肾小球疾病八年制

肾小球疾病八年制outlineAnatomyandfunctionGeneralpathogenesisClinicalsyndromesandpresentationSpecificglomerulardiseasesAnatomyandfunction

AnatomyAnatomyRenalFunctionRemovewastesMaintainhomeostasisSecreteEPOAnatomy-nephronGlomerularAnatomyCapillaryLumenEndothelialcellGlomerularbasementmembraneEpithelialcellPodocytesStructureofnormalglomerularcapillary系膜细胞系膜基质内皮细胞上皮细胞足突GeneralpathogenesisWhatcausesglomerulardisease?Mostareofimmunologicorigin,andcausedbyimmunecomplexes!AntibodymediatedGN-

CirculatingImmunecomplexLocation:Mesangialandsub-endothelialAntibodymediatedGN-

In-situImmunecomplex

Location:GBMsub-epithelialAntibodymediatedGN-

In-situImmunecomplex

(trappedAg)Location:GBMsub-epithelialpathogenesis原位免疫复合物形成循环免疫复合物激活T淋巴细胞补体激活细胞因子C5b-9C5a,C3a上皮,系膜,内皮细胞巨噬细胞多种核细胞,血小板系膜细胞氧化应激,蛋白酶,促凝GlomerularDiseaseGlomerularFiltrationBarrierGlomerularFiltrationBarrierInjuryFusionoffootprocess:ProteinuriaGBMInjury:Hematuria/ProteinuriaClassificationofGlomerularDiseaseEtiologyPathologyClinicalFeaturesClinicalsyndromesandpresentation

CharacteristicsofGlomerularDiseasesParameterGlomerularTubulointerstitialProteinuriaMWofProteinRenalmorphologyRBCMorphologyMassive>++>1.5~2.0g/dLarge/Medium/SmallSymmetrydysmorphicSmallamount<2+<1.0g/dSmallAsymmetrynormalClinicalsyndromesandpresentationLatentGNNephroticsyndromeAcuteGNRPGNChronicGN镜下或肉眼血尿蛋白尿畸形红细胞,棘型红细胞蛋白尿>3.5g/d低蛋白血症高脂血症水肿血尿蛋白尿(1-3g/d)ARF水肿高血压红细胞管型急进旳肾功能恶化血尿,蛋白尿进行性少尿,无尿红细胞管型有或无系统症状血尿蛋白尿高血压肾功能减退Howareglomurulardiseasesdiagnosed?Usuallybyhistory,physicalfindings,Urinalysisandotherlaboratorydata.Occasionallyarenalbiopsymustbeperformed!RenalBiopsyProcessingRenalBiopsyProcessingRenalBiopsyProcessingRenalBiopsyProcessingPathologyPASMASSONH&EPASMPathologicalclassificationofGN轻微病变性肾小球肾炎minimalchangeglomerulonephritis局灶节段性病变focalsegmentallesions弥漫性肾小球肾炎diffuseglomerulonephritis膜性肾病membranousnephropathy增生性肾炎proliferativeglomerulone-phritis硬化性肾炎sclerosingglomerulonephritis未分类性肾小球肾炎unclassifiedglomerulo-nephritis增生性肾炎proliferativeglomerulone-phritis

系膜增生性肾小球肾炎mesangialproliferativeGN毛细血管内增生性肾小球肾炎endocapillaryproliferativeGN系膜毛细血管内增生性肾小球肾炎mesan-gialcapillaryGN新月体肾炎crecenticGNPathologicalclassificationofGNClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritisChronicglomerularnephritisAsymptomatichematuria/orproteinuria

LatentnephritisMildchronicGNorrecoveryphaseofacuteGNIsolatedmicroscopichematuria(DysmorphicRBC)IsolatedproteinuriaNoHBP,edemaorAzotemiaTreatmentissimilartochronicGNCASEI

11year-oldmaleHistory: Intermittenthematuriax1year HxofrecurrentpharyngitisPhysical:tonsillitis

Urinalysis: 15RBC/HPF

1protein RBCcastsLabData:dysmorphicRBC

H&EPASIgAThePatientHasIgAnephropathy!IgANephropathyMostcommonGNMesangioproliferativeorotherpathologicaltypesPredominentmesangialIgAdepositPersistentorepisodeofhematuriaExacerbateoninfection1/3haveelevatedserumIgAClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritisChronicglomerularnephritisNephroticSyndromeInsidiousonsetManifestationsProteinuria>3.5g/dHypoalbuminemiaalb

<30g/l

EdemaHyperlipidemiaNephroticsyndrom-etiology(1)PrimaryNephroticsyndrom

minimalchangedisease FSGSmembranousnephropathymembranoproliferativeGNIgAN

Nephroticsyndrom-etiology(2)SecondaryNephroticsyndrom

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

Nephroticsyndrom-epidemiology

Children

Yongpeople

OldpeoplePrimary

MCDFSGS,MsGNMNMPGNSecondaryHSPSLEDNHepatitisBHSPTumorInheritedNSHepatitisBMM,AL

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

NoRBCsorRBCcastsLabData: proteinuria4g/d,alb20g/l,normalrenalfunction,Hepatitis(-),Auto-immunityAb(-)RenalbiopsyCASEIIThe

patienthasMinimalchangedisease!ElectronMicroscopy:effacementoffootprocessesIncidence:Etiology:ClinicalFeatures:ClinicalCourse:Lossofnetnegativechargeoncapillarybasementmembrane.Nephroticsyndrome.Prominentproteinuria&edemaNohypertensionSensitivetosteroid,relapsemayoccur.80%ofnephroticsyndromeinchildrenMinimalChangeDiseaseCASEIII65year-old,male,Smokefor40yearsHistory: Fatiguex3months

Coughandchestpainx2months

Facialedemax1weekPhysical: edema,Urinalysis: protein++++

LabData:

proteinuria8g/d,alb24g/l,normalrenalfunction,

Hepatitis(-),Auto-immunityAb(-)WhyisathoroughClinicalevaluationimportantinpatientswiththenephroticsyndrome!Manysuchpatientshaveanoccultmalignancy!CASEIIILungCarcinomaSilverPASCASEIIILM-PASM:”spikes”alongtheGBMCASEIIIIF:IgGdepositionalongGBMCASEIIIEM:subepithelialelectrondensematerialIt’sClearlyacaseOfcarcinomarelatedMembranousnephropathy!CASEII-MNCommonlyoccurredinmiddle&old-agedpeopleEtiology：Primary

Secondary：Tumor-related,HepatitisBrelated,Drugs-related

Presentation:HT&Renalfailure,Thrombosis

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

Commonlyoccurredinmiddle&old-agedpeopleHowtotreattheNephroticSyndrome?Pathogenesis/ComplicationLiverEdemaHypoalbuminemiaGlominflammation

Proteinuria↑Permeability↑LipoproteinSynthesis↑BloodLipid↑PrimarySecondaryCausesBloodvolume↓ThrombosisCVdisease↑ARFInfectionDevelopment↓TreatmentofNSLiverEdemaHypoalbuminemiaGlominflammation

Proteinuria↑Permeability↑LipoproteinSynthesis↑BloodLipid↑PrimarySecondaryCausesCausativeTherapySteroid/CTX/CsAACEI/ARBAlbumininfusion?DiureticsLiverEdemaHypoalbuminemiaGlominflammationProteinuria↑Permeability↑LipoproteinSynthesis↑BloodLipid↑PrimarySecondaryCausesTreatmentofComplicationBloodvolume↓ThrombosisCVdisease↑ARFInfectionAntithromboticAnti-infectionDiuretics/DialysisStatins0.25mg/kg.dSlowthespeedoftapering1mg/kg.d×8w0.5mg/kg.dTaper5mgperweekHowtouseglucosteroids(1)Maintenancefor1year0.25mg/kg.dSlowthespeedoftapering1mg/kg.d×8w0.5mg/kg.dTaper5mgperweekHowtouseglucosteroids(2)Maintenancefor1yearSufficientinitialdose0.25mg/kg.dSlowthespeedoftapering1mg/kg.d×8w0.5mg/kg.dTaper5mgperweekHowtouseglucosteroids(3)Maintenancefor1yearSufficientinitialdoseSlowtapering0.25mg/kg.dSlowthespeedoftapering1mg/kg.d×8w0.5mg/kg.dTaper5mgperweekHowtouseglucosteroidsMaintenancefor1yearSufficientinitialdoseSlowtaperingLongmaintenanceClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritisChronicglomerularnephritis急性肾小球肾炎AcuteGNHistoryofstreptococcusinfection2weeksagoAcuteonsetProminenthematuriaandRBCcastsARF&HTLowC3，for8weeksESRincreased，Anti-DNAseB（＋）急性肾小球肾炎AcuteGN急性肾小球肾炎AcuteGNClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritis

ChronicglomerularnephritisRapidprogressiveGNSimilartoacuteGNononsetRapiddeteriorationofrenalfunctionCr↑,OliguriaandobviousmacroscopichematuriaCrescentformation>50%Needaggressivetherapy(Largedoseofsteroidpulsetherapy＋CTX；Plasmaphoresis)RapidprogressiveGNRapidprogressiveGNClinicalsyndromesofglomerulardiseasesAsymptomatichematuria/orproteinuriaNephroticsyndromeAcuteglomerularnephritisRapidlyprogressiveglomerularnephritisChronicglomerularnephritis

ChronicglomerulonephritisProteinuria(<3.5g/d)HematuriaHypertensionEdemaA