儿科学课件（重庆医科大学）15ns肾病综合征

Nephrotic Syndrome,NS 肾病综合征,Contents,Definition Classification Etiology and Pathogenesis Pathophysiology Clinical manifestation Complication Diagnosis Treatment Prognosis,Definition,NS is an accumulation of symptoms and signs for abnormal increase in perme-ability of the glomerular basement mem- brane (GBM) to protein.,Clinical features: Edema Proteinuria Hypoalbuminemia Hyperlipidemia,NS AGN,Epidemiological Investigation Of Urine System In Hospitalization,The second commonest renal disease hospitalized in China,General Information,General Information,Occurs at any age: most common between the ages of 3 and 5 years Gender: M:F=3.7:1,Classification of NS,Primary NS (PNS) Secondary NS Congenital NS,See P322-323,Primary Nephrotic Syndrome 原发性肾病综合征 (PNS),Classification of PNS,Clinical classification: Simple type NS(SNS) Nephritic NS(NNS),See P322-323,Sensitivity to steroid therapy: Steroid-sensitive NS (SSNS)激素敏感型NS Steroid-resistant NS (SRNS)激素耐药型NS Steroid-dependant NS (SDNS)激素依赖型NS,Classification of PNS,小儿内科学 P323,Pathologic classification: Minimal change NS (MCNS): Non-minimal change NS： Diffuse mesangial proliferation (DMP)弥漫系膜增生性肾炎 Focal segmental glomerulosclerosis (FSGS)局灶节段肾小球硬化 Membranoproliferative glomerulonephritis (MPGN)膜增生性肾小球肾炎 Membranous glomerulopathy (MN)膜性肾病,Classification of PNS,Etiology and Pathogenesis,Are unclear by far Possible mechanisms: T cell-mediated immune disorder (MCNS) Immune complex-mediated (Non MCNS),glomerular filtration membrane,分子屏障（孔径屏障）,静电屏障,上皮细胞足突,内皮细胞,基膜,Sialoprotein (-),硫酸肝素糖蛋白(-),Electrostatic Barrier,Molecular Barrier,Negative charge of GBM lose, electrostatic Barrier disappear,increased permeability to proteins will result in MCNS,Etiology and Pathogenesis,Molecular Barrier is damaged, increased permeability to proteins will result in non-MCNS,Pathology,EM 10,000 MCNS,EM 10,000 Normal glomeruli,Finding on electron microscopy simply reveals effacement of the epithelial cell foot processes,FSGS,normal glomeruli,Non-minimal change dieases,Pathophysiology,Proteinuria Fundamental change Caused by : Damage in Electrostatic Barrier or Molecular Barrier The quantity of protein passing through GBM is greater than the tubular resorption capacity. Heavy proteinuria : 24-hours urine protein quantitation50mg/Kg urine protein/creatinine ratio尿蛋白/尿肌酐: exceeds 2.0,Hypoalbuminemia Caused by Lost from urine Raise of proteolysis by tubular Loss of albumin is more than synthesis in liver hypoalbuminemia: Alb 25g/L,Pathophysiology,微量元素载体蛋白丢失 激素结合蛋白丢失,Edema Caused by Decreased plasma osmotic pressure The activation of the renin-angiotensinaldo-sterone system (RAAS) increase Characteristic: pitting edema凹陷性水肿,Pathophysiology,Hyperlipidemia Caused by Increased compensatory synthesis by liver Lipid conversion disorder (LDL) lost from urine (HDL) Serum Cholesterol5.7mmol/L,Pathophysiology,导致肾小球纤维化 导致高凝、血栓形成,肾病综合征病理生理,水肿,impairment of GBM,Increased permeability of GBM,massive proteinuria,Hypoalbuminemia,Plasma oncotic pressure,Edema,compensatory synthesis and lipidprotein metabolism disorder,Hyperlipidemia,plasmavolume,Fluid shift to tissue space,Pathophysiology,activiation of RAAS,water-sodium retention,Edema The most common complain Feature : pitting, dependent edema Site : first periorbital edema, proceed into scrotum, limbs , ascites, pleural effusions,Clinical Manifestations,Proteinuria Glomerular capillary wall permeability Quantity is greater than the tubular resorption capacity Heavy proteinuria : 24-hours urine protein quantitation50mg/Kg urine protein to creatinine ratio 2.0,Clinical Manifestations,Hypoalbuminemia Result of urinary protein loss and low protein synthesis Serum albumin25g/L,Clinical Manifestations,Hyperlipidemia Result of increased compensatory synthesis and lipid metabolism disorder Serum cholesterol 5.7mmol/L, most serum lipoproteins increase（ Ch, TG, LDL , HDL ）,Clinical Manifestations,Clinical classification of PNS,Clinical Manifestations,Complications,The most common complication Lead to failure of treatment or relapse of NS Atypical manifestations Fever and physical findings may be minimal because of cortical steroid therapy,Infections,Complications,Reasons: Decreased IgG levels Edema acting as a potential culture media Immunosuppressive therapy,Infections,Pathogen: viral , bacterial, particularly streptoccocus pneumoniae, fungi Site: Respiratory tractUrinary tractSkin Spontaneous peritonitis ，Sepsis, Cellulitis,Complications,Infections,Reasons: salt prohibition excessive usage of diuretic ( iatrogenic医源性) hypokalemia低钾血症 hyponatremia 低钠血症 hypocalcaemia低钙血症,Complications,Electrolyte disturbance,Complications Thrombosis,Increased tendency to develop arterial and venous thrombosis,Reasons: Elevated coagulation factors and inhibitors of fibrinolysis Decreased anti-thrombin III Increased platelet aggregation,下肢静脉血栓 下肢水肿固定差别 不随体位改变,下肢动脉血栓 皮温下降、动脉搏动消失、疼痛,肾静脉血栓 急性-发作性血尿、腰痛 慢性-蛋白尿持续不缓解,Urinalysis: protein: 2+4+，granular and red cell casts 24hr total urinary protein quantitation 50mg/kg，Urine protein to creatinine ratio 2.0 Albumin levels25g/L .Serum cholesterol and triglycerides: Total Cholesterol 5.7mmol/L (220mg/dl). Renal function: varying degree of decline Immunologic tests:Serum complement level : vary with clinical type. low level immunoglobin G( IgG) Renal biopsy,Lab Studying,qualitative test of urinary protein,：阴性,在黑色背景时，看不到浊表现 -：尿里有微量蛋白，白色轻度混浊，仅在黑色背景时可以看到 ：尿里有中等量蛋白，白色轻度混浊，无絮状颗粒出现 ：尿里有中等量-多量蛋白，出现明显白色沉淀 ：尿里有多量蛋白，出现絮状白色沉淀 ：尿里有大量蛋白，出现凝固成块,PNS肾活检指征：,对糖皮质激素治疗耐药或频繁复发者 对临床或实验室证据支持肾炎型肾病或慢性肾小球肾炎,Diagnosis,Step 1: NS or no Step 2: Primary or Secondary Step 3: Simple NS or Nephritic NS Step 4: Any complications ?,Urinary protein quantitation exceeds 50mg/kg/24 hr , urine protein to creatinine ratio exceeds 2.0, serum albumin level is g less than 25 g/L, the serum cholesterol and triglyceride levels are elevated , Varous degree of edma,No systemic disease, no infecton, no congenital disease,Hematuria?, hypertention?,Infections?where?pathogens?,Differential Diagnosis,APSGN Secondary NS - SLE, HSP, HBV Congenital NS,Treatment,Multiple treatments majored by cortical steroid therapy. 激素为主的综合治疗,Treatment,Diet: Sodium: usually normal sodium intake, restriction while severe edema Lipid: low lipid uptake recommended Protein:1.5-2g/kg.d,general treatment,Treatment,Edema management ( in cases with severe edema ) Diuresis: initiate with oral administration of Furosemide Albumin or plasma : intravenous administration of 25% human albumin or plasma if necessary Scrotal edema: elevate scrotum with pillow to remove fluid by gravity Anti-infection,Treatment,steroid therapy: a. Prednisone standard procedure : 1.5-2mg/kg.d, divided to 3 times a day, persists 4-8 weeks, then 1.5-2mg/kg every other day, reduce 2.5-5mg every 2 weeks. Average response time: 2 weeks,Steroid-sensitive NS (SSNS) Steroid-resistant NS (SRNS) Steroid-dependant NS (SDNS),Treatment,steroid therapy: b. Methylprednisolone 15-30mg/kg，IV，3 days，,Treatment,Immunosuppressive Agents免疫抑制剂 CTX环磷酰胺, MMF霉酚酸酯， cyclosporine环孢霉素, FK506 NS with repeated relapse Steroid-dependant NS Steroid-resistant NS,Others: Immune function adjustment ACEI, IVIG, traditional medicine中药,Treatment,Prognosis,Most children with steroid-responsive NS have good prognosis Steroid resistant NS may have worse prognosis.,Comparison of NSAPSGN,Terminology,Hypertensive encephalopathy 高血压脑病 Cylinduria管型尿 Acute renal failure 急性肾功能衰竭 Hemodialysis 血液净化,Hematuria 血尿 Prote