（实用课件）肾病综合征(英文版)

1、NEPHROTIC SYNDROMENEPHROTIC SYNDROMENephrotic SyndromeProteinuria (“nephrotic range”3.5g/24h)Hypoalbumimenia (serum albumin 3.0 to 3.5 g/pe/24hours), which leads to hypoproteinemia,decreased levels of serum albumin (albumin 3.5 gTubular proteinuria never exceeds 2 g per 24 h andnever causes NSUrinar

2、y excretion of more than 3.5 g per 24 hours isalways glomerular diseaseCAUSE OF PROTEINURIA AS RELATENON-PATHOLOGIC FORMS OF PROTEINURIA Orthostatic proteinuria typically in healthy teens and young adults occurs upon assuming upright position usually less than 2g/24 h Functional proteinuria patients

3、 with normal kidneys but experiencing:- high fever- congestive heart failure- exposure to cold- resolves with resolution of precipitating eventPersons younger than 30 years who excrete less than 2 gof protein per day and who have a normal creatinineclearance should be tested for orthostatic proteinu

4、riaNON-PATHOLOGIC FORMS OF PROTEHYPOALBUMINEMIA most common clinical correlate of severe proteinuriawith almost always associated with hypoalbumemia relationship between proteinuria and hypoalbuminia isvariable variability partly depends on livers capacity tosynthesize albumin 6-10 percent of albumi

5、n pool normally catabolizeddailyHYPOALBUMINEMIA most common cHYPOALBUMINEMIA IN NEPHROTIC SYNDROME MAYRESULT FROM: Increased loss (in urine) or catabolism (filteredalbumin increased tubular reabsorption enhancedcatabolism by tubular cells; increased renal catabolismin part offset by decreased extrar

6、enal catabolism.Decreased synthesis of albumin (hepatic synthesis innephrotic syndrome is normal or increased, but belowmaximal rate achieved in other hypoalbuminemicstates) Changes in albumin distribution (some evidence forredistribution into other capillary beds)HYPOALBUMINEMIA IN NEPHROTIC SHYPOA

7、LBUMINEMIAHigh glomerular permeability leads to hyperalbuminuriaand, eventually, to hypoalbuminemia.Hypoalbuminemia lowers the plasma colloid osmoticpressure, causing greater transcapillary filtration of waterand the development of edema.Capillary hydrostatic pressure and the gradient of plasmato in

8、terstitial fluid oncotic pressure determine themovement of fluid from the vascular compartment to theinterstitium.Fluid that is not absorbed back into the vascular systemuntil it has reached the venous end of the capillary bed isusually absorbed by the lymphatics and returned back tothe vascular spa

9、ce.HYPOALBUMINEMIAHigh glomerulHYPOALBUMINEMIAResponses to decreased blood volume Decreased renal perfusion, renin release, sequentialgeneration of angiotensin II, aldosterone, andsubsequent sodium reabsorption ADH release and resultant water retention atcollecting duct Decreased atrial naturetic pe

10、ptide release andresultant decreased sodium excretionEdema is result of salt and water retentionHYPOALBUMINEMIAResponses to deHYPERLIPIDEMIA Clinical correlate of severe proteinuriaTotal plasma cholesterol levels increase as proteinuriabecomes heavy Levels of triglycerides only mildly increasedPatho

11、genesis loss of albumin & associated hypoalbuminemia directlyor indirectly stimulates hepatic protein synthesis reduced colloid osmotic pressure results in increasedalbumin and lipoprotein synthesis and decreasedcatabolism of lipoproteins in nephrotic syndromeincrease in total plasma and LDL cholest

12、erol with anormal or reduced HDL cholesterol increased risk ofpremature atherosclerosisHYPERLIPIDEMIA Clinical correHYPERCOAGULABILITY (I)Low zymogen factors, factor IX, factor XI.Inreased prooagulatory cofators, factor V, factor VIIIIncreased fibrinogen levelsDecreased oaulatory inhibitors: antithr

13、ombin III (butprotein C and S increased)Altered fibrinolytic system (2-antiplasmin increased,plasminogen decreased)Increased platelet reactivity:thromoytosisIncreased release reaction in vitro (ADP, thrombin,collagen, arachidonic acid, epinephrine)Altered endothelial cell funtionHYPERCOAGULABILITY (

14、I)Low zymHYPERCOAGULABILITY (II)Patients can develop spontaneous peripheral arterial orvenous thrombosis, renal vein thrombosis, and pulmonaryembolism.Clinical features of acute renal vein thrombosis include sudden onset of flank or abdominal pain, gross hematuria, a left-sided varicocele (the left

15、testicular vein drains intothe renal vein), increased proteinuria, and an acute decline in glomerularfiltration rate.Chronic renal vein thrombosis is asymptomatic.HYPERCOAGULABILITY (II)PatientMETABOLIC COMPLICATIONS Metabolic complications of NS include proteinmalnutrition and iron-resistant microc

16、ytic hypochromicanemia due to transferrin loss. High glomerular permeability causes the excretion ofvitamin Dbinding protein and complexes in the urine,leading to (1) malabsorption of calcium and development of bonedisease (eg, osteitis fibrosa cystica) because ofenhanced parathyroid hormone product

17、ion and(2) osteomalacia because of impairment inmineralization.METABOLIC COMPLICATIONS MetabSYMPTOMS AND SIGNSMost often, the edema is mobile -detected in the eyelids in themorning and in the ankles afterambulation.Oliguria and even acute renalfailure may develop because ofhypovolemia and diminished

18、perfusion.SYMPTOMS AND SIGNSMost often,COMPLICATIONSProlonged NS may result in nutritional deficiencies, includingprotein malnutrition resembling kwashiorkor, brittle hair and nails,alopecia, stunted growth, demineralization of bone, glucosuria,hyperaminoaciduria of various types, K+ depletion, myop

19、athy,decreased total Ca, tetany, and hypometabolism.Spontaneous peritonitis may occur, and opportunistic infectionsare prevalent. The high incidence of infection is thought to be dueto the urinary loss of immunoglobulins.Coagulation disorders, with decreased fibrinolytic activity andepisodic hypovol

20、emia, are a serious thrombotic risk (notably, renalvein thrombosis).COMPLICATIONSProlonged NS may（实用课件）肾病综合征(英文版)MINIMAL CHANGE DISEASE 90% childhood nephrotic syndrome Common in young adults 15% total adult cases Steroid responsive (80%) steroid sensitive 2nd line therapyAssociations NSAIDs Paraneo

21、plastic Hodgkins diseaseMINIMAL CHANGE DISEASEAssociaMINIMAL CHANGE DISEASEMINIMAL CHANGE DISEASEMINIMAL CHANGE GN:Synonyms:Incidence:Etiology:ClinicalFeatures:LabFeatures:Pathology:ClinicalCourse:Nil disease, lipoid nephrosis, foot processdisease80% of nephrotic syndrome inchildren (1-8 yrs.), most

22、ly male.Adults in 2nd-3rd decade.Idiopathic. Loss of net negativecharge on capillary basementmembrane.Nephrotic syndrome. History ofrecent URI in 30%. Associationwith Hodgkins lymphoma.Overlap with FSGS patients.Selective proteinuria. No specificlaboratory findings.LM - Normal. IF - Negative.EM - Fo

23、cal fusion/loss of footprocesses.Spontaneous remission in 25-40%.Complete remission in 65-70% ofpatients. Steroid resistant patientsmay progress to FSGS.MINIMAL CHANGE GN:Synonyms:NiFSGSMost common idiopathic nephroticsyndrome in adults (33%)Increasing incidenceMore common in blacksTreatment very di

24、fficultFSGSMost common idiopathicFSGSMildModerateCollapsingASSOCIATIONSIdiopathicMorbid obesityHeroin abuseHIV infectionNSAID(Minimal change disease)NormalFSGSMildModerateCollapsingASSLab:Mesangioproliferative GNIncidence:Common type, Almost all agesClinical:Almost everyone has hematuria. Part of th

25、em with Nephrotic syndrome. Slow progression.Not special, may IgA increase.Path:Diffuse proliferative GN in mesangial region. Electron-dense deposits.Clinical Slow progression. Normally no hypertension or GFR lossCourse:Lab:Mesangioproliferative GNInMEMBRANOUS GNSynonyms:Epimembranous, extramembrano

26、us GNIncidence:40-60 Years, 50% of adult nephroticsyndrome.Etiology:Immune complex disease. Idiopathic in mostpatients, associated with infections, drugs,carcinomas, and heavy metals.Clinical:Nephrotic syndrome in 80%, asymptomaticproteinuria in 20%. Microscopic hematuria.Lab:Non-selective proteinur

27、ia hematuria.Path:Diffuse, uniform BM thickening withsubepithelial projections (“spikes”). Diffuse,coarsely granular IgG and C3 deposits alongbasement membranes. Electron-densesubepithelial deposits.ClinicalCourse:Excellent prognosis in children. Some adultsdevelop ESRD. Exclusion of other diseasesi

28、s required.MEMBRANOUS GNSynonyms:EpimembrMEMBRANOUS GNMEMBRANOUS GNLab:MEMBRANOPROLIFERATIVE GNIncidence:Children and young adults (5-25 years).Etiology:Chronic immune complex GN. Associated withchronic infections, SLE, cancer, cirrhosis,heroin abuse, etc.Clinical:Nephrotic syndrome in 50%, acute ne

29、phriticsyndrome in 20%. Recent history of URI in 50%.Hypertension and/or renal insufficiency.Hypocomplementemia of classic and alternatepathways. C3 nephritic factor (C3NEF). Circulatingimmune complexes.Path:Diffuse proliferative GN with thickening of theglomerular capillary walls, and GBM splitting

30、(“tram-tracking”). Diffuse, coarsely granular C3and IgG deposits along GBMs. Electron-densesubendothelial deposits.Clinical Progressive deterioration of renal function shortCourse: remissions. ESRD within 10 years in 50% ofchildren and 80% of adults.Lab:MEMBRANOPROLIFERATIVE GNInMEMBRANOPROLIFERATIV

31、E GNType IType IIType IIIMEMBRANOPROLIFERATIVE GNType ITreatment 治疗1. General treatment2. Symptomatic treatment (e.g.diuresis to relieve edema, treating dyslipidemias, anticoagulate treatment, etc.)3. Immunosupressive treatment 一、一般治疗二、利尿消肿三、免疫抑制治疗四、调脂药物五、抗凝治疗Treatment 治疗1. GenerTREATMENT The treatment of NS in