丁小强肾小球疾病课件

1、丁小强肾小球疾病肾小球疾病Glomerular Diseases丁小强肾小球疾病Pathological changesPathological changes - glomerular injury - glomerular injuryClinical manifestationsClinical manifestations -proteinuria / hematuria -proteinuria / hematuriaA group of diseasesA group of diseases Complicated causes & Complicated causes & mec

2、hanismsmechanismsVarious clinical Various clinical manifestationsmanifestationsDifferent prognosisDifferent prognosisMultiple treatmentMultiple treatment丁小强肾小球疾病 primary glomerular diseases secondary glomerular diseases hereditary glomerular diseases丁小强肾小球疾病 Immune mechanismsHumoral Cell-mediatedNon

3、-immune mechanismsInflammationGlomerular diseases丁小强肾小球疾病A. Immune mechanisms (A)deposits of Circulating Immuno-Complex (CIC) circilationcircilation antigen+ antibody CIC kidneykidney CIC/deposits 丁小强肾小球疾病antigenantigen extrinsic extrinsic drugs-nonhomologous serum, penicillin foodsxenogenic protein

4、 pathogenspecific serotypes streptococci, HBV, HCV intrinsicintrinsic nucleus（SLE) cytoplasm（ANCA） cellular membrane antigen of tumor antigen of thyroid 丁小强肾小球疾病Why does CIC deposit in the glomeruli? Large area of glomerrular capillaries -more chances to contact Net structure of CIC -easy to deposit

5、 and settle down Clearance dysfunction of mesangial cells, disability of mononuclear macrophage, component or function defect of complements Decrease clearance of CIC 丁小强肾小球疾病(B)(B)in situ Immunocomplex 1. Native renal antigen1. Native renal antigen glomerular basement membrane + anti- glomerular ba

6、sement membrane antibody (anti- glomerular basement membrane glomerulonephritis) 2. Antigens trapped or planted2. Antigens trapped or planted DNA+ anti-DNA antibody (Lupus Nephritis)丁小强肾小球疾病Balance between the deposit and clearance of IC determines the situation of the diseases Persistence of antige

7、n Clearance dysfunction of mesangial cells disability of mononuclear macrophage component or function defect of complements IC deposit clearance丁小强肾小球疾病 B. Cell-mediated immune mechanisms minimal change glomerulopathy ? 丁小强肾小球疾病C. Non immune mechanisms glomerular hypertension hyperlipidemia (LDL- Ch

8、o) advanced glycosylation end products (protein) glomerulosclerosis丁小强肾小球疾病Inflammation 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 neutroph

9、il, lymphocyte, mononuclear macrophage , platelet Intrinsic cells in kidney Mesangial cells, tubular cells, endothelial cells丁小强肾小球疾病 Mediators of inflammation - active oxygen and active nitrogen - lipids - complements - cytokines - chemotatic factors - adhesion molecules - growth factors - vasoacti

10、ve substances丁小强肾小球疾病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 - ex

11、pression of immunomodulating molecules and adhension molecules molecules and adhension molecules Effects of the inflammation mediatorsEffects of the inflammation mediators丁小强肾小球疾病 Mechanisms of Primary GNMechanisms of Primary GNimmuneimmune non-immunenon-immune inflammationinflammationInflammatory c

12、ellsInflammatory cellsExtrinsic cells Intrinsic cells neutrophil, lymphcyte mesangial cells mononuclear macrophage epithelial cells platelet, tubular cells endothelial cellsInflammation mediatorsInflammation mediators cytokines TNF,IL-1 growth factors TGF,PDGF chemotatic factors MCP-1,IL-8 complemen

13、ts, vasoactive substances active oxygen and active nitrogenCoagulation and fibrolysis system, enzymeGlomerular injuriesGlomerular injuries Essential in the initiationEssential in the progressive period丁小强肾小球疾病immune non-immune initiation end stage Primary GNPrimary GN丁小强肾小球疾病Sites of pathological ch

14、angesMesangium Mesangial cell Mesangial matrixBasement membranePodocyteFoot processEndothelial cell丁小强肾小球疾病The peripheral portion of a glomerular lobule丁小强肾小球疾病Pathological changes LM Mesangial cells, matrix of mesangium Epithelial cells Endothelial cells Basement membrane Loops of glomeruli EM Foot

15、 process Basement membrane Hyperplasy of mesangium (electron-dense deposits ) IF Sites, appearances and types of the deposit (Ig or C) 丁小强肾小球疾病Basical changesProliferationFibrosis and sclerosisNecrosisInfiltration of inflammatory cells丁小强肾小球疾病Extents of Injuries primary GN glomerular injuriesonly or

16、 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%丁小强肾小球疾病 Pathological types of primary GN Minimal change glomerulonephritis Focal segmental lesions Diffu

17、se glomerulonephritis Unclassified glomerulonephritis丁小强肾小球疾病 Minor Lesions of glomeruliNo specific lesionsLMmild proliferation of mesangial cells and accumulation of ECMS minimal change disease，MCD mild mesangial proliferative GN recovery stage of endocapillary GN others丁小强肾小球疾病MCD (left)normal ,(r

18、ight) fusion & effacement of foot processes 丁小强肾小球疾病2. Focal and Segmental Lesions1) focal and segmental proliferative glomerulonephritis 2) focal and segmental glomerulosclerosis丁小强肾小球疾病segmental glomerulonephritis 丁小强肾小球疾病 3. 3. Diffusive glomerulonephritis membranous nephropathy MN (lesions in GB

19、M) 丁小强肾小球疾病MN (left) normal,(right)subepithelial deposits of IC(D), thickening of GBM,formation of spikes (S), fusion of foot processes丁小强肾小球疾病(2) proliferative glomerulonephritis mesangial proliferative GN ( lesions in mesangium) IgA nephropathy Non-IgA nephropathy domonating IgG deposit IgM nephro

20、pathy丁小强肾小球疾病MsPGN (left)normal, (right)proliferation of mesangial cells and matrix and electron-dense deposits (D)丁小强肾小球疾病endocapillary proliferative GN ( lesions in mesangium & endothelial cells)丁小强肾小球疾病endocapillary proliferative GN (left) normal, (right) endothelial(E) & mesangial(M) cell prolif

21、eration and subepithelial humplike dense deposits(D)丁小强肾小球疾病 mesangiocapillary GN or membranoproliferative GN (lesions in mesangium & GBM) dense desposit GN (electron-dense deposits)丁小强肾小球疾病MmPGN (left) normal, (right) proliferation of mesngium (M),electron-dense deposits(D), and subendothelial mesa

22、ngial cytoplasm interposition（I）丁小强肾小球疾病 crescentic GN or extracapillary GN 丁小强肾小球疾病Crescentic GN (left) normal, (right) splitting of GBM, leakage of fibrin(F), proliferation of epithelial cells,(E), infiltration of mononuclear macrophages(P), formation of crescents丁小强肾小球疾病(3) sclerosing GN丁小强肾小球疾病

23、4.4.unclassified glomerulonephritis丁小强肾小球疾病 Characters of lesions in GN Endocapillary proliferative GN丁小强肾小球疾病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 disea

24、se itself secondary- later-phase of other types of GNCrescents can presents in different types of GN丁小强肾小球疾病Clinical manifestationsProteinuria Urinary protein test positive Urinary protein excretion rate 150mg/d丁小强肾小球疾病Charge barrier of glomerule1.Epithelial cells 2. GBM 3. Endothelial cells 1.Epith

25、elial cells 2. GBM 3. Endothelial cells 4. Filtrated substances4. Filtrated substances丁小强肾小球疾病Filtration barrier丁小强肾小球疾病 mechanisms of production of proteinuria 机机 制制 性性 质质肾小球滤过肾小球滤过肾小管重吸收肾小管重吸收 中、高分子中、高分子 低分子低分子肾小球性肾小球性蛋白尿蛋白尿肾小管性肾小管性蛋白尿蛋白尿Moderate/high MW molecules丁小强肾小球疾病 filtration barrierpropert

26、ies 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丁小强肾小球疾病quantityMild 3.5g/d或或50mg/kg/

27、d丁小强肾小球疾病hematuriahematuria RBC 3个/HP (fresh, 10 ml sample, 1500rmp centrifuge for 5 min, sediment observation) gross hematuriaRed color of urine, 1ml blood /1L urine丁小强肾小球疾病 hematuriahematuria RBC from glomerulisqueezing through GBM dismorphic RBCPhase-contrastmicroscopydismorphic RBC50 Hypothesis:

28、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. hyperlipidemia 1+2 -essential丁小强肾小球疾病severe edemahyperlipidemiahypoalbuminemiaLarge-amount proteinuriaCenter k

29、eyEssential for diagnosis丁小强肾小球疾病Intake of protein Ingestion from GIsynthesis in liverlost through urineNSconsumptionMechanisms of hypoalbuminemia丁小强肾小球疾病Clinical manifestation of GNClinical manifestation of GNmanifestationinitiationhematuria proteinuria edema,hypertension renal failure急性GN综合征急性GN综合

30、征acute100%100%100%100%frequentresumableresumable急进性GN综合征急进性GN综合征acute100%100%100%100%frequentARF慢性GN综合征慢性GN综合征latentfrequentfrequentfrequentCRF隐匿性GN综合征*隐匿性GN综合征* latentfrequent1g/d(-)(-)丁小强肾小球疾病Linkage of clinical manifestation and pathological changes (1)Pathological proliferative non-proliferative

31、changes MsPGN MCD MmPGN MN* Endocapillary PGN FSGS Crescentic GNClinical hematuria proteinuria certain certain, sometimesManifestation nephritis syndrome nephrotic syndrome proteinuria hematuria possible occasional * 丁小强肾小球疾病Linkage of clinical manifestation and pathological changes (2) clinical pat

32、hological 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 丁小强肾小球疾病Acute Glomerulonephritis丁小强肾小球疾病EtiologyStreptococcus -hemolytic streptococcus, group A, type XII, nephritogenic strain

33、santigencomponents of cytoplasm & membranefrequently CIC, sometimes planted antigenOthers other bacteria, such as staphylococcus epidermidis viruses parasites丁小强肾小球疾病Pathological changes Endocapillary Proliferative GN Acute phase Proliferation of endothelial & mesangium Recovery phase Only mesangium

34、 proliferation, sometimes minor lesion 丁小强肾小球疾病 Clinical Manifestation1.1.Epidemiology:Epidemiology: primarily children, primarily children, sometimes adults & the agedsometimes adults & the aged2. 2. Preliminary infectionPreliminary infection frequentlyfrequently tonsillitis,upper respiratory tonsi

35、llitis,upper respiratory infectioninfectionLatent period:Latent period:1-3 w1-3 w occasionally occasionally skin infectionskin infectionLatent period:Latent period:longer,but less than 4wlonger,but less than 4w丁小强肾小球疾病3.Nephritis syndrome3.Nephritis syndrome(1)(1)hematuriahematuria 100% 100%，40% are

36、 gross hematuria40% are gross hematuria(2)(2)proteinuriaproteinuria frequentfrequent，20% are nephrotic syndrome90%90%(4)(4)hypertensionhypertension 80%80%(5)(5)renal failurerenal failure mild,acute renal failure mild,acute renal failure丁小强肾小球疾病4.Laboratory findings 4.Laboratory findings acute phase

37、of infection of Strep. acute phase of infection of Strep.elevated elevated ASO ASO titertiter (some Strep. (some Strep. NoNo hemolysin O) hemolysin 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 rea

38、ctionsserum serum C C3 3 & total complements & total complements ,return to ,return to normal within normal within 8w8w(1)(1)blood blood CICCIC 丁小强肾小球疾病Natural History edema and hypertension disappear in one month hematuria, proteinuria usually reduce in one month, resolve within 2 to 3 months some

39、resolve within 6 to 12 months C3 return to normal in two months丁小强肾小球疾病DiagnosisPoints preliminary infection &latent period acute onset surely hematuria, frequently edema and hypertension ASO , C3 dynamic change Self-limitation 丁小强肾小球疾病Differential DiagnosisDiseases presented with acute nephritis sy

40、ndrome GN secondary to infection of other pathogens other bacteria, viruses (Varicella-zoster virus, EB, influenza virus) Climax of infection or within 5 days Mild abnormal of urine examination Hypertension and edema are unusual Normal blood complement level 丁小强肾小球疾病 rapidly progressive GN CGN syste

41、mic diseases lupus nephritis Schnlein-Henoch purpura丁小强肾小球疾病Indications of kidney biopsy Oligouria 1w，except ECBV insufficient, urinary tract obstruction, etc Progressive renal failure Unresolved in 2 months untypical manifestation, or with nephrotic syndrome丁小强肾小球疾病Treatment1.Supportive treatment R

42、est Food & waterRestrictive intake ofNaCl 5 g/d if moderate to severe edema or hypertensionWater if decreased urine volume Protein Renal failure, but not dialysis yet丁小强肾小球疾病2.Treatment of infection Penicilin for 2 w Tonsillectomy if recurrent attacks of tonsillitistonsillitis patients condition is

43、stable, Upro1g/d, URBC 10/HPPenicilin for 2 wks before and after the surgery3. Symptomatic treatment Diuresis Antihypertension Dialysis丁小强肾小球疾病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?丁小强肾小球疾病Ra

44、pidly progressive glomerulonephritisRPGN Rapidly progressive nephritis syndromeSome induced by respiratory infectionAcute onset, rapidly progressiveRenal failure within a few weeks to a few months 丁小强肾小球疾病1.1.primary primary RPGN RPGN Crescentic GNCrescentic GN2.other primary GN other pathological2.

45、other primary GN other pathological changes with lots changes with lots of crescents of crescents3.secondary RPGN SLE, SHP, etc3.secondary RPGN SLE, SHP, etc丁小强肾小球疾病 RPGN Type I Type II Type III anti-GBM IC Pauci-immuneIF linear GBM Granular GBM （-） deposits & mesangium deposits anti-GBM AB（+）C3 、CI

46、C 70%-80% small vessel vasculitis ANCA （+） the young & the middle-aged the middle-aged middle aged & aged & aged Most frequently in China丁小强肾小球疾病Diagnosis Acute onset Rapidly progressive Renal failure within a few weeks to a few months Acute renal failure Chronic renal failure丁小强肾小球疾病Differential Di

47、agnosis 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 丁小强肾小球疾病Diseases with ARF ATN AIN - definite etiology -obsolete proteinuria and hematuria - spec

48、ific manifestation ATNlarge quantity of renal tubular epithelial cells in urine AINhypersensitiveness (rashes, fever, arthralgia) 丁小强肾小球疾病Treatment EARLY! Aim to humoral immune mechanisms 1.plasmapheresis discard the antibodies plasm exchange immoadsorption type I, III 2.drugs glucocorticoid +cytoto

49、xic drugs MP0.5-1.0g/d 3，repeat if necessary CTX type II, III丁小强肾小球疾病symptomatic treatment renal failure balance of fluid, electrolytes and acid-base dialysis infection hypertension丁小强肾小球疾病Prognosis Hardly relieve Hardly relieve mostmostCRF or deathCRF or deathRisk factors Type I-worst,II-worse,III-

50、bad Treatment not progressive & prompt Age the aged 丁小强肾小球疾病Chronic GlomerulonephritisManifestation chronic nephritis syndromePathological changes except MCD,MmPGN, Crescentic GN丁小强肾小球疾病Clinical manifestation 1.age any age, frequently young 2.preliminary infection upper respiratory tract, intestinal

51、 tract latent period 1 wk 3.nephritis syndrome Hematuria,proteinuria,edemaHypertension,renal failureuremia丁小强肾小球疾病4.Prognosis factors (1)pathological properties (2)treatment (3)hypertension (4)infection,prerenal factors (hypotension etc) (5)nephrotoxic drugs丁小强肾小球疾病Points of Diagnosis chronic onset

52、proteinuria and/or hematuria protracted and progressive Differential DiagnosisCGN丁小强肾小球疾病Differential Diagnosis丁小强肾小球疾病 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 freq

53、uently 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 丁小强肾小球疾病2.Essential hypertensive nephrosclerosis EHT CGNfirst present hypertension

54、 abnormal urinefunction injury in advance tubule glomerulehematuria occasionally frequentlynephrotic proteinuria occasionally frequentlysystemic hypertension manifestationheart, eyeground compared with kidney equal milder pathology arteriolar sclerosis 丁小强肾小球疾病3.secondary GN SLE (1)systemic presenta

55、tion (2)immune abnormolity(C,self-AB) (3)pathological changes SHP (1)purpura (2)stomach, joint丁小强肾小球疾病Chronic pyelonephritis CPN CGN mechanisms infection immunesites pelvis,calices,tubule glomerulepresents of infection + Upro excretive /tubular glomerularURBC non-glomerular glomerularhypertension in

56、frequently frequentlyedema infrequently frequentlykidney lesions tubule glomeruledysmorphosis one side two side丁小强肾小球疾病TreatmentTarget inhibit immune reaction halt the progression of disease 1.restrictive intake of protein dialation of afferent glomerular arteriole pressure in glomeruli Upro postpon

57、e glomerulosclerosis ACEI/ARB丁小强肾小球疾病 3.anti-platelet 4.immunosupression 丁小强肾小球疾病Clinical manifestation 1.Characteristics (1)large quantity of Upro (2)severe edema (3)hypoalbuminemia (4)hyperlipidemia Nephrotic Syndrome丁小强肾小球疾病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 drugsidiopa