肾小球疾病.ppt

肾小球疾病,GlomerularDiseases丁小强复旦大学附属中山医院,Pathologicalchanges-glomerularinjuryClinicalmanifestations-proteinuria/hematuria,Agroupofdiseases,Complicatedcauses&mechanismsVariousclinicalmanifestationsDifferentprognosisMultipletreatment,primaryglomerulardiseasessecondaryglomerulardiseaseshereditaryglomerulardiseases,ImmunemechanismsHumoralCell-mediated,Non-immunemechanisms,Inflammation,Glomerulardiseases,A.Immunemechanisms(A)depositsofCirculatingImmuno-Complex(CIC)circilationantigen+antibodyCICkidneyCIC/deposits,antigenextrinsicdrugs-nonhomologousserum,penicillinfoodsxenogenicproteinpathogenspecificserotypesstreptococci,HBV,HCVintrinsicnucleus（SLE)cytoplasm（ANCA）cellularmembraneantigenoftumorantigenofthyroid,WhydoesCICdepositintheglomeruli?,Largeareaofglomerrularcapillaries-morechancestocontactNetstructureofCIC-easytodepositandsettledownClearancedysfunctionofmesangialcells,disabilityofmononuclearmacrophage,componentorfunctiondefectofcomplementsDecreaseclearanceofCIC,(B)insituImmunocomplex1.Nativerenalantigenglomerularbasementmembrane+anti-glomerularbasementmembraneantibody(anti-glomerularbasementmembraneglomerulonephritis)2.AntigenstrappedorplantedDNA+anti-DNAantibody(LupusNephritis),BalancebetweenthedepositandclearanceofICdeterminesthesituationofthediseases,PersistenceofantigenClearancedysfunctionofmesangialcellsdisabilityofmononuclearmacrophagecomponentorfunctiondefectofcomplementsICdepositclearance,B.Cell-mediatedimmunemechanismsminimalchangeglomerulopathy?,C.Nonimmunemechanismsglomerularhypertensionhyperlipidemia(LDL-Cho)advancedglycosylationendproducts(protein)glomerulosclerosis,Inflammation,MediatorsofinflammationAgroupofmoleculeswhichactasmediatorsofinflammationandcomplicatedbiologicalfunctionOriginofinflammationmediatorsinkidneyExtrinsicCellsinkidneyinfiltrativeneutrophil,lymphocyte,mononuclearmacrophage,plateletIntrinsiccellsinkidneyMesangialcells,tubularcells,endothelialcells,Mediatorsofinflammation-activeoxygenandactivenitrogen-lipids-complements-cytokines-chemotaticfactors-adhesionmolecules-growthfactors-vasoactivesubstances,Toarouseorpromote-proliferationofcells-accumulationofextracellularmatrix-changesofhistologicalstructure-expressionofimmunomodulatingmoleculesandadhensionmolecules,Effectsoftheinflammationmediators,MechanismsofPrimaryGN,immunenon-immuneinflammationInflammatorycellsExtrinsiccellsIntrinsiccellsneutrophil,lymphcytemesangialcellsmononuclearmacrophageepithelialcellsplatelet,tubularcellsendothelialcellsInflammationmediatorscytokinesTNF,IL-1growthfactorsTGF,PDGFchemotaticfactorsMCP-1,IL-8complements,vasoactivesubstancesactiveoxygenandactivenitrogenCoagulationandfibrolysissystem,enzymeGlomerularinjuries,Essentialintheinitiation,Essentialintheprogressiveperiod,immunenon-immuneinitiationendstagePrimaryGN,SitesofpathologicalchangesMesangiumMesangialcellMesangialmatrixBasementmembranePodocyteFootprocessEndothelialcell,Theperipheralportionofaglomerularlobule,Pathologicalchanges,LMMesangialcells,matrixofmesangiumEpithelialcellsEndothelialcellsBasementmembraneLoopsofglomeruliEMFootprocessBasementmembraneHyperplasyofmesangium(electron-densedeposits)IFSites,appearancesandtypesofthedeposit(IgorC),BasicalchangesProliferationFibrosisandsclerosisNecrosisInfiltrationofinflammatorycells,ExtentsofInjuriesprimaryGNglomerularinjuriesonlyordominatingchangessecondaryGNglomerularinjuriesapartofsystematicdiseasesdiffuseimpairedglomeruli50%focalimpairedglomeruli50%segmentalimpairedcapillaryloopsofaglomerule3个/HP(fresh,10mlsample,1500rmpcentrifugefor5min,sedimentobservation)grosshematuriaRedcolorofurine,1mlblood/1Lurine,hematuriaRBCfromglomerulisqueezingthroughGBMdismorphicRBCPhase-contrastmicroscopydismorphicRBC50Hypothesis:glomerularbleedingdismorphicRBC70%Finaldiagnosis:glomerularbleeding,UrinaryRBCvolumedistributioncurvedissymmetrycurveMCVofurinaryRBC3.5g/d2.hypoalbuminemia1w，exceptECBVinsufficient,urinarytractobstruction,etcProgressiverenalfailureUnresolvedin2monthsuntypicalmanifestation,orwithnephroticsyndrome,Treatment1.SupportivetreatmentRestFood&waterRestrictiveintakeofNaCl5g/difmoderatetosevereedemaorhypertensionWaterifdecreasedurinevolumeProteinRenalfailure,butnotdialysisyet,2.TreatmentofinfectionPenicilinfor2wTonsillectomyifrecurrentattacksoftonsillitispatientsconditionisstable,Upro1g/d,URBC10/HPPenicilinfor2wksbeforeandafterthesurgery3.SymptomatictreatmentDiuresisAntihypertensionDialysis,Prognosishematuria,proteinuriausuallyreduceinonemonth,resolvewithin2to3monthssomeresolvewithin6to12months1%ARFDeath6%-18%CGN?,RapidlyprogressiveglomerulonephritisRPGNRapidlyprogressivenephritissyndromeSomeinducedbyrespiratoryinfectionAcuteonset,rapidlyprogressiveRenalfailurewithinafewweekstoafewmonths,1.primaryRPGNCrescenticGN2.otherprimaryGNotherpathologicalchangeswithlotsofcrescents3.secondaryRPGNSLE,SHP,etc,RPGNTypeITypeIITypeIIIanti-GBMICPauci-immuneIFlinearGBMGranularGBM（-）deposits&mesangiumdepositsanti-GBMAB（+）C3、CIC70%-80%smallvesselvasculitisANCA（+）theyoung&themiddle-agedthemiddle-agedmiddleaged&aged&aged,MostfrequentlyinChina,Diagnosis,AcuteonsetRapidlyprogressiveRenalfailurewithinafewweekstoafewmonthsAcuterenalfailureChronicrenalfailure,DifferentialDiagnosis,RapidlyprogressivenephritissyndromenotprimaryRPGN-otherprimaryGNAGN,IgAN,etc-secondaryGNGoodpastureSyndrome,LN,SHP*accompaniedbycrescenticGN*severepathologicalchanges,DiseaseswithARF,ATNAIN-definiteetiology-obsoleteproteinuriaandhematuria-specificmanifestationATNlargequantityofrenaltubularepithelialcellsinurineAINhypersensitiveness(rashes,fever,arthralgia),TreatmentEARLY!Aimtohumoralimmunemechanisms1.plasmapheresisdiscardtheantibodiesplasmexchangeimmoadsorptiontypeI,III2.drugsglucocorticoid+cytotoxicdrugsMP0.5-1.0g/d3，repeatifnecessaryCTXtypeII,III,symptomatictreatment,renalfailurebalanceoffluid,electrolytesandacid-basedialysisinfectionhypertension,PrognosisHardlyrelievemostCRFordeathRiskfactorsTypeI-worst,II-worse,III-badTreatmentnotprogressive&promptAgetheaged,ChronicGlomerulonephritis,ManifestationchronicnephritissyndromePathologicalchangesexceptMCD,MmPGN,CrescenticGN,Clinicalmanifestation1.ageanyage,frequentlyyoung2.preliminaryinfectionupperrespiratorytract,intestinaltractlatentperiod1wk3.nephritissyndrome,Hematuria,proteinuria,edema,Hypertension,renalfailure,uremia,4.Prognosisfactors(1)pathologicalproperties(2)treatment(3)hypertension(4)infection,prerenalfactors(hypotensionetc)(5)nephrotoxicdrugs,PointsofDiagnosis,c