内科学教学课件：Glomerular Disease

GlomerularDisease

Conception

Bilateralkidneysareinvolvedinglomerulardisease.Thediseaseiscategorizedinto:Primarydisease:onlyrenalabnormalitySecondarydisease:resultingfromasystemicdisease(SLE,DM).Hereditarydisease:causedbytheabnormalityofhereditarygeneClinicalclassificationofprimaryglomerulardisease1．acuteglomerulonephritis2．acuterapidlyprogressiveglomerulonephritis3．chronicglomerulonephritis4．latentglomerulonephritis5．nephroticsyndromeHistologicclassification

ofprimaryglomerulardisease(byWHO)

minorglomerularabnormalitiesfocalsegmentallesions(focalsegmentalglomerulonephritis,focalsegmentalglomerularsclerosisdiffuseglomerulonephritismembranousnephropathyproliferativeglomerulonephritisMesangialproliferativeglomerulonephritisEndocapillaryproliferariveglomerulonephritisMesangialcapillaryglomerulonephritisdensedepositglomerulonephritiscrescenticglomerulonephritissclerosingglomerulonephritisglomerulonephritishavingnotbeenclassifiedPathogenesis1.thedisorderofhumoralimmunityandcellularimmunitywhichcausetheinflammationofkidneys.Pathogenesis2.withtheprogressionofthedisease,someglomeruliaredamaged,thencompensatoryhyperfiltrationandhypertrophyoftheremainingglomerulioccur,whichleadtoglomerulosclerosis.CommonsymptomsofglomerulardiseaseProteinuriaHematuriaEdemaHypertensionRenalinsufficiencyProteinuriaproteinintheurine:＞150mg/24hoursor≥(+)Glomerularfilteredbarrierinjury:size-selectivebarriercharge-selectivebarrierHematuria

Whatishematuria?

＞3redcells/HP.

PainlessandtotalhematuriaProteinuriaandcastsdismorphicredcellsEdema

(Saltandwaterretention)Nephritisedema;NephroticedemaHypertentionSaltandwaterretentionvolumeoverloadHyperreninemicstates(RAASactiation)ExogenouserythropoietinadministrationDecreaseofantihypertensionsubstanceNephroticSyndromeClinicalmanifestation1．heavyproteinuria:＞3.5g/d2．hypoalbuminemia：＜30g/L3．edema4．hyperlipidemia

Categorization:primaryandsecondaryNS.Inthesechapter,primaryNSisdiscussed.isessentialforNSPathophysiologyofnephroticsymdromheavyproteinuriaThedamageofsize-selectivebarrierand/orcharge-selectivebarrieroftheglomerularfiltrationbarrier.adecreaseofserumproteinlose:alargeamountofproteinislostthroughurineDecompositiondecomposedbytheepithelialofproximaltubule.synthesis:whentheliversynthesiscannotcompensatetheloseanddecompositionofprotein,thenhypoproteinemiaoccur.inadequateintakeofproteinmayalsoleadtohypoproteinuria.edemahypoalbuminemia→colloidosmoticpressure↓→watersmovingfromcapillarytotissueSodiumretentionHyperlipidemia(hypercholestrolemia,hypertriglyceridemiaandlowdensitylipoproteins(LDL)

Thisisbecausethesynthesisofproteinbytheliverincreaseandthedecompositionofproteindecrease.EtiologyInpatientswithdifferentages,themostcommondiseaseare:InprimaryNS:children:minimalchangediseaseSenilepatient:membranousnephropathyAdolescentpatient:mesangialproliferativeglomerulonephritismesangialcapillaryglomerulonephritisfocalsegmentalglomerularsclerosisInsecondarydiseaseChildren:congenitalnephroticsyndromeanaphylactoidpurpurahepatitisBvirusassociatednephritis.YoungpatientslupusnephritisanaphylactoidpurpurahepatitisBvirusassociatednephritis.Senilepatients:diabeticnephropathymultiplemyeloma.

DifferentialDiagnosisNephritisresultfromanaphylactoidpurpura.

palpablepurpura,arthralgias,andabdominalsymptomssuchasnausea,colic,andmelena.lupusnephritisarthralgias,skinlesions(butterfly,discoidrash),etc.ANA+,DsDNA+,C3↓Diabetesnephropathy:inadultsoccuraftermorethan10yearsofdiabetes.WhenNSoccur,itprogresstorenalfailurerelativelyquickly.DifferentialDiagnosisAmyloidosis:

insenilepatients.Manyorganscanbeinvolved.biggerkidneythannormal.Renalbiopsyisthediagnosticway.multiplemyeloma.adults,amalepredominance.bonepaininthelowerbackmonoclonalparaproteinbyserumorurinemalignantplasmacellsinbonemarrowHistologictypeandit’sclinicalfeatures

minimalchangediseasemesangialproliferativeglomerulonephritismesangialcappilaryglomerulonephritismembranousnephropathyFocalsegmentalglomerularsclerosisMinimalchangedisease（MCD）

histologicalterations

lightmicroscopy：

noglomerularlesions,lipidresorptiondropletsintubularepithelialcellselectronmicroscopy

anextensivefootprocesseffacementimmunofluorescencemicroscopy：negative

微小病变型Figure1.minimalchangedisease.Left:normalglomeruleright:abnormalglomerule.1.anextensivefootprocesseffacement2.basementmembrane3.endothelialcell4.mesangialcellminimalchangedisease微小病变型肾病综合征。肾小球毛细血管壁呈典型的肾病综合征改变：弥漫足突（FP）融合。尿腔内微绒毛（MV）形成，足细胞（P）水肿，内皮细胞（En）轻度肿胀。EMx17000Clinicalfeatures：mostcommonlyseeninchildren,accountingfor70-90%ofNSinchildren.Itcanalsobeseeninadults,particularlyinsenilepatient.hematuria：about10%-20%,nomacroscopichematuria.atransienthypertensionsensitivetosteroidsmesangialploliferativeglomerulonephritis

Histologicalterationslightmicroscopy：

mesangialhypercellularityandincreaseofmatrix.Itcanbedividedintomild,moderate,severealterations.immunofluorescencemicroscopy:

IgAnephropathynonIgAnephropathyelectronmicroscopy：

mesangialelectron-densedeposit

Figure2:mesangialploliferativeglomerulonephritis

Left:normalglomeruleright:abnormalglomerule.1.Epithelialcell2.basementmembrane3.endothelialcell4.mesangialcell5.immunecomplexmildploliferationmoderateploliferationsevereploliferation免疫荧光：IgG系膜区沉积系膜增生性肾小球肾炎。显示系膜增生和散在的沉积物（D）。EMx7000clinicalfeatureahighincidence,commonlyseeninadolescent,dromalinfectioncanbeseen.hematuria：100%inIgAnephropathy,about70%innon-IgAnephropathy.sensitivetosteroidandcytotoxicdrugs,butcloselyassociatedwithseverityofhistologiclesions.mesangialcapillaryploliferativeglomerulonephritis(membran-oproliferativeglomerulonephritis)

histologicalterationslightmicroscopy:

endocapillaryhypercellularity,themesangialhypercellurarityandincreaseofmatrixwhichcaninsertbetweenendothelialandbasementmembraneandthenadoubletracksisformed.immunofluorescencemicroscopy:

mainlythedepositionofC3andIgG.Electronmicroscopy

electron-densedepositinmesangiumandalongcapillarywallcanbeseen.Figure2:mesangialcapillaryglomerulonephritis

Left:normalglomeruleright:abnormalglomerule.1.Epithelialcell2.basementmembrane3.endothelialcell4.mesangialcell5.immunecomplex6.basementmembranematerialalike.左为系膜毛细血管性肾炎，右为正常肾小球系膜毛细血管性肾小球肾炎（I型）。肾小球系膜区增宽，毛细血管壁增厚，局部双轨形成。PASx260doubletracksclinicalfeaturecommonlyseeninadults,amaleprevalence.hematuria：

allexhibithematuria,macroscopichematuriaiscommon.serumC3↓anddonotrecovertonormal

clinicalfeaturerenalfunctionfailure,hypertensionandanemiaappearsearly.onlyapartofchildrenrespondtosteroidsandcytotoxicdrugs,theremainsdonotrespondwell.

membranousnephropathyhistologicalterations

lightmicroscopy：

aspikepattern,basementmembranethickenesswithoutinflammatorychanges.Electronmicroscopy:

densedepositsalongthesubepithelialsurfaceofthebasementmembrane.Spikesandeffacementoffootprocesscanbeseen.immunofluorescencemicroscopy:

IgGandC3alongcapillaryloopsFigure4:membranousnephropathy

Left:normalglomeruleright:abnormalglomerule.

1.Epithelialcell2.basementmembrane3.endothelialcell4.mesangialcell5.immunecomplexclinicalfeatures

commonlyseeninadults,amalepredominance,commonlyintheirfifthandsixthdecades.occurindolentlydevelopslowly:often5-10years→renalfailureclinicalfeatures

patientsarepronetothrombosisandthromboembolism.25%mayhaveacompletelyspontaneousremission.Beforeappearanceofspikes,patientsaresensitivetosteroidsandcytotoxicdrugs.Afterspikesappears,patientsdonotrespondtotreatmentwell.focalsegmentalsclerosis

histologicalterations

lightmicroscopy：

Focalandsegmentalglomerularsclerosis.Electronmicroscopy:Densedepositsalongthesubendothelialsurfaceofthebasementmembrane.effacementoffootprocesscanbeseen.immunofluorescencemicroscopy:

StainingofIgMandC3canbeseeninthelesionsites.

局灶节段性肾小球硬化Focalandsegmentalglomerularsclerosisclinicalfeatures

commonlyseeninadolescencedeveloplatently.hematuria:oftenseen,20%exhibitmacroscopichematuria.Oftenproximaltubulardysfunction:glucose,aminoacidinurineDosenotrespondtosteroidandcytotoxicdrugswell.Onlyasmallpartofpatientsaresensitivetothetreatment.ComplicationofNSsusceptibilitytoinfectionCause:proteinmalnutrition,immunitydysfunction,administrationwithsteroids.Infectionseencommonly:respiratorytract,urinarytractinfectionandperitonitis,etc.ItwillinfluencetheeffectoftreatmentorleadtorelapseofNS.

Thrombosisandthromboembolism

cause:ImbalanceofCoagulationandanticoagulationsystem.increasedplateletactivationbloodviscositysteroidspromptthehypercoagulationstate.

Renalveinthrombosisandothervenousthromboemboli.acuterenalfailure

Cause:colloidosmoticpressure↓→hypovolemia→renalhypoperfusion→prerenalazotemiathetubulepressedbyextremeedemaoftheinterstitium.thetubulebeingblockedbyalargeamountofproteincastwhichleadtoadecreaseofGFR.

metabolicdisturbanceofproteinandlipidDiagnosisanddifferentialdiagnosis

Diagnosis:includingisitNS?Yesorno.Yes,thenIsitprimaryNS?PrimaryNS,thenwhatkindofglomerulardisease?Histologictype.Aretherecomplications?Treatment1.diet:Protein:0.8~1.0g/（kg·d）,Sodiumrestriction:2.Edema:

dietarysaltrestrictiondiuretictherapy:thiazideandloopdiureticsTreatment3.ReducingproteinuriaACEI

machanism:

loweringefferentarteriolarresistanceoutofproportiontoafferentarteriolarresistance→reducingglomerularcapillarypressureandloweringurinaryproteinexcretion.

Sideeffect:

worseningrenalfailureandhyperkalemia.4maintreatmentGlucocorticoid:

inhibitinginflammatoryreactionandimmunereaction,thesecretionofaldosteroneandADH↓.principle:sufficient

dosageshouldbegivenatthebeginning:prednisone1mg/(kg·d)for8-12weeks4maintreatmentGlucocorticoid:

principle:tapeslowly

tapethemedicinewithaspeedof10%ofthebeginningdoseevery1-2weeks.Whenitreach20mg/d,itisveryeasiertorelapse,themedicineshouldbetapedmoreslowly.4maintreatmentGlucocorticoid:

principle:Maintenanceofthemedicineforalongterm

10mg/doftenatleast6months.(prednisonecanbetakenoncedailyinthemorning)Sideeffectsofglucocorticoid:prolongedcorticosteroidtherapymayleadtoAlifethreateninginfectionOsteoporosisDiabetesmellitusAcceleratedatherosclerosisHypertensionGastritisorpepticulcerMentalillnessglucocorticoid:

accordingtotheresponsetoglucocorticoid,itcanbecategorizedintothreegroups:steroid-sensitiveremissionisachievedafter8~12weeksoftreatmentsteroid-dependentthediseaserelapseduringprednisonereducingsteroid-resistantnoeffectcanbeachievedafter8-12weeksoftreatment.4maintreatmentCytotoxicdrugsusedwhenpatientsaresteroid-dependentorsteroid-resistant.Generally,itisnotusedaloneorasprimarychoice.CyclophosphamideItcanbeusedorallyorbyintravenousway.Untilwhenthetotaldosereach6～8gor150mg/kg。Sideeffectsofcyclophosphamide:

BonemarrowsuppressionLivertoxicityGonadaldysfunctionLossofhairSymptomsofdigestivesystem:vomiting,nausea,abadappetite,etc.HemorrhagiccystitisCyclosporin

Applicabilityusedinrefractorynephroticsyndromeunresponsivetocorticosteroidandcyclophosphamide.Doses5mg/kg·dadministeredorallyin2divideddose.Cyclosporin

RelapseOncecyclosporineisdiscontinued,therelapseofnephrosisoccureasily.Analternativewaytothetreatmentisusinggraduallylowerdosesinordertomaintainthepatientinremission.Sideeffectsliverandkidneytoxicity,hypertension,TherapyfordifferenthistologictypeofnephroticsyndromeMinimalchangediseaseandmildmesangialproliferativeGN：

Corticosteroidisthemaintherapy.Ifthediseaseisunresponsivetothetherapyorrelapsefrequently,thencytotoxicdrugscanbeconsidered.

Membranousnephropathy：Itshouldbetreatedaggressively,Corticosteroidandcytotoxicdrugsshouldbeused.But,afterthetreatmentcourseisfinished,thesedrugsshouldnotbeusedwithabigdosefortoolongaterm.MembranousnephropathyHyperlipidemiaandhypercoagulablestateshouldbecontrolledtopreventthrombosisandthromboembolism.focalsegmentalglomerularsclerosis,severemesangialproliferativeglomerulonephritis,mesangialcapillaryglomerulonephritisIfrenaldysfunctionhasoccurred,thenusuallycorticosteroidandcytotoxicdrugsarenotgiven.focalsegmentalglomerularsclerosis,severemesangialproliferativeglomerulonephritis,mesangialcapillaryglomerulonephritisIfrenalfunctionisnormal,sufficientdoseofcorticosteroidandcytotoxicdrugsshouldbegivenandthentapeslowly,anddrugsforanti-coagulationandanti-aggregationofplateletscanbeadministersimultaneously.Treatmentforcomplicationinfection：

antimicrobialsensitiveforpathogenandwithoutnephrotoxicityshouldbegivenpromptly.Thrombosisandthromboembolism.ALB＜20g/L，patientscanbecomehypercoagulable.

drugsHeparinasmalldoseofaspirin

thrombosistreatmentthrombolytictherapy(bestusedwithin6hours,itisprobablyeffectivewithin3days.)streptokinasecanbeused.Acuterenalfailure

abigdoseofloopdiureticshemodialysisalkalizingtheurinemetabolicdisturbanceofproteinandlipidACEIcanalleviateproteinuriaAntihyperlipidemia:HMC-CoAreductaseinhibitorsPrognosisFactorsthataffecttheprognosishistologictypeClinicalpresentations:heavyproteinuria,hypertension,hyperlipidimia,anemia,plicationTotakehomepointsTalkingaboutthenephroticsymdrom(NS).WhatisclinicalthoughofNS.

WhatisHistologictypeofNSandit’sclinicalfeatures?TotakehomepointsTalkingaboutthecomplicationofNS?TalkingabouttheapplicationofglucocorticoidinNSandit’sSideeffects.Chronicglomerulonephritis

PanLing

Conception：

Chronicglomerulonephritisreferstoagroupofglomerulardiseasethatdevelopslowlyandeventuallyleadtochronicrenalfailure.Mechanism1.

Immune-mediated

inflammatoryreaction2.Non-immuneornon-inflammatoryfactors3.AcuteChronic

immunecomplexinsitu

circulatingimmunecomplexesHistologicalterationsMesangialproliferativeglomerulonephritisMesangialcapillaryglomerulonephritisMembranousnephropathyFocalsegmentalglomerularsclerosisSclerosingglomerulonephritis

Mesangialproliferative

glomerulonephritis

Mesangialcapillary

glomerulonephritisMembranousNephropathy

Focalsegmental

glomerulosclerosis

SclerosingglomerulonephritisDiffuseinfiltrationofneutrophilininterstitumClinicalmanifestationsandlaboratoryfindingsCommonlyseeninadults,amalepredominance.Generallyoccurindolently.Somepatientspresentasacutenephriticsymdromewithprodromalinfection.(MSPGN.MPGN)Clinicalpresentations

ProteinuriaHematuriaEdemaHypertensionRenalinsufficiencyClinicalpresentations

Proteinuria:A．1~3g/d.B．Glomerularproteinuriacause:abnormalitiesintheglomerularfiltrationbarriercharacteristic:bigormiddlemolecularproteinClinicalpresentations

Hematuria:A．GlomerularhematuriaPainlessandtotalhematuriaProteinuriaandcastsphasecontrast

microscopy:multiformity

typeandmixedtype

RBCinurineincreased>80%;Acanthoiderythrocytes>5%EVDC:asymmetricalcurve

棘形RBCClinicalpresentations

Edema--Nephritisedeman(morning,eyelid,face)

glomerulotubularimbalanceeGFR↓capillarypermeability↑RAAS↓ADH↓Clinicalpresentations

Hematuria:B．Mainlyinpatientswithproliferativeorfocalhistologicalterations→itcanbemacroscopichematuriaClinicalpresentations

HypertensionSaltandwaterretentionvolumeoverloadHyperreninemicstates(RAASactiation)ExogenouserythropoietinadministrationDecreaseofantihypertensionsubstanceHBP

Clinicalpresentations

Renalinsufficiency---DifferentdegreeSerumcreatinine↑

Ccr↓eGFR↓UrinevolumeabnormalChronicprogressionofthediseaseisassociatedwith:

HistologictypeTherapycondition.Theexistofworseningfactors:tiredness,infection,uncontrolledhypertension,nephrotoxicdrugs.DiagnosisanddifferentialdiagnosisDiagnosis:Clinicalmanifestation：

proteinuia,hematuria,edema,hypertension,renalinsufficiency.Secondaryandhereditaryglomerulonephritisshouldbeexcluded.Course>3M,mostonsethidden,complicationBultrasound:bilateralsmallkidney

2.DifferentialdiagnosisSecondaryGN:

lupusnephritis,anaphylactoidpurprua.Alportsyndrome

commonlyseeninchildren（<10ys）abnormalityofrenal,eyesandearsexistsimultaneously.Apositivefamilyhistoryisfound.Otherprimaryglomerulonephritis

AcuteGNpostinfection:mainlyseeninchildrenprodromalsymptom:1-3weeksbeforehematuria:almost100%serumC3

,yetrecovertonormallevelwithin8weeks.Otherprimaryglomerulonephritis

AcuteGNpostinfection:histologiclesions:endocapillaryproliferativeGN

favorableprognosisinchildren,butadultsaremorepronetochronicrenalinsufficiency.Renaldamagecausedbyprimaryhypertensionrenaldamageisseenafteralongtermofhypertension.tubulardysfunctionoccurearlierthanglomerulardysfunction.Renaldamagecausedbyprimaryhypertensionotherta