肾小球肾炎自动保存的.ppt

1、Glomerular Disease,Qiaoyuan Wu Department of nephrology,Glomerular Disease,Conception and categorization Clinical classification Histologic classification Pathogenesis Clinical presentation,Conception,Bilateral kidneys are involved in glomerular disease. The disease is categorized into:,Primary dise

2、ase: only renal abnormality,Secondary disease: resulting from a systemic disease (SLE,DM).,Hereditary disease: caused by the abnormality of hereditary gene,Glomerular Disease,Conception and categorization Clinical classification Histologic classification Pathogenesis Clinical presentation,Clinical c

3、lassification of primary glomerular disease,1acute glomerulonephritis 2acute rapidly progressive glomerulonephritis 3chronic glomerulonephritis 4latent glomerulonephritis 5nephrotic syndrome,Glomerular Disease,Conception and categorization Clinical classification Histologic classification Pathogenes

4、is Clinical presentation,正常肾小球模式图,Histologic classification of primary glomerular disease (by WHO) minor glomerular abnormalities focal segmental lesions (focal segmental glomerulonephritis, focal segmental glomerular sclerosis,MCD,FSGS,3) diffuse glomerulonephritis membranous nephropathy proliferat

5、ive glomerulonephritis Mesangial proliferative glomerulonephritis Endocapillary proliferarive glomerulonephritis Mesangial capillary glomerulonephritis dense deposit glomerulonephritis crescentic glomerulonephritis,MN,MsPGN,sclerosing glomerulonephritis glomerulonephritis having not been classified,

6、11,Classification of Glomerular Disease,Etiology,Pathology,Clinical Features,Glomerular Disease,Conception and categorization Clinical classification Histologic classification Pathogenesis Clinical presentation,Pathogenesis of Glomerular Disease,1.Immune disorder 2.Kideny involvement 3.Injury by inf

7、lammation and other mediators 4.Glomerular dysfunction,1. Circulating Immune complex nephritis (type III hypersensitivity),Antigen is not glomerular origin Intrinsic- SLE(Systemic lupus erythematosus) Extrinsic- Poststreptococcal GN, HepB, Malaria Ag-Ab complex is trapped in glomeruli Complement act

8、ivation injury,1. Circulating Immune complex nephritis (type III hypersensitivity),1. Circulating Immune complex nephritis (type III hypersensitivity),Morphology: IF: deposits (glomerular) EM: electron-dense deposits (mesangial, subendothelial, subepithelial) Proliferative: leukocytes, endothelial,

9、mesangial, epithelial,In-situ Intrinsic Extrinsic/planted,2. In-situ Immune complex nephritis,2. In-situ Immune complex nephritis,Anti-GBM Goodpasture syndorme In human: auto antibodies Pathology: Severe glomerular damage Cresentic GN Ag: alpha3 chain of collagen type IV,2. In-situ Immune complex ne

10、phritis,Haymann Nephritis: Immunizing rats to proximal tubular brush border IF: granular deposits of Ig and complement along the GBM Ag (megalin) on visceral epithelial cells Result in membranous GN,2. In-situ Immune complex nephritis,2. In-situ Immune complex nephritis,Sensitized T cells suspected,

11、3. Cell mediated Immune GN,23,Mediators of Immune Injury,Mediators Cells Neutrophils Proteases, oxygen free radicals Monocytes Platelets Epithelial cells Plasma products,24,Mediators Cells Plasma products Direct cytotoxicity by Ab Fibrin related products Complement activiation C5-C9 membrane attack

12、complex,Mediators of Immune Injury,25,Epithelial cell injury,Ab to visceral epithelium Toxins Cytokins Loss of foot processes, vacuolization, detachment proteinuria,Non-immune factors Glomerular hypertension ：加重肾损害的最危险因素 Proteinuria：促进肾小管-间质纤维化过程 Hyperlipidemia ：诱发和加重肾小球损伤,Glomerular Disease,Concept

13、ion and categorization Clinical classification Histologic classification Pathogenesis Clinical presentation,Clinical presentation Proteinuria Hematuria Edema Hypertension Renal insufficiency,Being mentioned already,Edema Nephritic edema GFR，Tubular reabsorption is normalglomerulotubular imbalance Wa

14、ter-sodium retention Bp,Edema Nephrotic edema Low serum albumin colloid osmotic pressure Effective circulating blood volume RAAS ADS ADH ,Water-sodium retention,Clinical presentation Proteinuria Hematuria Edema Hypertension Renal insufficiency,Hypertension Incidence：Chronic nephritis 61%，ESRD 90% Me

15、chanisms： Water-sodium retention：GFR blood-volume volume-dependent hypertension Increased renin angiotensin secretion ： Renal ischemia Renin angiotensin system (Angiotensin II ) Small artery contraction renin dependent hypertension Decreased renal hypotensive substance secretion ： Renal parenchyma d

16、amage Renal prostaglandin bradykinin Renal hypertension,Clinical presentation Proteinuria Hematuria Edema Hypertension Renal insufficiency,Renal insufficiency Acute renal failure ：rapidly progressing glomerulonephritis Transient impairment of renal function ： Acute glomerulonephritis Chronic renal f

17、ailure ：Chronic glomerulonephritis and late stage of nephrotic syndrome,Nephrotic Syndrome,Nephrotic Syndrome(NS),Definition Etiology and Pathogenesis Pathological type and Clinical presentation Complication Diagnosis and Differential diagnosis Treatment,What is Nephrotic Syndrome (NS)?,Main Complai

18、ns: Edema of both legs, eyelids for 1 month,What test?,Urine protein: 3+ Serum ALB: 13.5g/L,Nephrotic Syndrome,1heavy proteinuria: 3.5g/d 2hypoalbuminemia：30g/L 3edema 4hyperlipidemia,is essential for NS,Categorization and Etiology,In these chapter, primary NS is discussed.,Nephrotic Syndrome(NS),De

19、finition Etiology and Pathogenesis Pathological type and Clinical presentation Complication Diagnosis and Differential diagnosis Treatment,Sodium/water retention,GLOMERULAR DAMAGE,Reduced GFR,Protein loss Massive Proteinuria,Activation of the renein-angiotensin system,Increased aldosterone,Hypoalbum

20、inemia,Reduced blood oncotic pressure,Systemic edema,Hepatic lipoprotein synthesis,Hyper-lipidemia,Hyper-coaguability,Pathophysiology,Nephrotic Syndrome(NS),Definition Etiology and Pathogenesis Pathological type and Clinical presentation Complication Diagnosis and Differential diagnosis Treatment,Hi

21、stologic type and its clinical features,1. Minimal change disease（MCD） histologic alterations light microscopy： no glomerular lesions, lipid resorption droplets in tubular epithelial cells electron microscopy an extensive foot process effacement immunofluorescence microscopy： negative,MINIMAL CHANGE

22、 DISEASE,Clinical features： most commonly seen in children, accounting for 70-90% of NS in children. It can also be seen in adults, particularly in senile patient. hematuria：about 10%-20%, no macroscopic hematuria . a transient hypertension sensitive to steroids,Histologic type and its clinical feat

23、ures,2. Focal Segmental Glomerular Sclerosis(FSGS) histologic alterations light microscopy ： Focal and segmental glomerular sclerosis. Electron microscopy: Dense deposits along the subendothelial surface of the basement membrane. effacement of foot process can be seen. immunofluorescence microscopy:

24、 Staining of IgM and C3 can be seen in the lesion sites.,FSGS,FSGS,Normal,IF: IgM,clinical features of FSGS,commonly seen in adolescence develop latently. hematuria: often seen, 20% exhibit macroscopic hematuria. Dose not respond to steroid and cytotoxic drugs well. Only a small part of patients are

25、 sensitive to the treatment.,Histologic type and its clinical features,3. membranous nephropathy(MN) histologic alterations light microscopy ： a spike pattern basement membrane thickeness without inflammatory changes. Electron microscopy: dense deposits along the subepithelial surface of the basemen

26、t membrane. Spikes and effacement of foot process can be seen. immunofluorescence microscopy: IgG and C3 along capillary loops,Membranous nephropathy,Membranous nephropathy,Membranous nephropathy,Membranous nephropathy,clinical features,commonly seen in adults, a male predominance, commonly in their

27、 fifth and sixth decades. occur indolently develop slowly: often 5-10 years renal failure,clinical features,patients are prone to thrombosis and thromboembolism. 25% may have a completely spontaneous remission. Before appearance of spikes, patients are sensitive to steroids and cytotoxic drugs. Afte

28、r spikes appears, patients do not respond to treatment well.,Histologic type and its clinical features,4. mesangial ploliferative glomerulonephritis Histologic alterations light microscopy ： mesangial hypercellurarity and increase of matrix: mild, moderate, severe alterations. immunofluorescence mic

29、roscopy: IgA nephropathy : IgA non IgA nephropathy : IgG+C3 electron microscopy ： mesangial electron-dense deposit,Figure2: mesangial ploliferative glomerulonephritis Left:normal glomerule right:abnormal glomerule. 1 . Epithelial cell 2. basement membrane 3. endothelial cell 4.mesangial cell 5.immun

30、e complex,mild ploliferation,moderate ploliferation,severe ploliferation,免疫荧光：IgG 系膜区沉积,系膜增生性肾小球肾炎。显示系膜增生和散在的沉积物（D）。 EM x 7000,系膜增生性肾小球肾炎，系膜区可见电子致密物沉积（电镜x 400）,clinical feature a high incidence, commonly seen in adolescent, a male predominance. prodromal infection can be seen. hematuria：100% in IgA

31、nephropathy, about 70% in non-IgA nephropathy. sensitive to steroid and cytotoxic drugs, but closely associated with severity of histologic lesions.,Histologic type and its clinical features,histologic alterations light microscopy: endocapillary hypercellularity, the mesangial hypercellurarity and i

32、ncrease of matrix which can insert between endothelial and basement membrane and then a double tracks is formed. immunofluorescence microscopy: mainly the deposition of C3 and IgG. Electron microscopy electron-dense deposit in mesangium and along capillary,5. mesangial capillary ploliferative glomer

33、ulonephritis (MPGN),Figure2: mesangial capillary glomerulonephritis Left:normal glomerule right:abnormal glomerule. 1 . Epithelial cell 2. basement membrane 3. endothelial cell 4.mesangial cell 5.immune complex 6. basement membrane material alike.,左为系膜毛细血管性肾炎，右为正常肾小球,系膜毛细血管性肾小球肾炎（I型）。肾小球系膜区增宽，毛细血管壁增

34、厚， 局部双轨形成。 PAS x 260,double tracks,clinical feature commonly seen in adults, a male prevalence. hematuria： all exhibit hematuria, macroscopic hematuria is common. serum C3and do not recover to normal,clinical feature Renal failure, hypertension and anemia appears early. only a part of children respo

35、nd to steroids and cytotoxic drugs, the remains do not respond well.,Nephrotic Syndrome(NS),Definition Etiology and Pathogenesis Pathological type and Clinical presentation Complication Diagnosis and Differential diagnosis Treatment,Complication of NS,susceptibility to infection Cause: protein malnu

36、trition, immunity dysfunction, administration with steroids. Infection seen commonly: respiratory tract, urinary tract infection and peritonitis, etc. It will influence the effect of treatment or lead to relapse of NS.,Case: Female, 23Y Diagnosis:NS Treatment: Pre+Cys,Thrombosis and thromboembolism

37、cause: Imbalance of Coagulation and anticoagulation system. increased platelet activation blood viscosity steroids prompt the hypercoagulation state. Renal vein thrombosis and other venous thromboemboli.,CTPA：右侧肺动脉主干栓塞,Case: Male,58Y Diagnosis: NS MN Treatment: Pre+CTX, Yet Poor compliance,acute ren

38、al failure Cause: colloid osmotic pressure hypovolemia renal hypoperfusion prerenal azotemia the tubule pressed by extreme edema of the interstitium. the tubule being blocked by a large amount of protein cast which lead to a decrease of GFR.,metabolic disturbance of protein and lipid,Nephrotic Syndr

39、ome(NS),Definition Etiology and Pathogenesis Pathological type and Clinical presentation Complication Diagnosis and Differential diagnosis Treatment,Diagnosis and differential diagnosis,Diagnosis: including is it NS? Yes or no. Yes, then Is it primary NS ? Primary NS, then what kind of glomerular di

40、sease? Histologic type. Are there complications?,Nephrotic Syndrome(NS),Definition Etiology and Pathogenesis Pathological type and Clinical presentation Complication Diagnosis and Differential diagnosis Treatment,Treatment,1.diet: Protein: 0.81.0g/（kgd）, Sodium restriction: 2. Edema: dietary salt re

41、striction diuretic therapy: thiazide and loop diuretics,Treatment,3.Reducing proteinuria ACEI machanism: lowering efferent arteriolar resistance out of proportion to afferent arteriolar resistance reducing glomerular capillary pressure and lowering urinary protein excretion. Side effect: worsening r

42、enal failure and hyperkalemia.,4 main treatment,Glucocorticoid: inhibiting inflammatory reaction and immune reaction, the secretion of aldosterone and ADH. principle: sufficient dosage should be given at the beginning : prednisone 1mg/(kgd) for 8-12weeks,4 main treatment,Glucocorticoid: principle: t

43、ape slowly tape the medicine with a speed of 10% of the beginning dose every 1-2 weeks. When it reach 20mg/d, it is very easier to relapse, the medicine should be taped more slowly.,4 main treatment,Glucocorticoid: principle: Maintenance of the medicine for a long term 10mg/d often at least 6 months

44、. (prednisone can be taken once daily in the morning),Side effects of glucocorticoid:,prolonged corticosteroid therapy may lead to A life threatening infection Osteoporosis Diabetes mellitus Accelerated atherosclerosis Hypertension Gastritis or peptic ulcer Mental illness,glucocorticoid:,according t

45、o the response to glucocorticoid, it can be categorized into three groups: steroid-sensitive remission is achieved after 812 weeks of treatment steroid-dependent the disease relapse during prednisone reducing steroid-resistant no effect can be achieved after 8-12 weeks of treatment.,4 main treatment

46、,Cytotoxic drugs used when patients are steroid-dependent or steroid-resistant. Generally, it is not used alone or as primary choice. Cyclophosphamide It can be used orally or by intravenous way. Until when the total dose reach 68g or 150mg/kg。,Side effects of cyclophosphamide:,Bone marrow suppressi

47、on Liver toxicity Gonadal dysfunction Loss of hair Symptoms of digestive system: vomiting, nausea, a bad appetite, etc. Hemorrhagic cystitis,Cyclosporin,Applicability used in refractory nephrotic syndrome unresponsive to corticosteroid and cyclophosphamide. Doses 5mg/kgd administered orally in 2 div

48、ided dose.,Cyclosporin,Relapse Once cyclosporine is discontinued, the relapse of nephrosis occur easily. An alternative way to the treatment is using gradually lower doses in order to maintain the patient in remission . Side effects liver and kidney toxicity, hypertension,Therapy for different histo

49、logic type of nephrotic syndrome,Minimal change disease and mild mesangial proliferative GN： Corticosteroid is the main therapy. If the disease is unresponsive to the therapy or relapse frequently, then cytotoxic drugs can be considered.,Membranous nephropathy： It should be treated aggressively, Cor

50、ticosteroid and cytotoxic drugs should be used. But , after the treatment course is finished, these drugs should not be used with a big dose for too long a term.,Membranous nephropathy Hyperlipidemia and hypercoagulable state should be controlled to prevent thrombosis and thromboembolism.,focal segm

51、ental glomerular sclerosis, severe mesangial proliferative glomerulonephritis, mesangial capillary glomerulonephritis If renal dysfunction has occurred, then usually corticosteroid and cytotoxic drugs are not given.,focal segmental glomerular sclerosis, severe mesangial proliferative glomerulonephri

52、tis, mesangial capillary glomerulonephritis If renal function is normal, sufficient dose of corticosteroid and cytotoxic drugs should be given and then tape slowly, and drugs for anti-coagulation and anti-aggregation of platelets can be administer simultaneously.,Treatment for complication infection

53、： antimicrobial sensitive for pathogen and without nephrotoxicity should be given promptly.,Thrombosis and thromboembolism. ALB20g/L，patients can become hypercoagulable. drugs Heparin a small dose of aspirin thrombosis treatment thrombolytic therapy (best used within 6 hours, it is probably effectiv

54、e within 3 days.) streptokinase can be used.,Acute renal failure a big dose of loop diuretics hemodialysis alkalizing the urine metabolic disturbance of protein and lipid ACEI can alleviate proteinuria Antihyperlipidemia: HMC-CoA reductase inhibitors,Prognosis,Factors that affect the prognosis histo

55、logic type Clinical presentations:heavy proteinuria,hypertension, hyperlipidimia, anemia, azotemia. complication,To take home points,Talking about the nephrotic symdrom(NS). What is clinical though of NS. What is Histologic type of NS and its clinical features?,To take home points,Talking about the

56、complication of NS? Talking about the application of glucocorticoid in NS and its Side effects .,Chronic glomerulonephritis,Conception： Chronic glomerulonephritis refers to a group of glomerular disease that develop slowly and eventually lead to chronic renal failure.,Histologic alterations,Mesangia

57、l proliferative glomerulonephritis Mesangial capillary glomerulonephritis Membranous nephropathy Focal segmental sclerosis Sclerosing glomerulonephritis,肾小球纤维化，肾小管萎缩，肾间质炎症细胞浸润,glomerulosclerosis,Diffuse infiltration of neutrophil in interstitum,Clinical manifestations and laboratory findings,Commonl

58、y seen in adults, a male predominance. Generally occur indolently. Some patients present as acute nephritic symdrome with prodromal infection.,Clinical presentations,Proteinuria: A13g/d. BGlomerular proteinuria Hematuria: AGlomerular hematuria BMainly in patients with proliferative or focal histologic alterations it can be macroscopic hematuria,Clinical presentations,Edema Hypertension R