腎小球疾病八年制

腎小球疾病八年制第1頁outlineAnatomyandfunctionGeneralpathogenesisClinicalsyndromesandpresentationSpecificglomerulardiseases第2頁Anatomyandfunction

第3頁Anatomy第4頁AnatomyRenalFunctionRemovewastesMaintainhomeostasisSecreteEPO第5頁Anatomy-nephron第6頁第7頁第8頁第9頁GlomerularAnatomyCapillaryLumenEndothelialcellGlomerularbasementmembraneEpithelialcellPodocytes第10頁Structureofnormalglomerularcapillary系膜細(xì)胞系膜基質(zhì)內(nèi)皮細(xì)胞上皮細(xì)胞足突第11頁第12頁第13頁Generalpathogenesis第14頁Whatcausesglomerulardisease?Mostareofimmunologicorigin,andcausedbyimmunecomplexes!第15頁AntibodymediatedGN-

CirculatingImmunecomplexLocation:Mesangialandsub-endothelial第16頁AntibodymediatedGN-

In-situImmunecomplex

Location:GBMsub-epithelial第17頁AntibodymediatedGN-

In-situImmunecomplex

(trappedAg)Location:GBMsub-epithelial第18頁pathogenesis原位免疫復(fù)合物形成循環(huán)免疫復(fù)合物激活T淋巴細(xì)胞補(bǔ)體激活細(xì)胞因子C5b-9C5a,C3a上皮,系膜,內(nèi)皮細(xì)胞巨噬細(xì)胞多種核細(xì)胞,血小板系膜細(xì)胞氧化應(yīng)激,蛋白酶,促凝GlomerularDisease第19頁GlomerularFiltrationBarrier第20頁GlomerularFiltrationBarrierInjuryFusionoffootprocess:ProteinuriaGBMInjury:Hematuria/Proteinuria第21頁ClassificationofGlomerularDiseaseEtiologyPathologyClinicalFeatures第22頁Clinicalsyndromesandpresentation

第23頁CharacteristicsofGlomerularDiseasesParameterGlomerularTubulointerstitialProteinuriaMWofProteinRenalmorphologyRBCMorphologyMassive>++>1.5~2.0g/dLarge/Medium/SmallSymmetrydysmorphicSmallamount<2+<1.0g/dSmallAsymmetrynormal第24頁ClinicalsyndromesandpresentationLatentGNNephroticsyndromeAcuteGNRPGNChronicGN鏡下或肉眼血尿蛋白尿畸形紅細(xì)胞,棘型紅細(xì)胞蛋白尿>3.5g/d低蛋白血癥高脂血癥水腫血尿蛋白尿(1-3g/d)ARF水腫高血壓紅細(xì)胞管型急進(jìn)旳腎功能惡化血尿,蛋白尿進(jìn)行性少尿,無尿紅細(xì)胞管型有或無系統(tǒng)癥狀血尿蛋白尿高血壓腎功能減退第25頁Howareglomurulardiseasesdiagnosed?Usuallybyhistory,physicalfindings,Urinalysisandotherlaboratorydata.Occasionallyarenalbiopsymustbeperformed!第26頁RenalBiopsyProcessing第27頁RenalBiopsyProcessing第28頁RenalBiopsyProcessing第29頁RenalBiopsyProcessing第30頁P(yáng)athologyPASMASSONH&EPASM第31頁P(yáng)athologicalclassificationofGN輕微病變性腎小球腎炎minimalchangeglomerulonephritis局灶節(jié)段性病變focalsegmentallesions彌漫性腎小球腎炎diffuseglomerulonephritis膜性腎病membranousnephropathy增生性腎炎proliferativeglomerulone-phritis硬化性腎炎sclerosingglomerulonephritis未分類性腎小球腎炎u(yù)nclassifiedglomerulo-nephritis第32頁增生性腎炎proliferativeglomerulone-phritis

系膜增生性腎小球腎炎mesangialproliferativeGN毛細(xì)血管內(nèi)增生性腎小球腎炎endocapillaryproliferativeGN系膜毛細(xì)血管內(nèi)增生性腎小球腎炎mesan-gialcapillaryGN新月體腎炎crecenticGNPathologicalclassificationofGN第33頁ClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritisChronicglomerularnephritis第34頁第35頁第36頁第37頁Asymptomatichematuria/orproteinuria

LatentnephritisMildchronicGNorrecoveryphaseofacuteGNIsolatedmicroscopichematuria(DysmorphicRBC)IsolatedproteinuriaNoHBP,edemaorAzotemiaTreatmentissimilartochronicGN第38頁CASEI

11year-oldmaleHistory: Intermittenthematuriax1year HxofrecurrentpharyngitisPhysical:tonsillitis

Urinalysis: 15RBC/HPF

1protein RBCcastsLabData:dysmorphicRBC

第39頁H&E第40頁P(yáng)AS第41頁IgA第42頁第43頁ThePatientHasIgAnephropathy!第44頁IgANephropathyMostcommonGNMesangioproliferativeorotherpathologicaltypesPredominentmesangialIgAdepositPersistentorepisodeofhematuriaExacerbateoninfection1/3haveelevatedserumIgA第45頁ClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritisChronicglomerularnephritis第46頁NephroticSyndromeInsidiousonsetManifestationsProteinuria>3.5g/dHypoalbuminemiaalb

<30g/l

EdemaHyperlipidemia第47頁Nephroticsyndrom-etiology(1)PrimaryNephroticsyndrom

minimalchangedisease FSGSmembranousnephropathymembranoproliferativeGNIgAN

第48頁Nephroticsyndrom-etiology(2)SecondaryNephroticsyndrom

Autoimmunity:SLE,Infection:HepatitisBorC,HIVTumor:solidcarcinoma,lymphomaMetabolic:DM,AmyloidosisDrugs:NSAIDS

第49頁Nephroticsyndrom-epidemiology

Children

Yongpeople

OldpeoplePrimary

MCDFSGS,MsGNMNMPGNSecondaryHSPSLEDNHepatitisBHSPTumorInheritedNSHepatitisBMM,AL

第50頁14year-old,male,high-schoolstudentHistory: Nosignificantmedicalhistory Fatiguex3weeks Edemax1weekPhysical: MildgeneralizededemaUrinalysis: 4protein Manyhyalinecasts Fewgranularcasts

NoRBCsorRBCcastsLabData: proteinuria4g/d,alb20g/l,normalrenalfunction,Hepatitis(-),Auto-immunityAb(-)RenalbiopsyCASEII第51頁The

patienthasMinimalchangedisease!第52頁第53頁ElectronMicroscopy:effacementoffootprocesses第54頁Incidence:Etiology:ClinicalFeatures:ClinicalCourse:Lossofnetnegativechargeoncapillarybasementmembrane.Nephroticsyndrome.Prominentproteinuria&edemaNohypertensionSensitivetosteroid,relapsemayoccur.80%ofnephroticsyndromeinchildrenMinimalChangeDiseaseIntroduction第55頁CASEIII65year-old,male,Smokefor40yearsHistory: Fatiguex3months

Coughandchestpainx2months

Facialedemax1weekPhysical: edema,Urinalysis: protein++++

LabData:

proteinuria8g/d,alb24g/l,normalrenalfunction,

Hepatitis(-),Auto-immunityAb(-)第56頁WhyisathoroughClinicalevaluationimportantinpatientswiththenephroticsyndrome!Manysuchpatientshaveanoccultmalignancy!第57頁CASEIIILungCarcinoma第58頁SilverPAS第59頁CASEIIILM-PASM:”spikes”alongtheGBM第60頁CASEIIIIF:IgGdepositionalongGBM第61頁CASEIIIEM:subepithelialelectrondensematerial第62頁It’sClearlyacaseOfcarcinomarelatedMembranousnephropathy!第63頁CASEII-MNCommonlyoccurredinmiddle&old-agedpeopleEtiology：Primary

Secondary：Tumor-related,HepatitisBrelated,Drugs-related

Presentation:HT&Renalfailure,Thrombosis

第64頁MembranousNephropathyIncidence:Etiology:Path:ClinicalCourse:Immunecomplexdisease.Mayassociatedwithcarcinomas,infections,drugs,andheavymetals.SomeadultsdevelopESRD.Diffuse,uniformbasementmembranethickeningwithsubepithelialprojections(“spikes”).

Commonlyoccurredinmiddle&old-agedpeopleIntroduction第65頁HowtotreattheNephroticSyndrome?第66頁P(yáng)athogenesis/ComplicationLiverEdemaHypoalbuminemiaGlominflammation

Proteinuria↑Permeability↑LipoproteinSynthesis↑BloodLipid↑PrimarySecondaryCausesBloodvolume↓ThrombosisCVdisease↑ARFInfectionDevelopment↓第67頁TreatmentofNSLiverEdemaHypoalbuminemiaGlominflammation

Proteinuria↑Permeability↑LipoproteinSynthesis↑BloodLipid↑PrimarySecondaryCausesCausativeTherapySteroid/CTX/CsAACEI/ARBAlbumininfusion?Diuretics第68頁LiverEdemaHypoalbuminemiaGlominflammationProteinuria↑Permeability↑LipoproteinSynthesis↑BloodLipid↑PrimarySecondaryCausesTreatmentofComplicationBloodvolume↓ThrombosisCVdisease↑ARFInfectionAntithromboticAnti-infectionDiuretics/DialysisStatins第69頁0.25mg/kg.dSlowthespeedoftapering1mg/kg.d×8w0.5mg/kg.dTaper5mgperweekHowtouseglucosteroids(1)Maintenancefor1year第70頁0.25mg/kg.dSlowthespeedoftapering1mg/kg.d×8w0.5mg/kg.dTaper5mgperweekHowtouseglucosteroids(2)Maintenancefor1yearSufficientinitialdose第71頁0.25mg/kg.dSlowthespeedoftapering1mg/kg.d×8w0.5mg/kg.dTaper5mgperweekHowtouseglucosteroids(3)Maintenancefor1yearSufficientinitialdoseSlowtapering第72頁0.25mg/kg.dSlowthespeedoftapering1mg/kg.d×8w0.5mg/kg.dTaper5mgperweekHowtouseglucosteroidsMaintenancefor1yearSufficientinitialdoseSlowtaperingLongmaintenance第73頁ClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritisChronicglomerularnephritis第74頁急性腎小球腎炎AcuteGNHistoryofstreptococcusinfection2weeksagoAcuteonsetProminenthematuriaandRBCcastsARF&HTLowC3，for8weeksESRincreased，Anti-DNAseB（＋）第75頁急性腎小球腎炎AcuteGN第76頁急性腎小球腎炎AcuteGN第77頁ClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritis

Chronicglomerularnephritis第78頁RapidprogressiveGNSimilartoacuteGNononsetRapiddeteriorationofrenalfunctionCr↑,OliguriaandobviousmacroscopichematuriaCrescentformation>50%Needaggressivetherapy(Largedoseofsteroidpulsetherapy＋CTX；Plasmaphoresis)第79頁RapidprogressiveGN第80頁RapidprogressiveGN第81頁ClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritisChronicglomerularnephritis

第82頁ChronicglomerulonephritisProteinuria(<3.5g/d)HematuriaHypertens