兒科學(xué)教學(xué)課件：10-2Nephrotic Syndrome,NS

1、Case 2A 2-year-old boy was brought to hospital with complain of periorbital edema. His urinalysis is remarkable for proteinuria and microscopic hematuria. During his hospitalization, he was noted to have depended edema墜積性水腫,and have abnormal serum chemistries of low-level immune globulin G, hypoalbu

2、minemia低蛋白血癥, and hyperlipidemia高脂血癥. And his urine looks frothy. His parents didnt find antescedent infection. which of the following is the most likely diagnosis?A post streptococcal glomerulonephritisB primary nephrotic syndromeC IgA nephropathyD urinary tract infectionE primary immune deficiency

3、 Nephrotic Syndrome,NS 腎病綜合征Definition NS is an accumulation ofsymptoms and signs for abnormal increase in perme-ability of the glomerular basement mem- brane (GBM) to protein. Clinical features: Edema（水腫） Proteinuria（蛋白尿） Hypoalbuminemia(低蛋白血癥) Hyperlipidemia（高脂血癥）NSAGNEpidemiological Investigation

4、 Of Urine System In Hospitalization The second commonest renal disease hospitalized in ChinaGeneral InformationPeek age: 3 - 5 years Gender: M:F=3.7:1Classification of NSPrimary NS (PNS)Secondary NS Congenital NS See P322-323Primary Nephrotic Syndrome原發(fā)性腎病綜合征(PNS)Classification of PNSClinical classi

5、fication:Simple type NS(SNS)Nephritic NS(NNS)Pathologic classification:Minimal change NS Non-minimal change NS：Diffuse mesangial proliferation (DMP)彌漫系膜增生性腎炎Focal segmental glomerulosclerosis (FSGS)局灶節(jié)段腎小球硬化Membranoproliferative glomerulonephritis (MPGN)膜增生性腎小球腎炎 Sensitivity to steroid therapy:Stero

6、id-sensitive NS 激素敏感型NSSteroid-resistant NS 激素耐藥型NSSteroid-dependant NS 激素依賴型NSEtiology and PathogenesisAre unclear by farPossible mechanisms:T cell-mediated immune disorder (MCNS)Immune complex-mediated (Non MCNS) Electrostatic BarrierMolecular BarrierNegative charge of GBM lose, electrostatic Barr

7、ier disappear,increased permeability to proteins will result in MCNSEtiology and PathogenesisMolecular Barrier is damaged, increased permeability to proteins will result in non-MCNS PathologyEM 10,000MCNSEM 10,000Normal glomeruliFinding on electron microscopy simply reveals effacement of the epithel

8、ial cell foot processesMCNS is the most common type. impairment of GBMIncreased permeability of GBMmassive proteinuriaHypoalbuminemiaPlasma oncotic pressureEdemacompensatory synthesis and lipidprotein metabolism disorderHyperlipidemiaplasmavolumeFluid shift to tissue spacePathophysiologyactiviation

9、of RAAS water-sodium retention impairment of GBMIncreased permeability of GBMmassive proteinuriaHypoalbuminemiaPlasma oncotic pressureEdemacompensatory synthesis and lipidprotein metabolism disorderHyperlipidemiaplasmavolumeFluid shift to tissue spacePathophysiologyactiviation of RAAS water-sodium r

10、etention fundamental change 腎病綜合征病理生理水腫大量蛋白尿低蛋白血癥高脂血癥腎內(nèi)蛋白質(zhì)分解代謝水分向間質(zhì)轉(zhuǎn)移水鈉潴留醛固酮增高抗利尿激素增高腎小球?yàn)V過(guò)率下降血容量下降膠體滲透壓下降脂質(zhì)代謝紊亂腎小球?yàn)V過(guò)膜通透性增高致病因素EdemaThe most common complain Feature : pitting, dependent edema Site : first periorbital edema, proceed into scrotum, limbs , ascites, pleural effusions Clinical Manifestati

11、ons Proteinuria Heavy proteinuria : 24-hours urine protein quantitation50mg/Kg urine protein to creatinine ratio 2.0Clinical ManifestationsHypoalbuminemia Serum albumin 5.7mmol/L, most serum lipoproteins increase（ Ch, TG, LDL , HDL ）Clinical classification of PNSSimple type NSNephritic NSMicroscopic

12、 hematuria_+Blood pressureusually normalhighComplement levelsnormallowRenal functionnormalinsufficientClinical ManifestationsComplicationsInfectionsElectrolyte disturbancehypercoagulable state and thrombosisComplications InfectionsThe most common complicationPathogen: viral , bacterial, particularly

13、 streptoccocus pneumoniae, fungiSite: Respiratory tractUrinary tractSkin Spontaneous peritonitis ，Sepsis, Cellulitis Complications ThrombosisIncreased tendency to develop arterial and venous thrombosisReasons:Elevated coagulation factors and inhibitors of fibrinolysisDecreased anti-thrombin IIIIncre

14、ased platelet aggregation下肢靜脈血栓下肢水腫固定差別不隨體位改變下肢動(dòng)脈血栓皮溫下降、動(dòng)脈搏動(dòng)消失、疼痛Urinalysis: protein: 2+4+，granular and red cell casts 24hr total urinary proteinquantitation 50mg/kg，Urine protein to creatinine ratio 2.0Albumin levels25g/L .Serum cholesterol and triglycerides: Total Cholesterol 5.7mmol/L (220mg/dl).

15、Renal function: varying degree of declineImmunologic tests:Serum complement level : vary with clinical type. low level immunoglobin G( IgG)Renal biopsy Lab Studyingqualitative test of urinary protein ：陰性,在黑色背景時(shí)，看不到濁表現(xiàn) -：尿里有微量蛋白，白色輕度混濁，僅在黑色背景時(shí)可以看到 ：尿里有中等量蛋白，白色輕度混濁，無(wú)絮狀顆粒出現(xiàn) ：尿里有中等量-多量蛋白，出現(xiàn)明顯白色沉淀 ：尿里有多量

16、蛋白，出現(xiàn)絮狀白色沉淀 ：尿里有大量蛋白，出現(xiàn)凝固成塊DiagnosisStep 1: NS or noStep 2: Primary or SecondaryStep 3: Simple NS or Nephritic NSStep 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 choleste

17、rol and triglyceride levels are elevated ,Varous degree of edmaNo systemic disease, no infecton, no congenital diseaseHematuria?, hypertention?Infections?where?pathogens?Differential DiagnosisAPSGNSecondary NS - SLE, HSP, HBVCongenital NSTreatmentMultiple treatments majored by cortical steroid thera

18、py.激素為主的綜合治療Treatment Diet: Sodium: usually normal sodium intake, restriction while severe edema Lipid: low lipid uptake recommended Protein:1.5-2g/kg.d general treatmentTreatment Edema management ( in cases with severe edema )Diuresis: initiate with oral administration of FurosemideAlbumin or plasm

19、a : intravenous administration of 25% human albumin or plasma if necessary Scrotal edema: elevate scrotum with pillow to remove fluid by gravity Treatmentsteroid 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, re

20、duce 2.5-5mg every 2 weeks. b. Methylprednisolone 15-30mg/kg，IV，3 days TreatmentImmunosuppressive Agents免疫抑制劑 CTX環(huán)磷酰胺, MMF霉酚酸酯， cyclosporine環(huán)孢霉素, FK506 NS with repeated relapseSteroid-dependant NSSteroid-resistant NSRenal biopsy腎活檢Others:Immune function adjustmentACEI, IVIG, traditional medicine中藥Tr

21、eatmentComparison of NSAPSGNNSAPSGNpre-school ageschool ageelectrostatic barrier disapear or Molecular Barrier is damaged decreased GFR and impairment of GBMmajored by proteinuriamajored by hematuriaminimal change capillaries proliferative glomerulonephritiscorticosteroid therapy symptomatic treatme

22、ntalteration with different pathological patternbenign prognosisCase 2A 2-year-old boy was brought to hospital with complain of periorbital edema. His urinalysis is remarkable for proteinuria and microscopic hematuria. during his hospitalization, he was noted to have depended edema,and have abnormal serum chemistries of low-level immune globulin G, h