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1、Chapter 11Diseases of urinary system(一一)Functionsofkidney1.Excretesthewasteproductsofmetabolism2.Preciselyregulatesthebodysconcentrationofwaterandsalt3.Maintainstheappropriateacid-alkalinebalanceofplasma4.Servesasanendocrineorgan:erythropoietinreninprostaglandin(二二)RenalstructureNephronCollectingduc
2、t GlomerulusRenaltubuleCapillarytuft Renalcapsule(Bowmanscapsule) Proximaltubule ThinsegmentDistaltubule RenalstructureproximaltubuledistaltubuleRenalstructureRenalstructure1.FilteringmembraneEndothelialcells(EC) Glomerularbasementmembrane(GBM) Visceralepithelialcell(podocyte)FilteringmembraneFilter
3、ingmembrane(1)EndothelialCellsAthinlayeroffenestratedECfenestrum70100nmindiameterSurfacesialoglycoproteinwithnegativeelectriccharge(2)GBMComposedof laminararainterna(thin) laminadensa(thick)laminararaexterna(thin)UltrastructureofGBMIngredientsCollagen:mostlytypeIVformsanetworksuprastructureLaminin:P
4、olyanionicproteoglycan:(mostlyheparinsulfate)Fibronectin:Entactinandotherglycoproteins(3)VisceralepithelialC(Podocyte)FootprocessadjacentfootprocessesfiltrationslitslitdiaphragmSurfacesialoglycoproteinwithnegativeelectricchargePodocyte2.Mesangium(1)MesangialcellContractionPhagocytosisProducingmatrix
5、andcollagenSecretinganumberofcytokines(2)Mesangialmatrix3.Renalcapsule4.Glomerularbarrierfunctionhighpermeabilitytowatersmallsolutesrelatedtostructurechargeoffilteringmembrane (1)Size-dependentbarrierfunctiondiscriminatesproteinmoleculesdependingontheirsize(2)Charge-dependentbarrierfunctionimportant
6、becausealbuminisananionicmoleculesendothelialcellepithelialcellbasalmembraneheparinsulfatesialoglycoproteinnegativechargeStructureofGBMAlbuminNormal:cannotthroughthefiltrationmembraneChangesofstructureandfunctionproteinuria1Glomerulonephritis(GN)Primaryglomerulonephritis:ImmunemechanismsSecondaryglo
7、merulonephritis:SLE,Hypertension,Diabetesandsoon一一.EtiologyandPathogenesisImmunemechanismsPrimaryGN(一一)Antigen-AntibodyreactionmaincauseAb-Agcomplexhypersensitivity1.Antigen（1）EndogenousAgGlomerularAgGBMAgFootprocessAgMembraneofECNon-glomerularAgDNAImmunoglobulinTumorAg（2）ExogenousAgbacterium,virusp
8、arasite,fungusdrugs,foreignserum2.Ag-AbcomplexesInsituimmunecomplexdepositionCirculatingimmunecomplexdeposition（1）ImmunecomplexdepositioninsituGlomerularAgPlantedAgInsituimmunecomplexAbAnti-GBMnephritis(Masugisnephritis)RabbitimmunizedwithrattissueinjectratAbdirectagainstintrinsicfixedAgintheGBMneph
9、ritis)ImmunofluorescencemicroscopyAbdepositionintheGBMcontinuouslinearpatternfluorescence)FormationofGBMAga.Structuralchangesofmembraneb.Cross-reactionbecauseofthesameAgwithorganismLinearpatternfluorescenceHeymannnephritisImmunizedratwithmicrovillioftubularepithelialcellAbtomicrovilliAgsubepithelial
10、depositsMembranousGNHeymannnephritis)EMNumerouselectron-densedepositsbetween epithelium and basementmembrane(subepithelialaspect)ImmunofluorescenceGranulardepositsGranularfluorescenceAbagainstplantedAg)Abreactinsituwithpreviously“planted”non-glomerularAg)PlantedAgCationicmoleculesorproteinsDNABacter
11、ialproductsLargeaggregatedprotein(suchasaggregatedIgG)Virus,parasiticproductDrugs)ImmunofluorescenceGranular or heterogeneouspatternofIgdeposits（2）Circulatingimmunecomplexdeposition)Typehypersensitivityreaction)EM:Electron-densedepositslocalizesubECsubepitheliummesangialregion)Immunofluorescencealon
12、gtheBMinthemesangium GranularGranularfluorescence)Factorsaffecteddepositingofcomplexmolecularchargesizeofcompleximportant(二二)Anti-glomerularcellAbwithoutICdepositsAbdirectedtoglomerularcellAgdirectcellinjuryAbtomesangialcellAgmesangiolysismesangiolcproliferatoinAbtoECAgECinjury,thrombosis(三三)Cell-im
13、munity(cellmediatedimmunity)sensitizedTcellcauseglomerularinjury(四四)Activationofalternativecomplementpathwaycausemembrane-proliferativeGNindependentlyofimmune-complexdeposition(五五)Mediatorsofglomerularinjury 1.cellularcomponentChemotacticagents(C5a)Fc-mediatedimmuneadherenceReleaseproteasesGBMdegrad
14、ationOxygen-derivedfreeradicalscelldamageArachidonicacidmetabolitesreductioninGFR(1)Neutrophils(2)Phagocytes、LCandNKCGNinfiltratetheglomerulusreleaseavastnumberofbiologicallyactivemoleculessuchasIL-1、protease(3)Plateletsplateletsaggregatedintheglomerulusduringimmune-mediatedinjuryreleaseeicosanoidsg
15、rowthfactors (4)MesangialcellsProduceoxygenfreeradicals,cytokines,NO(nitricoxide),andsoonIntheabsenceofleukocyticinfiltrationinitiateinflammatoryresponses2.Solublemediators(1)ComplementcomponentschemotacticfactormacrophagocyteneutrophilsinfiltrationC5b-9celllysisstimulatesmesangialcellchemicalmediat
16、ors(2)Eicosanoids、NO、endothelin：involvedinthehemodynamicchanges(3)CytokinesIL-1TNFinduceleucocyteadhension(4)ChemokinesandGFChemokinespromotelymphocyte、monocyteaggregationPDGF:MesangialcellproliferationTGF-PromoteECMdepositionHyalinizationGF(5)Clottingsystem formationoffibrinleakintoBowmannsspacesti
17、mulateparietalepithelialcellproliferation二二.Basicpathologicalchanges1.GlomerularhypercellularityProliferationMesangialcellsECsParietalepithelialcellsInfiltrationNeutrophilsLCsMonocytes2.GBMthickeningmesangialmatrixincreasingLM:PAS、PSAMBMthickenEM(1)BMBecauseofBMBecauseofthedepositingofimmunecomplex(
18、2)Mesangialmatrixglomerulosclerosis3.InflammatoryexudationandnecrosisExudation:neutrophil、fibrinNecrosis:fibrinousnecrosis4.HyalinizationandsclerosisLM:EvenacidophilicsubstancedepositingEM(1)HyalinizationPlasmaproteinThickenedBMIncreasedmesangialmatrixextracellularamorphoussubstance(2)SclerosisFibro
19、sishyalinechangeMassonstainingblue三三.Clinicalmanifestation1.AcutenephriticsyndromeHematuria,proteinuria,oliguriaEdemaHypertensionSevereazotemia 2.RapidlyprogressivenephriticsyndromeHematuriaProteinuriaOliguriaorAnuriaEdemaAzotemiaacuterenalfailure3.NephroticsyndromeHeavyproteinuria(3.5g)SevereedemaH
20、ypoalbuminemia(50%)Focal:involvingacertainproportionofglomeruli(50%)Segmental:affectingapartofeachglomerulus(95%recoverfullydeveloparapidlyprogressiveglomerulonephritis:lessthan1%undergotochronicGN:1-2% (2)Inadults:poorlyprognosisRecover:60%SomedeveloprapidlyprogressiveGNSomedevelopchronicGN(二二)Rapi
21、dlyprogressiveGNRPRNCrescenticGNExtracapillaryproliferativeGN1.PathogenesisandclassificationInmostcases,theinjuryisimmunologicallymediated.Accordingtopathologyandimmunology:threetypes(1)TypeRPGN:anti-GBMnephritisImmunofluorescence:lineardepositsofIgG,C3glomerularandalveolarBMClinicalmanifestation:Go
22、odpasturesyndromepulmonaryhemorrhageassociatedwithrenalfailure;anti-GBMAbcross-reactionwithpulmonaryalveolarBMhemoptysis,hematuria,proteinuria,hypertensionTheGoodpastureAg:UnclearinmostpatientExposuretovirusesvariousdrugsCigarettesmokingGeneticpredispositiontoautoimmunity(2)Typeimmune-complexGNCause
23、s:postinfectiousGNdevelopmentassociatedwithsystemiclupuserythematosus(SLE)EM:electron-densedepositsBMandmesangiumImmunofluorescence:granular(BM,mesangium)Features:crescentformationimmunecomplex(3)Type:orpauci-immunetypeEMorimmunofluorescence:ThereareminimalimmunedepositsornonePathogenesis:Non-immune
24、mechanismorCellimmunityAntineutrophilcytoplasmicantibody(ACNA):alwayspresentassociatedwithsomeformsofvasculitis2.Pathologicalchanges(1)GrossEnlargedPaleCorticalpetechialhemorrhage(2)LMGlomerulus:Features:theformationofdistinctivecrescents:Crescentsproliferationofparietalcellsinfiltrationofmonocytesm
25、acrophagesCrescentformation:Causeexudationoffibrinincitescrescentformation:CellularcrescentFibrous-cellularcrescentFibrouscrescentCellularcrescentMassonstainRenaltubules:hyalinechangeIntracellularhyalinehyalinedropletsAtrophyInterstitiumedemainflammatoryinfiltration(3)EM:DistinctrupturesofGBM(4)ImmunofluorescenceType:linearType:granularType:nofluorescence3.CPC(1) HematuriaProteinuria:injuryofthecapillarywall(GBM)permeability (2)OliguriaoranuriacrescentformationobstructionofBowmansspacecompressthecapillarytuftGFR (3)Renalfailurefibrosisandhyalinechangeofglomeruluslossofnephronfunction
