(ANP)• Producedbyatrialmyocardialcells
• StimulusforANP:• Atrialstretch- highbloodvolume• Increasedsympatheticactivation• Vasoconstriction• Exercise
• TheResponsetoANP• ReducesNa+ reabsorptionintheDCT andCD• Causesnatriuresis• IncreasesrenalNa+ excretion
• Causesdiuresis• Decreasesbloodvolume• Decreasessecretionofrenin• DecreasesTPR
• vasodilation
↓ BloodPressure
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RegulationofBloodPressureAtrialNatriureticPeptide(ANP)
• Vasodilatesafferentarteriole• DecreasesGFR• ↓Na+ reabsorption
• DecreasesNa+ permeabilityintheDCT andCD• ↓Na+ reabsorption
• Inhibitsaldosteronesecretion• ↓Na+ reabsorption
↓ BloodPressure
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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
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RegulationofAcid-BaseBalance100%ReabsorptionofHCO3
-
• 100%reabsorptionoffilteredHCO3
-
• PCT ,LOH,corticalCD• Thebicarbonatethatisfilteredactsasabuffertoaccepthydrogenions
• Renaltubularcellshavecarbonicanhydrase• HCO3
- productionmatchesHCO3-
excretion• Resultsin100%reabsorption• Thisreactionisongoing
Acid/BaseBalance
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RegulationofAcid-BaseBalanceAdditionofNewHCO3
-
• Increasedmetabolismproducesmoreacid∴morebufferisneeded• Filteredhydrogenphosphateisusedasanadditionalbufferinurine• Bicarbonatereactionintherenaltubularcells:• NewHCO3
- isproduced• SecretionofH+
• HPO42- combineswithH+ toform
H2PO4-
• Dihydrogenphosphateisexcreted
Acid/BaseBalance
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RegulationofAcid-BaseBalanceAdditionofNewHCO3
- AND ExcretionofNH4
Acid/BaseBalance
• Renalammoniagenesis (PCT)• RenalNH4
+ excretionisderivedfromintrarenalproduction• notfromNH4
+filtration• Renalmetabolismofglutamineproduces:• HCO3
-
• AdditionofnewHCO3-
• NH4+
• Excreted• PromotesH+ excretion