肾小球疾病英语课件

primary glomerular diseases secondary glomerular diseases hereditary glomerular diseases第1页，共84页。Immune mechanismsHumoral Cell-mediatedNon-immune mechanismsInflammationGlomerular diseases第2页，共84页。A.Immune mechanisms (A)deposits of Circulating Immuno-Complex (CIC)circilation antigen+antibody CIC kidney CIC/deposits 第3页，共84页。antigenantigen extrinsicextrinsic drugs-nonhomologous serum,penicillin foodsxenogenic protein pathogenspecific serotypes streptococci,HBV,HCV intrinsicintrinsic nucleus（SLE)cytoplasm（ANCA）cellular membrane antigen of tumor antigen of thyroid 第4页，共84页。Why does CIC deposit in the glomeruli?vLarge area of glomerrular capillaries -more chances to contactvNet structure of CIC -easy to deposit and settle down vClearance dysfunction of mesangial cells,disability of mononuclear macrophage,component or function defect of complements Decrease clearance of CIC 第5页，共84页。(B)in situ Immunocomplex 1.Native renal antigen glomerular basement membrane +anti-glomerular basement membrane antibody (anti-glomerular basement membrane glomerulonephritis)2.Antigens trapped or planted DNA+anti-DNA antibody (Lupus Nephritis)第6页，共84页。Balance between the deposit and clearance of IC determines the situation of the diseasesvPersistence of antigenvClearance dysfunction of mesangial cellsvdisability of mononuclear macrophagevcomponent or function defect of complements IC deposit clearance第7页，共84页。B.Cell-mediated immune mechanisms minimal change glomerulopathy?第8页，共84页。C.Non immune mechanismsglomerular hypertensionhyperlipidemia(LDL-Cho)advanced glycosylation end products (protein)glomerulosclerosis第9页，共84页。InflammationvMediators of inflammation A group of molecules which act as mediators of inflammation and complicated biological functionvOrigin of inflammation mediators in kidneyExtrinsic Cells in kidneyinfiltrative neutrophil,lymphocyte,mononuclear macrophage,platelet Intrinsic cells in kidneyMesangial cells,tubular cells,endothelial cells第10页，共84页。LOGO Mediators of Mediators of inflammation inflammation -active oxygen and -active oxygen and active nitrogenactive nitrogen -lipids -lipids -complements -complements -cytokines -cytokines -chemotatic factors -chemotatic factors -adhesion molecules -adhesion molecules -growth factors -growth factors -vasoactive substances -vasoactive substances第11页，共84页。To arouse or promote To arouse or promote -proliferation of cells -proliferation of cells -accumulation of extracellular matrix -accumulation of extracellular matrix -changes of histological structure -changes of histological structure -expression of immunomodulating -expression of immunomodulating molecules and adhension molecules molecules and adhension molecules Effects of the inflammation mediatorsEffects of the inflammation mediators第12页，共84页。Mechanisms of Primary GN Mechanisms of Primary GNimmune non-immune inflammationInflammatory cellsExtrinsic cells Intrinsic cells neutrophil,lymphcyte mesangial cells mononuclear macrophage epithelial cells platelet,tubular cells endothelial cellsInflammation mediators cytokines TNF,IL-1 growth factors TGF,PDGF chemotatic factors MCP-1,IL-8 complements,vasoactive substances active oxygen and active nitrogenCoagulation and fibrolysis system,enzymeGlomerular injuries Essential in Essential in the initiationthe initiationEssential in the Essential in the progressive periodprogressive period第13页，共84页。Sites of pathological changesMesangium Mesangial cell Mesangial matrixBasement membranePodocyteFoot processEndothelial cell第14页，共84页。Pathological changesvLM Mesangial cells,matrix of mesangiumEpithelial cellsEndothelial cellsBasement membraneLoops of glomerulivEM Foot processBasement membraneHyperplasy of mesangium (electron-dense deposits)vIF Sites,appearances and types of the deposit(Ig or C)第15页，共84页。Basical changesProliferationFibrosis and sclerosisNecrosisInfiltration of inflammatory cells第16页，共84页。Extents of Injuries primary GN glomerular injuriesonly or dominating changes secondary GN glomerular injuries a part of systematic diseases diffuse impaired glomeruli50%focal impaired glomeruli 50%segmental impaired capillary loops of a glomerule 50%第17页，共84页。Pathological types of primary GNvMinimal change glomerulonephritisvFocal segmental lesionsvDiffuse glomerulonephritisvUnclassified glomerulonephritis第18页，共84页。1.Minor Lesions of glomeruliNo specific lesionsLMmild proliferation of mesangial cells and accumulation of ECMSvminimal change disease，MCDvmild mesangial proliferative GNvrecovery stage of endocapillary GNvothers第19页，共84页。2.Focal and Segmental Lesions1)focal and segmental proliferative glomerulonephritis 2)focal and segmental glomerulosclerosis第20页，共84页。3.3.Diffusive glomerulonephritis(1)membranous nephropathy MN (lesions in GBM)第21页，共84页。(2)proliferative glomerulonephritisvmesangial proliferative GN (lesions in mesangium)IgA nephropathyNon-IgA nephropathydomonating IgG deposit IgM nephropathy第22页，共84页。endocapillary proliferative GN (lesions in mesangium&endothelial cells)第23页，共84页。vmesangiocapillary GN or membranoproliferative GN (lesions in mesangium&GBM)vdense desposit GN (electron-dense deposits)第24页，共84页。Characters of lesions in GN Proliferative changesProliferative changesProliferative changesMsPGNMsPGNMsPGNIgANIgANIgANIgMNIgMNIgMNOthersOthersOthersIncluding segmental proliferative Including segmental proliferative Including segmental proliferative GNGNGNMmPGNMmPGNMmPGNCrescentic GNCrescentic GNCrescentic GNEndocapillary proliferative GNEndocapillary proliferative GNNon-proliferative changesNon-proliferative changesNon-proliferative changesFSGSFSGSFSGSMCDMCDMCDMNMNMN第25页，共84页。Proliferation of mesangium can presents in varied types of GNProliferation and subsequent stiffness of mesangium may be the results of varied types of GNFSGS primary-later-phase of the disease itselfsecondary-later-phase of other types of GNCrescents can presents in different types of GN第26页，共84页。LOGOClinical Clinical manifestationsmanifestations第27页，共84页。filtration barrierproperties charge-size-selective selective Selective albumin impaired normalproteinuria (moderate MW molecules)Non-selective albumin&proteinuria high MW proteins impaired impaired*Mixed proteinuria:moderate/high MW or moderate/low MW;glomerular&tubular proteinuris第28页，共84页。quantityMild 3.5g/d或50mg/kg/d第29页，共84页。hematuria RBC 3个/HP(fresh,10 ml sample,1500rmp centrifuge for 5 min,sediment observation)gross hematuriaRed color of urine,1ml blood/1L urine第30页，共84页。hematuria RBC from glomerulisqueezing through GBM dismorphic RBCPhase-contrastmicroscopydismorphic RBC50 Hypothesis:glomerular bleedingdismorphic RBC70%Final diagnosis:glomerular bleeding Urinary RBC volume Urinary RBC volume distribution curvedistribution curve dissymmetry curvedissymmetry curve MCV MCV of urinary RBCthat of urinary RBC 3.5g/d 2.hypoalbuminemia 30g/L 3.edema 4.hyperlipidemia 1+2-essential第35页，共84页。severe edemahyperlipidemiahypoalbuminemiaLarge-amount proteinuriaCenter keyEssential for diagnosis第36页，共84页。Intake of protein Ingestion from GIsynthesis in liverlost through urineNSconsumptionMechanisms of hypoalbuminemia第37页，共84页。第38页，共84页。Linkage of clinical manifestation and pathological changes(1)Pathological proliferative non-proliferativechanges MsPGN MCD MmPGN MN*Endocapillary PGN FSGS Crescentic GNClinical hematuria proteinuria certain certain,sometimesManifestation nephritis syndrome nephrotic syndrome proteinuria hematuria possible occasional*第39页，共84页。Linkage of clinical manifestation and pathological changes(2)clinical pathological AGN endocapillary PGN possible NS RPGN crescentic GN possible NS CGN nephritis syndrome MsPGN 2 MmPGN 2 nephritis syndrome FSGS 2+nephrotic syndrome MN2 NS MCD 1 第40页，共84页。Acute Glomerulonephritis第41页，共84页。EtiologyStreptococcus -hemolytic streptococcus,group A,type XII,nephritogenic strainsantigencomponents of cytoplasm&membranefrequently CIC,sometimes planted antigenOthersother bacteria,such as staphylococcus epidermidisvirusesparasites第42页，共84页。Pathological changes Endocapillary Proliferative GN Acute phase Proliferation of endothelial&mesangium Recovery phase Only mesangium proliferation,sometimes minor lesion 第43页，共84页。Clinical Manifestation1.Epidemiology:primarily children,sometimes adults&the aged2.Preliminary infectionfrequently tonsillitis,upper respiratory infectionLatent period:1-3 woccasionally skin infectionLatent period:longer,but less than 4w第44页，共84页。3.Nephritis syndrome(1)hematuria 100%，40%are gross hematuria(2)proteinuria frequent，90%(4)hypertension 80%(5)renal failure mild,acute renal failure第45页，共84页。4.Laboratory findings(1)acute phase of infection of Strep.elevated ASO titer(some Strep.No hemolysin O)only the marker of infection,not nephritis(2)acute phase of immune reactionsserum C3&total complements,return to normal within 8wblood CIC 第46页，共84页。Natural Historyvedema and hypertension disappear in one monthvhematuria,proteinuriausually reduce in one month,resolve within 2 to 3 monthssome resolve within 6 to 12 monthsvC3return to normal in two months第47页，共84页。DiagnosisPointsvpreliminary infection&latent periodvacute onsetvsurely hematuria,frequently edema and hypertensionvASO ,C3 dynamic changevSelf-limitation 第48页，共84页。Differential DiagnosisDiseases presented with acute nephritis syndromev GN secondary to infection of other pathogensother bacteria,viruses(Varicella-zoster virus,EB,influenza virus)Climax of infection or within 5 daysMild abnormal of urine examinationHypertension and edema are unusual Normal blood complement level 第49页，共84页。v rapidly progressive GNv CGNv systemic diseases lupus nephritis Schnlein-Henoch purpura第50页，共84页。Indications of kidney biopsyvOligouria 1w，except ECBV insufficient,urinary tract obstruction,etcvProgressive renal failurevUnresolved in 2 monthsvuntypical manifestation,or with nephrotic syndrome第51页，共84页。Treatment1.Supportive treatment Rest Food&waterRestrictive intake ofNaCl 5 g/dif moderate to severe edema or hypertensionWaterif decreased urine volume ProteinRenal failure,but not dialysis yet第52页，共84页。2.Treatment of infectionPenicilin for 2 wTonsillectomy if recurrent attacks of tonsillitistonsillitis1)patients condition is stable,Upro1g/d,URBC 10/HP2)Penicilin for 2 wks before and after the surgery3.Symptomatic treatmentDiuresisAntihypertensionDialysis第53页，共84页。Prognosis hematuria,proteinuriausually reduce in one month,resolve within 2 to 3 monthssome resolve within 6 to 12 months 1%ARF Death 6%-18%CGN?第54页，共84页。Rapidly progressive glomerulonephritisRPGN Rapidly progressive nephritis syndromeSome induced by respiratory infectionAcute onset,rapidly progressiveRenal failure within a few weeks to a few months 第55页，共84页。1.primary RPGN Crescentic GN2.other primary GN other pathological changes with lots of crescents3.secondary RPGN SLE,SHP,etc第56页，共84页。RPGN Type I Type II Type III anti-GBM IC Pauci-immuneIF linear GBM Granular GBM （-）deposits&mesangium deposits anti-GBM AB（+）C3、CIC 70%-80%small vessel vasculitis ANCA（+）the young&the middle-aged the middle-aged middle aged&aged&aged Most frequently in China第57页，共84页。DiagnosisvAcute onsetvRapidly progressivevRenal failure within a few weeks to a few monthsvAcute renal failure Chronic renal failure第58页，共84页。LOGODifferential Diagnosis Rapidly progressive nephritis syndrome not primary RPGN -other primary GN AGN,IgAN,etc -secondary GN Goodpasture Syndrome,LN,SHP *accompanied by crescentic GN *severe pathological changes 第59页，共84页。Diseases with ARFvATNvAIN -definite etiology -obsolete proteinuria and hematuria -specific manifestation ATNlarge quantity of renal tubular epithelial cells in urine AINhypersensitiveness(rashes,fever,arthralgia)第60页，共84页。Treatment EARLY!Aim to humoral immune mechanisms 1.plasmapheresis discard the antibodies plasm exchange immoadsorption type I,III 2.drugs glucocorticoid+cytotoxic drugs MP0.5-1.0g/d3，repeat if necessary CTX type II,III第61页，共84页。symptomatic treatment v renal failurebalance of fluid,electrolytes and acid-basedialysisv infectionv hypertension第62页，共84页。Prognosis Hardly relieve mostCRF or deathRisk factors Type I-worst,II-worse,III-bad Treatment not progressive&prompt Age the aged 第63页，共84页。Chronic GlomerulonephritisManifestation chronic nephritis syndromePathological changes except MCD,MmPGN,Crescentic GN第64页，共84页。Clinical manifestation 1.age any age,frequently young 2.preliminary infection upper respiratory tract,intestinal tract latent period 1 wk 3.nephritis syndrome Hematuria,proteinuria,edemaHypertension,renal failureuremia第65页，共84页。4.Prognosis factors (1)pathological properties (2)treatment (3)hypertension (4)infection,prerenal factors (hypotension etc)(5)nephrotoxic drugs第66页，共84页。Points of Diagnosisv chronic onsetv proteinuria and/or hematuriav protracted and progressive Differential DiagnosisCGN第67页，共84页。1.AGN AGN CGN age children young&middle-aged preliminary infection frequently sometimes latent period 1-3w 1w onset acute chronic,insidious hematuria 100%sometimes no edema frequently sometimes no hypertension frequently sometimes no ASO frequently normal blood C3 frequently,persistent/normal return within 8wks prognosis resolved within 1yr protracted and progressive pathology MmPGN/MsPGN 第68页，共84页。2.Essential hypertensive nephrosclerosis EHT CGNfirst present hypertension abnormal urinefunction injury in advance tubule glomerulehematuria occasionally frequentlynephrotic proteinuria occasionally frequentlysystemic hypertension manifestationheart,eyeground compared with kidney equal milder pathology arteriolar sclerosis 第69页，共84页。3.secondary GN SLE (1)systemic presentation (2)immune abnormolity(C,self-AB)(3)pathological changes SHP (1)purpura (2)stomach,joint第70页，共84页。Chronic pyelonephritis CPN CGN mechanisms infection immunesites pelvis,calices,tubule glomerulepresents of infection +Upro excretive/tubular glomerularURBC non-glomerular glomerularhypertension infrequently frequentlyedema infrequently frequentlykidney lesions tubule glomeruledysmorphosis one side two side第71页，共84页。TreatmentTarget inhibit immune reaction halt the progression of disease 1.restrictive intake of protein dialation of afferent glomerular arteriole pressure in glomeruli Upro postpone glomerulosclerosis ACEI/ARB第73页，共84页。3.anti-platelet 4.immunosupression 第74页，共84页。Clinical manifestation 1.Characteristics (1)large quantity of Upro (2)severe edema (3)hypoalbuminemia (4)hyperlipidemia Nephrotic Syndrome第75页，共84页。2.Others (1)thrombosis&embolism renal veins or inferior vena cava 25%(2)infection (3)acute renal failureBlood volumeperfusion of kidneys ischemia of kidneys,tubule necrosisSevere glomerular lesionscrescent formationSevere proliferation of mesangiumNecrosis of capillary loopsNephrotoxic drugsidiopathetic 第76页，共84页。1.among varied types of pathology 2.between secondary GN（1）SLE（2）SHP（3）DN history,hematuria,pathological changes（4）amyloidosis history of chronic infection,systemic lesions(heart,liver,GI,tongue),pathological changes(kidney,tongue,rectum)（5）MM Middle-aged/aged,ostalgia,osteonecrosis(X-ray,isotope scanning),abnormal protein(blood single-peak protein,blood and urine light chain protein,urine BJ protein)Diagnosis&Differential Diagnosis第77页，共84页。1.Supportive treatment 1.rest 2.Food and water (1)water&sodium restriction when with severe edema (2)protein 1-1.2g/kg/d (3)lipid restriction when with hypoalbuminemia (4)energy 30-35 Kal/kg/dTREATMENT第78页，共84页。2.symptomatic treatment 1.diuresis osmotic diuretics plasma colloid osmotic pressure tubule fluid osmotic pressure fluid transmit from tissue readsorption of water space to blood vessels blood volume diuretics mannitol,dextran,albumindiuresis第79页，共84页。3.Major treatment 1.glucocorticoid mechanisms(1)immuosupression (2)anti-inflammation principles(1)sufficient dose when initiation 0.8-1.2g/kg/d reduce 2wks after Upro is negative *if Upro doesnt reduced apparently in 8-12wksineffective (2)reduce the dose slowly 10%/2-3wks (3)sustaining treatment minimal dose:10-15mg/d，6m-1y 第80页，共84页。Sensitivity of glucocorticoid 1mg/kg/d 8w negative Upro positive relapse when reduce to some dosage sensitivedependentineffective第81页，共84页。2.immunosuppressive agents cytotoxic drugs alkylating agentCTX,chlormethine,CB1348 inhibit duplication of DNA Aza,MMF inhibit synthesis of RNA inhibit proliferation of B lymphocyte CyA inhibit synthesis of L-2 inhibit proliferation of T lymphocyte第82页，共84页。indications glucocorticoid dependent or ineffective glucocorticoid untolerated第83页，共84页。4.Treatment of complications anticoagulation,thrombolysis anti-infection balance of electrolyte 第84页，共84页。