肾小球疾病(英语)课件

1、 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

2、 kidney CIC/deposits 第3页，共84页。antigen extrinsic drugs-nonhomologous serum, penicillin foodsxenogenic protein pathogenspecific serotypes streptococci, HBV, HCV intrinsic 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?L

3、arge area of glomerrular capillaries -more chances to contactNet structure of CIC -easy to deposit and settle down Clearance 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

4、. 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 sit

5、uation of the diseasesPersistence of antigenClearance dysfunction of mesangial cellsdisability of mononuclear macrophagecomponent 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 mechanismsglomer

6、ular hypertensionhyperlipidemia (LDL- Cho)advanced glycosylation end products (protein) glomerulosclerosis第9页，共84页。InflammationMediators of inflammation A group of molecules which act as mediators of inflammation and complicated biological functionOrigin of inflammation mediators in kidneyExtrinsic

7、Cells in kidneyinfiltrative neutrophil, lymphocyte, mononuclear macrophage , platelet Intrinsic cells in kidneyMesangial cells, tubular cells, endothelial cells第10页，共84页。 Mediators of inflammation - active oxygen and active nitrogen - lipids - complements - cytokines - chemotatic factors - adhesion

8、molecules - growth factors - vasoactive substances第11页，共84页。To arouse or promote - proliferation of cells - accumulation of extracellular matrix - changes of histological structure - expression of immunomodulating molecules and adhension molecules Effects of the inflammation mediators第12页，共84页。 Mech

9、anisms 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 fact

10、ors MCP-1,IL-8 complements, vasoactive substances active oxygen and active nitrogenCoagulation and fibrolysis system, enzymeGlomerular injuries Essential in the initiationEssential in the progressive period第13页，共84页。Sites of pathological changesMesangium Mesangial cell Mesangial matrixBasement membr

11、anePodocyteFoot processEndothelial cell第14页，共84页。Pathological changesLM Mesangial cells, matrix of mesangiumEpithelial cellsEndothelial cellsBasement membraneLoops of glomeruliEM Foot processBasement membraneHyperplasy of mesangium (electron-dense deposits )IF Sites, appearances and types of the dep

12、osit (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% foc

13、al impaired glomeruli 50% segmental impaired capillary loops of a glomerule 50%第17页，共84页。 Pathological types of primary GNMinimal change glomerulonephritisFocal segmental lesionsDiffuse glomerulonephritisUnclassified glomerulonephritis第18页，共84页。Minor Lesions of glomeruliNo specific lesionsLMmild pro

14、liferation of mesangial cells and accumulation of ECMSminimal change disease，MCDmild mesangial proliferative GNrecovery stage of endocapillary GNothers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

15、. Diffusive glomerulonephritis membranous nephropathy MN (lesions in GBM) 第21页，共84页。(2) proliferative glomerulonephritismesangial proliferative GN ( lesions in mesangium)IgA nephropathyNon-IgA nephropathydomonating IgG deposit IgM nephropathy第22页，共84页。endocapillary proliferative GN ( lesions in mesa

16、ngium & endothelial cells)第23页，共84页。mesangiocapillary GN or membranoproliferative GN (lesions in mesangium & GBM)dense desposit GN (electron-dense deposits)第24页，共84页。 Characters of lesions in GN Proliferative changesMsPGNIgANIgMNOthersIncluding segmental proliferative GNMmPGNCrescentic GNEndocapilla

17、ry proliferative GNNon- proliferative changesFSGSMCDMN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

18、 of GNCrescents can presents in different types of GN第26页，共84页。Clinical manifestations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* M

19、ixed 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。 hematur

20、ia RBC from glomerulisqueezing through GBM dismorphic RBCPhase-contrastmicroscopydismorphic RBC50 Hypothesis:glomerular bleedingdismorphic RBC70% Final diagnosis:glomerular bleeding Urinary RBC volume distribution curvedissymmetry curveMCV of urinary RBC 3.5g/d 2. hypoalbuminemia 30g/L 3. edema 4. h

21、yperlipidemia 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 m

22、anifestation 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

23、* 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

24、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 Prolifera

25、tive 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 infectionL

26、atent 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 acute phase of infection of

27、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 Historyedema and hypertension disappear in one monthhematuria, proteinuriausually redu

28、ce in one month, resolve within 2 to 3 monthssome resolve within 6 to 12 monthsC3return to normal in two months第47页，共84页。DiagnosisPointspreliminary infection &latent periodacute onsetsurely hematuria, frequently edema and hypertensionASO , C3 dynamic changeSelf-limitation 第48页，共84页。Differential Diag

29、nosisDiseases presented with acute nephritis syndrome 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 leve

30、l 第49页，共84页。 rapidly progressive GN CGN systemic diseases lupus nephritis Schnlein-Henoch purpura第50页，共84页。Indications of kidney biopsyOligouria 1w，except ECBV insufficient, urinary tract obstruction, etcProgressive renal failureUnresolved in 2 monthsuntypical manifestation, or with nephrotic syndro

31、me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 ton

32、sillitispatients condition is stable, Upro1g/d, URBC 10/HPPenicilin 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%AR

33、F 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 pathologi

34、cal 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 middl

35、e aged & aged & aged Most frequently in China第57页，共84页。DiagnosisAcute onsetRapidly progressiveRenal failure within a few weeks to a few monthsAcute renal failure Chronic renal failure第58页，共84页。Differential Diagnosis Rapidly progressive nephritis syndrome not primary RPGN - other primary GN AGN, IgAN

36、, etc - secondary GN Goodpasture Syndrome, LN, SHP * accompanied by crescentic GN * severe pathological changes 第59页，共84页。Diseases with ARFATNAIN - definite etiology -obsolete proteinuria and hematuria - specific manifestation ATNlarge quantity of renal tubular epithelial cells in urine AINhypersens

37、itiveness (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 treatmen

38、t renal failurebalance of fluid, electrolytes and acid-basedialysis infection 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

39、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。

40、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 Diagnosis chronic onset proteinuria and/or hematuria protracted and progressive Differential DiagnosisCGN第67页，共84页。 1. AGN AGN CGN age c

41、hildren 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 pr

42、ognosis 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 frequentlysys

43、temic 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 me

44、chanisms 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。TreatmentTarge

45、t 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)larg

46、e 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 lesio

47、nscrescent 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-r