肾小球疾病(英语)课件.ppt

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 kid

2、ney 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?vLarge are

3、a 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

4、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 d

5、iseasesvPersistence 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 mechanisms glomerular hypertensi

6、on hyperlipidemia(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 kidney Extrinsic Cells in kidne

7、y infiltrative neutrophil,lymphocyte,mononuclear macrophage,platelet Intrinsic cells in kidney Mesangial cells,tubular cells,endothelial cells第10页，共84页。LOGO Mediators of inflammation -active oxygen and active nitrogen -lipids -complements -cytokines -chemotatic factors -adhesion molecules -growth fa

8、ctors -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 immunomodul

9、ating -expression of immunomodulating molecules and adhension molecules molecules and adhension molecules Effects 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,lymphcy

10、te 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,enzy

11、meGlomerular injuries Essential in the initiationEssential in the progressive 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 mesangium Epithelial ce

12、lls Endothelial cells Basement membrane Loops of glomerulivEM Foot process Basement membrane Hyperplasy 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

13、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 G

14、NvMinimal change glomerulonephritisvFocal segmental lesionsvDiffuse glomerulonephritisvUnclassified glomerulonephritis第18页，共84页。Minor Lesions of glomeruliNo specific lesionsLMmild proliferation of mesangial cells and accumulation of ECMSvminimal change disease，MCDvmild mesangial proliferative GNvrec

15、overy 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 membranous nephropathy MN (lesions in GBM)第21页，共84页。(2)proliferative glomerulonephrit

16、isvmesangial proliferative GN (lesions in mesangium)IgA nephropathy Non-IgA nephropathy domonating 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

17、desposit GN (electron-dense deposits)第24页，共84页。Characters of lesions in GN Endocapillary proliferative GN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

18、disease itself secondary-later-phase of other types of GNCrescents can presents in different types of GN第26页，共84页。LOGOClinical manifestations第27页，共84页。filtration barrierproperties charge-size-selective selective Selective albumin impaired normalproteinuria (moderate MW molecules)Non-selective albumi

19、n&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 u

20、rine,1ml blood/1L urine第30页，共84页。hematuria RBC from glomerulisqueezing through GBM dismorphic RBCPhase-contrastmicroscopydismorphic RBC50 Hypothesis:glomerular bleeding dismorphic RBC70%Final diagnosis:glomerular bleeding Urinary RBC volume distribution curvedissymmetry curveMCV of urinary RBC 3.5g/

21、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，

22、共84页。Clinical manifestation of GNClinical manifestation of GNmanifestationinitiationhematuria proteinuria edema,hypertension renal failure急性GN综合征急性GN综合征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

23、合征*隐匿性GN综合征*latentfrequent1g/d(-)(-)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 syndro

24、me 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 syn

25、drome MN2 NS MCD 1 第40页，共84页。Acute Glomerulonephritis第41页，共84页。Etiology Streptococcus-hemolytic streptococcus,group A,type XII,nephritogenic strainsantigencomponents of cytoplasm&membranefrequently CIC,sometimes planted antigen Others other bacteria,such as staphylococcus epidermidis viruses parasit

26、es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 infection fre

27、quently tonsillitis,upper respiratory infectionLatent period:1-3 w occasionally 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.

28、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 第46页，共84页。Natural Historyvedema and hypertension disappear in

29、one monthvhematuria,proteinuria usually reduce in one month,resolve within 2 to 3 months some resolve within 6 to 12 monthsvC3 return to normal in two months第47页，共84页。DiagnosisPointsvpreliminary infection&latent periodvacute onsetvsurely hematuria,frequently edema and hypertensionvASO ,C3 dynamic ch

30、angevSelf-limitation 第48页，共84页。Differential DiagnosisDiseases presented with acute nephritis syndromev 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 an

31、d 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 mon

32、thsvuntypical manifestation,or with nephrotic syndrome第51页，共84页。Treatment1.Supportive treatment Rest 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第52页，共84页。2.Treatment of infectionPenici

33、lin for 2 wTonsillectomy if recurrent attacks of tonsillitispatients 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

34、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 Cr

35、escentic 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

36、 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 pri

37、mary 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 epitheli

38、al 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

39、页。symptomatic treatment v renal failure balance of fluid,electrolytes and acid-base dialysisv 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 GlomerulonephritisManifes

40、tation 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 f

41、ailureuremia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8

42、4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 ret

43、urn 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 occasion

44、ally 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 pyelonephr

45、itis 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。T

46、reatmentTarget 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.Characteris

47、tics (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 glomerula

48、r 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(

49、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.re

50、st 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 f