内科学-肾小球疾病-课件

ppt课件1GlomerularDiseasesppt课件2Theperipheralportionofaglomerularlobuleppt课件3GlomerularDiseasesClassificationPrimarySecondaryHereditaryppt课件4Pathogenesisppt课件5ImmunologicglomerularinjuryHumoralantibody-mediatedCellularantibody-independentppt课件6Antibody-mediatedCirculatingautoantibodieswithintrinsicautoantigens:eg.anti-GBMdiseaseInsituformationofimmunecomplexs/circulationgantibodieswithextrinsicantigensthathavebeen“planted”withintheglomerulus:eg.PostinfectiousglomerulonephritisANCA/AECAassociated:nodisernibleimmunecomplexesintheglomerularparenchymappt课件7Cellularantibody-independentglomerularinjuryLesswelldefinedInitiatorsofinjuryinpauci-immuneglomerulonephritis,whichsharethedownstreammediatorswiththeantibody-dependentinjurySolublefactorsfromTcells:inMCDandprimaryFSGSppt课件8NonimmunologicglomerularinjuryMetabolicHemodynamictoxicppt课件9

immunologichumoralcellularnon-immunologicinflammationGlomerularinjuryppt课件10Clinicopathologiccorrelatesinglomerulardiseaseppt课件11Majorclinicopathologicentities(cont’d)NephroticsyndromeGlomerularfiltrationbarrieraffectedNephrotic-rangeproteinuria>=3.5g/24hHypoalbuminemia,edema,hyperlipidemia,andlipiduria,andaprothromboticstateMembranousglomerulopathyMinimalchangedisease(MCD)FSGSMembranoproliferative:hybridlesionofnephriticandnephroticfeaturesppt课件12OthersGlomerulardepositiondiseases:extravasculardepositionofparaproteinorfibrillarmaterialThromboticmicroangiopathies:thrombiwithintherenalmicrovasculatureppt课件13PrimaryinsultInflammatory√Metabolic√Hemodynamicormechanic√ToxicInfectiousMayoverlapMayinducesimilarclinicopahtologicpresentationsppt课件14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ppt课件15Theperipheralportionofaglomerularlobuleppt课件16

基本病变

增生proliferation

硬化sclerosisppt课件171.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ppt课件18MCD

（左）正常，（右）上皮细胞足突广泛融合、消失ppt课件192.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,FSGSppt课件20局灶性肾小球肾炎ppt课件213.弥漫性肾小球肾炎

(diffusiveglomerulonephritis)(1)膜性肾病membranousnephropathy,MN

肾小球基底膜

ppt课件22membranousnephropathy

（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ppt课件23(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ppt课件24mesangialproliferativeglomerulonephritis（左）正常，（右）系膜细胞和基质增生，电子致密物（D）沉积ppt课件25

毛细血管内增殖性肾小球肾炎

endocapillaryproliferativeglomerulonephritis

系膜+内皮细胞ppt课件26endocapillaryproliferativeglomerulonephritis

（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ppt课件27

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ppt课件28mesangiocapillaryglomerulonephritis

（左）正常，（右）系膜增生（M），电子致密物（D），广泛插入（I）ppt课件29

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

sclerosingglomerulonephritisppt课件30cresenticglomerulonephritis

（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ppt课件314.未分类的肾小球肾炎

unclassifiedglomerulonephritisppt课件32Clinicalpresentationsppt课件33ClinicalclassificationAcuteglomerulonephritis,AGNRapidlyprogressiveglomerulonephritis,RPGNChonicglomerulonephritis,CGNNephroticsyndrome,NSLatentglomerulonephritis,asymptomatichematuriaand/orproteinuriappt课件34AcutenephriticsyndromeSuddenonset(daystoweeks)NephriticurinarysedimentHematuria:Redbloodcasts,dysmorphicredbloodcellsSubnephroticproteinuria(<3.0g/24h)Extracellularfluidvolumeexpansion,edema,andhypertensionAcuterenalfailureandoliguriappt课件35Acutenephriticsyndrome(cont’d)ProliferativeglomerulonephritisInfiltrationoftheglomerulartuftbyneutropilsandmonocytes,followedbyproliferationofresidentendothelialandmesangialcellsEndocapillaryproliferativeGNppt课件36Streptococcalinfection(PSGN)

-symptomsandsigns1-3weeksafterpharyngitisor1-4weeksafteraskininfection(impetigo)NephritogenicstrainofgroupAbeta-hemolyticstreptococcusNephriticsyndromewitholiguricARF,ormilderHeadache,anorexia,nausea,vomiting,andmalaise,flankorbackpainppt课件37PSGN–labinvestigationsSerumcreatinineoftenmildlyelevatedC3andCH50depressedwithin2weeksin~90%patients,C4characteristicallynormal;returntonormalwithin6-8weeksTransienthypergammaglobulinemiaandmixedcryoglobulinemiaCirculatingantibodiesagainststreptococcalexoenzymessuchasASOppt课件38PSGN-pathologyDiffuseproliferativeGNCrescentsuncommonExtraglomerularinvolvementmildIFmicroscopy:diffusegranulardepositionofIgGandC3EM:largeelectron-densedepositsinthesubendothelial,subepithelialandmesangialareasppt课件39PSGN-treatmentEliminatingthestreptococcalinfectionwithantibioticsDiureticsandantihypertensiveagentstocontrolECFvolumeandBPSpontaneousresolutionwithin6-8weeksinchildren>20%adultsmayhavepersistentproteinuriaand/orcompromiseofGFRppt课件40RPGNOverweekstomonthsNephriticurinarysediment,subnephroticproteinuriaandvariableoliguria,hypervolemia,edema,andhypertensionCrescenticGNCrenscentscanalsodevelopconcomitantlywithproliferativeGN,membranousGNandotherGNppt课件41RPGN-Immunofluorescencemicroscopyanti-GBMdis---morediscretelineardepositionofIgalongtheGBMimmunecomplexGN---scatteredgranulardepositsofimmunoglobulinpauci-immuneGN---paucityorabsenceofIgppt课件42RPGN-SerologicmarkersDepressedC3level---TypeIIanti-GBMantibody---TypeIANCA---TypeIIIMayoverlapppt课件43Anti-GBMdisease(Goodpasture’ssyndrome)Antibodytoa3chain(noncollagenousdomain)oftypeIVcollagen,whichpreferentiallyexpressedinglomerularandpulmonaryalveolarbasementmembraneRPGN/crescenticGN,hematuria,nephriticurinarysediment,subnephroticproteinuria50-70%havelunghemorrhagewithhemoptysisorseverealveolarhemorrhageppt课件44Anti-GBM–labtestsAnti-GBMantibodiesRenalbiopsy,goldstandardfordiagnosisofanti-GBMnephritisDiffuseproliferativeGNFocalnecrotizinglesionsCrescentsin>50%ofglomeruliLinearribbon-likedepositionofIgGalongtheGBMppt课件45pauci-immuneRPGNIdiopathicrenal-limitedcrescenticGNMicrosopicpolyangiitisnodosaWegener’sgranulomatosisChurg-strausssyndromeAll-encompassingterm:ANCA-associatedsmallvesselvasculitisppt课件46ANCA-associatedrenaldiseaseLethargy,malaise,anorexia,weightloss,fever,arthralgias,myalgiasElevatedESR/CRP,leukocytosis,thrombocytosis,normochromicnormocyticanemia,complementleveltypicallynormalNephriticurinesedimentandsubnephroticproteinuriaRenaldysfunctionBiopsy:focalsegmentalnecrotizingGNwithcrescentformationPaucityorabsenceofIg,complementandimmunedepositsppt课件47

RPGN

I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、CIC

70%-80%为微血管炎

ANCA阳性

青、中年中、老年中、老年

我国多见ppt课件48treatmentGlucocorticoid,pulsetreatmentandmaintenancetreatmentCTXorAZAplasmaphereses,immunoadsorptionBetterprognosisinrelativelyearlycases(Scr<442mmol/L)Relapsesnotunusualppt课件49Nephroticsyndrome,NSProteinuria>3.5g/24hHypoalbuminemia<3.0g/LEdemaHyperlipidemia,lipiduriaandhypercoagulabilityppt课件50MainentitiesofNSMinimalchangedisease,MCDFocalandsegmentalglomerulosclerosis,FSGSMembranousglomerulopathy,MNMsPGNMembranoproliferativeglomerulonephritis,MPGNDiabeticnephropahy,DNAmyloidosis,MMppt课件51Complications---thrombosis

deepveinthrombosis

renalveinthrombosisSuddenonsetofflankorabdominalpainGrosshematuriaAleft-sidedvaricoceleIncreasedproteinuriaAcutedeclineinGFRPaticularlycommoninMN/MPGN/Amyloidosisppt课件52OthercomplicationsProteinmalnutritioninfectionppt课件53NS-treatmentSpecifictreatmentoftheunderlyingdiseaseGlucocorticoid,immunosuppressionGeneralmeasuresofproteinuriacontrolACEI/ARBNephroticcomplicationscontrolandpreventionppt课件54Sensetivityofsteroidprednisone(prednisolone)1mg/kg/d8w

negetive

proteinuria

remainpositive

relapseduringtaper

sentsetiveSteroid-dependentresistanceppt课件55NScomplicationscontrolEdemaSaltrestriction1-2g/d;judicioususeofloopdiuretics;LipidloweringHMGCoAreductaseAnticoagulationIndications:deepvenousthrombosis,arterialthrombosis,pulmonaryembolismppt课件56Minimalchangedisease,MCD80%ofNSinchildrenyoungerthan16yo,20%inadultsGlomerularsizeandarchitecturenormalbylightmicroscopyIFmicroscopynegativeforIgandC3EMcharacteristicdiffuseeffacementoffootprocessesofvisceralepithelialcellsppt课件57MCD-proteinuriaselectivitySelectiveproteinuriainchildrenwithalbuminprincipallyandminimalamountsofhighermolecularweightprotiensSelectivitypoorinadultssuggestingmoreextensiveperturbationofmembraneppt课件58MCD-treatmentHighlysteroid-responsiveGenerallyexcellentprognosisRemissionafter8weeksofhigh-doseoralglucocorticoids:90%inchildrenand50%inadultsppt课件59MCD-treatment(cont’d)RelapsescommonfollowingwithdrawalofglucocorticoidsAlkylatingagentsreservedforsteroid-resistant,steroid-dependentorfrequentlyrelapsing:CTX,chlorambucil,azathioprine,cyclosporineppt课件60Focalsegmentalglomerulosclerosis,FSGSSclerosiswithhyalinosisinvolvingportions(segmental)offewerthan50%(focal)ofglomeruliIdiopathicFSGS:Nephroticsyndrome(2/3)orsubnephroticproteinuria(1/3),nonselectiveHypertension,mildrenalinsufficiency,abnormalurinesedimentppt课件61FSGS(cont’d)IdiopathicSecondary:apotentiallong-termconsequenceofnephronloss(>50%)fromanycauseCongenitaloligomeganephronia,extensivesurgicalablationofrenalmass,refluxnephropathy,GN,interstitialnephritis,sicklecelldisease,ischemia,cyclosporinenephrotoxicity,rejectionofallograftppt课件62FSGS-treatmentRenalprognosisrelativelypoorRemissionratesfor8weekglucocorticoids:20-40%,upto70%forprolongedtherapy(16-24weeks)Immunosuppressants:CTX,cyclosporine,MMFPoorprognosticfactors:hypertension,abnormalrenalfunction,persistentheavyproteinuriappt课件63Membranousglomerulopathy(membranousnephropathy,MN)Peakincidence30-50yearsofageMale:femal2:1Namedafterlightmicrscopic:diffuseGBMthickening>80%representswithNS,nonselectiveMicroscopichematuria50%ppt课件64MN-pathologyLM:DiffusethickeningofGBMwithoutinflammationorcellularproliferationIF:granulardepositionofIgG,C3andterminalcomponentsofcomplementsalongtheglomerularcapillarywallppt课件65MN-pathogenesisIdiopathicMNincompletelyunderstoodImmunedepositssuggestinganimmuneprocess1/3withsystemicdisease:SLE,infectionssuchashepatitisB,malignancy,drug(eg.goldandpenicillamine)ppt课件66MN-treatmentandprognosisremitsspontaneouslyandcompletelyinupto40%another30to40%repeatedrelapsesandremissionsThefinal10to20%slowprogressivedeclineinGFRthattypicallyculminatesinESRDafter10to15yearsPoorprognosisindicators:malegender,olderage,hypertension,severeproteinuriaandhyperlipidemia,andimpairedrenalfunctionControlledtrialsofglucocorticoidshavefailedtoshowconsistentimprovementinproteinuriaorrenalprotection.Cyclophosphamide,chlorambucil,andcyclosporinehaveeachbeenshowntoreduceproteinuriaand/orslowthedeclineinGFRinpatientswithprogressivediseaseinsmalloruncontrolledstudies.ppt课件67Membranoproliferativeglomerulonephritis,MPGNthickeningoftheGBMandproliferativechangesonlightmicroscopytypeIMPGN:subendothelialandmesangialdepositsonelectronmicroscopythatcontainC3andIgGorIgM;rarely,IgAdepositstypeIIMPGN(densedepositdisease):electron-densedepositswithintheGBMandotherrenalbasementmembranes(shownbyelectronmicroscopy)thatstainforC3,butlittleornoimmunoglobulin.ppt课件68MPGNtypeI-clinicalfeaturesTypeIAnimmune-complex(IC)GNnephroticsyndrome,activeurinarysediment,andnormalormildlyimpairedGFR.C3levelsusuallydepressed,andC1qandC4levelsborderlineorlowAssociatedwithinfections,systemicICdiseases(SLE,cryoglobulinemia),malignancies50%ofpatientsreachESRDby10yearsppt课件69MPGNtypeII-clinicalfeaturesTypeIIanautoimmun