临床医学】丁小强－肾小球疾病

单击以编辑母版标题样式,单击以编辑母版文本样式,第二级,第三级,第四级,第五级,*,肾小球疾病,Glomerular Diseases,丁小强,复旦大学附属中山医院,Pathological changes,- glomerular injury,Clinical manifestations,-proteinuria / hematuria,A group of diseases,Complicated causes & mechanisms,Various clinical manifestations,Different prognosis,Multiple treatment,primary glomerular diseases,secondary glomerular diseases,hereditary glomerular diseases,Immune mechanisms,Humoral,Cell-mediated,Non-immune,mechanisms,Inflammation,Glomerular diseases,A. Immune mechanisms,(A),deposits of,Circulating Immuno-Complex (CIC),circilation,antigen+ antibody,CIC,kidney,CIC/deposits,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,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 dysfunction of mesangial cells, disability of mononuclear macrophage, component or function defect of complements,Decrease clearance of CIC,(B),in situ,Immunocomplex,1.,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),Balance,between the deposit and clearance of IC,determines,the situation of the diseases,Persistence of antigen,Clearance dysfunction of mesangial cells,disability 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),glomerulosclerosis,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 neutrophil, lymphocyte, mononuclear macrophage , platelet,Intrinsic cells in kidney,Mesangial cells, tubular cells, endothelial cells,Mediators of inflammation,- active oxygen and active nitrogen - lipids - complements - cytokines - chemotatic factors - adhesion molecules - growth factors - vasoactive substances,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,Mechanisms of Primary GN,immune,non-immune,inflammation,Inflammatory cells,Extrinsic cells Intrinsic cells,neutrophil, lymphcyte mesangial cells,mononuclear macrophage epithelial cells,platelet, tubular cells endothelial cells,Inflammation mediators,cytokines TNF,IL-1,growth factors TGF,PDGF,chemotatic factors MCP-1,IL-8,complements,vasoactive substances,active oxygen and active nitrogen,Coagulation and fibrolysis system, enzyme,Glomerular injuries,Essential in the initiation,Essential in the progressive period,immune,non-immune,initiation end stage,Primary GN,Sites of pathological changes,Mesangium,Mesangial cell,Mesangial matrix,Basement membrane,Podocyte,Foot process,Endothelial cell,The peripheral portion of a glomerular lobule,Pathological 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 C),Basical changes,Proliferation,Fibrosis and sclerosis,Necrosis,Infiltration of inflammatory cells,Extents of Injuries,primary GN glomerular injuries,only or dominating,changes,secondary GN glomerular injuries,a part of,systematic diseases,diffuse impaired glomeruli,50%,focal impaired glomeruli,50%,segmental impaired capillary loops of a glomerule,g/d或50mg/kg/d,hematuria,RBC 3,个,/,HP,(fresh,10,ml sample, 1500,rmp,centrifuge for,5 min, sediment observation),gross,hematuria,Red color of urine,1,ml,b,lood,/,1L,u,rine,hematuria,RBC from glomeruli,squeezing,through GBM,dismorphic RBC,Phase-contrast,microscopy,dismorphic,RBC50,Hypothesis:glomerular bleeding,dismorphic,RBC70%,Final diagnosis:glomerular bleeding,Urinary RBC volume distribution curve,dissymmetry curve,MCV,of urinary RBCthat in b,lood,changing when passing tubules with different osmosis,edema,fluid retention in tissue spaces,peripheral edema,fluid retention in,serous cavity,glomerular diseases,GFR,large amount of urinaryprotein lost,Intrinsic RAS & Aldosterone,hypoalbuminemia,water & sodium filtration,colloid osmotic pressure,water & sodium readsorption,primary water & sodium retention secondary water & sodium retention,Effective circulation blood volumn,edema,Effective circulation blood volumn,Hypertension,glomerular diseases,primary water & stimulus, such asischemia,sodium retention,Volumn-dependent,vessoconstrictive vessodilatory,substances,substances,RAS,Ald PGI,2,PGE,2,vessoactive substances-dependent,Hypertension,Clinical types of GN,Glomerulo,nephropathy,Confined concept,leading manifestation:,proteinuria, with/without,hematuria,Extensive concept,glomerular,diseases ( disorders ),Glomerulo,nephritis,leading manifestation:,hematuria, with/without,proteinuria,Nephrotic syndrome,1.,Large-amount proteinuria,2.,hypoalbuminemia, 30g/L,3.,edema,4.,hyperlipidemia,1+2,-essential,severe edema,hyperlipidemia,hypoalbuminemia,Large-amount,proteinuria,Center,key,Essential for,diagnosis,Intake of protein,Ingestion from GI,synthesis in liver,lost through urine,NS,consumption,Mechanisms of hypoalbuminemia,Linkage of clinical manifestation and pathological changes (1),Pathological,proliferative non-proliferative,changes,MsPGN MCD,MmPGN MN,*,Endocapillary PGN FSGS,Crescentic GN,Clinical,hematuria proteinuria,certain certain, sometimes,Manifestation,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,nephritis syndrome MsPGN 2,MmPGN 2,nephritis syndrome FSGS 2,+nephrotic syndrome MN2,NS MCD 1,Acute Glomerulonephritis,Etiology,Streptococcus,-hemolytic streptococcus, group A, type XII,nephritogenic,strains,antigen,components of cytoplasm & membrane,frequently CIC, sometimes planted antigen,Others,other bacteria, such as staphylococcus,epidermidis,viruses,parasites,Pathological changes,Endocapillary Proliferative,GN,Acute phase,Proliferation of endothelial &,mesangium,Recovery phase,Only,mesangium,proliferation, sometimes minor lesion,Clinical Manifestation,1.,Epidemiology:,primarily children, sometimes adults & the aged,2.,Preliminary infection,frequently,tonsillitis,upper respiratory infection,Latent period:,1-3 w,occasionally,skin infection,Latent period:,longer,but less than 4w,3.Nephritis syndrome,(1),hematuria,100%，,40% are gross hematuria,(2),proteinuria,frequent,，90%,(4),hypertension,80%,(5),renal failure,mild,acute renal failure,4.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 reactions,serum,C,3,& total complements,return to normal within,8w,blood,CIC,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,C,3,return to normal in two months,Diagnosis,Points,preliminary infection &latent period,acute onset,surely hematuria, frequently edema and hypertension,ASO, C,3, dynamic change,Self-limitation,Differential Diagnosis,Diseases presented with acute nephritis syndrome,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,rapidly progressive GN,CGN,systemic diseases,lupus nephritis,Sch,nlein-Henoch purpura,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,Treatment,1.Supportive treatment,Rest,Food & water,Restrictive intake of,NaCl,5 g/d,if moderate to severe edema or hypertension,Water,if decreased urine volume,Protein,Renal failure, but not dialysis yet,2,.,Treatment of infection,Penicilin,for 2 w,Tonsillectomy,if recurrent attacks of,tonsillitis,patients condition is stable,Upro,1g/d, U,RBC, 10/HP,Penicilin,for 2 wks before and after the surgery,3.,Symptomatic treatment,Diuresis,Antihypertension,Dialysis,Prognosis,hematuria, proteinuria,usually reduce in one month, resolve within 2 to 3 months,some resolve within 6 to 12 months,1%ARF,Death,6%-18% ,CGN?,Rapidly progressive glomerulonephritis,RPGN,Rapidly progressive nephritis syndrome,Some induced by respiratory infection,Acute onset,rapidly progressive,Renal failure,within,a few weeks to a few months,1.,primary,RPGN,Crescentic GN,2.other primary GN other pathological,changes with lots,of crescents,3.secondary RPGN SLE, SHP, etc,RPGN,Type I Type II,Type,III,anti-GBM IC,Pauci-immune,IF,linear GBM,Granular GBM,（-）,deposits,& mesangium,deposits,anti-GBM AB（+）,C,3,、CIC,70%-80%,small vessel vasculitis,ANCA,（+）,the young &,the middle-aged,the middle-aged,middle aged,& aged,& aged,Most frequently in China,Diagnosis,Acute onset,Rapidly progressive,Renal failure,within,a few weeks to a few months,Acute,renal failure,Chronic,renal failure,Differential Diagnosis,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,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,immune mechanisms,1.,plasmapheresis,discard the antibodies,p,lasm,exchange,immoadsorption,type I, III,2,.drugs,glucocorticoid,+,cytotoxic,drugs,3，,repeat if necessary,CTX,type II, III,symptomatic treatment,renal failure,balance of fluid, electrolytes and acid-base,dialysis,infection,hypertension,Prognosis,Hardly relieve,most,CRF or death,Risk factors,Type,I-worst,II-worse,III-bad,Treatment,not,progressive & prompt,Age,the aged,Chronic Glomerulonephritis,Manifestation,chronic nephritis syndrome,Pathological changes,except,MCD,MmPGN,Crescentic GN,Clinical manifestation,any age, frequently young,2.preliminary infection,upper respiratory tract,intestinal tract,latent period, 1 wk,3.nephritis syndrome,Hematuria,proteinuria,edema,Hypertension,renal failure,uremia,4.Prognosis factors,(1)pathological properties,(2)treatment,(3)hypertension,(4)infection,prerenal factors,(hypotension etc),(5)nephrotoxic drugs,Points of Diagnosis,chronic onset,proteinuria and/or hematuria,protracted and progressive,Differential,Diagnosis,CGN,Differential Diagnosis,1. AGN,AGN,CGN,age,children,young&middle-aged,preliminary infection,frequently,sometimes,latent period,1-3w, dialation of,afferent,glomerular arteriole,pressure in glomeruli Upro,postpone glomerulosclerosis,ACEI/ARB,3.anti-platelet,4.immunosupression,Clinical manifestation,(1)large quantity of Upro,(2)severe edema,(3)hypoalbuminemia,(4)hyperlipidemia,Nephrotic Syndrome,2.,Others,(1) thrombosis & embolism,renal veins or inferior vena cava,25%,(2)infection,(3)acute renal failure,Blood volume,perfusion of kidneys ,ischemia,of kidneys, tubule necrosis,Severe glomerular lesions,crescent formation,Severe proliferation of,mesangium,Necrosis of capillary loops,Nephrotoxic,drugs,idiopathetic,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-ray, isotope scanning), abnormal protein (blood single-peak protein, blood and urine light chain protein,urine BJ protein),Diagnosis & Differential Diagnosis,1. Supportive treatment,1. rest,2. Food and water,(1) water & sodium,restriction when with severe edema,(2) protein,(3) lipid,restriction when with hypoalbuminemia,(4) energy,30-35 Kal/kg/d,TREATMENT,2. symptomatic treatment,1. diuresis,osmotic diuretics,plasma colloid osmotic pressure,tubule fluid osmotic pressure,fluid transmit from tissue,readsorption of water,space to blood vessels,blood volume ,diuretics,mannitol, dextran, albumin,diuresis,2. Aim to proteinuria,ACEI/ARB,3. Major treatment,1.,glucocorticoid,mechanisms,(1)immuosupression,(2)anti-inflammation,principles,(1)sufficient dose when initiation,reduce 2wks after Upro is negative,*if Upro doesnt reduced apparently,in,8-12wks,ineffective,(2) reduce the dose slowly,10%/2-3wks,(3) sustaining treatment,minimal dose:,10-15mg/d，6m-1y,Sensitivity of glucocorticoid,1mg/kg/d, 8w,negative,Upro,positive,relapse when reduce to some dosage,sensitive,dependent,ineffective,2.,immunosuppressive agents,cytotoxic,drugs,alkylating,agentCTX,chlormethine, CB1348,inhibit duplication of,DNA,Aza,MMF,inhibit synthesis of,RNA,inhibit proliferation of B lymphocyte,CyA,inhibit synthesis of,L-2,inhibit proliferation