内科学-肾小球疾病-丁小强

GlomerularDiseases,ForInternalMedicine,Theperipheralportionofaglomerularlobule,GlomerularDiseasesClassification,PrimarySecondaryHereditary,Pathogenesis,Immunologicglomerularinjury,Humoralantibody-mediatedCellularantibody-independent,Antibody-mediated,Circulatingautoantibodieswithintrinsicautoantigens:eg.anti-GBMdiseaseInsituformationofimmunecomplexs/circulationgantibodieswithextrinsicantigensthathavebeen“planted”withintheglomerulus:eg.PostinfectiousglomerulonephritisANCA/AECAassociated:nodisernibleimmunecomplexesintheglomerularparenchyma,Cellularantibody-independentglomerularinjury,LesswelldefinedInitiatorsofinjuryinpauci-immuneglomerulonephritis,whichsharethedownstreammediatorswiththeantibody-dependentinjurySolublefactorsfromTcells:inMCDandprimaryFSGS,Nonimmunologicglomerularinjury,MetabolicHemodynamictoxic,immunologichumoralcellular,non-immunologic,inflammation,Glomerularinjury,Clinicopathologiccorrelatesinglomerulardisease,Majorclinicopathologicentities(contd),NephroticsyndromeGlomerularfiltrationbarrieraffectedNephrotic-rangeproteinuria=3.5g/24hHypoalbuminemia,edema,hyperlipidemia,andlipiduria,andaprothromboticstateMembranousglomerulopathyMinimalchangedisease(MCD)FSGSMembranoproliferative:hybridlesionofnephriticandnephroticfeatures,Others,Glomerulardepositiondiseases:extravasculardepositionofparaproteinorfibrillarmaterialThromboticmicroangiopathies:thrombiwithintherenalmicrovasculature,Primaryinsult,InflammatoryMetabolicHemodynamicormechanicToxicInfectiousMayoverlapMayinducesimilarclinicopahtologicpresentations,病变部位系膜mesangium系膜细胞mesangialcell系膜基质mesangialmatrix基膜basementmembrane上皮细胞足细胞podocyte、足突footprocess内皮细胞,Theperipheralportionofaglomerularlobule,基本病变增生proliferation硬化sclerosis,1.轻微肾小球病变（MinorLesion)无特异性病变光镜下可见轻度系膜细胞增生和系膜基质增多,轻微病变肾病minimalchangedisease，MCD轻度系膜增殖性肾小球肾炎毛细血管内增殖性肾小球肾炎恢复期其它,MCD（左）正常，（右）上皮细胞足突广泛融合、消失,2.局灶节段性病变,(1)局灶节段性增殖性肾小球肾炎focalandsegmentalproliferativeglomerulonephritis(2)局灶节段性肾小球硬化focalandsegmentalglomerulosclerosis,FSGS,局灶性肾小球肾炎,3.弥漫性肾小球肾炎(diffusiveglomerulonephritis),(1)膜性肾病membranousnephropathy,MN肾小球基底膜,membranousnephropathy（左）正常，（右）上皮下免役复合物沉积（D），GBM增厚，钉突形成（S），上皮细胞足突融合,(2)增殖性肾小球肾炎proliferativeglomerulonephritis系膜增殖性肾小球肾炎mesangialproliferativeglomerulonephritisMsPGN肾小球系膜IgA肾病IgAnephropathy非IgA肾病IgG沉积为主IgM肾病,mesangialproliferativeglomerulonephritis（左）正常，（右）系膜细胞和基质增生，电子致密物（D）沉积,毛细血管内增殖性肾小球肾炎endocapillaryproliferativeglomerulonephritis系膜+内皮细胞,endocapillaryproliferativeglomerulonephritis（左）正常，（右）内皮（E）和系膜（M）细胞增生，上皮下驼峰状电子致密物（D）沉积,系膜毛细血管性肾小球肾炎mesangiocapillaryglomerulonephritis又称膜增殖性肾小球肾炎membranoproliferativeglomerulonephritis系膜+基底膜致密沉积物性肾小球肾炎densedespositglomerulonephritis电子致密沉积物,mesangiocapillaryglomerulonephritis（左）正常，（右）系膜增生（M），电子致密物（D），广泛插入（I）,新月体性肾小球肾炎cresenticglomerulonephritis又称毛细血管外肾小球肾炎extracapillaryglomerulonephritis肾小球囊上皮细胞(3)硬化性肾小球肾炎sclerosingglomerulonephritis,cresenticglomerulonephritis（左）正常，（右）GBM断裂，纤维蛋白漏出(F)，上皮细胞增生(E)，单核巨噬细胞浸润(P)，新月体形成,4.未分类的肾小球肾炎unclassifiedglomerulonephritis,Clinicalpresentations,Clinicalclassification,Acuteglomerulonephritis,AGNRapidlyprogressiveglomerulonephritis,RPGNChonicglomerulonephritis,CGNNephroticsyndrome,NSLatentglomerulonephritis,asymptomatichematuriaand/orproteinuria,Acutenephriticsyndrome,Suddenonset(daystoweeks)NephriticurinarysedimentHematuria:Redbloodcasts,dysmorphicredbloodcellsSubnephroticproteinuria(20%adultsmayhavepersistentproteinuriaand/orcompromiseofGFR,RPGN,OverweekstomonthsNephriticurinarysediment,subnephroticproteinuriaandvariableoliguria,hypervolemia,edema,andhypertensionCrescenticGNCrenscentscanalsodevelopconcomitantlywithproliferativeGN,membranousGNandotherGN,RPGN-Immunofluorescencemicroscopy,anti-GBMdis-morediscretelineardepositionofIgalongtheGBMimmunecomplexGN-scatteredgranulardepositsofimmunoglobulinpauci-immuneGN-paucityorabsenceofIg,RPGN-Serologicmarkers,DepressedC3level-TypeIIanti-GBMantibody-TypeIANCA-TypeIIIMayoverlap,Anti-GBMdisease(Goodpasturessyndrome),Antibodytoa3chain(noncollagenousdomain)oftypeIVcollagen,whichpreferentiallyexpressedinglomerularandpulmonaryalveolarbasementmembraneRPGN/crescenticGN,hematuria,nephriticurinarysediment,subnephroticproteinuria50-70%havelunghemorrhagewithhemoptysisorseverealveolarhemorrhage,Anti-GBMlabtests,Anti-GBMantibodiesRenalbiopsy,goldstandardfordiagnosisofanti-GBMnephritisDiffuseproliferativeGNFocalnecrotizinglesionsCrescentsin50%ofglomeruliLinearribbon-likedepositionofIgGalongtheGBM,pauci-immuneRPGN,Idiopathicrenal-limitedcrescenticGNMicrosopicpolyangiitisnodosaWegenersgranulomatosisChurg-strausssyndromeAll-encompassingterm:ANCA-associatedsmallvesselvasculitis,ANCA-associatedrenaldisease,Lethargy,malaise,anorexia,weightloss,fever,arthralgias,myalgiasElevatedESR/CRP,leukocytosis,thrombocytosis,normochromicnormocyticanemia,complementleveltypicallynormalNephriticurinesedimentandsubnephroticproteinuriaRenaldysfunctionBiopsy:focalsegmentalnecrotizingGNwithcrescentformationPaucityorabsenceofIg,complementandimmunedeposits,RPGNI型II型III型抗基膜抗体型免疫复合物型非免疫复合物型IF线样、沿基膜颗粒样、系膜（-）区和基膜GBM抗体（+）C3、CIC70%-80%为微血管炎ANCA阳性青、中年中、老年中、老年,我国多见,treatment,Glucocorticoid,pulsetreatmentandmaintenancetreatmentCTXorAZAplasmaphereses,immunoadsorptionBetterprognosisinrelativelyearlycases(Scr3.5g/24hHypoalbuminemia50%)fromanycauseCongenitaloligomeganephronia,extensivesurgicalablationofrenalmass,refluxnephropathy,GN,interstitialnephritis,sicklecelldisease,ischemia,cyclosporinenephrotoxicity,rejectionofallograft,FSGS-treatment,RenalprognosisrelativelypoorRemissionratesfor8weekglucocorticoids:20-40%,upto70%forprolongedtherapy(16-24weeks)Immunosuppressants:CTX,cyclosporine,MMFPoorprognosticfactors:hypertension,abnormalrenalfunction,persistentheavyproteinuria,Membranousglomerulopathy(membranousnephropathy,MN),Peakincidence30-50yearsofageMale:femal2:1Namedafterlightmicrscopic:diffuseGBMthickening80%representswithNS,nonselectiveMicroscopichematuria50%,MN-pathology,LM:DiffusethickeningofGBMwithoutinflammationorcellularproliferationIF:granulardepositionofIgG,C3andterminalcomponentsofcomplementsalongtheglomerularcapillarywall,MN-pathogenesis,IdiopathicMNincompletelyunderstoodImmunedepositssuggestinganimmuneprocess1/3withsystemicdisease:SLE,infectionssuchashepatitisB,malignancy,drug(eg.goldandpenicillamine),MN-treatmentandprognosis,remitsspontaneouslyandcompletelyinupto40%another30to40%repeatedrelapsesandremissionsThefinal10to20%slowprogressivedeclineinGFRthattypicallyculminatesinESRDafter10to15yearsPoorprognosisindicators:malegender,olderage,hypertension,severeproteinuriaandhyperlipidemia,andimpairedrenalfunctionControlledtrialsofglucocorticoidshavefailedtoshowconsistentimprovementinproteinuriaorrenalprotection.Cyclophosphamide,chlorambucil,andcyclosporinehaveeachbeenshowntoreduceproteinuriaand/orslowthedeclineinGFRinpatientswithprogressivediseaseinsmalloruncontrolledstudies.,Membranoproliferativeglomerulonephritis,MPGN,thickeningoftheGBMandproliferativechangesonlightmicroscopytypeIMPGN:subendothelialandmesangialdepositsonelectronmicroscopythatcontainC3andIgGorIgM;rarely,IgAdepositstypeIIMPGN(densedepositdisease):electron-densedepositswithintheGBMandotherrenalbasementmembranes(shownbyelectronmicroscopy)thatstainforC3,butlittleornoimmunoglobulin.,MPGNtypeI-clinicalfeatures,TypeIAnimmune-complex(IC)GNnephroticsyndrome,activeurinarysediment,andnormalormildlyimpairedGFR.C3levelsusuallydepressed,andC1qandC4levelsborderlineorlowAssociatedwithinfections,systemicICdiseases(SLE,cryoglobulinemia),malignancies50%ofpatientsreachESRDby10years,MPGNtypeII-clinicalfeatures,TypeIIanautoimmunediseasewithanIgGautoantibody,termedC3nephriticfactorproteinuriaandnephroticsyndrome;somewithnephriticsyndrome,RPGN,orrecurrentmacroscopichematuriaavariablecourse;theGFRremainsstableinsomepatientsanddeclinesgraduallytoESRDover5to10yearsinothers,MPGNtypeIII,RareSubepithelialimmunedeposits,IgAnephropathy(Bergersdisease)andHenoch-Schonleinpurpura,Pathologicallyidentical,mildsesangialproliferationtodiffuseproliferationwithcrescents,mesangialIgAdeposition,withIgGandC