过敏性紫癜的诊断和治疗.ppt

泌尿系统疾病,苏州大学儿科学系 肾内科,World Kidney Day,March 9th 2019 was the first WKD and then the second Thursday on march will be anniversary for kidney diseases. About 10% population involved Chronic Kidney disease (CKD) in USA About 100 million CKD in china of the total medical cost,Introduction :background,Effective management of the patient with renal disease is dependent upon establishing an accurate diagnosis. The clinician must be aware of the possible presentations of renal diseases and gather these symptoms and signs which form recognized diseases and syndrome What is the possible presentations suggesting renal problem ?,Clinical presentation of renal disease,The patient is asymptomatic, but an abnormality has been detected on clinical or laboratory examination which indicates an underlying renal disorder. The patient complains of a symptom or has a physical sign which directly or indirectly indicates underlying renal diseases The patient has a systemic disease which is known to be associated with renal involvement The patient has a family history of an inherited renal disorder.,Symptoms of urinary tract disease,A fever; dysuria; frequency; loinpain/abdominal pain; urinary inconsistency;offensive smelling;cloudy urine; Frothy urine :Proteinuria; Smokey urine : Haematuria,Signs of urinary tract disease,Dysmorphic syndromes; Anaemia; Oedema; High blood pressure; Renal masses; Distended bladder.,Acute glomerulonephritis(AGN),急性肾小球肾炎,Acute glomerulonephritis(AGN),概述 病因 发病机制 病理生理 病理 临床表现 实验室检查 诊断 鉴别诊断 治疗 预后,急性肾小球肾炎,目的要求,了解急性肾炎的病因及发病机理。 掌握一般病例与严重病例的临床表现及治疗原则。 掌握急性肾炎的实验室检查。 了解急性肾炎与其他病原体引起急性肾炎、慢性肾炎急性发作、特发性肾病综合症、IgA肾病综合症、急进性肾炎等疾病的鉴别诊断。,重点和难点,重点：本病的一般病例及严重病例的临床表现及其产生机理。 该病的尿液及血生化检查。 小儿单纯性血尿的诊断要点和处理原则。 难点：本症重症病例的治疗，高血压脑病急性肾功能不全，严重循环充血治疗及处理原则。,Acute poststreptococcal glomerulonephritis 急性链球菌感染后肾炎 Hematuria 血尿 Oliguria 尿少 Edema 浮肿,关键词：Key words,概 述,定义：急性起病，双侧性，弥漫性，前趋感染（非化脓性炎症），临床上以血尿为主，可有水肿、少尿、高血压，或肾功能不全等特点 发病情况：年龄5-14岁、性别男女2：1、发生率下降,病 因,细菌：A组溶血性链球菌的某些致 肾炎菌株；其他细菌有。 病毒：巨细胞、乙肝病毒等 其他：支原体、霉菌、原虫等,发病机制 病理生理,链球菌致肾炎菌株的抗原成分 循环免疫复合物 原位免疫复合物 自身免疫 激活补体系统 释放生物活性因子 肾素血管紧张素醛固酮 肾小球基底膜断裂 GRF 水钠储留 血尿、蛋白尿、管型尿 水肿、少尿、高血压 肾衰,病 理,毛细血管内增生性肾小球肾炎 光镜：内皮细胞、系膜细胞增生、肿胀，系膜基质增多，中性粒细胞浸润，严重时可有“新月体”形成 电镜：上皮细胞下“驼峰样”电子致密物沉积 免疫荧光：IgG、C3沉积,AA：入球小动脉 EA：出球小动脉 EGM：肾小球外系膜 PE：壁层上皮细胞 PO：足突细胞 GBM：肾小球基底膜 F：足突 US：尿液腔 M：系膜 PT：近曲小管 MD：致密斑 G：颗粒细胞 N：交感神经 E：内皮细胞,PO： 足突细胞 podocyte GBM：肾小球基底膜 glomerular basement membrane M：系膜 mesangial cell MM：系膜基质 mesangial matrix E：内皮细胞 fenestrated endothelium,新月体肾炎,临床表现（一）,前驱感染 ( Precede infection) 秋冬季呼吸道感染为主 夏秋季皮肤感染多见,临床表现（二）,典型表现 ( typical manifestation ) 水肿 (部位, 性质, 时间) 尿少 （少尿，无尿） 血尿 （肾小球性） 高血压 (头晕, 头痛),电镜扫描 尿红细胞形态,临床表现（三）,严重表现(Serious manifestation) 循环充血 “心衰”征象 高血压脑病 剧烈头痛 恶心呕吐 惊厥昏迷 急性肾功能不全 少尿 氮质血症 电解质紊乱,呼吸困难, 肺底湿罗音 心脏扩大, 心率增快 肝肿大,临床表现（四）,不典型表现 (Atypical manifestation) 无症状病例 无临床症状,有尿改变,补体C3下降 肾外症状型 水肿,高血压等表现明显 尿改变轻微 肾病综合征型 大量蛋白尿 肾活检病理改变类似典型病例,实 验 室 检 查,尿常规 血常规 肾功能 血沉 ASO 血补体（C3下降）,诊 断,前驱链球菌感染史 临床症状：血尿、水肿、高血压等 实验室检查：尿检、ASO 、C3等,鉴 别 诊 断,非典型病例（大量蛋白尿型） 非链球菌感染肾炎（病毒性） IgA肾炎 全身性疾病（SLE，APN，乙肝肾） 慢肾急发 急进性肾炎 尿路感染 肾病综合症,治 疗（一）,一般治疗 卧床休息（约2周）：水肿退，血压降，肉眼血尿消失；血沉正常上学；12小时尿沉渣正常恢复体力活动 饮食：低盐：60mg/kg。d；低蛋白0。5mg/kg。d 抗感染： 青霉素 对症治疗 利尿（速尿，双氢克尿噻） 降压 （心痛定， ACEI：SQ14225）,治 疗（二）,严重病例 高血压脑病：止惊，降压，脱水 （硝普钠，二氮嗪） 严重循环充血：利尿为主（速尿）、扩血管、透析 急性肾衰： 液体 ，电解质，酸碱，感染关,预后和预防,95%完全恢复 5%尿异常 1%死亡 预防：,总结,定义 病理、生理 临床表现 诊断 治疗,肾病综合征,（nephrotic syndrome),【目的要求】 了解该病发病机理及病理生理。 掌握原发性肾病综合征的分型（临床，激素治疗效应，病理分型）。 掌握该病临床表现，并发症，诊断及治疗。 【重点和难点】 重点：本病的病理生理，临床表现，诊断治疗，并发症。 难点：该病的临床与病理分型。,Nephrotic syndrome 肾病综合征 Proteinuria 蛋白尿 Hypoalbuminemia 低蛋白血症,关键词：Key words,（一）定义 是由于肾小球滤过膜对血浆蛋白的通透性增高，导致大量血浆白蛋白自尿中丢失而引起的一种临床症侯群。,（二）病因和发病机制,病因不明 发病机制： 微小病变与T细胞功能紊乱有关，非微小病变与体液免疫与细胞免疫均相关 细胞因子（IL-2，6，8） 有遗传基础与HLA相关：SSNS：DR7 FRNS：DR9 裂隙膜分子的变化,（三）病理生理,致病因素 分子屏障 肾小球滤过膜通透性 静电屏障 大量蛋白尿 高脂血症 脂代谢紊乱 心血管、小球硬化 低蛋白血症 IgG感染 血浆胶体渗透压 抗凝血酶, 、高凝，血栓 铁结合蛋白VitD3结合蛋白 水 血容量 甲状腺素结合蛋白T3、T4 分 入 (ADH，醛固酮、利钠因子、肾小球滤过率) 间 质 水 钠储留 水肿,肾小球滤过膜通透性与分子 大小的关 系,不同的电荷其通透性不同,阳电荷,阴电荷,中性电荷,正常与肾病综合征情况下白蛋白代谢,（四） 病 理,肾病综合征常见病理改变,足 突 细 胞,足 突 细 胞 的 超 微 机 构,MCD 微小病变,FSGS （局灶性节段性肾小球硬化）,MN 膜性肾病,MPGN （膜增生性肾小球肾炎）,（五）临床表现,病前常有感染 水肿为主要表现,（六）并 发 症,感染：呼吸道感染，皮肤感染，腹膜炎，尿路感染 低血容量休克：烦躁，四肢湿冷，皮肤花纹，心 音低，血压下降 电解质紊乱：低钠，低钾，低钙 血栓形成：肾静脉血栓（腰痛，肉眼血尿） 肾功能衰竭：休克所致的肾前性衰竭多见 肾小管功能障碍,（七）实验室检查,尿常规：蛋白定性 + + 24H尿蛋白定量：大于0.05 /kg 肝肾功能：血清白蛋白 6.7mmol/L 免疫学检测：ANA，抗-dsDNA抗体 肾活检,（八）诊 断,四大特征：三高一低（一高一低为主） 大量蛋白尿：定性 + + 定量 24H尿蛋白 大于0.05g/kg 低蛋白血症：血浆白蛋白小于30g/L(儿童) 高脂血症： 胆固醇大于5.7mmol/L(儿童) 不同程度的水肿,（九）分 型,临床分型 病理分型 激素分型,临 床 分 型,原发性 90% 单纯性肾病 ：三高一低 肾炎性肾病：三高一低外，还有至少以下之一 血尿：RBC大于10/HP 高血压 氮质血症：BUN大于10.7mmol/L 血补体CH50，C3反复下降 继发性：SLE，APN，乙肝肾 先天性：较少见,病 理 分 型,微小病变（MCD） 局灶性节段性肾小球硬化（FsGs） 膜增殖性肾炎（MPGN） 系膜增生性肾炎（MsPGN） 膜性肾病（MGN）,激 素 分 型,激素敏感：8周内尿蛋白转阴 激素部分敏感：8周内水肿退，尿蛋白+ 激素耐药：8周尿蛋白+ （激素依赖，反复与复发，频复发）,（十） 治 疗,一般治疗：休息和饮食 利尿：当水肿严重时，尤其有腹水时 双克，速尿，氨苯喋啶 低分子右旋糖酐 激素治疗 抗凝治疗 免疫调节治疗 中药,激素治疗(一),激素使用阶段 诱导缓解：强的松1.5-2mg/kg/d 4-8w 巩固阶段：间歇用药或清晨顿服 激素使用方法 短程：强的松2mg/kg/d 4w 强的松1.5mg/kg/d qod 4w 共8周,激素治疗(二),激素使用方法 中长程：强的松1.5-2mg/kg/d 4w 4w后蛋白转阴，改强的松2mg/kg,隔日早餐后顿服，继用4周，以后每2-4周减量一次，直致停药，总疗程6-9个月,激素治疗(三),复发和反复的治疗 延长强的松使用时间 加用免疫抑制剂：CTX，VCR 激素耐药的治疗 延长强的松诱导期 甲基强的松龙冲击 加用免疫抑制剂：CTX，环孢霉素A，酶芬酸酯,激素副作用,激素应用前注意事项：感染 、胃肠道炎症、水肿、高血压 代谢紊乱 消化溃疡和精神欣快感 白白内障，股骨头坏死 高凝状态 生长停止 易发感染 急性肾上腺功能不全,免 疫 抑 制 剂,化学制剂 烷化剂（CTX）、 抗代谢药（VCR、MMF） 真菌代谢产物：环孢素A、FK-506 中药及其有效成分： 雷公藤 掌握剂量、疗程 注意副作用：骨髓抑制、胃肠道反应、性腺抑制,其 它,抗凝：低分子肝素，潘生丁 溶栓：尿激酶 免疫调节：左旋咪唑 控制病情发展：ACEI and ARB 中药,预后,微小病变好 常常死于感染和激素严重副作用 非微小病变肾病综合症：,总结,概念：三高一低 病因及发病机制：了解 病理生理：重要 临床表现 ：重要 诊断：分型 治疗：激素的应用,谢谢,泌 尿 道 感 染,Anaphylactoid Purpura (AP) & AP Nephritis (APN) OR Henoch-Schonlein Purpura (HSP),Xiao zhong Li,Main content,Introduce definition, the etiology, Pathophysiology of HSP Emphasis pathologic changes and clinical manifestations of HSP Introduce the treatment of HSP,Description,Definition : Henoch-Schonlein Purpura Syndrome, HSP: Clinical features characterized by skin rash, joint pain , abdomen symptoms, renal damage, et al. Pathologic change: Systemic vasculitis Common seen in 2-8 ys of child in spring and autumn , boys more than girls about ratio of 2:1.,Etiology：antigen,Infection related: A recent history of an intercurrent infection, particularly streptococcal respiratory infections Food Drug Vaccine & plasma product Others: insect bite, cool, trauma , sex hormones during special phase,Environmental agents which have been implicated in the causation of Henoch-schonlein purpura,Micro-organisms b-Haemolytic streptococcus Mycobacterium tuberculosis Varicella zoster Vaccinia Jim閚ez and Darrington Haemophilus parainfluenzae Streptococcus pneumoniae Rubella Measles Mycoplasma pneumoniae Yersinia enterocolitica Human parvovirus ) Human immunodeficiency virus Staphylococcus sp. Legionella sp. Influenzae vaccine Salmonella hirschfeldii Campylobacter jejuni,Drugs Aspirin Erthromycin Griseofulvin Penicillin Phenacetin Phenothiazines Quinidine Sulphonamide Tetracycline Thiazide diuretics Chlorpromazine Paracetamol-dihydrocodeine Thiram Carbamazepine Streptokinase Enalapril Lisinopril Fluoroquinolones,Foods Crab shrampe Nuts Blackberries Egg Milk Potato Wheat Meat (various) Fish Chocolate Chicken Tomato Alcohol,Mechanism,Immunologic basis: antigen, antibody, IgA-CiC T cells: Impaired ability of T cells to suppress B-cell function B cells: In vitro production of both IgA and IgG by B cells is increased in patients compared with controls IgA IC deposit on the vascular wall of skin and glomeruli cause Vasculitis. Proinflammatory and inflammatory factors HLA related: HLA DRB1 or HLA DR DW35,Pathology-skin,Leucocytoclastic vasculitis : inflammatory cells, mostly polymorphonuclear leucocytes and mononuclear cells with occasional eosinophils, surrounding the capillaries,光镜,免疫荧光,Crescent GN,免疫病理分型 根据肾小球内沉积的免疫复合物不同，分为四型： 1、单纯IgA沉积型（IgA） 2、IgA+IgG沉积型（IgA+G） 3、IgA+IgM沉积型（IgA+M） 4、IgA+IgG+IgM沉积型（IgA+G+M） 其中IgAGM沉积型其病理为为IVVI者占41.7%。,Clinic features,Purpura rash Abdomen symptoms: Arthralgia : Renal diseases:,Skin rash,Distinctive in both its distribution and the nature of the lesions. Palpable purpura Appearing on the extensor surfaces of the arms and legs Particularly round the ankles and over the buttocks and elbows.,Other manifestation of skin rash,May infusion Dermal necrosis and scarring Haemorrhagic bullae Other area:,A severe but fairly typical purpuric rash of HSP affecting the buttocks of an 11-year-old boy. Some of the larger lesions are bullous, which is unusual in children but may be seen more commonly in adults.,This is uncommon in older children, but may be seen in infants, young children, and adults.,The rash of severe Henoch-Scholein purpura affecting the face.,Skin lesion duration,Average: 3 days to 2 yrs One third : within 2 weeks One third : 2-4 weeks Other third : more than 4 weeks,Joint manifestations,Joint pain: 2 thirds of all cases, one quarter as presenting symptom Always affect large joint such as ankle and knee Joint swelling usually , but not common X-ray shows periarticular edema without effusion or enlargement of joint space No response to salicylate Recovery earlier than rash, no permanently damage,Abdominal and gastrointestinal symptoms(1),Abdominal symptoms occur in the majority of patients The abdominal pain is colicky, frequently severe, and may mimic an abdominal emergency Intestinal bleeding: melaena, haematemesis,Abdominal and gastrointestinal symptoms(2),Intussusception: Serial ultrasonography of the abdomen reliably distinguishes intussusception from other causes of abdominal pain Ileus Other rare abdominal manifestations of the disease include pancreatitis, intestinal perforation and massive gastric haemorrhage,Must pay attention to,Abdominal and gastrointestinal symptoms may proceed other signs and symptoms (particular skin rash) !,Renal involvement (1),haematuria, proteinuria, oliguria with fluid retention, oedema and hypertension, impaired glomerular filtration rate.,Renal involvement (2),Mostly mild , less severity the nephritis either appears later commonly within 6 months or is present at onset only in the form of urinary abnormalities. severity of renal involvement cannot be predicted from the severity of the non-renal symptoms and signs. different incidence from different criteria,紫癜性肾炎的临床分型,1. 孤立性血尿或蛋白尿 2. 血尿和蛋白尿 3. 急性肾炎型 4. 肾病综合征型 5. 急进性肾炎型 6. 慢性肾炎型,Pathologykidney,I Minimal changes II Pure mesangial proliferation without crescents (a) Focal (b) Diffuse III Mesangial proliferative glomerulonephritis with less than 50% crescents (a) Focal (b) Diffuse IV Mesangial proliferative glomerulonephritis with 50-75% crescents (a) Focal (b) Diffuse V Mesangial proliferative glomerulonephritis with more than 75% crescents (a) Focal (b) Diffuse VI Membranoproliferative (mesangiocapillary) glomerulonephritis,Investigations,Full blood count: normal platelet Urine test: hematuria and proteinuria Stool test: positive occult blood test Hematology: hyper coagulation Biochemistry: BUN and Scr, liver function and myocardial enzyme Immunology: ESR , Ig, complement Pathology: skin and renal biopsy Image : ultrasound,诊断,根据本病特征的临床表现典型的皮肤紫癜，又 同时合并消化道、关节或肾脏症状以及反复发作史，即可诊断。 同时应与ITP、急腹症、风湿性关节炎、流脑等鉴别。,American College of Rheumatology(1990),1. 20 years at onset, 2. Palpable purpura, 3. Acute abdominal pain, The presence of granulocytes in the walls of small arterioles or venules in biopsy , 5. The presence of two or more of these criteria identified Henoch-scholein purpura,Treatment- no-special,Supportive treatment Rest Diet: Avoid some food and drugs Antibiotics if need Fluid and electrolyte balance when diet restricted,Treatment- Other drugs,Steroid : abdomen symptoms and renal disease Immunosuppressive drugs: CTX AZA 雷公藤 Anti-allergic drugs: Anticoagulation fibrolytic and anti-platelet drugs,Others,Operation: sever intestinal bleeding intussusception and perforation,紫癜性肾炎的治疗 孤立性血尿或病理级予潘生丁和（或）清热活血中药 血尿和蛋白尿或病理a级：雷公藤1mg/kg/