丁小强-肾小球疾病.ppt

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 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 3.5g/d或50mg/kg/d hematuria RBC 3个/HP (fresh, 10 ml sample, 1500rmp centrifuge for 5 min, sediment observation) gross hematuria Red color of urine, 1ml blood /1L urine 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 RBC 3.5g/d 2. hypoalbuminemia 90% (4)hypertension 80% (5)renal failure mild,acute renal failure 4.Laboratory findings (1) 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 C3 & 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 C3 return to normal in two months Diagnosis Points preliminary infection &latent period acute onset surely hematuria, frequently edema and hypertension ASO , C3 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 Schnlein-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 dialation of afferent glomerular arteriole 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 Syndrome 2.Others (1) thrombosis & embolism renal veins or inferior vena cava 25% (2)infection (3)acute renal failure Blood volumeperfusion 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 1-1.2g/kg/d (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)a