丁小強腎小球疾病

1、腎小球疾病glomerular diseases丁小強復(fù)旦大學附屬中山醫(yī)院pathological changespathological changes - glomerular injury - glomerular injuryclinical manifestationsclinical manifestations -proteinuria / hematuria -proteinuria / hematuriaa group of diseasesa group of diseases complicated causes & complicated causes &

2、; mechanismsmechanismsvarious clinical various clinical manifestationsmanifestationsdifferent prognosisdifferent prognosismultiple treatmentmultiple treatment primary glomerular diseases secondary glomerular diseases hereditary glomerular diseases immune mechanismshumoral cell-mediatednon-immune mec

3、hanismsinflammationglomerular diseasesa. immune mechanisms (a)deposits of circulating immuno-complex (cic) circilationcircilation antigen+ antibody cic kidneykidney cic/deposits antigenantigen extrinsicextrinsic drugs-nonhomologous serum, penicillin foodsxenogenic protein pathogenspecific serotypes

4、streptococci, hbv, hcv intrinsicintrinsic nucleus（sle) cytoplasm（anca） cellular membrane antigen of tumor antigen of thyroid why does cic deposit in the glomeruli? large area of glomerrular capillaries -more chances to contact net structure of cic -easy to deposit and settle down clearance dysfuncti

5、on of mesangial cells, disability of mononuclear macrophage, component or function defect of complements decrease clearance of cic (b)(b)in situ immunocomplex 1. 1. native renal antigennative renal antigen glomerular basement membrane + anti- glomerular basement membrane antibody (anti- glomerular b

6、asement membrane glomerulonephritis) 2. antigens trapped or planted2. antigens trapped or planted dna+ anti-dna antibody (lupus nephritis)balance between the deposit and clearance of ic determines the situation of the diseases persistence of antigen clearance dysfunction of mesangial cells disabilit

7、y of mononuclear macrophage component or function defect of complements ic deposit clearance b. cell-mediated immune mechanisms minimal change glomerulopathy ? c. non immune mechanisms glomerular hypertension hyperlipidemia (ldl- cho) advanced glycosylation end products (protein) glomerulosclerosisi

8、nflammation mediators of inflammation a group of molecules which act as mediators of inflammation and complicated biological function origin of inflammation mediators in kidney extrinsic cells in kidney infiltrative neutrophil, lymphocyte, mononuclear macrophage , platelet intrinsic cells in kidney

9、mesangial cells, tubular cells, endothelial cells mediators of inflammation - active oxygen and active nitrogen - lipids - complements - cytokines - chemotatic factors - adhesion molecules - growth factors - vasoactive substancesto arouse or promote to arouse or promote - proliferation of cells - pr

10、oliferation 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 and adhension molecules molec

11、ules effects of the inflammation mediatorseffects of the inflammation mediators mechanisms of primary gnmechanisms of primary gnimmuneimmune non-immunenon-immune inflammationinflammationinflammatory cellsinflammatory cellsextrinsic cells intrinsic cells neutrophil, lymphcyte mesangial cells mononucl

12、ear macrophage epithelial cells platelet, tubular cells endothelial cellsinflammation mediatorsinflammation 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, enzyme

13、glomerular injuriesglomerular injuries essential in the initiationessential in the progressive periodimmune non-immune initiation end stage primary gnprimary gnsites of pathological changesmesangium mesangial cell mesangial matrixbasement membranepodocytefoot processendothelial cellthe peripheral po

14、rtion of a glomerular lobulepathological changes lm mesangial cells, matrix of mesangium epithelial cells endothelial cells basement membrane loops of glomeruli em foot process basement membrane hyperplasy of mesangium (electron-dense deposits ) if sites, appearances and types of the deposit (ig or

15、c) basical changesproliferationfibrosis and sclerosisnecrosisinfiltration of inflammatory cellsextents 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% segmen

16、tal impaired capillary loops of a glomerule 50% pathological types of primary gn minimal change glomerulonephritis focal segmental lesions diffuse glomerulonephritis unclassified glomerulonephritis1. minor lesions of glomerulino specific lesionslmmild proliferation of mesangial cells and accumulatio

17、n of ecms minimal change disease，mcd mild mesangial proliferative gn recovery stage of endocapillary gn othersmcd (left)normal ,(right) fusion & effacement of foot processes 2. focal and segmental lesions1) focal and segmental proliferative glomerulonephritis 2) focal and segmental glomeruloscle

18、rosissegmental glomerulonephritis 3. 3. diffusive glomerulonephritis(1) membranous nephropathy mn (lesions in gbm) mn (left) normal,(right)subepithelial deposits of ic(d), thickening of gbm,formation of spikes (s), fusion of foot processes(2) proliferative glomerulonephritis mesangial proliferative

19、gn ( lesions in mesangium) iga nephropathy non-iga nephropathy domonating igg deposit igm nephropathymspgn (left)normal, (right)proliferation of mesangial cells and matrix and electron-dense deposits (d)endocapillary proliferative gn ( lesions in mesangium & endothelial cells)endocapillary proli

20、ferative gn (left) normal, (right) endothelial(e) & mesangial(m) cell proliferation and subepithelial humplike dense deposits(d) mesangiocapillary gn or membranoproliferative gn (lesions in mesangium & gbm) dense desposit gn (electron-dense deposits)mmpgn (left) normal, (right) proliferation

21、 of mesngium (m),electron-dense deposits(d), and subendothelial mesangial cytoplasm interposition（i） crescentic gn or extracapillary gn crescentic gn (left) normal, (right) splitting of gbm, leakage of fibrin(f), proliferation of epithelial cells,(e), infiltration of mononuclear macrophages(p), form

22、ation of crescents(3) sclerosing gn 4.4.unclassified glomerulonephritis characters of lesions in gn endocapillary proliferative gnproliferation of mesangium can presents in varied types of gnproliferation and subsequent stiffness of mesangium may be the results of varied types of gnfsgs primary-late

23、r-phase of the disease itself secondary- later-phase of other types of gncrescents can presents in different types of gnclinical manifestationsproteinuriaurinary protein test positiveurinary protein excretion rate 150mg/dcharge barrier of glomerule1.epithelial cells 2. gbm 3. endothelial cells 1.epi

24、thelial cells 2. gbm 3. endothelial cells 4. filtrated substances4. filtrated substancesfiltration barrier mechanisms of production of proteinuria 機機 制制 性性 質(zhì)質(zhì)腎小球濾過腎小球濾過腎小管重吸收腎小管重吸收 中、高分子中、高分子 低分子低分子腎小球性腎小球性蛋白尿蛋白尿腎小管性腎小管性蛋白尿蛋白尿moderate/high mw molecules filtration barrierproperties charge- size- sele

25、ctive 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 proteinurisquantitymild 3.5g/d或或50mg/kg/dhematuriahematuria rb

26、c 3個/hp (fresh, 10 ml sample, 1500rmp centrifuge for 5 min, sediment observation) gross hematuriared color of urine, 1ml blood /1l urine hematuriahematuria rbc from glomerulisqueezing through gbm dismorphic rbcphase-contrastmicroscopydismorphic rbc50 hypothesis:glomerular bleedingdismorphic rbc70% f

27、inal 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 -essentialsevere edemahyperlipidemiahypoalbuminemialarge-amount proteinuriacenter keyessential for diagnosisintake of protein ing

28、estion from gisynthesis in liverlost through urinensconsumptionmechanisms of hypoalbuminemiaclinical manifestation of gnclinical manifestation of gnmanifestationinitiationhematuria proteinuria edema,hypertension renal failure急性gn綜合征急性gn綜合征acute100%100%100%100%frequentresumableresumable急進性gn綜合征急進性gn綜

29、合征acute100%100%100%100%frequentarf慢性gn綜合征慢性gn綜合征latentfrequentfrequentfrequentcrf隱匿性gn綜合征*隱匿性gn綜合征* latentfrequent1g/d(-)(-)linkage of clinical manifestation and pathological changes (1)pathological proliferative non-proliferativechanges mspgn mcd mmpgn mn* endocapillary pgn fsgs crescentic gnclinic

30、al hematuria proteinuria certain certain, sometimesmanifestation nephritis syndrome nephrotic syndrome proteinuria hematuria possible occasional * linkage of clinical manifestation and pathological changes (2) clinical pathological agn endocapillary pgn possible ns rpgn crescentic gn possible ns cgn

31、 nephritis syndrome mspgn 2 mmpgn 2 nephritis syndrome fsgs 2 +nephrotic syndrome mn2 ns mcd 1 acute glomerulonephritisacute glomerulonephritisetiologystreptococcus -hemolytic streptococcus, group a, type xii, nephritogenic strainsantigencomponents of cytoplasm & membranefrequently cic, sometime

32、s planted antigenothers other bacteria, such as staphylococcus epidermidis viruses parasitespathological changes endocapillary proliferative gn acute phase proliferation of endothelial & mesangium recovery phase only mesangium proliferation, sometimes minor lesion clinical manifestation1.1.epide

33、miology:epidemiology: primarily children, primarily children, sometimes adults & the agedsometimes adults & the aged2. 2. preliminary infectionpreliminary infection frequentlyfrequently tonsillitis,upper respiratory tonsillitis,upper respiratory infectioninfectionlatent period:latent period:

34、1-3 w1-3 w occasionally occasionally skin infectionskin infectionlatent period:latent period:longer,but less than 4wlonger,but less than 4w3.3.nephritis syndromenephritis syndrome(1)(1)hematuriahematuria 100% 100%，40% are gross hematuria40% are gross hematuria(2)(2)proteinuriaproteinuria frequentfre

35、quent，20% are nephrotic syndrome90%90%(4)(4)hypertensionhypertension 80%80%(5)(5)renal failurerenal failure mild,acute renal failure mild,acute renal failure4.4.laboratory findings laboratory findings (1)(1) acute phase of infection of strep acute phase of infection of strep. .elevated elevated aso

36、aso titertiter (some strep(some strep. . nono hemolysin hemolysin o)o)only the marker of infection, not only the marker of infection, not nephritisnephritis(2) acute phase of immune reactions(2) acute phase of immune reactionsserum serum c c3 3 & total complements & total complements ,return

37、 to ,return to normal within normal within 8w8wblood blood ciccic natural history edema and hypertension disappear in one month hematuria, proteinuria usually reduce in one month, resolve within 2 to 3 months some resolve within 6 to 12 months c3 return to normal in two monthsdiagnosispoints prelimi

38、nary infection &latent period acute onset surely hematuria, frequently edema and hypertension aso , c3 dynamic change self-limitation differential diagnosisdiseases presented with acute nephritis syndrome gn secondary to infection of other pathogens other bacteria, viruses (varicella-zoster viru

39、s, eb, influenza virus) climax of infection or within 5 days mild abnormal of urine examination hypertension and edema are unusual normal blood complement level rapidly progressive gn cgn systemic diseases lupus nephritis schnlein-henoch purpuraindications of kidney biopsy oligouria 1w，except ecbv i

40、nsufficient, urinary tract obstruction, etc progressive renal failure unresolved in 2 months untypical manifestation, or with nephrotic syndrometreatment1.supportive treatment rest food & waterrestrictive intake ofnacl 5 g/d if moderate to severe edema or hypertensionwater if decreased urine vol

41、ume protein renal failure, but not dialysis yet2.treatment of infection penicilin for 2 w tonsillectomy if recurrent attacks of tonsillitistonsillitis1) patients condition is stable, upro1g/d, urbc 10/hp2) penicilin for 2 wks before and after the surgery3. symptomatic treatment diuresis antihyperten

42、sion dialysisprognosis hematuria, proteinuriausually reduce in one month, resolve within 2 to 3 monthssome resolve within 6 to 12 months 1%arf death 6%-18% cgn?rapidly progressive glomerulonephritisrpgn rapidly progressive nephritis syndromesome induced by respiratory infectionacute onset, rapidly p

43、rogressiverenal failure within a few weeks to a few months 1.1.primary primary rpgn rpgn crescentic gncrescentic gn2.other primary gn other pathological2.other primary gn other pathological changes with lots changes with lots of crescents of crescents3.secondary rpgn sle, shp, etc3.secondary rpgn sl

44、e, shp, etc 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 chinad

45、iagnosis acute onset rapidly progressive renal failure within a few weeks to a few months acute renal failure chronic renal failuredifferential diagnosis rapidly progressive nephritis syndrome not primary rpgn - other primary gn agn, igan, etc - secondary gn goodpasture syndrome, ln, shp * accompani

46、ed by crescentic gn * severe pathological changes diseases with arf atn ain - definite etiology -obsolete proteinuria and hematuria - specific manifestation atnlarge quantity of renal tubular epithelial cells in urine ainhypersensitiveness (rashes, fever, arthralgia) treatment early! aim to humoral

47、immune mechanisms 1.plasmapheresis discard the antibodies plasm exchange immoadsorption type i, iii 2.drugs glucocorticoid +cytotoxic drugs mp0.5-1.0g/d 3，repeat if necessary ctx type ii, iiisymptomatic treatment renal failure balance of fluid, electrolytes and acid-base dialysis infection hypertens

48、ionprognosis hardly relieve hardly relieve mostmostcrf or deathcrf or deathrisk factors type i-worst,ii-worse,iii-bad treatment not progressive & prompt age the aged chronic glomerulonephritismanifestation chronic nephritis syndromepathological changes except mcd,mmpgn, crescentic gnclinical man

49、ifestation 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 failureuremia4.prognosis factors (1)pathological properties (2)treatment (3)hypertension (4)infection,pre

50、renal factors (hypotension etc) (5)nephrotoxic drugspoints of diagnosis chronic onset proteinuria and/or hematuria protracted and progressive differential diagnosiscgndifferential diagnosis 1. agn agn cgn age children young&middle-aged preliminary infection frequently sometimes latent period 1-3

51、w 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 2.essent

52、ial 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 ar

53、teriolar sclerosis 3.secondary gn sle (1)systemic presentation (2)immune abnormolity(c,self-ab) (3)pathological changes shp (1)purpura (2)stomach, jointchronic pyelonephritis cpn cgn mechanisms infection immunesites pelvis,calices,tubule glomerulepresents of infection + upro excretive /tubular glome

54、rularurbc non-glomerular glomerularhypertension infrequently frequentlyedema infrequently frequentlykidney lesions tubule glomeruledysmorphosis one side two sidetreatmenttarget inhibit immune reaction halt the progression of disease 1.restrictive intake of protein dialation of afferent glomerular ar

55、teriole pressure in glomeruli upro postpone glomerulosclerosis acei/arb 3.anti-platelet 4.immunosupression clinical manifestation 1.characteristics (1)large quantity of upro (2)severe edema (3)hypoalbuminemia (4)hyperlipidemia nephrotic syndrome2.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 loopsnephrot