RenalFailurePathophysiologyDepartmentTongjiMedicalCollege,HUSTExcretionfiltration,resorptionandsecretion,tomaintainthebalanceinwater,electrolytes,acidandalkali

Endocrinerenin,prostaglandins,erythropoietin,1,25(OH)2VitD3InactivationPTH,pepsinReviewofnormalrenalfunction

Thefundamentalunitforrenalfiltrationandresorption

ClassificationofRenalFailureAcuteRenalFailureThekidneysabruptlystopworking

ChronicRenalFailureThekidneyslosetheirfunctionsgraduallyAcuteRenalFailure—conceptionApathologicalprocessthatthekidneylosesitsfunctionabruptlyandthusleadstodisturbanceofinternalhomeostasisARF—causesandclassificationPrerenalhypovolemia,reducedcardiacoutputorvascularobstructionIntrarenal

vasculopathies,glomerulonephritis,tubulointerstitialnephropathies,

acutetubularnecrosisPostrenalobstructioninbladderneck,intra-andextra-urethralARF—characteristicsSudden&

DramaticDecreaseinGFRGFRTheCenterTache

BloodAfferentArterioleEfferentArterioleCapillarypressureBowman’spressurePlasmacolloidOsmoticpressureParametersinfluencetheeffectiveglomerularfiltrationpressure1.Alterationinrenalhemodynamics

Renalperfusion

Renalvasoconstriction

Renalischemic-reperfusioninjuryRenalhemorheologyabnormality

PathogenesisGFRPathogenesis2.GlomeruliinjuryStreptococcusinfectionImmunereaction(Ag+Ab,entrappedintheglomeruli)MesangialproliferationBlocktheglomeruliArea,porosity(

f=LPxA)GFRLPporosityofglomerularmembraneAsurfaceareaofglomerularmembrane

（1）Tubuloglomerularfeedback

Hypoxia,

poisons

ATN

Na+reabsorption

RAS

constrictAArenalbloodflow

GFR

adenosine

A1RconstrictAA，A2RdilateEAQ:WhytheGFRisstilllowwhenthecardiacoutputorsystemicbloodpressurearerestoredinsomeARFpatients?AAafferentarterioleEAefferentarteriolePathogenesis

3.TubularlesionsGFRPathogenesis

（2）TubularbackleakofultrafiltrateAcuterenalischemiaorrenalpoisoningLossoffunctionalintegrityoftubularepithelialcellsDestroybasementmembranePassivebackflowoffiltratestotheinterstitiumInterstitialedemaIncreaseinBowman’scapsuleGFRQ:Whatkindofmaterialweshouldchooseforbackleakstudy??Pathogenesis

（3）ObstructionSevererenalischemia,renaltoxin,traumaorhemolysis

Precipitationofnephrotoxins(uricacid,myoglobin,hemoglobinoroxalate)orcongealedproteinintheformofcast,sloughoffcells,cellulardebrisorswollencellsPlugthetubulesIntratubularpressureBowman’sspacepressure

GFRRenalvascularsystemQ:WhyischemicdamageismoresevereincortexandouterzoneofmedullainATN?

Q:Whynephrontoxinspreferentiallydamagetheproximaltubules???AlterationsofMetabolismandFunctions

OliguriatypeofARF

1.Oliguriaphase

2.Diureticphase

3.RecoveryphaseAlterationsofMetabolismandFunctions

Oliguriaphase

(changesinurine)Thevolumeislessthan400ml/dayorlessthan100ml/day(anuria)ThesedimentmaycontainRBC,WBC,epithelialcellsbythemselvesorincasts,theprot.lossmaybeinsignificantTheS.Gandosmolarityarelow4.TheurinaryNaishigherthan20~40mmol/L

DifferentiationoffunctionalfromparenchymalARF

Urine

functionalparenchymalSpecificgravity

>1.020<1.015Osmoticpressure>500mmol/L<400mmol/LUNa

<20mmol/L>40mmol/LUcr/Pcr>40<20Index<1>2FractionofUNa<1>2MicroscopicurinalysisNBrowngranularcasts

UNaUNa/PNaRFI=FENa=X100Ucr/PcrUcr/PcrAlterationsofMetabolismandfunctionsOliguriaphase1.Disordersofinternalhomeostasis(1)Azotemia:BUN,creatinine,uricacidnitrogen(2)Metabolicacidosis:

Catabolismacidicproducts

AcidexcretionSecretionofammoniaandhydrogenQ:WhathappenstoAGhere?AlterationsofMetabolismandFunctions

Oliguriaphase(3)

HyperkalemiaK+ExcretionTransferofK+fromintracellulartoextracellular（catabolism,acidosis）DistaltubularK+-Na+exchange（hypoNa）AlterationsofMetabolismandFunctions

Oliguriaphase(4)Waterretention

GFRADHsecretionCatabolismendogenouswater

DilutedhypoNaEdema/waterintoxicationAlterationsofMetabolismandFunctions2.Diureticphase

(urine>400ml/day)Mechanismsofdiuresis:Non-integratedfunctionofpalingenetictubules

Cumulationofureaduringoliguriaphase(leadstoosmoticdiuresis)RelieveofthetubularobstructionCaution:BUN，Pcr>NormalAlterationsofMetabolismandFunctions3.RecoveryphaseFullyrecoveryofrenalfunctiontakesseveralweeks(mosttypically)

toayear,characterizedbyhealingoftubularepithelialcells;ThemortalityassociatedwithATNis~50%,thedeathsarerelatedtotheconditioncausingrenalfailureorinfectionsAlterationsofMetabolismandFunctionsNon-oliguretictypeofARFPossiblemechanisms:UnabletoformhighosmosisinmedullaWeaktubuloglomerularfeedbackDysfunctionoftubuleshasprecedenceoverdecreasedGFR

PrinciplesofTreatment

TreatmentoftheoriginaldiseasesTreatmentagainstsymptomsCorrecthyperkalemia,acidosisandazotemiaDialysisisstronglyrecommendedPrinciplesofTreatmentTreatmentofATNissupportiveMaintenanceofbloodvolume,avoidanceoffluidoverload,managementofacid-baseandelectrolytedisorders,andadjustmentofmedicationforrenalfunction.Nutrition

supportmayberequiredVigilanttothegastrointestinalbleedingandinfectionDialysisindicators:fluidoverload,severeacidosisorhyperkalemia,thelevelofplasmaureaandcreatinineistoohigh,toaverturemiaMr.Ma,Male,22yearsold,hospitalizedinOct.27,1997Chiefcomplaint:Leftthightraumaandendlessbleeding.PE:Dottiness,pale,Bpwasnotdetectable,weakheartbeats,woundonleftthigh5X5cm,bleeding.Processbeinhospital:Bloodtransfusion8000ml,operationtoinosculatenervesandvessels,injectcedilanid,hydrogenate-cortisoneandisoproterenol

CaseanalysisOct.28Bp100/80mmHg,P130/min,conscious,urine2-30ml/h,injectmannitol,diuretics,sodiumbicarbonate,glucoseplusinsulin,takeorallymagnesiumsulfate,butstillanuriawithaggravatedazotemia,acidosisandhyperkalemia.Nov.6Bp120/80mmHg,P128/min,NPN168mg/dl,CO2CP40vol/dl,plasmaK6.2mmol/L,specificgravityofurine1.010,urinaryprotein(++),RBC(+++),WBC(++)Afterdialysisfor7h,NPN79mg%,CO2CP38.1vol/dl,plasmaK

4.7mmol/L,Na140mmol/L，Cl100mmol/L,AG=22.7mmol/L.Caseanalysis

(Cont.)Nov.12Dialysisforanther5h,urinevolumewasincreasing.Nov.19Urine2000ml/d,S.G.1.012,plasmaNPN95mg%,CO2CP47Vol%,K:3.3mmol/L,Na:150mmol/L,Cl:114mmol/L,AG=14.6mmol/LInDec.UrinaryvolumeandotherparametersrestoredtonormalCaseanalysis(Cont.)Discussion:WhythepatientwasstillwitholiguriawhentheBpwasnearlyrestoredtonormalleveldetectedonnextdayofhishospitalization?ThemechanismsforincreasedNPN,decreasedCO2CPandhyperkalemia?Themechanismsfortheformationofdiuresis？Havingdiuresisforaweek,whytheNPNwasstillhigh?CO2CPwasstilllow?stillhyperkalemia？Discussion5.Isdiuresisphasesafetothepatient?

6.Whydidtheyusemannitol?Insulinplusglucose?Andmagnesiumsulfateintreatment？7.DidthepatientsufferfromfunctionalorparenchymaARF?8.Whythepatientswithnon-oliguriatypeARFshowdisturbanceofinternalhomeostasiswhentheydonothaveoliguria？ChronicRenalFailure-ConceptionItisaprocessthatthekidneysareaffectedprogressivelybytheinsultsandthusanirreversiblelossoflargenumbersoffunctioningnephronsoccursThedisordersinbothexcretionandendocrineareshown;Internalenvironmentaldisturbanceandmayhavemultifunctionalderegulation

clearanceofendogenouscreatinine

[Ucr]XV/min[Pcr]Repertorycapacity>30%Renalinsufficiency<25-30%Renalfailure<25-20%Uremia<20%ClinicalProgressionPathogenesis(1)

1.Intactnephronhypothesis

Adaptationmechanism:

Nephron

destroyedtheremainingcounterpartsadaptbyincreasingGFR,tubularresorptionandexcretionWhentheintactnephronisde