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1、DiseasesofurinarysystemandmalegenitalsystemNephrologyUrologyOutlinen nGlomerulonephritis(GN)n nTubulointerstitialnephritisn nUrinaryoutflowobstructionn nTumorsofurinarysystemn nProstateDisease,TestisandPenisTumorn nTheincidencerateofchronickidneyTheincidencerateofchronickidneydisease(CKD)is9.4%to11.
2、8%inChina,disease(CKD)is9.4%to11.8%inChina,thereisonepatientforeverytenpeoplethereisonepatientforeverytenpeoplen nTheoccurrenceisoccult,20%oftheTheoccurrenceisoccult,20%ofthepatientsatdiagnosisareonlatestagepatientsatdiagnosisareonlatestagen nThesecondThursdayofMarchisdeclaredThesecondThursdayofMarc
3、hisdeclaredastheWorldKidneyDay(WKD).March12,astheWorldKidneyDay(WKD).March12,2015isthe10thWKD.ThetopicforWKD2015isthe10thWKD.ThetopicforWKD2015is2015is“KidneyHealthforAllKidneyHealthforAll”Etiologyofglomerulardiseasesn nPrimary(majority):diseaseprocessappearsPrimary(majority):diseaseprocessappearsto
4、startwithintheglomerulitostartwithintheglomerulin nSecondary:diseaseprocessissecondarytoSecondary:diseaseprocessissecondarytosystemicdisease(SLE,vasculardiseases,systemicdisease(SLE,vasculardiseases,diabetesmellitus,amyloidosis)diabetesmellitus,amyloidosis)n nHereditary:congenitaldiseases(AlportHere
5、ditary:congenitaldiseases(Alportsyndrome,Fabrysdisease)syndrome,Fabrysdisease)Primaryglomerulonephritisn nkidneyistheonlyorpredominantorganinvolvedEtiologyandPathogenesisn n ImmunemechanismsunderlietheImmunemechanismsunderliethemajorityofprimaryGN.ThemostmajorityofprimaryGN.Themostcommonmechanismisa
6、ntibody-commonmechanismisantibody-medicatedinjury.medicatedinjury.n nTwobasicformsofantibody-associatedTwobasicformsofantibody-associatedinjury:injury:(1)(1)InjuryresultingfromdepositionofInjuryresultingfromdepositionofsolublecirculatingantigen-antibodysolublecirculatingantigen-antibodycomplexesinth
7、eglomerulicomplexesintheglomeruli(2)(2)InjurybyantibodiesreactinginsituInjurybyantibodiesreactinginsituwithintheglomeruliwithintheglomeruliCirculatingImmuneComplexNephritisnCausedbythetrappingofcirculatingantigen-antibodycomplexeswithinglomerulinTheantibodieshavenoimmunologicspecificityforglomerular
8、constituentsnTypehypersensitivityreactionnTheantigensmaybeofendogenousorexogenousoriginsCirculatingImmuneComplexNephritisnTheelectron-densedepositslieinthemesangium,betweentheendothelialcellsandtheGBM(subendothelialdeposits)orbetweentheGBMandthepodocytes(subepithelialdeposits)nThedepositsmaybedegrad
9、edbymonocytesandmesangialcellsInSituImmuneComplexDepositionnAntibodiesreactdirectlywithintrinsictissueantigen,orantigens“planted”intheglomerulifromthecirculation.nAutoantibodiesagainstcomponentsoftheGBMarethecauseofanti-GBMmediateddisease,oftenassociatedwithsevereinjury.Thepatternofdepositionislinea
10、r.nAntibodiesmayalsobeformedagainstantigensthatareplantedintheGBM.Theresultantinsituimmunecomplexesmayshowagranularpatternofdeposition.LinearpatternImmunofluorescenceGranularpatternImmunofluorescence(IF)Mechanismofglomerularinjuryn nCirculatingimmunecomplexnephritisn nimmunecomplexnephritisinsitun n
11、Cell-mediatedimmunity(sensitizedTcells)n nOthermechanismsSummaryofpathogenesisnAntibody-mediatedimmuneinjuryisanimportantmechanismofglomerulardamage,mainlyviacomplement-andleukocyte-mediatedpathways.Antibodiesmayalsobedirectlycytotoxictocellsintheglomerulus.nThemostcommonformsofantibody-mediatedGNar
12、ecausedbythedepositionofcirculatingimmunecomplexesStepsindiagnosesofglomerularlesionsnClinicalpresentationnRenalbiopsyLightmicroscopicexaminationLightmicroscopicexamination(HE(HE，PASPAS，MASSONMASSON，PASMstain)PASMstain)ImmunofluorescenceexaminationImmunofluorescenceexaminationElectronmicroscopicexam
13、inationElectronmicroscopicexamination CTscan12Clinicalmanifestationsn nHematuria(redbloodcellsinurine)Hematuria(redbloodcellsinurine)n nProteinuria(proteinlostinurineProteinuria(proteinlostinurine,3.5g/d,3.5g/d)n nOliguria(urineflow400ml/24hours)Oliguria(urineflow400ml/24hours)n nAnuria(urineflow100
14、ml/24hours)Anuria(urineflow3.5g/d),hypoalbuminemia,severeedema,3.5g/d),hypoalbuminemia,severeedema,hyperlipidemiaandlipiduriahyperlipidemiaandlipidurian nChronicnephriticsyndromeChronicnephriticsyndrome:slowly:slowlydevelopingrenalfailureaccompaniedbydevelopingrenalfailureaccompaniedbyproteinuria,he
15、maturia,hypertensionandproteinuria,hematuria,hypertensionanduremiauremian nAsymptomatichematuriaorproteinuriaAsymptomatichematuriaorproteinuriaRenalfailuren nTwotypes(acuteandchronicrenalfailure)Twotypes(acuteandchronicrenalfailure)n nTwomainsyndromesofTwomainsyndromesofpartialpartialrenalfailureren
16、alfailure(nephriticsyndromeandnephrotic(nephriticsyndromeandnephroticsyndrome)syndrome)n nChronicrenalfailureisChronicrenalfailureisirreversibleirreversible,asitis,asitiscausedbypermanentdestructionofcausedbypermanentdestructionofnephronsnephronsn nAcuterenalfailuresometimesrecoversAcuterenalfailure
17、sometimesrecoverswhenthedamagingstimulusresolveswhenthedamagingstimulusresolvesBasicpathologicalchangen nHypercellularityn nBasementmembranethickeningn nNecrosisn nHyalinizationandsclerosisfocal 50%)n nThecrescentsliningBowmanscapsulearecomposedofamixtureofepithelialcellsandmacrophagesproliferatingC
18、resenticglomerulonephritisCresenticglomerulonephritisCrescenticglomerulonephritisCrescentBasementmembranedestructionCresenticglomerulonephritisn nAnti-GBMdiseaseAnti-GBMdiseasen nDamagetothepulmonaryalveolarDamagetothepulmonaryalveolarcapillarybasementmembrane,producingcapillarybasementmembrane,prod
19、ucingtheclinicalfeaturesofpulmonarytheclinicalfeaturesofpulmonaryhemorrhagesassociatedwithrenalfailurehemorrhagesassociatedwithrenalfailuren nAnti-GBMantibodiesintheserumAnti-GBMantibodiesintheserum(plasmapheresisisuseful)(plasmapheresisisuseful)GoodpasturesyndromeGoodpasturesyndromeClinicalfeatures
20、n nRPGNischaracterizedbyrapidandprogressivelossofrenalfunctionassociatedwithsevereoliguriaevenanurian nPrognosisispoorPrimaryglomerulonephritisn nAcutediffuseproliferativeglomerulonephritisn nCrescenticglomerulonephritisn nMembranousglomerulopathyn nMinimalchangeglomerulopathyn nFocalsegmentalglomer
21、ulosclerosis(FSGS)n nMembranoproliferativeglomerulonephritisn nIgAnephropathyn nChronicglomerulonephritisMembranousglomerulopathyn nMajorcauseofnephroticsyndromeinMajorcauseofnephroticsyndromeinadultsadultsn nCharacterizedbyelectron-dense,Characterizedbyelectron-dense,immunoglobulin-containingdeposi
22、tsimmunoglobulin-containingdepositsalongtheepithelialsideoftheBM.DiffusealongtheepithelialsideoftheBM.DiffusethickeningofthecapillarywallthickeningofthecapillarywallMembranousglomerulopathyMembranousglomerulopathyMembranousglomerulopathyIgGImmunofluorescenceClinicalManifestationsn nTheconditionusual
23、lystartsasinsidiousTheconditionusuallystartsasinsidiousonsetofnephroticsyndromeorsub-onsetofnephroticsyndromeorsub-nephrotic-rangeproteinuria.Upto40%ofnephrotic-rangeproteinuria.Upto40%ofcasesprogresstorenalinsufficiencyovercasesprogresstorenalinsufficiencyoveranunpredictabletimespanof2to20anunpredi
24、ctabletimespanof2to20years.years.Primaryglomerulonephritisn nAcutediffuseproliferativeglomerulonephritisn nCrescenticglomerulonephritisn nMembranousglomerulonephritisn nMinimalchangeglomerulopathyn nFocalsegmentalglomerulosclerosis(FSGS)n nMembranoproliferativeglomerulonephritisn nIgAnephropathyn nC
25、hronicglomerulonephritisn nMajorcauseofnephroticsyndromeinMajorcauseofnephroticsyndromeinchildrenchildrenn nCharacterizedbynormalglomerulionCharacterizedbynormalglomerulionlightmicroscopybutuniformanddiffuselightmicroscopybutuniformanddiffuseeffacementofthefootprocessesofeffacementofthefootprocesses
26、ofvisceralepithelialcellsonEMvisceralepithelialcellsonEMn nImmunofluorescenceshowsnoimmuneImmunofluorescenceshowsnoimmunedepositsdepositsMinimalchangediseaseMinimalchangediseaseClinicalmanifestationsn nProteinuriaisusuallyselectiven nThemostcharacteristicfeatureofthisconditionisthedramaticresponseto
27、corticosteroidtherapyn nThelong-termprognosisisexcellentforchildrenandadultsPrimaryglomerulonephritisn nAcutediffuseproliferativeglomerulonephritisn nCrescenticglomerulonephritisn nMembranousglomerulopathyn nMinimalchangeglomerulopathyn nFocalsegmentalglomerulosclerosis(FSGS)n nMembranoproliferative
28、glomerulonephritisn nIgAnephropathyn nChronicglomerulonephritisFocalsegmentalglomerulosclerosis(FSGS)n nCharacterizedbysclerosisofsegmentofCharacterizedbysclerosisofsegmentoftheglomeruli,andonlyaffectedfocaltheglomeruli,andonlyaffectedfocalglomeruli(50%)glomeruli(femalesn nPubertytomiddleage:females
29、malesn nPost-40years:malesfemalesThreeagepeaksGenderdifferencesRoutesofbacterialinfectionn nAscendinginfectionfromthelowerurinarytract(mostcommon):entericgram-negativerods(Escherichiacoli)n nBloodstreamspreadinbacteremicorsepticemicstates:staphylococciRouteofinfectionHematogenousinfection(descending
30、infection)AscendinginfectionGrossfeaturen nSuppurativeinflammationn nCorticalabscessesn nMedullaryabscessesAcutepyelonephritisAcutepyelonephritisHistologicalfeaturen nInfiltrationoftubulesbyneutrophilsn nAbscessformationn nInterstitialedemaAcutepyelonephritisClinicalfeaturen nSuddenonsetSuddenonsetn
31、 nPaininthebackPaininthebackn nEvidenceofsystemicinfection(chills,Evidenceofsystemicinfection(chills,fever,malaise)fever,malaise)n nIndicationsofbladderandurethralirritationIndicationsofbladderandurethralirritation(dysuria,urgency,frequencyof(dysuria,urgency,frequencyofmicturition)micturition)Urinar
32、yfindingsn nPyuria(whitebloodcellsandpuscellsinurine)n nBacteriuria(bacteriainurine)Complicationsandsequelaen nResolutionResolutionn nHealingwithscarringHealingwithscarringn nChronicityChronicityn nPyonephrosisPyonephrosisn nRenalpapillarynecrosisRenalpapillarynecrosisn nPerinephricabscessPerinephri
33、cabscessn nDeathinuremiaDeathinuremiaPapillarynecrosisPyelonephritisnAcutepyelonephritisnChronicpyelonephritisChronicpyelonephritisn nChronicpyelonephritisisdefinedasaChronicpyelonephritisisdefinedasamorphologicentityinwhichmorphologicentityinwhichpredominantlyinterstitialinflammationpredominantlyin
34、terstitialinflammationandandscarringscarring oftherenalparenchymaisoftherenalparenchymaisassociatedwithgrosslyassociatedwithgrosslyvisiblescarringvisiblescarringandanddeformitydeformity ofthepelvicalycealsystemofthepelvicalycealsystemn nAncauseofchronicrenalfailureAncauseofchronicrenalfailureChronic
35、pyelonephritisn nChronicobstructivepyelonephritisn nChronicreflux-associatedpyelonephritis(vesicoureteralreflux)Grossfeaturen nKidneysarenotequallydamagedn nIrregularareasofscarringn nMarkedcalycealdeformitiesGrossfeaturenotequallydamagedIrregularareasofscarringMarkedcalycealdeformitiesChronicpyelon
36、ephritisChronicpyelonephritisnotequallydamagedIrregularareasofscarringMarkedcalycealdeformitiesHistologicalfeaturen nChronicinflammatorycellsinfiltration,occasionallyneutrophilsn nUneveninterstitialfibrosisn nDilationorcontractionoftubulesn nGlomerulishowperiglomerularfibrosisChronicpyelonephritis“T
37、hyroidization”DilationoftubulesClinicalfeaturesn nGradualonsetofrenalinsufficiencyn nTubulardysfunction(polyuria,nocturia)n nUrinarytractinfectionn nUremiaDiagnosisnIntravenouspyelogramnUrineculture急性肾小管坏死(Acutetubularnecrosis)过敏性间质性肾炎Outlinen nGlomerulonephritis(GN)n nTubulointerstitialnephritisn n
38、Urinaryoutflowobstructionn nTumorsofurinarysystemn nProstateDisease,TestisandPenisTumorUrinaryoutflowobstructionnRenalstonesnHydronephrosisRenalstonesn nUrolithiasisiscalculusformationatanylevelintheurinarycollectingsystemn nmostcommonsites:pelvicalycealsystemandbladderMainpredisposingfactorsn nIncr
39、easedconcentrationofsoluteinurinen nReducedsolubilityofsoluteinurineEtiologynAcquirednInheritedRenalcalculusRenalstaghorncalculusSFluoroscopyUreteralcalculusClinicalfeaturen nWithoutsymptomsn nRenalcolicwithnausea,vomitingandhematurian nDualacheintheloinsn nRecurrenturinarytractinfectionUrinaryoutfl
40、owobstructionn nRenalstonesn nHydronephrosisHydronephrosisn nHydronephrosisreferstodilationoftherenalpelvisandcalyces,withaccompanyingatrophyoftheparenchyma,causedbyobstructiontotheoutflowofurinen nRenalpelvisRenalpelvisn nPelviuretericPelviuretericjunctionjunctionn nUreterUretern nBladderBladdern n
41、UrethraUrethraHydronephrosisObstructionofthelevelsMorphologyn nUnilateral:causedbyobstructionattheleveloftheureter,pelviuretericjunctionorrenalpelvisn nBilateral:causedbyobstructionofthelevelofthebladderorurethraHydronephrosisNormalurinarytractIntravenouspyelogram(IVP)HydronephrosisIntravenouspyelog
42、ram(IVP)Hydronephrosis(cutsurface)ClinicalfeaturenClinicalfeaturesdependonthecauseandsiteofthelesionEffectsofhydronephrosisn nObstructionisremoved:renalfunctionreturnstonormaln nPersistenceofobstruction:atrophyofrenaltubuleswithglomerularhyalinizationandfibrosisStaghorncalculusHydronephrosisAbscessO
43、utlinen nGlomerulonephritis(GN)n nTubulointerstitialnephritisn nUrinaryoutflowobstructionn nTumorsofurinarysystemn nProstateDisease,TestisandPenisTumorTumorsofurinarysystemn nTumorsofthekidneyn nTumorsofthebladdern nTumorsoftheuretern nTumorsoftheurethraKeyfactsrenalcellcarcinoman n80%-85%ofallprima
44、ryrenalmalignant80%-85%ofallprimaryrenalmalignanttumor,2%-3%ofalladultcancerstumor,2%-3%ofalladultcancersn nMale:femaleincidenceis3:1Male:femaleincidenceis3:1n nIncidenceisgreatestinthoseover50Incidenceisgreatestinthoseover50years,andincreaseswithageyears,andincreaseswithagen nRiskfactors:smokers,ex
45、posuretoRiskfactors:smokers,exposuretocadmium,geneticfactors(VHLgene,TFE3cadmium,geneticfactors(VHLgene,TFE3fusiongene)fusiongene)CTRenalcellcarcinomaRenalcellcarcinomaRenalcellcarcinomainvadeintotherenalveinRenalcellcarcinoma(clearcelltype)Renalcellcarcinoma(clearcelltype)Papillary renal cell carci
46、nomachromophobe renal cell carcinomaKeyfactsrenalcellcarcinoman nCommonpresentingsymptomsincludeCommonpresentingsymptomsincludepainlesshematuriapainlesshematuria,loinpain,loinmass,loinpain,loinmassn nOccasionalpresentingsymptomsincludeOccasionalpresentingsymptomsincludebonemetastasis,pulmonarymetast
47、asis,bonemetastasis,pulmonarymetastasis,brainmetastasis,paraneoplasticsyndromebrainmetastasis,paraneoplasticsyndrome(hypercalcemia,hypertension,Cushing(hypercalcemia,hypertension,Cushingsyndrome)syndrome)Keyfactsrenalcellcarcinoman nLocalspreadthroughrenalcapsuleintoLocalspreadthroughrenalcapsuleint
48、operinephriticfattissueperinephriticfattissuen nLymphaticspreadtopara-aorticandotherLymphaticspreadtopara-aorticandothernodesnodesn nBloodstreamspreadtolungs,bone,brain,Bloodstreamspreadtolungs,bone,brain,liverlivern nPrognosisdependsonstageatPrognosisdependsonstageatpresentationpresentationWilmstum
49、or(Nephroblastoma)CommonmalignanttumorsofchildhoodAbdominalenlargementGeneticdefectsonchromosome11WilmstumorAngiomyolipoma Angiomyolipoma MetastaticcarcinomaofthekidneyQuestionsn nListfivekindsofdiseasesofunilateralenlargementofthekidney.n nWhatarethecausesofurinarytractobstruction?Tumorsoftheloweru
50、rinarytractn nMosttumorsofthelowerurinarytractarisefromtransitional-cellepithelium（urothelium)Urothelial carcinomaofthebladderUrothelialcarcinomaoftheureterIntravenouspyelogram(IVP)CarcinomaofthebladderCarcinomaofrenalpelvisUrothelialcarcinomaofpelvisKeyfactsWHOclassification:n nUrothelialpapilloman
51、 nurothelialneoplasmoflowmalignantpotentialn npapillaryurothelialcarcinoma,lowgraden npapillaryurothelialcarcinoma,highgraden ninvasiveurothelialcarcinoma,lowgraden ninvasiveurothelialcarcinoma,highgradeKeyfactsn nCommonpresentingsymptomsispainlesshematurian nIndicationsofbladderandurethralirritatio
52、n(dysuria,urgency,frequencyofmicturition)n nOutflowobstructionn nPrognosisdependsonstageatpresentation,recuriscommonOutlinen nGlomerulonephritis(GN)n nTubulointerstitialnephritisn nUrinaryoutflowobstructionn nTumorsofurinarysystemn nProstateDisease,TestisandPenisTumorn nProstatitisn nHyperplasia of
53、the prostate n nCarcinoma of the prostate ProstateProstatitisClinical manifestationn nEvidenceofsystemicinfection(chills,Evidenceofsystemicinfection(chills,fever,malaise)fever,malaise)n nLocalpainLocalpainn nIndicationsofurethralirritation(Indicationsofurethralirritation(dysuria,urgency,frequencyofd
54、ysuria,urgency,frequencyofmicturition)micturition)Hyperplasia of the prostateHyperplasia of the prostateClinical manifestationnSigns and symptoms of urinary tract obstructionnDysuria, urinary frequency, nocturia increasednUrinary retention, bladder expansionnUrinary tract infections, hydronephrosiso
55、bstructionwithbladderhypertrophyandformationofthestoneCarcinoma of the prostateProstatic intraepithelial neoplasiaProstatic intraepithelial neoplasia， PINPINCarcinoma of the prostateCarcinoma of the prostateCarcinoma of the prostate: Gleason gradingCarcinoma of the prostate: Gleason gradingProstate
56、carcinoma with bone metastasisProstate specific antigen, PSATreatment n nProstatectomyn nLower androgen levelsn nOrchiectomyn nEstrogenTesticular tumorn nGerm cell tumorn nSex cord stroma tumorTesticular seminomaTesticular seminomaTesticular seminomaTesticular teratomaMature teratomaMature teratoma(
57、Dermoid cyst)Mature teratomaImmature teratomaClinical features of germ cell tumorn nYoungageofonsetYoungageofonsetn nImmatureteratomaImmatureteratoma TeratogeniccancerTeratogeniccancern nRapidprogressionRapidprogressionn nChemotherapyandradiotherapyareeffectiveChemotherapyandradiotherapyareeffective
58、Squamous cell carcinoma of the penisSquamous cell carcinoma of the penisSquamouscellcarcinomaOutlinen nGlomerulonephritis(GN)n nTubulointerstitialnephritisn nUrinaryoutflowobstructionn nTumorsofurinarysystemn nProstateDisease,TestisandPenisTumorSuggestedreadingCasestudyn nA57-year-oldmanwhopresentst
59、ohisA57-year-oldmanwhopresentstohisfamilydoctorcomplainingofadraggingfamilydoctorcomplainingofadraggingsensationinhisleftloin.Onquestioning,sensationinhisleftloin.Onquestioning,headmitstohavinghadintermittentheadmitstohavinghadintermittentpainlesshematuriaforthreeweeks.painlesshematuriaforthreeweeks
60、.Followingreferraltoaurologicalsurgeon,Followingreferraltoaurologicalsurgeon,investigationrevealsalargemassinvestigationrevealsalargemassreplacingtheleftkidney.Heundergoesareplacingtheleftkidney.Heundergoesaleftnephroectomyfromwhichhemakesaleftnephroectomyfromwhichhemakesagoodrecovery.goodrecovery.Q
61、uestionsn nWhatisthemostlikelydiagnosis?ThemostlikelydiagnosisisrenalcellcarcinomaQuestionsn nWhatisthemostcommonhistologicalpatternofthislesionandwhatcausesthisappearance?ThemostcommonpatternisclearcelltypeofRCC.ThecauseisoflipidandglycogenwithinthecytoplasmofneoplasticcellsQuestionsn nWhatfactorsi
62、nthepathologistWhatfactorsinthepathologistsreportsreportwouldhaveaparticularbearingonthewouldhaveaparticularbearingontheprognosisforthispatient?prognosisforthispatient?Thesizeofthetumor,theperinephroticinfiltration,theinvolvementoflymphnodeandtheinvolvementofvessels.Ifthetumorisconfinedwithintherenalcapsule,thereisa70%10-yearsurvival.
