病理學英文教學課件：ch11 Diseases of urinary system1

Chapter11

DiseasesofurinarysystemIntroduction(一)

Functionsofkidney1.Excretesthewasteproductsofmetabolism2.Preciselyregulatesthebody’sconcentrationofwaterandsalt3.Maintainstheappropriateacid-alkalinebalanceofplasma4.Servesasanendocrineorgan:

erythropoietinrenin

prostaglandin(二)

RenalstructureNephronCollectingduct

GlomerulusRenaltubuleCapillarytuft

Renalcapsule

(Bowman’scapsule)

Proximaltubule

Thinsegment

Distaltubule

RenalstructureproximaltubuledistaltubuleRenalstructureRenalstructure1.

FilteringmembraneEndothelialcells(EC)

Glomerularbasementmembrane(GBM)

Visceralepithelialcell(podocyte)Filteringmembrane

Filteringmembrane(1)EndothelialCells①AthinlayeroffenestratedEC

fenestrum→70~100nmindiameter②Surface→sialoglycoprotein

withnegativeelectriccharge(2)GBM①

Composedof

laminararainterna(thin)

laminadensa(thick)laminararaexterna(thin)UltrastructureofGBM②

IngredientsCollagen:mostlytypeIV→formsanetworksuprastructureLaminin:

Polyanionicproteoglycan:

(mostlyheparinsulfate)

Fibronectin:

Entactinandotherglycoproteins(3)VisceralepithelialC(Podocyte)①

Footprocessadjacentfootprocesses→filtrationslit→slitdiaphragm②

Surface→sialoglycoprotein

withnegativeelectricchargePodocyte

2.

Mesangium(1)MesangialcellContractionPhagocytosisProducingmatrixandcollagenSecretinganumberofcytokines(2)Mesangialmatrix3.

Renalcapsule4.

Glomerularbarrierfunctionhighpermeabilitytowatersmallsolutesrelatedtostructurechargeoffilteringmembrane

(1)

Size-dependent

barrierfunction

discriminatesproteinmolecules

dependingontheirsize(2)Charge-dependent

barrierfunction①

important→becausealbuminisananionicmolecules②

endothelialcellepithelialcell

basalmembrane→heparinsulfatesialoglycoproteinnegativechargeStructureofGBM③AlbuminNormal:cannotthroughthefiltrationmembraneChangesofstructureandfunctionproteinuria

§1Glomerulonephritis(GN)Primaryglomerulonephritis:

ImmunemechanismsSecondaryglomerulonephritis:SLE,Hypertension,Diabetesandsoon一.EtiologyandPathogenesisImmunemechanismsPrimaryGN(一)Antigen-Antibodyreaction

maincause

Ab-Agcomplex

hypersensitivity1.

Antigen（1）Endogenous

Ag①GlomerularAgGBMAgFootprocessAgMembraneofEC②Non-glomerularAgDNA

Immunoglobulin

TumorAg（2）ExogenousAg

bacterium,virusparasite,fungusdrugs,foreignserum2.

Ag-AbcomplexesInsitu

immunecomplexdepositionCirculatingimmunecomplexdeposition（1）Immunecomplex

depositioninsitu

GlomerularAgPlantedAg

InsituimmunecomplexAb①Anti-GBMnephritis

(Masugi’snephritis)RabbitimmunizedwithrattissueinjectratAbdirectagainstintrinsicfixedAgintheGBMnephritisⅰ)Immunofluorescencemicroscopy

AbdepositionintheGBM

continuouslinearpatternfluorescenceⅱ)FormationofGBMAga.Structuralchangesofmembraneb.Cross-reactionbecauseofthesameAgwithorganismLinearpatternfluorescence②

HeymannnephritisImmunizedratwithmicrovillioftubularepithelialcell

AbtomicrovilliAg

subepithelialdepositsMembranousGNHeymannnephritisⅰ)EM

Numerouselectron-densedepositsbetweenepitheliumandbasementmembrane(subepithelialaspect)ⅱ)Immunofluorescence

Granulardeposits

Granularfluorescence③AbagainstplantedAgⅰ)Abreactinsituwithpreviously“planted”non-glomerularAgⅱ)PlantedAgCationicmoleculesorproteinsDNABacterialproductsLargeaggregatedprotein(suchasaggregatedIgG)Virus,parasiticproductDrugsⅲ)ImmunofluorescenceGranularorheterogeneouspatternofIgdeposits（2）Circulatingimmune

complexdepositionⅰ)TypeⅢhypersensitivityreactionⅱ)EM:Electron-densedepositslocalizesubEC

subepitheliummesangialregionⅲ)ImmunofluorescencealongtheBM

inthemesangium

GranularGranularfluorescenceⅳ)Factorsaffected

depositingofcomplexmolecularchargesizeofcompleximportant

(二)Anti-glomerularcellAb

withoutICdepositsAbdirectedtoglomerularcellAg→directcellinjuryAbtomesangialcellAg→mesangiolysismesangiolcproliferatoinAbtoECAg→ECinjury,thrombosis(三)Cell-immunity

(cellmediatedimmunity)sensitizedTcellcauseglomerularinjury(四)Activationofalternative

complementpathwaycausemembrane-proliferativeGNindependentlyofimmune-complexdeposition(五)Mediatorsof

glomerularinjury

1.

cellularcomponentChemotacticagents(C5a)Fc-mediatedimmuneadherenceReleaseproteases→GBMdegradationOxygen-derivedfreeradicals→celldamageArachidonicacidmetabolites→reductioninGFR

(1)Neutrophils(2)Phagocytes、LCandNKCGNinfiltratetheglomerulusreleaseavastnumberofbiologicallyactivemoleculessuchasIL-1、protease(3)Plateletsplateletsaggregatedintheglomerulus

duringimmune-mediatedinjury

releaseeicosanoidsgrowthfactors

(4)

MesangialcellsProduceoxygenfreeradicals,cytokines,NO(nitricoxide),andsoonIntheabsenceofleukocyticinfiltration→initiateinflammatoryresponses2.Solublemediators(1)Complementcomponentschemotacticfactor→macrophagocyteneutrophilsinfiltrationC5b-9→celllysisstimulatesmesangialcellchemicalmediators(2)Eicosanoids、NO、

endothelin：involvedinthehemodynamicchanges(3)CytokinesIL-1

TNFinduceleucocyteadhension(4)ChemokinesandGF

Chemokines

promotelymphocyte、

monocyteaggregationPDGF:MesangialcellproliferationTGF-βPromoteECMdepositionHyalinizationGF(5)Clottingsystem

formationoffibrinleakintoBowmann’sspace

stimulateparietalepithelialcellproliferation二.Basicpathologicalchanges1.

GlomerularhypercellularityProliferationMesangialcells

ECs

ParietalepithelialcellsInfiltration

NeutrophilsLCsMonocytes

2.GBMthickening

mesangialmatrixincreasingLM:PAS、PSAM→BMthickenEM(1)BM

BecauseofBM↑

Becauseofthedepositingofimmunecomplex(2)Mesangialmatrix↑

glomerulosclerosis

3.

Inflammatoryexudation

andnecrosisExudation:

neutrophil、fibrinNecrosis:

fibrinousnecrosis4.

HyalinizationandsclerosisLM:EvenacidophilicsubstancedepositingEM(1)HyalinizationPlasmaproteinThickenedBMIncreasedmesangialmatrixextracellularamorphoussubstance

(2)Sclerosis

Fibrosis→hyalinechange

Massonstaining→blue三.Clinicalmanifestation1.

AcutenephriticsyndromeHematuria,proteinuria,oliguriaEdemaHypertensionSevere→azotemia

Rapidlyprogressive

nephriticsyndromeHematuriaProteinuriaOliguriaorAnuriaEdemaAzotemia→acuterenalfailure3.

NephroticsyndromeHeavyproteinuria(≥3.5g)SevereedemaHypoalbuminemia(<30g/L)HyperlipidemiaandlipiduriaAsymptomatichematuria

orproteinuriaContinuousorrecurrenthematuria

(macroscopicormicroscopic)Mildproteinuria5.ChronicnephriticsyndromePolyuria,nocturia

lowspecificgravityurineHypertensionAzotemiaanduremiaAnemia四.PathologicaltypesAcutediffuseproliferativeGNRapidlyprogressiveGN(RPGN)MembranousGNMinimalchangeGNFocalsegmentalGNMembranoproliferativeGNMesangialproliferativeGNIgAnephropathyChronicglomerulonephritisNomenclatureofglomerularinjuryDiffuse

:involvingallormajorityof

glomeruli(>50%)Focal

:involvingacertainproportionofglomeruli(<50%)Global:involvingtheentireglomerulusorlargepartofeachglomerulus(>50%)Segmental:affectinga

partofeach

glomerulus(<50%)

(一)Acutediffuseproliferative

glomerulonephritis(GN)EndocapillaryproliferativeGN

PostinfectiousGN

PoststreptococcalGN

NonstreptococcalGN

1.

Introduction(1)FeaturesMesangialCECproliferationNeutrophilMacrophageinfiltration

(2)AssociatedwithinfectionofStreptococci:main

poststreptococcalGN

Otherpathogens:

nonstreptococcalGN(3)Common

:5-14yearsofage(4)Clinicalmenifestation:acutenephriticsyndrome2.Etiologyandpathogenesis(1)

Mainfactors:mostcommon:GroupAβ-hemolyticstreptococci90%→type12.4.1others:pneumococci,staphylococcushepatitisBvirus(HBV)(2)Immunemediateddisease

ImmunecomplexdepositingAnti-oAb↑Serumcomplementlevel↓PathogenasAgAbformationAg-Abcomplexincirculationdepositattheglomerulusinflammatoryreaction(1)GrossEnlargeDarkredPetechialhemorrhageflea-bitingkidney3.Pathologicalchanges

(2)LM

①Glomeruli

EnlargedglomeruliHypercellularityⅰProliferativecellEndothelialcell

MesangialcellⅱInfiltrativecell

Neutrophil

Macrophage

ⅲBloodlessofglomeruli

proliferatingofcSwellingofECobliteratecapillarylumens

blood↓→GFR↓CausesEndocapillaryproliferativeGNEndocapillaryproliferativeGNⅳ:CapillarywallSegmentalfibrinousnecrosisHematuria

②RenaltubulesProximaltubule→epithelialcdegenerationTubulescontainsproteinorRBCcasts

③Renalinterstitium

CongestionEdemaInflammatorycellinfiltrationRBCcast

(3)Immunofluorescence

Granularfluorescence

GBM,mesangium(4)EM:“humps”electron-densedeposits:

subepithelialcells(commonly)

subendothelialcells

intramembraneGranularfluorescence“humps”electron-densedepositshumps”electron-densedeposits4.CPC:Acutenephriticsyndrome(1)

Thechangesofurine①Hematuria,proteinuria

hematuriaproteinuria:injuryofthecapillarywall(GBM)permeability

②Oliguria

proliferationofcellsswellingofendothelialc

bloodlessglomeruli

declineofGFR

(2)Edema①GlomerularGFR↓depositingofwaterandsodium②Hypersensitivityreactioncapillarypermeability(3)HypertensionDepositingofwaterandsodiumIncreasedcapacityofblood5.Results(1)Children:goodprognosis①>95%→recoverfully②developarapidlyprogressive

glomerulonephritis:lessthan1%③undergotochronicGN:1-2%

(2)Inadults:poorlyprognosis

①Recover:60%

②SomedeveloprapidlyprogressiveGN

③SomedevelopchronicGN(二)RapidlyprogressiveGNRPRN

CrescenticGN

ExtracapillaryproliferativeGN

1.Pathogenesis

and

classificationInmostcases,theinjuryis

immunologicallymediated.Accordingtopathologyandimmunology:threetypes(1)TypeⅠRPGN:

anti-GBMnephritis①Immunofluorescence:

lineardepositsofIgG,C3→glomerularandalveolarBM②

Clinicalmanifestation:

Goodpasturesyndromepulmonaryhemorrhageassociatedwithrenalfailure;anti-GBMAbcross-reactionwithpulmonaryalveolarBM

hemoptysis,hematuria,

proteinuria,hypertension→③TheGoodpastureAg:UnclearinmostpatientExposuretovirusesvariousdrugsCigarettesmokingGeneticpredispositiontoautoimmunity

(2)TypeⅡ

immune-complexGN①Causes:postinfectiousGNdevelopmentassociatedwithsystemiclupuserythematosus(SLE)②EM:

electron-densedeposits

BMandmesangium③Immunofluorescence:

granular(BM,mesangium)④Features:

crescentformationimmune