丁小强-肾小球疾病

1、肾小球疾病Glomerular Diseases1Pathological changes - glomerular injuryClinical manifestations -proteinuria / hematuriaA group of diseases Complicated causes & mechanismsVarious clinical manifestationsDifferent prognosisMultiple treatment2 primary glomerular diseases secondary glomerular diseases heredita

2、ry glomerular diseases3Immune mechanismsHumoral Cell-mediatedNon-immune mechanismsInflammationGlomerular diseases4A. Immune mechanisms (A)deposits of Circulating Immuno-Complex (CIC) circilation antigen+ antibody CIC kidney CIC/deposits 5antigen extrinsic drugs-nonhomologous serum, penicillin foodsx

3、enogenic protein pathogenspecific serotypes streptococci, HBV, HCV intrinsic nucleus（SLE) cytoplasm（ANCA） cellular membrane antigen of tumor antigen of thyroid 6Why does CIC deposit in the glomeruli?Large area of glomerrular capillaries -more chances to contactNet structure of CIC -easy to deposit a

4、nd settle down Clearance dysfunction of mesangial cells, disability of mononuclear macrophage, component or function defect of complements Decrease clearance of CIC 7(B)in situ Immunocomplex 1. Native renal antigen glomerular basement membrane + anti- glomerular basement membrane antibody (anti- glo

5、merular basement membrane glomerulonephritis) 2. Antigens trapped or planted DNA+ anti-DNA antibody (Lupus Nephritis)8Balance between the deposit and clearance of IC determines the situation of the diseasesPersistence of antigenClearance dysfunction of mesangial cellsdisability of mononuclear macrop

6、hagecomponent or function defect of complements IC deposit clearance9 B. Cell-mediated immune mechanisms minimal change glomerulopathy ? 10C. Non immune mechanismsglomerular hypertensionhyperlipidemia (LDL- Cho)advanced glycosylation end products (protein) glomerulosclerosis11InflammationMediators o

7、f inflammation A group of molecules which act as mediators of inflammation and complicated biological functionOrigin of inflammation mediators in kidneyExtrinsic Cells in kidneyinfiltrative neutrophil, lymphocyte, mononuclear macrophage , platelet Intrinsic cells in kidneyMesangial cells, tubular ce

8、lls, endothelial cells12 Mediators of inflammation - active oxygen and active nitrogen - lipids - complements - cytokines - chemotatic factors - adhesion molecules - growth factors - vasoactive substances13To arouse or promote - proliferation of cells - accumulation of extracellular matrix - changes

9、 of histological structure - expression of immunomodulating molecules and adhension molecules Effects of the inflammation mediators14 Mechanisms of Primary GNimmune non-immune inflammationInflammatory cellsExtrinsic cells Intrinsic cells neutrophil, lymphcyte mesangial cells mononuclear macrophage e

10、pithelial 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 the i

11、nitiationEssential in the progressive period15immune non-immune initiation end stage Primary GN16Sites of pathological changesMesangium Mesangial cell Mesangial matrixBasement membranePodocyteFoot processEndothelial cell17The peripheral portion of a glomerular lobule18Pathological changesLM Mesangia

12、l cells, matrix of mesangiumEpithelial cellsEndothelial cellsBasement membraneLoops of glomeruliEM Foot processBasement membraneHyperplasy of mesangium (electron-dense deposits )IF Sites, appearances and types of the deposit (Ig or C)19Basical changesProliferationFibrosis and sclerosisNecrosisInfilt

13、ration of inflammatory cells20Extents 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%21 Pathological ty

14、pes of primary GNMinimal change glomerulonephritisFocal segmental lesionsDiffuse glomerulonephritisUnclassified glomerulonephritis22Minor Lesions of glomeruliNo specific lesionsLMmild proliferation of mesangial cells and accumulation of ECMSminimal change disease，MCDmild mesangial proliferative GNre

15、covery stage of endocapillary GNothers23MCD (left)normal ,(right) fusion & effacement of foot processes 242. Focal and Segmental Lesions1) focal and segmental proliferative glomerulonephritis 2) focal and segmental glomerulosclerosis25segmental glomerulonephritis 26 3. Diffusive glomerulonephritis m

16、embranous nephropathy MN (lesions in GBM) 27MN (left) normal,(right)subepithelial deposits of IC(D), thickening of GBM,formation of spikes (S), fusion of foot processes28(2) proliferative glomerulonephritismesangial proliferative GN ( lesions in mesangium)IgA nephropathyNon-IgA nephropathydomonating

17、 IgG deposit IgM nephropathy29MsPGN (left)normal, (right)proliferation of mesangial cells and matrix and electron-dense deposits (D)30endocapillary proliferative GN ( lesions in mesangium & endothelial cells)31endocapillary proliferative GN (left) normal, (right) endothelial(E) & mesangial(M) cell p

18、roliferation and subepithelial humplike dense deposits(D)32mesangiocapillary GN or membranoproliferative GN (lesions in mesangium & GBM)dense desposit GN (electron-dense deposits)33MmPGN (left) normal, (right) proliferation of mesngium (M),electron-dense deposits(D), and subendothelial mesangial cyt

19、oplasm interposition（I）34 crescentic GN or extracapillary GN 35Crescentic GN (left) normal, (right) splitting of GBM, leakage of fibrin(F), proliferation of epithelial cells,(E), infiltration of mononuclear macrophages(P), formation of crescents36(3) sclerosing GN37 4.unclassified glomerulonephritis

20、38 Characters of lesions in GN Proliferative changesMsPGNIgANIgMNOthersIncluding segmental proliferative GNMmPGNCrescentic GNEndocapillary proliferative GNNon- proliferative changesFSGSMCDMN39Proliferation of mesangium can presents in varied types of GNProliferation and subsequent stiffness of mesan

21、gium 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 GN40Clinical manifestationsProteinuriaUrinary protein test positiveUrinary protein excretion rate 150mg/d41Charge barrier

22、 of glomerule1.Epithelial cells 2. GBM 3. Endothelial cells 4. Filtrated substances42Filtration barrier43 mechanisms of production of proteinuriaModerate/high MW moleculesmechanismsmolecular wieghtsfiltration from GlomeruliReadsorption from tululesLow MW moleculesGlomerular proteinuriaTubular protei

23、nuria44 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 proteinuris45qu

24、antityMild 3.5g/d或50mg/kg/d46hematuria RBC 3个/HP (fresh, 10 ml sample, 1500rmp centrifuge for 5 min, sediment observation) gross hematuriaRed color of urine, 1ml blood /1L urine47 hematuria RBC from glomerulisqueezing through GBM dismorphic RBCPhase-contrastmicroscopydismorphic RBC50 Hypothesis:glom

25、erular 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. hyperlipidemia 1+2 -essential52severe edemahyperlipidemiahypoalbuminemiaLarge-amount proteinuriaCenter keyEssentia

26、l for diagnosis53Intake of protein Ingestion from GIsynthesis in liverlost through urineNSconsumptionMechanisms of hypoalbuminemia5455Linkage of clinical manifestation and pathological changes (1)Pathological proliferative non-proliferativechanges MsPGN MCD MmPGN MN* Endocapillary PGN FSGS Crescenti

27、c GNClinical hematuria proteinuria certain certain, sometimesManifestation nephritis syndrome nephrotic syndrome proteinuria hematuria possible occasional * 56Linkage of clinical manifestation and pathological changes (2) clinical pathological AGN endocapillary PGN possible NS RPGN crescentic GN pos

28、sible NS CGN nephritis syndrome MsPGN 2 MmPGN 2 nephritis syndrome FSGS 2 +nephrotic syndrome MN2 NS MCD 1 57Acute Glomerulonephritis58EtiologyStreptococcus -hemolytic streptococcus, group A, type XII, nephritogenic strainsantigencomponents of cytoplasm & membranefrequently CIC, sometimes planted an

29、tigenOthersother bacteria, such as staphylococcus epidermidisvirusesparasites59Pathological changes Endocapillary Proliferative GN Acute phase Proliferation of endothelial & mesangium Recovery phase Only mesangium proliferation, sometimes minor lesion 60 Clinical Manifestation1.Epidemiology: primari

30、ly children, sometimes adults & the aged2. Preliminary infectionfrequently tonsillitis,upper respiratory infectionLatent period:1-3 woccasionally skin infectionLatent period:longer,but less than 4w613.Nephritis syndrome(1)hematuria 100%，40% are gross hematuria(2)proteinuria frequent，90%(4)hypertensi

31、on 80%(5)renal failure mild,acute renal failure624.Laboratory findings 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 63Nat

32、ural Historyedema and hypertension disappear in one monthhematuria, proteinuriausually reduce in one month, resolve within 2 to 3 monthssome resolve within 6 to 12 monthsC3return to normal in two months64DiagnosisPointspreliminary infection &latent periodacute onsetsurely hematuria, frequently edema

33、 and hypertensionASO , C3 dynamic changeSelf-limitation 65Differential DiagnosisDiseases 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

34、 examinationHypertension and edema are unusual Normal blood complement level 66 rapidly progressive GN CGN systemic diseases lupus nephritis Schnlein-Henoch purpura67Indications of kidney biopsyOligouria 1w，except ECBV insufficient, urinary tract obstruction, etcProgressive renal failureUnresolved i

35、n 2 monthsuntypical manifestation, or with nephrotic syndrome68Treatment1.Supportive treatment Rest Food & waterRestrictive intake ofNaCl 5 g/dif moderate to severe edema or hypertensionWaterif decreased urine volume ProteinRenal failure, but not dialysis yet692.Treatment of infectionPenicilin for 2

36、 wTonsillectomy if recurrent attacks of tonsillitispatients condition is stable, Upro1g/d, URBC 10/HPPenicilin for 2 wks before and after the surgery3. Symptomatic treatmentDiuresisAntihypertensionDialysis70Prognosis hematuria, proteinuriausually reduce in one month, resolve within 2 to 3 monthssome

37、 resolve within 6 to 12 months 1%ARF Death 6%-18% CGN?71Rapidly progressive glomerulonephritisRPGN Rapidly progressive nephritis syndromeSome induced by respiratory infectionAcute onset, rapidly progressiveRenal failure within a few weeks to a few months 721.primary RPGN Crescentic GN2.other primary

38、 GN other pathological changes with lots of crescents3.secondary RPGN SLE, SHP, etc73 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

39、-aged middle aged & aged & aged Most frequently in China74DiagnosisAcute onsetRapidly progressiveRenal failure within a few weeks to a few monthsAcute renal failure Chronic renal failure75Differential Diagnosis Rapidly progressive nephritis syndrome not primary RPGN - other primary GN AGN, IgAN, etc

40、 - secondary GN Goodpasture Syndrome, LN, SHP * accompanied by crescentic GN * severe pathological changes 76Diseases with ARFATNAIN - definite etiology -obsolete proteinuria and hematuria - specific manifestation ATNlarge quantity of renal tubular epithelial cells in urine AINhypersensitiveness (ra

41、shes, fever, arthralgia) 77Treatment 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, III78symptomatic treatment renal failurebalance of flu

42、id, electrolytes and acid-basedialysis infection hypertension79Prognosis Hardly relieve mostCRF or deathRisk factors Type I-worst,II-worse,III-bad Treatment not progressive & prompt Age the aged 80Chronic GlomerulonephritisManifestation chronic nephritis syndromePathological changes except MCD,MmPGN

43、, Crescentic GN81Clinical 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 failureuremia824.Prognosis factors (1)pathological properties (2)treatment (

44、3)hypertension (4)infection,prerenal factors (hypotension etc) (5)nephrotoxic drugs83Points of Diagnosis chronic onset proteinuria and/or hematuria protracted and progressive Differential DiagnosisCGN84Differential Diagnosis85 1. AGN AGN CGN age children young&middle-aged preliminary infection frequ

45、ently 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 progressiv

46、e pathology MmPGN/MsPGN 862.Essential hypertensive nephrosclerosis EHT CGNfirst present hypertension abnormal urinefunction injury in advance tubule glomerulehematuria occasionally frequentlynephrotic proteinuria occasionally frequentlysystemic hypertension manifestationheart, eyeground compared wit

47、h kidney equal milder pathology arteriolar sclerosis 873.secondary GN SLE (1)systemic presentation (2)immune abnormolity(C,self-AB) (3)pathological changes SHP (1)purpura (2)stomach, joint88Chronic pyelonephritis CPN CGN mechanisms infection immunesites pelvis,calices,tubule glomerulepresents of inf

48、ection + Upro excretive /tubular glomerularURBC non-glomerular glomerularhypertension infrequently frequentlyedema infrequently frequentlykidney lesions tubule glomeruledysmorphosis one side two side89TreatmentTarget inhibit immune reaction halt the progression of disease 1.restrictive intake of pro

49、tein dialation of afferent glomerular arteriole pressure in glomeruli Upro postpone glomerulosclerosis ACEI/ARB91 3.anti-platelet 4.immunosupression 92Clinical manifestation 1.Characteristics (1)large quantity of Upro (2)severe edema (3)hypoalbuminemia (4)hyperlipidemia Nephrotic Syndrome932.Others

50、(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 94 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,systemi