病理學 04 泌尿系統(tǒng)疾病

12023/3/31ReviewUrinarysystem-kidneys,ureters,urinarybladderandurethra.Kidneystructureandfunctioniscomplexandimportant:nephron(腎單位)Primarykidneyfunction-excretethewasteproductsofmetabolisminurine.Morethan1700Lofblood/dayconvertedto1Lofurine.Preciseregulationofthebody’swaterandsaltconcentration;maintainsappropriateacidbalanceofplasma;servesasanendocrineorgan.22023/3/31RenalDiseases

1.Glomerular（腎小球）

diseases

Primaryglomerulonephritis（腎小球腎炎）SecondaryglomerulonephritisSystemicrenaldiseaseHereditaryrenaldisease2.DiseasesaffectingtubulesandinterstitiumAcutetubularnecrosisTubulointerstitialNephritis:

Pyelonephritis（腎盂腎炎）3.Diseasesofrenalbloodvessels4.TumorsRenalcellcarcinoma,

Wilmstumor(Nephroblastoma),

Urothelialtumors32023/3/31KeypointsPrimaryGlomerularDiseases:Definition,pathogenesis,clinicalsyndromes,morphologyofeachtypePyelonephritis:Infectiouspathway,pathologicfeatureofacuteandchronicdisease,clinicalmanifestationsComparisonofglomerulardiseasesandpyelonephritisComparisonofRenalcellcarcinomaandWilm’stumorUrothelialcarcinomaofurinarybladder42023/3/31Glomerulonephritis(GN)-腎小球腎炎DefinitionGN:nonsuppurativeinflammation,

hypersensitiveimmunemechanism.Mainclinicalmanifestations:proteinuria,hematuria,edema,hypertension,renalinsufficiency52023/3/3162023/3/3172023/3/3182023/3/31ThereisevidenceGNisinducedbyantigen-antibodyreactions(immunemechanisms).Glomerular

depositsofimmunoglobulinswithvariouscomplementproteinsarefound.Cell-mediatedimmunemechanismsalsoplayaroleincertainglomerulardiseases.

PathogenesisofGN

92023/3/31Antigen：

1)Exogenous：Drugs,Foods,Pathogenicorganisms2)Endogenous：

a.Non-glomerularantigens

（nuclear,cytoplasm,tumorcell,immunoglobulins)b.Glomerularantigens(GBM,cells）Antibody：

IgG、IgA、IgM102023/3/31Ag+Ab=ImmuneComplex(IC)

SolublecirculatingIC:DepositionintheglomerulusInsituIC:Antibodiesreactinginsituwithintheglomerulus,eitherwithinsolublefixed(intrinsic)glomerularAgorwithmoleculesimplantedwithintheglomerulus.112023/3/31OnceIClocalizeintheglomerulus,howdoesglomerulardamageensue?MediatorsofimmuneinjuryComplement-leukocytemediatedmechanismisonewell-establishedpathwayOthermediatorsinclude:Monocytes/Macrophages,Platetes,Residentglomerularcells,Fibrin-relatedproducts.Antibodiesdirectlydamageglomeruliafterbindingwithantigenswithinglomeruli.122023/3/31GlomerularsyndromesanddisordersAcuteNephriticSyndrome

hematuria,redcellcastinurine,azotemia,oliguria,hypertension2.NephroticSyndromeClinicalcomplexwhichincludes:(1)Massiveproteinuria,dailylossof≥3.5gofprotein/day.(2)Hypoalbuminemiawithplasmaalbuminlevels≤30g/L.(3)Generalizededema,themostobviousclinicalmanifestation.(4)Hyperlipidemia,andlipiduria(lipidintheurine)littleornoazotemia,hematuria,orhypertension.

132023/3/313.RapidlyProgressiveNephriticSyndromerapidandprogressivelossofrenalfunction,severeoliguria,nephriticsyndrome,renalfailure4.AsymptomaticHematuriaorProteinuria

frequentlyrecurrentgrossormicroscopichematuria,proteinuria

5.Acuterenalfailure6.Chronicrenalfailure

142023/3/31MasangialcellMasangialmatrix（足C）ParietalepitheliumFenestraeinendotheliumVisceralepithelium(Podocyte)FootprocessEndotheliumBowmanspaceGBMCapillarylumen152023/3/31a.入球小動脈b.出球小動脈

c.腎小囊基底膜d.壁層上皮細胞e.腎小囊腔f.GBMg.臟層上皮細胞h.內(nèi)皮細胞i.系膜細胞腎小球162023/3/31172023/3/31a.腎小囊基底膜b.腎小囊腔c.臟層上皮細胞d.GBMe.內(nèi)皮f.系膜細胞182023/3/31PathologicchangesofGNHypercellularity:1.Cellularproliferation:

MsorEn2.Leukocyticinfiltration:neutrophils,monocytes,lymphocytes3.FormationofcrescentsBasementmembranethickening:1.Depositionofamorphouselectron-densematerial2.IncreasedsynthesisofGBMproteincomponentsHyalinosisandsclerosis:

192023/3/31MethodsLM:

HEPASMMassonPASIF:

IgGIgAIgMetcEM:

electrondensedeposit202023/3/31MinimalChangeDisease

（腎小球微小病變）

（LipoidNephrosis）

212023/3/31Morphology：

LM:GlomuruliareofnormalappearanceProximaltubularcellsareoftenheavilyladenwithlipidsEM:Diffuselossof

podocytesfootprocesses

(onlyobviousglomerularabnormality)IF:Negative222023/3/31Minimalchangedisease232023/3/31Clinicalfeatures:Relativelybenigndisorder,

nephroticsyndrome,children,renalfunctionpreserved,nohypertension,

>90%

ofcasesrespondtoashortcourseofcorticosteroidtherapy,

goodprognosis.Pathogenesis:immunedysfunction→cytokineelaboration→damagevisceralepithelialcell→proteinuria

MCD242023/3/31

MembranousNephropathy

（膜性腎?。?/p>

（MembranousGN）

252023/3/31LM:

Basicchange-diffusethickeningoftheGBMSmallspikelikeprotrusions-severecases262023/3/31IF:

Typicalgranulardeposition

ofIgGandcomplementalongGBM.272023/3/31EM:

(Spikeanddomepattern)Electron-densesubepithelialdepositionsnestleagainstGBMSpikelikeprotrusionsofGBMareseparatedbydepositions.

Podocyteslosefootprocesses.282023/3/31MembranousGN

MembranousNephropathy正常292023/3/31Clinicalfeatures:Adults30-50,insidiousdevelopment,nephroticsyndrome,Doesnotresponsewelltocorticosteroidtherapy.Etiology:Idiopathic;secondary(hepatitisB,malignanttumor,SLE,exposuretoinorganicsalts,drugs)Progress:Slowlyprogressivedisease.Pathogenesis:Chronicimmunecomplexnephritis

MN302023/3/31

DiffuseMembranoproliferativeGN

（彌漫性膜增生性腎小球腎炎）

(MPGN)312023/3/31MorphologyMesangialcellproliferationandinfiltratingleukocytesmakeglomerulilargewithlobularappearance.GBMthickened,oftenshowsadoublecontouror“tramtrack”appearanceEMandIFfindingsyields2subtypes

322023/3/31TypeI:(2/3cases)EM:Subendothelialelectron-densedeposits.IF:C3andIgG,earlycomplementcomponents(C1qandC4),suggestICpathogenesis.332023/3/31TypeII:(DenseDepositDisease,DDD)

EM:Depositionofunknownmaterialgivesthe

GBMaribbon-likeelectron-densestructure.IF:C3ispresent.IgGandearly-actingcomplementcomponentsusuallyabsent342023/3/31DiffuseMembranoproliferativeGN正常352023/3/31Clinicalfeatures:Idiopathicnephroticsyndrome(10%-20%)Prognosisuniformlypoor.40%→end-stagerenalfailure,30%→variabledegreeofrenalinsufficiency,30%→nephroticsyndromewithoutrenalfailure.TypeIIhasworseprognosis,withrecurranceafterrenaltransplantation.

MPGN362023/3/31DiffuseProliferativeGN

（彌漫性增生性腎小球腎炎）

DiffuseEndocapillaryGN

（彌漫性毛細血管內(nèi)增生性腎小球腎炎）

Poststreptococcal,PostinfectiousGN

（感染后腎小球腎炎）372023/3/31LM:

UniformlyincreasedglomerularcellularityCharacteristicchange:proliferationofendothelialandmesangialcells,withneutrophilandmonocyteinfiltrates.382023/3/31IF:

GranularIgGandcomplementdepositsalongGBM392023/3/31EM:Immunecomplexesdepositionarrayedassubepithelial

“humps”nestledagainstGBM.402023/3/31Endothelial＋MscellsproliferationNeutrophilinfiltrate“Hump”likesubepithelialdeposition

PathogenesisofDffuseProliferativeGN

正常412023/3/31Clinicalfeatures:Abruptonset,nephriticsyndrome,grosshematuria,lowserumcomplement.Poststreptococcalcases:serumantistreptolysinOtiters↑Prognosis:Mostchildrenrecover.Pathogenesis:immunologicallymediateddiseaseDiffuseProliferativeGN422023/3/31CrescenticGN

(新月體性腎小球腎炎)

RapidlyProgressiveGN

（快速進行性腎小球腎炎）432023/3/31Morphology:

1.Glomerulishowcrescent

formation

2.Crescentsformedbyparietalcellproliferation

andmonocyte

migrationintoBowman’space.

3.Fibrinstrandsprominentbetweencellularlayersincrescents.

4.CrGNdividedinto3groupsbasedonimmunefindings442023/3/31

TypeICrGN:Anti-GBMdisease

1.

Clinically-Goodpasturesyndrome

2.Serum-Anti-GBMantibodiespresent(helpfulindiagnosis)

3.IF:lineardepositsofIgGandC3onGBM

4.Treatment:plasmapheresis452023/3/31TypeIICrGN:Immunecomplex-mediateddisorder

Potentialcomplicationofanyimmunecomplexnephritis,includingPoststreptococcalGN,LupusNephritis,IgAnephropathy.

TypeIIICrGN:Pauci-immunetypeCrGN

1.

Definedbylackofanti-GBMantibodiesorICbyIFandEM.

2.

MostpatientshaveserumANCA(Anti-NeutrophilCytoplasmicAntibody).

3.Componentofsystemicvasculitis:Wegner’sgranulomatosis,Microscopicpolyarteritis

462023/3/31正常ParietalcellsproliferationMigrationofmonocytesFibrinins

RapidlyProgressive/CrescenticGNCrescentsformation472023/3/31Clinicalfeatures:Nephriticsyndrome,oliguria,azotemia,ProteinuriaPrognosis:roughlyrelatedtonumberofcrescents.

RPGN482023/3/31

IgANephropathy

(IgA腎病)492023/3/31LM:lesionsvaryconsiderablyFocalGNCrescenticGNDiffuseMsPGN502023/3/31IF:

CharacteristicfeatureismesangialdepositionofIgA,oftenwithC3.512023/3/31EM:confirmsthepresenceofIFdepositioninmesangium.522023/3/31

IgANephropathyClinicalfeatures:Recurrentmicroscopicorgrosshamaturia;

mostcommonGNworldwide,Usuallyaffectschildrenandyoungadults

Typicalacutenephriticsyndromein5-10%Subsequentcoursehighlyvariable.Manypatientsmaintainnormalrenalfunctionfordecades,25%-50%progresstochronicrenalfailureover20years.532023/3/31IgANephropathyPathogenesis

IncreasedIgAsynthesis(marrow).ReducedIgAclearanceIgAandIgAcomplexestrappedinmesangium,andactivatealternativecomplementpathway,andinitiateglomerularinjury.542023/3/31ChronicGlomerulonephritis

(慢性腎小球腎炎)

SclerosingGlomerulonephritis

（硬化性腎小球腎炎）552023/3/31

ChronicGNClinicalCoursePooroutcomeinallformsofGN

Clinically-chronicrenalfailure,firstnotedinyoungandmiddle-agedadults20%-nohistoryofsymptomaticrenaldisease30%to50%requirehemodialysisorrenaltransplantation562023/3/31Macroscopic:

KidneyssymmetricallycontractedKidneysurfacesred-brownanddiffuselygranular.End-stagekidney,reducedsize572023/3/31End-stagekidneys-microscopic

Scarring(hyaline)ofglomeruli(difficulttodiscernnatureoforiginallesions)

Atrophyandreplacementofmanytubulesincortex.Markedinterstitialfibrosisandlymphocytesinfiltration

Smallandmedium-sizedarteries

thickwalled,withnarrowedlumina.582023/3/31RenalDiseases

1.Glomerular（腎小球）

diseases

Primaryglomerulonephritis（腎小球腎炎）SecondaryglomerulonephritisSystemicrenaldiseaseHereditaryrenaldisease2.DiseasesaffectingtubulesandinterstitiumAcutetubularnecrosisTubulointerstitialNephritis:

Pyelonephritis（腎盂腎炎）3.Diseasesofrenalbloodvessels4.TumorsRenalcellcarcinoma,

Wilmstumor(Nephroblastoma),

Urothelialtumors592023/3/31Glomerulonephritis(GN)-腎小球腎炎DefinitionGN:nonsuppurativeinflammation,

hypersensitiveimmunemechanism.Mainclinicalmanifestations:proteinuria,hematuria,edema,hypertension,renalinsufficiency602023/3/31MinimalChangeDisease

（腎小球微小病變）

（LipoidNephrosis）

612023/3/31Minimalchangedisease622023/3/31

MembranousNephropathy

（膜性腎病）

（MembranousGN）

632023/3/31MembranousGN

MembranousNephropathy正常642023/3/31

DiffuseMembranoproliferativeGN

（彌漫性膜增生性腎小球腎炎）

(MPGN)652023/3/31DiffuseMembranoproliferativeGN正常662023/3/31DiffuseProliferativeGN

（彌漫性增生性腎小球腎炎）

DiffuseEndocapillaryGN

（彌漫性毛細血管內(nèi)增生性腎小球腎炎）

Poststreptococcal,PostinfectiousGN

（感染后腎小球腎炎）672023/3/31Endothelial＋MscellsproliferationNeutrophilinfiltrate“Hump”likesubepithelialdeposition

PathogenesisofDffuseProliferativeGN

正常682023/3/31CrescenticGN

(新月體性腎小球腎炎)

RapidlyProgressiveGN

（快速進行性腎小球腎炎）692023/3/31正常ParietalcellsproliferationMigrationofmonocytesFibrinins

RapidlyProgressive/CrescenticGNCrescentsformation702023/3/31TubulointestitialNephritis(TIN)TIN-groupofrenalinflammatorydiseasesprimarilyinvolvinginterstitiumandtubules.Glomerulimaybesparedoraffectedlateindiseasecourse.MostTINcausedbybacterialinfection.

Renalpelvisprominentlyinvolved-pyelonephritis.712023/3/31AcutePyelonephritisCommonsuppurativeinflammationofkidneyandrenalpelvis,causedbybacterialinfection.Almostalwaysassociatedwithinfectionofthelowerurinarytract.722023/3/31Principalorganisms-entericgram-negativerods.Mostcommon-E.coliBacteriareachkidneyby2routes:

1)Mostimportantandcommonroute-lowerurinarytract(ascendinginfection).2)Lesscommonroute-bloodstream(hematogeousinfection).Wheredobacteriacomefrom?732023/3/31PredisposingfactorsinrecurrentinfectionUrinaryobstruction:CongenitaloracquiredInstrumentation:Cystoscopy,catheterizationVesicoureteralreflux(VUR):CongenitalPregnancySexandage:Sexualinjury,benignprostatehyperplasiaPre-existingrenallesions:CauseintrarenalscarringDiabetesmellitusImmunosuppressionandImmunodeficiency742023/3/31Macroscopicfindings:DiscreteyellowishraisedabscessesGrosslyapparentontherenalsurfaceWidelyscatteredorlimitedtooneregion752023/3/31Microscopicfindings:Characteristicsuppurativenecrosisorabscessformationwithinrenalparenchyma.Neutrophilinfiltrateandcastswithintubularlumen.Pyelonephrosis,necrotizingpapillitisorpapillarynecrosis.762023/3/31AcutePyelonephritisClinicalCourse

EvidenceofsystemicinfectionUrinaryfindings-pyuriaandbacteriuriaClinicalcourse-benignandself-limited.Necrotizingpapillitisassociatedwithmuchpoorerprognosis.772023/3/31ChronicPyelonephritisChronicpyelonephritis–morphologicallydefinedentityInflammationpredominantlyinterstitialwithscarringofrenalperanchymaGrosslyvisiblescarringanddeformityofpelviccalycealsystemImportantcauseofchronicrenalfailureTwoforms-obstructiveandreflux-associatedpyelonephritis782023/3/31Macroscopicfindings:Characteristic-Unevenscarring,asymmetricallycontractedkidneyHallmark-scarringinvolvingpelvisorcalycesleadingtopapillarybluntingandmarkedcalycealdeformity792023/3/31MicroscopicfindingslargelynonspecificUneveninterstitialfibrosis,

chronicinflammatoryinfiltrate,occasionallywithneutrophils.LesionsinvolvecalycealmucosaandwallDilationorcontractionoftubuleswithcolloidcastsGlomerulosclerosisandarteriolosclerosis802023/3/31ChronicPyelonephritisClinicalCourseRenalinsufficiencyorhypertension,orfoundonroutinemedicalexamination.Ultrasonographyfindingsarecharacteristic.Absenceofsignificantbacteriuriashouldnotruleoutthisdisease.Tubulardysfunctionoccursinbilateral&progressivecasesGlomerulosclerosismaydevelopandleadtochronicrenalfailure.812023/3/31GNPyelonephritisEtiology

AgInflammationImmunereactiontypeIIINon-suppurativeLocationGlomeruliRangeDiffuseorFocalClinically

Proteinuria,hematuria,BUNScrNoirritationofurethraTreatmentCorticosteroidtherapyKidneytransplantationG-Bacteria,E.coliSuppurativeinflammationTubulointerstitiumCalyceal&pelvismucosaFocalBacteriuria,PyuriaTubulardysfunctionBladderandurethrairritationAntibioticsRemovepredisposingfactors822023/3/31Renalneoplasms832023/3/31Renaltumors

epidemiologyBenigntumorshavenoclinicalsignificance-corticalpapillaryadenomaormedullaryfibroma.Renalcellcarcinoma-mostcommonprimarymalignanttumorofkidney,followedinfrequencybynephroblastomaandprimarytumorsofcalycesandpelvis.Otherrenalcancersrare.Tumorsoflowerurinarytractaretwiceascommonasrenalcellcarcinoma(e.g.urinarybladdercarcinoma)842023/3/31DerivedfromrenaltubularepithelialcellsRepresents80%-85%ofprimarymalignantkidneytumorsMostcommon-60-70years.M:F=2:1RiskhigherinsmokersandwithexposuretocadmiumRisk30foldhigherinacquiredpolycysticdiseaseasacomplicationofchronicdialysis.RenalCellCarcinoma852023/3/31Newclassificationbasedonmoleculartumororiginssecondarytorecentadvancesintumorgenetics.Threemostcommonforms:1.Clearcellcarcinoma2.Papillaryrenalcellcarcinoma3.ChromophoberenalcarcinomaNewClassificationofRCC862023/3/3170%to80%ofrenalcellcancersMostaresporadic,somearefamilialassociatedwithvonHipple-Linda(VHL)disease.VHL-autosomaldominantdiseasecharacterizedbypredispositiontoavarietyofneoplasms.Germ-linemutationofVHLgeneandlossofsecondallelebysomaticmutationresultsinhemozygouslossofVHLVHLgeneisatumorsuppressorgeneonchromosome3p25ClearCellCarcinoma872023/3/31Macroscopic:Ariseanywhereinrenalcortex

WelldemarcatednoduleCutsurfaceyellowtoorange

togray-whitewithprominentareasofcysticchangeand

necrosisorhemorrhage.Occasionaldirectinvasionintotheperinephricfatandadrenalgland.882023/3/31Microscopicfindings:

Classic-

clearcellswithvacuolated(lipid-laden)cytoplasm,smallandroundnuclei,welldelineatedcellmembrane,cellswithpinkgranularcytoplasmresemblingtubularcells.

StromausuallyscantbuthighlyvascularizedAbortivetubules,clusterincords

ordisorganizedmasses892023/3/31Papillaryrenalcellcarcinoma10%-15%ofallrenalcancersEtiology-overdoseofMETprotooncogeneonchromosome7q31.Familialcases:chromosome7trisomy,andmutationofMETgenecommonlyseen.Sporadiccases:chromosome7trisomywithoutMETgenemutation,andtrisomyof16,17andlossofchromosomeY.902023/3/31MacroscopicfindingsMultilocalandbilateralgrowthLessvibrantlyorange-yellow,duetolowerlipidcontent.912023/3/31HistologicfindingsPapillarygrowthpattern,papillawithfibrovascularcoresCytoplasmclearoroftenpink922023/3/31Chromophoberenalcarcinoma5%ofrenalcellcancersNamederivesfromfactcellsstainmoredarkly(lessclear)Arisefromcorticalcollectingductsortheirintercalatedcells.Uniqueinhavingmultiplelossesofentirechromosomes1,2,6,10,13,17and21-extremehypodiploidy.Ingeneralhasgoodprognosis932023/3/31Macroscopicfindings:Tan-brownnoduleHistologicfindingsClearflocculentcytoplasmwithprominent,distinctcellmembranes.Nucleisurroundedbyhalosofclearedcytoplasm.EM-macrovesicles942023/3/31RCCClinicalcourseVariableclinicalmanifestationscreatedifficultandchallengingdiagnosticproblemsCharacterisedbytriadofpainlesshematuria,long-standingfever,anddullflankpainSometimesdetectedaftermetastasisPrevalentlocationsformetastases-lungandbone952023/3/31WilmsTumor

Nephroblastoma

(腎母細胞瘤)962023/3/31Grossfindings:Large,solitary,well-circumscribedmassCutsurface-soft,homogenous,tantogray972023/3/31Microscopicfindings:RepresentsdifferentstagesofnephrogenesisClassictriphasiccombinationofblastemal,stromalandepithelialcellstypesobservedinmostlesionsBlastemalcomponent:SheetsofsmallbluecellswithfewdistinctivefeaturesEpithelialdifferentiation:abortivetubulesandglomeruliStromaldifferentiation:Smoothmuscle,adipisetissue,cartilage,osteoidandneurogenictissue982023/3/31WilmsTumorClinicalcourseReadilypalpableabdominalmass.Mayhavefever,abdominalpainPrognosisgenerallyverygood.Excellentresultsobtainedwithcombinationofnephrectomyandchemotherapy.2yearsurvivalrateupto90Tumorswithdiffuseanaplasia,especiallywithextrarenalspreadhaveleastfavorableoutcome.992023/3/31Urothelialneoplasms

（尿路上皮腫瘤）

(Transitionalneoplasms)1002023/3/31OccurintransitionalepitheliumfromrenalpelvistourethraFocusonhistologicpatternsandclinicalimplicationsinurinarybladdertumors.1012023/3/31Macroscopicfindings-Tumorsarisinginurinarybladderrangefromsmallbenignpapillomastolargeinvasivecancers1022023/3/31Classification

ofurothelialneoplasmsarisinginurinarybladderBenigntumor:PapillomaMalignanttumor:urothelialcarcinoma1)lowGrade2)highGrade

1032023/3/31Veryrarebenigntumor,usua