過(guò)敏性紫癜的診斷和治療

1、泌尿系統(tǒng)疾病,蘇州大學(xué)兒科學(xué)系 腎內(nèi)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

2、 USAAbout 100 million CKD in china ¼ of the total medical cost,Introduction :background,Effective management of the patient with renal disease is dependent upon establishing an accurate diagnosis.The clinician mu

3、st 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 presenta

4、tion 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 phys

5、ical sign which directly or indirectly indicates underlying renal diseasesThe patient has a systemic disease which is known to be associated with renal involvementThe patient has a family history of an inherited renal

6、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 u

7、rinary tract disease,Dysmorphic syndromes; Anaemia; Oedema; High blood pressure; Renal masses; Distended bladder.,Acute glomerulonephritis(AGN),急性腎小球腎炎,Acute glomerulonephritis(AGN),概述病因發(fā)病機(jī)制 病

8、理生理病理臨床表現(xiàn)實(shí)驗(yàn)室檢查診斷 鑒別診斷治療 預(yù)后,急性腎小球腎炎,目的要求,了解急性腎炎的病因及發(fā)病機(jī)理。掌握一般病例與嚴(yán)重病例的臨床表現(xiàn)及治療原則。掌握急性腎炎的實(shí)驗(yàn)室檢查。了解急性腎炎與其他病原體引起急性腎炎、慢性腎炎急性發(fā)作、特發(fā)性腎病綜合癥、IgA腎病綜合癥、急進(jìn)性腎炎等疾病的鑒別診斷。,重點(diǎn)和難點(diǎn),重點(diǎn)：本病的一般病例及嚴(yán)重病例的臨床表現(xiàn)及其產(chǎn)生機(jī)理。該病的尿液及血生化檢查。小兒?jiǎn)渭冃匝虻脑\斷要點(diǎn)

9、和處理原則。難點(diǎn)：本癥重癥病例的治療，高血壓腦病急性腎功能不全，嚴(yán)重循環(huán)充血治療及處理原則。,Acute poststreptococcal glomerulonephritis 急性鏈球菌感染后腎炎Hematuria 血尿Oliguria 尿少 Edema 浮腫

10、,關(guān)鍵詞：Key words,概 述,定義：急性起病，雙側(cè)性，彌漫性，前趨感染（非化膿性炎癥），臨床上以血尿?yàn)橹鳎捎兴[、少尿、高血壓，或腎功能不全等特點(diǎn)發(fā)病情況：年齡5-14歲、性別男女2：1、發(fā)生率下降,病 因,細(xì)菌：A組β溶血性鏈球菌的某些致 腎炎菌株；其他細(xì)菌有。。。。。病毒：巨細(xì)胞、乙肝病毒等其他：支原體、霉菌、原蟲(chóng)等,發(fā)病機(jī)制 病理生理,鏈球菌致腎炎菌株的抗原成分 循環(huán)免疫復(fù)合

11、物 原位免疫復(fù)合物 自身免疫激活補(bǔ)體系統(tǒng) 釋放生物活性因子 腎素—血管緊張素—醛固酮 腎小球基底膜斷裂 GRF

12、 水鈉儲(chǔ)留 血尿、蛋白尿、管型尿 水腫、少尿、高血壓 腎衰,,,,,,,,,,,,,,病 理,毛細(xì)血管內(nèi)增生性腎小球腎炎光鏡：內(nèi)皮細(xì)胞、系膜細(xì)胞

13、增生、腫脹，系膜基質(zhì)增多，中性粒細(xì)胞浸潤(rùn)，嚴(yán)重時(shí)可有“新月體”形成電鏡：上皮細(xì)胞下“駝峰樣”電子致密物沉積免疫熒光：IgG、C3沉積,AA：入球小動(dòng)脈EA：出球小動(dòng)脈EGM：腎小球外系膜PE：壁層上皮細(xì)胞PO：足突細(xì)胞GBM：腎小球基底膜F：足突US：尿液腔M：系膜PT：近曲小管MD：致密斑G：顆粒細(xì)胞N：交感神經(jīng)E：內(nèi)皮細(xì)胞,,PO： 足突細(xì)胞 podocyte GBM：腎

14、小球基底膜 glomerular basement membrane M：系膜 mesangial cell MM：系膜基質(zhì) mesangial matrix E：內(nèi)皮細(xì)胞 fenestrated endothelium,新月體腎炎,臨床表現(xiàn)（一）,前驅(qū)感染 ( Precede infection)秋冬季呼吸道

15、感染為主夏秋季皮膚感染多見(jiàn),臨床表現(xiàn)（二）,典型表現(xiàn) ( typical manifestation )水腫 (部位, 性質(zhì), 時(shí)間)尿少 （少尿，無(wú)尿）血尿 （腎小球性）高血壓 (頭暈, 頭痛),電鏡掃描 尿紅細(xì)胞形態(tài),臨床表現(xiàn)（三）,嚴(yán)重表現(xiàn)(Serious manifestation)循環(huán)充血 “心衰”征象 高血壓腦病劇烈頭痛 惡心嘔吐 驚厥昏迷 急性腎功能不全

16、 少尿 氮質(zhì)血癥 電解質(zhì)紊亂,,呼吸困難, 肺底濕羅音心臟擴(kuò)大, 心率增快肝腫大,臨床表現(xiàn)（四）,不典型表現(xiàn) (Atypical manifestation)無(wú)癥狀病例無(wú)臨床癥狀,有尿改變,補(bǔ)體C3下降腎外癥狀型水腫,高血壓等表現(xiàn)明顯尿改變輕微腎病綜合征型大量蛋白尿腎活檢病理改變類似典型病例,實(shí) 驗(yàn) 室 檢 查,尿常規(guī)血常規(guī) 腎功能血沉ASO血補(bǔ)體（C3下降）,診 斷,前驅(qū)鏈球菌感

17、染史臨床癥狀：血尿、水腫、高血壓等實(shí)驗(yàn)室檢查：尿檢、ASO 、C3等,鑒 別 診 斷,非典型病例（大量蛋白尿型） 非鏈球菌感染腎炎（病毒性） IgA腎炎 全身性疾病（SLE，APN，乙肝腎） 慢腎急發(fā) 急進(jìn)性腎炎 尿路感染 腎病綜合癥,治 療（一）,一般治療臥床休息（約2周）：水腫退，血壓降，肉眼血尿消失；血沉正常上學(xué)；12小時(shí)尿沉渣正常恢復(fù)體力活動(dòng)飲食：低鹽：60mg/kg。d；低蛋白0。5m

18、g/kg。d抗感染： 青霉素對(duì)癥治療利尿（速尿，雙氫克尿噻）降壓 （心痛定， ACEI：SQ14225）,治 療（二）,嚴(yán)重病例 高血壓腦?。褐贵@，降壓，脫水 （硝普鈉，二氮嗪） 嚴(yán)重循環(huán)充血：利尿?yàn)橹鳎ㄋ倌颍?、擴(kuò)血管、透析 急性腎衰： 液體 ，電解質(zhì)，酸堿，感染關(guān),預(yù)后和預(yù)防,95%完全恢復(fù)《5%尿異常〈1%死亡預(yù)防：,總結(jié),定義病理、生理臨床表現(xiàn)診斷治

19、療,腎病綜合征,（nephrotic syndrome),【目的要求】了解該病發(fā)病機(jī)理及病理生理。掌握原發(fā)性腎病綜合征的分型（臨床，激素治療效應(yīng)，病理分型）。掌握該病臨床表現(xiàn)，并發(fā)癥，診斷及治療?！局攸c(diǎn)和難點(diǎn)】重點(diǎn)：本病的病理生理，臨床表現(xiàn)，診斷治療，并發(fā)癥。難點(diǎn)：該病的臨床與病理分型。,Nephrotic syndrome 腎病綜合征Proteinuria

20、 蛋白尿 Hypoalbuminemia 低蛋白血癥,關(guān)鍵詞：Key words,（一）定義 是由于腎小球?yàn)V過(guò)膜對(duì)血漿蛋白的通透性增高，導(dǎo)致大量血漿白蛋白自尿中丟失而引起的一種臨床癥侯群。,（二）病因和發(fā)病機(jī)制,病因不明發(fā)病機(jī)制： 微小病變與T細(xì)胞功能紊亂有關(guān)，非微小病變與體液免疫與細(xì)胞免疫均相關(guān)細(xì)胞因子（IL-2，6，8）有遺傳基礎(chǔ)與HLA相關(guān)：SSNS：D

21、R7 FRNS：DR9裂隙膜分子的變化,（三）病理生理,致病因素 　 　　 分子屏障 腎小球?yàn)V過(guò)膜通透性↑

22、 靜電屏障 大量蛋白尿 高脂血癥

23、 脂代謝紊亂 心血管、小球硬化 低蛋白血癥 IgG↓—感染

24、 血漿膠體滲透壓↓ 抗凝血酶Ⅲ↓, Ⅳ、Ⅴ↑→高凝，血栓 　　　　　　　　　 鐵結(jié)合蛋白↓VitD3結(jié)合蛋白↓水 血容量↓ 甲狀腺素結(jié)合蛋白→T3、T4

25、 ↓分 入 (ADH↑，醛固酮↑、利鈉因子↓、腎小球?yàn)V過(guò)率↓)間　　　　　　　　　　　質(zhì)

26、 水 鈉儲(chǔ)留 水腫,,,,,,,,,,,,,,,,,,腎小球?yàn)V過(guò)膜通透性與分子大小的關(guān) 系,不同的電荷其通透性不同,陽(yáng)電荷,陰電荷,中性電荷,正常與腎病綜合征情況下白蛋白代謝,（四） 病 理,腎病綜合征常見(jiàn)病理改變,足突細(xì)胞,足突細(xì)胞的超微機(jī)構(gòu),MCD

27、 微小病變,FSGS（局灶性節(jié)段性腎小球硬化）,MN 膜性腎病,MPGN（膜增生性腎小球腎炎）,（五）臨床表現(xiàn),病前常有感染水腫為主要表現(xiàn),（六）并 發(fā) 癥,感染：呼吸道感染，皮膚感染，腹膜炎，尿路感染低血容量休克：煩躁，四肢濕冷，皮膚花紋，心 音低，血壓下降電解質(zhì)紊亂：低鈉，低鉀，低鈣血栓形成：腎靜脈血栓（腰痛，肉眼血尿）腎功

28、能衰竭：休克所致的腎前性衰竭多見(jiàn)腎小管功能障礙,（七）實(shí)驗(yàn)室檢查,尿常規(guī)：蛋白定性 +++ ~ ++++24H尿蛋白定量：大于0.05 /kg肝腎功能：血清白蛋白 6.7mmol/L免疫學(xué)檢測(cè)：ANA，抗-dsDNA抗體腎活檢,（八）診 斷,四大特征：三高一低（一高一低為主）大量蛋白尿：定性 +++ ~ ++++ 定量 24H尿蛋白 大于0.05g/k

29、g低蛋白血癥：血漿白蛋白小于30g/L(兒童) 高脂血癥： 膽固醇大于5.7mmol/L(兒童) 不同程度的水腫,（九）分 型,臨床分型 病理分型 激素分型,臨 床 分 型,原發(fā)性 90%單純性腎病

30、：三高一低腎炎性腎病：三高一低外，還有至少以下之一血尿：RBC大于10/HP高血壓氮質(zhì)血癥：BUN大于10.7mmol/L血補(bǔ)體CH50，C3反復(fù)下降繼發(fā)性：SLE，APN，乙肝腎先天性：較少見(jiàn),病 理 分 型,微小病變（MCD）局灶性節(jié)段性腎小球硬化（FsGs）膜增殖性腎炎（MPGN）系膜增生性腎炎（MsPGN）膜性腎?。∕GN）,激 素 分 型,激素敏感：8周內(nèi)尿蛋白轉(zhuǎn)陰激素部分敏感：8周內(nèi)水腫退，尿蛋白+~

31、++激素耐藥：8周尿蛋白>++（激素依賴，反復(fù)與復(fù)發(fā)，頻復(fù)發(fā)）,（十） 治 療,一般治療：休息和飲食利尿：當(dāng)水腫嚴(yán)重時(shí)，尤其有腹水時(shí)雙克，速尿，氨苯喋啶低分子右旋糖酐激素治療抗凝治療免疫調(diào)節(jié)治療中藥,激素治療(一),激素使用階段誘導(dǎo)緩解：強(qiáng)的松1.5-2mg/kg/d 4-8w鞏固階段：間歇用藥或清晨頓服激素使用方法短程：強(qiáng)的松2mg/kg/d 4w

32、 強(qiáng)的松1.5mg/kg/d qod 4w 共8周,激素治療(二),激素使用方法中長(zhǎng)程：強(qiáng)的松1.5-2mg/kg/d 4w 4w后蛋白轉(zhuǎn)陰，改強(qiáng)的松2mg/kg,隔日早餐后頓服，繼用4周，以后每2-4周減量一次，直致停藥，總療程6-9個(gè)月,激素治療(三),復(fù)發(fā)和反復(fù)的治療延長(zhǎng)強(qiáng)的松使用時(shí)間加用免疫抑制劑：CTX，VCR激素耐藥的治療延長(zhǎng)強(qiáng)的松誘導(dǎo)期甲

33、基強(qiáng)的松龍沖擊加用免疫抑制劑：CTX，環(huán)孢霉素A，酶芬酸酯,激素副作用,激素應(yīng)用前注意事項(xiàng)：感染 、胃腸道炎癥、水腫、高血壓代謝紊亂消化潰瘍和精神欣快感白白內(nèi)障，股骨頭壞死高凝狀態(tài)生長(zhǎng)停止易發(fā)感染急性腎上腺功能不全,免 疫 抑 制 劑,化學(xué)制劑 烷化劑（CTX）、 抗代謝藥（VCR、MMF）真菌代謝產(chǎn)物：環(huán)孢素A、FK-506中藥及其有效成分： 雷

34、公藤掌握劑量、療程 注意副作用：骨髓抑制、胃腸道反應(yīng)、性腺抑制,其 它,抗凝：低分子肝素，潘生丁溶栓：尿激酶免疫調(diào)節(jié)：左旋咪唑控制病情發(fā)展：ACEI and ARB中藥,預(yù)后,微小病變好常常死于感染和激素嚴(yán)重副作用非微小病變腎病綜合癥：,總結(jié),概念：三高一低病因及發(fā)病機(jī)制：了解 病理生理：重要臨床表現(xiàn) ：重要診斷：分型治療：激素的應(yīng)用,謝謝,泌 尿 道 感 染,Anaphylactoid Purpura (

35、AP) & AP Nephritis (APN) OR Henoch-Schonlein Purpura (HSP),Xiao zhong Li,Main content,Introduce definition, the etiology, Pathophysiology of HSPEmphasis pathologic changes and clinical ma

36、nifestations of HSPIntroduce 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.

37、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

38、, particularly streptococcal respiratory infectionsFoodDrugVaccine & plasma productOthers: insect bite, cool, trauma , sex hormones during special phase,Environmental agents which have been implicated in the cau

39、sation of Henoch-schonlein purpura,Micro-organismsb-Haemolytic streptococcus Mycobacterium tuberculosis Varicella zoster VacciniaJim閚ez and Darrington Haemophilus parainfluenzae Streptococcus pneumoniae

40、Rubella Measles Mycoplasma pneumoniae Yersinia enterocolitica Human parvovirus )Human immunodeficiency virusStaphylococcus sp. Legionella sp. Influenzae vaccine Salmonella hirschfeldii Campyloba

41、cter jejuni,Drugs Aspirin Erthromycin Griseofulvin Penicillin Phenacetin Phenothiazines Quinidine Sulphonamide Tetracycline Thiazide diuretics Chlorpromazine Paracetamol-dihydrocodeine Thiram Carb

42、amazepine Streptokinase Enalapril Lisinopril Fluoroquinolones,FoodsCrabshrampeNuts Blackberries Egg Milk Potato Wheat Meat (various) Fish Chocolate Chicken Tomato Alcohol,Mechanism,Immunol

43、ogic basis: antigen, antibody, IgA-CiCT cells: Impaired ability of T cells to suppress B-cell functionB cells: In vitro production of both IgA and IgG by B cells is increased in patients compared with controls IgA I

44、C 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 cell

45、s, mostly polymorphonuclear leucocytes and mononuclear cells with occasional eosinophils, surrounding the capillaries,光鏡,免疫熒光,Crescent GN,免疫病理分型根據(jù)腎小球內(nèi)沉積的免疫復(fù)合物不同，分為四型：1、單純IgA沉積型（IgA）2、IgA+IgG沉積型（IgA+G）3、IgA+IgM沉積型（I

46、gA+M）4、IgA+IgG+IgM沉積型（IgA+G+M）其中IgAGM沉積型其病理為為IV~VI者占41.7%。,Clinic features,Purpura rashAbdomen symptoms: Arthralgia : Renal diseases:,Skin rash,Distinctive in both its distribution and the nature of the lesions.P

47、alpable purpuraAppearing on the extensor surfaces of the arms and legsParticularly round the ankles and over the buttocks and elbows.,Other manifestation of skin rash,May infusion Dermal necrosis and scarringH

48、aemorrhagic bullaeOther 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 comm

49、only 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 yrsOn

50、e third : within 2 weeksOne third : 2-4 weeksOther 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

51、Joint swelling usually , but not commonX-ray shows periarticular edema without effusion or enlargement of joint spaceNo response to salicylateRecovery earlier than rash, no permanently damage,Abdominal and gastrointe

52、stinal symptoms(1),Abdominal symptoms occur in the majority of patientsThe abdominal pain is colicky, frequently severe, and may mimic an abdominal emergency Intestinal bleeding: melaena, haematemesis,Abdomin

53、al and gastrointestinal symptoms(2),Intussusception: Serial ultrasonography of the abdomen reliably distinguishes intussusception from other causes of abdominal painIleus Other rare abdominal manifestations of the dise

54、ase 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 invol

55、vement (1),haematuria, proteinuria, oliguriawith fluid retention, oedema and hypertension, impaired glomerular filtration rate.,Renal involvement (2),Mostly mild , less severity the nephritis either appears later com

56、monly 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 d

57、ifferent criteria,紫癜性腎炎的臨床分型,1. 孤立性血尿或蛋白尿2. 血尿和蛋白尿3. 急性腎炎型4. 腎病綜合征型5. 急進(jìn)性腎炎型6. 慢性腎炎型,Pathology—kidney,I Minimal changes IIPure mesangial proliferation without crescents(a) Focal(b) DiffuseIIIMesangial pr

58、oliferative glomerulonephritis with less than 50% crescents(a) Focal(b) DiffuseIVMesangial proliferative glomerulonephritis with 50-75% crescents(a) Focal(b) DiffuseVMesangial proliferative glomerulonephritis

59、 with more than 75% crescents(a) Focal(b) DiffuseVIMembranoproliferative (mesangiocapillary) glomerulonephritis,Investigations,Full blood count: normal platelet Urine test: hematuria and proteinuria Stool test: p

60、ositive 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,診斷,根據(jù)本病特

61、征的臨床表現(xiàn)典型的皮膚紫癜，又 同時(shí)合并消化道、關(guān)節(jié)或腎臟癥狀以及反復(fù)發(fā)作史，即可診斷。同時(shí)應(yīng)與ITP、急腹癥、風(fēng)濕性關(guān)節(jié)炎、流腦等鑒別。,American College of Rheumatology(1990),,1. ? 20 years at onset, 2. Palpable purpura, 3. Acute abdominal pain, The presence of granulocytes

62、 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 RestDiet: Avoid some fo

63、od and drugsAntibiotics if needFluid and electrolyte balance when diet restricted,Treatment- Other drugs,Steroid : abdomen symptoms and renal disease Immunosuppressive drugs: CTX AZA 雷公藤Anti-allergic dru

64、gs:Anticoagulation \fibrolytic and anti-platelet drugs,,Others,Operation: sever intestinal bleeding \ intussusception and perforation,紫癜性腎炎的治療孤立性血尿或病理Ⅰ級(jí)予潘生丁和（或）清熱活血中藥血尿和蛋白尿或病理Ⅱa級(jí)：雷公藤1mg/kg/d（每日最大量＜45mg，療程3月急性腎炎型（尿蛋尿＞

65、1g/d）或 病理Ⅱ b、Ⅲa級(jí)：雷公藤，療程3~6月腎病綜合征型病理Ⅲ b、Ⅳ級(jí)：強(qiáng)的松＋雷公藤或環(huán)磷酰胺＋強(qiáng)的松沖擊療法急進(jìn)性腎炎型或病理Ⅳ 、Ⅴ級(jí)：甲強(qiáng)龍沖擊（15~30mg/kg）＋CTX＋肝素＋潘生丁四聯(lián)療法,The great majority of patients , recover completely from Henoch-schonlein purpura with no measurable impairm

66、ent of renal functionIn large studies of unselected children: death or endstage renal disease ensued in seven of 245 patients and persisting urinary abnormalities were present in 5 to 15 per cent after follow-up

67、 for several years.,Prediction of renal outcome,Classification of clinical status at follow-up of patients with Henoch-schonlein purpura nephritis --Outcome group,ANormalNormal physical examination, no urinary abnorm

68、ality,normal renal functionBMinor urinary abnormalityNormal physical examination, haematuria(microscopic-intermittent macroscopic) and/orproteinuria 1 g/24 h and/or hypertension, normal renalfunctionDRenal