1、首都儿科研究所附属儿童医院 陈朝英 要求要求 掌握急性肾小球肾炎典型表现、重症表现及非典 型表现 掌握急性肾小球肾炎的诊断 掌握急性肾小球肾炎的治疗原则 Anatomy and physiology characteristics of urologic system 解剖特点Anatomy characteristics 生理特点Physiology characteristics 肾功能的临床评估Estimate of renal function Physiology characteristics 出生后一段时期内呈动态成熟过程：贮备能力 差，调节机制不成熟， 肾功能1-1岁半接近成人
2、。 Estimate of renal function 肾功能检查 检查结果的临床意义应考虑年龄、身长、体重 等因素 BUN SCr CCr 胱抑素C 肾小球疾病的临床分类肾小球疾病的临床分类 原发性肾小球疾病 肾小球肾炎 急性肾小球肾炎 急进性肾炎 迁延性肾炎 慢性肾炎 肾病综合征 单纯性肾病 肾炎性肾病 无症状性血尿或蛋白尿 继发性肾小球疾病 紫癜性肾炎 狼疮性肾炎 乙型肝炎病毒相关肾炎 药物中毒 其他 遗传性肾小球疾病遗传性肾小球疾病 遗传性进行性肾炎遗传性进行性肾炎 家族性血尿家族性血尿 其他其他 General Information Acute glomerulonephriti
3、se acute postinfectious other secondary /primary glomerulonephritis glomerulonephritis acute poststreptococcal glomerulonephritis Other pathogens A group of glomerular diseases by different causes Etiology cases of GN follow infection with group A hemolytic streptococci, such as upper respiratory tr
4、act infection, Scarlet fever, skin infection. Pathogenesis It is now generally accepted that glomerulonephritis is a form of immune - complex disease. The antigenic component of the immune complex be related somehow to the streptococcus. Some strains of A group hemolytic streptococcus URI skin infec
5、tion antibody production circulating in site antigen-antibody complexes immune complexes deposit in the GBM activate the complement system incite media of inflammation Pathogenesis Autoimmune reaction immune injuriesimmune injuries ( (Ag-AbIC C3 ) Cells proliferation media of inflammationCells proli
6、feration media of inflammation capillary lumen narrowed capillary lumen narrowed hematuria hematuria protineruriaprotineruria Glomerular bloodGlomerular blood flow flow azotemiaazotemia GFR GFR oliguria /anuriaoliguria /anuria Retention of water and natriumRetention of water and natrium edemaedema h
7、ypertensionhypertension blood volumeblood volume hypertensive encephalopathhypertensive encephalopath circulatory congestioncirculatory congestion Pathogenesis Pathology In gross observation the kidneys appear Symmetrically enlarged. By light microscopy -all glomeruli appear enlarged and relatively
8、bloodless -show cells proliferation, such as epithelial cells, endothelial cells,mesangial cells. -polymorphonuclear leukocytes invade in glomeruli during the early stage of the disease, and increase in mesangialmatrix. Pathology By immunofluorescent microscopy show lumpy-bumpy granular staining for
9、 IgG in peripheral capillary loops and mesangial areas By electron microscopy electron-dense deposits or humps are observed on the epithelial side of the glomerular bacementmembrane (GBM) 毛细血管内增生性肾小球肾炎，毛细血管内增生性肾小球肾炎， IgG 粗大颗粒沿毛细血管粗大颗粒沿毛细血管 壁沉积壁沉积 （荧光，（荧光， 400 400） In AGN, immunofluorescent studies s
10、how lumpy-bumpy granular staining for IgG in peripheral capillary loops and in mesangial areas Clinical manifestation Incubation: 1-3 weeks after infection. r r ： Clinical manifestation 1.Typical cases (1) Edema and oliguria: mild degree edema only in eyelids in the morning severe degree all over th
11、e body, edema is non pitting. urinary output decreased oliguria 120/80 School age 130/90 Frequency of clinical Manifestations in APSGN Gross hematuria 50 70 % Volume overload Edema 70% Hypertension 30-80% Circulatory congestion 20% CNS symptoms 10% Progressive GN 3/HP , malformation RBC60%. (2) Prot
12、einuria:1+ 3+. (3) The urinary sediment: WBC and epithelial cells, hyaline, granular and red blood cell casts Laboratory findings 2.Blood test (1) a mild anemia (3) ESR: the erythrocyte sedimentation rate (4) Hypocomplementemia: C3, CH50. Laboratory findings 2.Boold test (5) ASO: Antistreptolycin 0
13、titer elevated from 1 to 3 weeks after infection, the highest level from 3 to 5 weeks. Anti-DNAse B and anti hyaluronidase are elevated in patients with polyderma. (6) Renal function: SCr, BUNand GFR due to severe oliguria. Diagnosis3 steps 1st Clinical manifestation abruptly with hematuria Proteinu
14、ria Hypertension azotemia asymptomatic oliguric acute renal failure latent period Pharyngitis skin infection nephritis 2nd 3rd evidence of recent group A streptococcal infection a positive skin or throat culture ASO(+)、Anti-SpeB Diagnosis Special important Low C3（90%） Returns to normal in 8 weeks in
15、 all patients with uncomplicated PSGN Is helpful for diagnosis subclinical APSGN（ mild abnormalities of urine，transient drop in complement） Indications for renal biopsy Massive proteinuria Complement is persistently reduced after 3- 4months Acute nephrosis syndrome with normal serum complement Serum
16、 creatinine increases progressively Differential diagnosis 1.Other primary GN are frequently confused. IgA nephropathy Membrane proliferative disease 2. Secondary GN atypical cases resulted from systemic disease such purpura nephroitis, systemic lupus nephritis HBV associated GN Differential diagnos
17、is 3. Chronic nephritis also may easily be mistaken for acute disease. 4. RPGN Rapidly Progressive glomerulonephritis 5. Primary NS Summary of Primary Renal Diseases That Manifest as Acute Glomerulonephritis DISEASES POSTSTREPTOCOCCAL GLOMERULONEPHRITIS IGA NEPHROPATHY GOODPASTURE SYNDROME IDIOPATHI
18、C RAPIDLY PROGRESSIVE GLOMERULONEPHR ITIS (RPGN) Clinical manifestations Age and sex All ages, mean 7 yr, 2 : 1 male 1035 yr, 2 : 1 male 1530 yr, 6 : 1 male Adults, 2 : 1 male Acute nephritic syndrome 90% 50% 90% 90% Asymptomatic hematuria Occasionally 50% Rare Rare Nephrotic syndrome 1020% Rare Rar
19、e 1020% Hypertension 70% 3050% Rare 25% Acute renal failure 50% (transient) Very rare 50% 60% Other Latent period of 13 wk Follows viral syndromes Pulmonary hemorrhage; iron deficiency anemia None Laboratory findings ASO titers (70%) Serum IgA (50%) Positive anti-GBM antibody Positive ANCA in some P
20、ositive streptozyme (95%) IgA in dermal capillaries C3C9;normal C1, C4 Immunogen etics HLA-B12, D “EN” (9)* HLA-Bw 35, DR4 (4)* HLA-DR2 (16)* None established Renal pathology Light microscopy Diffuse proliferation Focal proliferation Focal diffuse proliferation with crescents Crescentic GN Immunoflu
21、 orescence Granular IgG, C3 Diffuse mesangial IgA Linear IgG, C3 No immune deposits Electron microscopy Subepithelial humps Mesangial deposits No deposits No deposits Prognosis 95% resolve spontaneously Slow progression in 2550% 75% stabilize or improve if treated early 75% stabilize or improve if t
22、reated early 5% RPGN or slowly progressive Treatment Supportive Uncertain (options include steroids, fish oil, and ACE inhibitors) Plasma exchange, steroids, cyclophosphamide Steroid pulse therapy ACE, angiotensin-converting enzyme; ANCA, antineutrophil cytoplasmic antibody; ASO, anti-streptolysin O
23、;GBM, glomerular basement membrane; GN, glomerulonephritis; HLA, human leukocyte antigen; Ig, immunoglobulin. From Kliegman RM, Greenbaum LA, Lye PS: Practical Strategies in Pediatric Diagnosis and Therapy, 2nd ed. Philadelphia, Elsevier, 2004, p 427. Treatment 1.Nursing and diet Bed rest is indicat
24、ed as long as there are clinical manifestations of active disease, such as edema, hypertension, or gross hematuria Protein restricted( intake 0.5g/kg.d) Salt restricted ( 60mg/kg.day) ESR normal go to school Treatment 2 Antibiotics Penicillin is used for 10 to 14 days . 3 Diuretic therapy Salt restr
25、iction, HCT 23mg/kg d PO, Furosemide 25mg/kg.d PO or l2mg/kg dose iv 4 Antihypertensive therapy: Reserpine: O. 07mg/kg.im Nifedipine: O. 25 to 0 . 5mg/kg. d P.O. Captopril: for treating severe hypertension ( O. 3mg/kg d Tid Po). Treatment 5.Treatment of severe complications Hypertensive encephalopat
26、hy: Sodium nitroprusside( l8g/kg ) introvenously drop continually, regulating the dropping speed according to the level of BP. Anticonvulsant water deprivation with Mannitol oxygen therapy Treatment 5.Treatment of severe complications Severe Circulatory Congestion: Restriction of salt and water, diu
27、retics. Sodium nitroprusside Acute renal failure: Maintaining balance of water, electrolytes and acid base,applying energy and preventing complications. Peritoneal and hemodialysis may be needed. Course and prognosis 2 weeks edema gross hematuria Hypertension Abnormal urine usually lasts 1 years or
28、longer. The prognosis of AGN is very good. Prognosis The early mortality is very low in children Cardiovascular complications are the main cause Irreversible renal failure may fellow acute nephrisis with crescentic proliferation 10-20 yrs later 20% -abnormal urine analysis or creatinine clearence 1%
29、 -azotaemia 8-13%-proteinuria and hypertension The incidence of glomerular sclerosis and fibrosis is nearly 50%,but their relevance is uncertain Microhaematuria Intermittent Proteinuria Gross H Hypertention Low C3 Persistent Proteinuria 2 weeks 4 weeks 2 months 6 months 1 years 2 years Clinical and
30、Laboratory features Time course to revolution of APSGN Summery 循环免疫复合物循环免疫复合物 氮质血症、尿毒症氮质血症、尿毒症 水肿、高血压、心力衰竭水肿、高血压、心力衰竭 钠水潴留、血容量增加钠水潴留、血容量增加少尿、无尿少尿、无尿 球管失衡球管失衡 GFR下降GFR下降 肾小球滤过面积下降肾小球滤过面积下降 毛细血管官腔闭塞毛细血管官腔闭塞 内皮细胞肿胀、系膜细胞增生内皮细胞肿胀、系膜细胞增生 蛋白尿、血尿、管型尿 蛋白尿、血尿、管型尿 肾小球基底膜破坏肾小球基底膜破坏 肾小球炎性病变肾小球炎性病变 激活补体及各类炎症物资激活补
31、体及各类炎症物资 原位免疫复合物原位免疫复合物其它因素其它因素 链球菌致肾炎株链球菌致肾炎株 ASO+ C3 实验室检查 临床表现 诊断 治疗 Reference Brenner and Rectors The Kidney Nelson Textbook of Pediatrics - 18Ed Oxford Textbook of Clinical Nephrology(3rd Ed) 思考题思考题 病历摘要 患儿，女，因“双眼睑浮肿、血尿6天”入院。6天前出现双眼睑浮 肿，排茶色全程血尿，伴尿频、尿急，尿中无血块，尿量无减少。当 地医院予抗生素治疗（具体不详）。4天前，患儿浮肿加重，渐波
32、及 全身，尿量每日130-150ml，血压130/90mmHg，予利尿、降压治疗 ，患儿病情无好转，转来我院。病前2周曾出现发热，并伴有咳嗽。 过去史、家族史、生长发育及喂养史、预防接种史无特殊。查体：血 压140/95mmHg，双眼睑、颜面浮肿，睑结膜苍白，双肺音粗，可闻 及细湿罗音。心率120次/分，律齐，心音有力，未闻杂音。腹软，肾 区叩击痛（+），双下肢非可凹性水肿。实验室及影像学检查：血常规 ：血色素93g/L，红细胞3.81012/L,网织红1.4%，白细胞11.3109 /L,分叶82%，淋巴16%，单核2%，血小板207109 /L；尿常规：尿 蛋白（+），红细胞30-40个/HP，比重1.010。 思考题思考题 该患儿的初步诊断是什么？ 诊断依据是什么？ 还需补充哪些症状、体征及实验室检查？ Thank You For Your Attention
