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儿童链球菌咽炎青霉素250~500mg/次,一日2次或一日3次,疗程10天。
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青霉素G或青霉素V也可使用,后者更好些,因为即使在空腹时它也可达到满意的血浓度。
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单剂量肌内注射长效的苯唑青霉素G(22kg以下小儿,60万U/次;22kg以上儿童120万U/次),对于治疗和预防复发是非常有效的。
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红霉素40mg/(kg•d)、克林霉素30mg/(kg•d)或一代头孢菌素类可以用来治疗青霉素过敏的咽炎患者,一般来说,复发率是很低的。
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四环素和磺胺嘧啶不能用于治疗。
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当一个疗程青霉素治疗后,仍有链球菌持续存在,被定义为治疗失败。
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这种情况在5%~20%的儿童中出现,且常出现在口服治疗的患者,可能是由于再感染、持续携带β内酰胺酶阳性的菌株、对青霉素耐药株的带菌状态。
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在高危人群,青霉素足疗程治疗后,应反复咽培养检查,对于咽培养再次阳性的患者,一些临床医生建议给予第二次治疗疗程。
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如果第二个疗程后仍是带菌状况,这时发展为风湿热的危险性很小,不需进一步治疗。
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患有严重猩红热、链球菌菌血症、肺炎、脑膜炎、深部软组织感染、丹毒、链球菌中毒休克样综合征或链球菌咽炎并发症的病例,应该肌内或最好是静脉给予青霉素,其用量和疗程则依疾病的自然病程而定。
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而非常严重感染的病例,应给予40万U/(kg•24h)的大剂量青霉素。
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有研究建议深部或坏死性感染可能需要增加一种二线抗生素,如克林霉素,以确保彻底杀死细菌。
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TSS也可能需要附加的治疗,包括早期积极的液体供应,静脉免疫球蛋白或糖皮质激素的应用。
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【预防】如果在症状发生前应用青霉素,可以预防多数链球菌感染发生,对风湿热以外的其他感染化学药物预防效果尚不清。
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或者60万U苯唑青霉素连同60万U水剂普鲁卡因青霉素,给予一次性肌内注射,这一用法适用于一定范围内的流行。
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对无症状的恢复期患者的持续咽培养阳性可不必再次治疗,因为他们一般是带菌者,不会有持续的或者再发的感染存在。
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一些携带者常患有病毒性呼吸道感染,很像链球菌感染,可能被认为是再发性链球菌感染。
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应用非青霉素类药物如头孢菌素类、红霉素、克林霉素对于消灭带菌症状是有效的,但是对一些少见病例应慎用。
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目前尚无临床可应用的A族链球菌疫苗。
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【预后】经适当治疗的链球菌感染的预后是非常好的,多数化脓性并发症是可以预防和治疗的。
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早期治疗是防止非化脓性并发症和完全治愈的关键。
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尽管应用足够的疗程,但仍有少数病例如新生儿或有免疫缺陷的儿童患暴发性肺炎、败血症而发生死亡。
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二、肾小球功能检查肾小球功能主要为滤过和清除功能。
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临床上常将血肌酐、尿素氮、尿酸以及肾小球滤过率(GFR)、血浆蛋白清除率等作为肾小球滤过和清除功能的指标。
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(一)血尿素氮及血肌酐血尿素氮(BUN)及血肌酐(Scr)来评估肾小球滤过率(GFR),已在临床得到广泛应用。
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BUN正常值新生儿为1.8~6.4mmol/L,婴儿及儿童为2.5~6.4mmol/L,青春期为2.9~7.5mmol/L。
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尿素主要由肾小球滤过,可以从BUN上升来评估GFR下降的程度。
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但尿素的产生不如肌酐恒定,受多种因素影响:①肝脏合成尿素是将未合成蛋白质的氨基酸脱氨后再合成尿素,当肝内氨基酸代谢增加时(如高蛋白饮食),以及组织分解代谢旺盛而蛋白合成减少时,尿素生成增加,BUN上升。
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②严重肝病或低蛋白饮食时BUN会下降。
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③尿素排泄不仅决定于肾小球滤过,正常时约有40%~50%的尿素随着钠及水一起而被肾小管被动回吸收。
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血容量下降时,尿素可随着近曲小管钠的回吸收增加而增加使BUN升高,这时并不代表GFR下降。
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④BUN与GFR之间的负相关并非直线关系而是呈反抛物线形式,只有当GFR下降至50%~60%以上才引起BUN上升。
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因此,在用BUN评估肾脏病进展时必须考虑多方面因素的影响,尤其是饮食中蛋白质含量。
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如GFR稳定时,饮食中蛋白质加倍,BUN将升高而造成肾功能下降的错觉。
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此外,小儿分解代谢旺盛如发热时也可出现一过性BUN升高。
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血肌酐(Scr)浓度不受蛋白质摄入量影响,是更可靠而有用的肾功能指标。
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肌酐是体内肌酸代谢的终产物,分子量为113D,因而正常人Scr浓度也极为恒定,人每日的动态变化小于10%。
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血肌酐的浓度直接与体内肌肉组织的总量有关。
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故Scr的正常值与性别、年龄和身长有关。
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可参照下列两个公式:男孩Scr(mg/dl)=0.35+0.03×年龄女孩Scr(mg/dl)=0.37+0.02×年龄或Scr(mg/dl)=0.004×身长(cm)小儿血肌酐正常值约为27~62μmol/L,随年龄增长及肌肉发育而增高。
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正常小儿血肌酐初生时较高,接近成人水平,约2~4周下降至8.84~17.68μmol/L。
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当GFR降至正常70%以下时,Scr才可能升高。
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(二)肾小球滤过率肾小球滤过率(glomerularfiltrationrate,GFR)是指单位时间(分钟)内从双肾滤过的血浆毫升数。
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临床上常用清除率来表示GFR。
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清除率指每分钟多少毫升血中的某物质被肾小球滤过清除,当这种物质既不被肾小管重吸收,也不被肾小管分泌时,可以认定该物质的清除率与GFR相等。
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菊粉(inulin)是从植物块基中提取的不带电荷的果糖聚合物,分子量5.2kD,只从肾小球滤过,不被肾小管重吸收和分泌,故菊粉清除率(Cin)=GFR,Cin被认为是测定GFR的金标准。
[ { "end_idx": 44, "entity": "肾小球", "start_idx": 42, "type": "bod" }, { "end_idx": 52, "entity": "肾小管", "start_idx": 50, "type": "bod" }, { "end_idx": 65, "entity": "菊粉清除率", "start_idx": 61, "type": "ite" }, { "end_idx": 69, "entity": "Cin", "start_idx": 67, "type": "ite" }, { "end_idx": 74, "entity": "GFR", "start_idx": 72, "type": "ite" }, { "end_idx": 78, "entity": "Cin", "start_idx": 76, "type": "ite" }, { "end_idx": 87, "entity": "GFR", "start_idx": 85, "type": "ite" } ]
但菊粉需给病人静脉注入,然后分时段多次采血后以高效液相色谱法分析后才能计算出Cin,过程繁琐,程序复杂,因而临床上仍普遍以内生肌酐廓清率(Ccr)来代替Cin。
[ { "end_idx": 2, "entity": "菊粉", "start_idx": 1, "type": "dru" }, { "end_idx": 10, "entity": "静脉注入", "start_idx": 7, "type": "pro" }, { "end_idx": 20, "entity": "采血", "start_idx": 19, "type": "pro" }, { "end_idx": 31, "entity": "高效液相色谱法分析", "start_idx": 23, "type": "pro" }, { "end_idx": 40, "entity": "Cin", "start_idx": 38, "type": "ite" }, { "end_idx": 67, "entity": "内生肌酐廓清率", "start_idx": 61, "type": "ite" }, { "end_idx": 71, "entity": "Ccr", "start_idx": 69, "type": "ite" }, { "end_idx": 78, "entity": "Cin", "start_idx": 76, "type": "ite" } ]
内生肌酐由体内肌酸衍生而来,其产生及排泄均较稳定。
[ { "end_idx": 3, "entity": "内生肌酐", "start_idx": 0, "type": "bod" }, { "end_idx": 8, "entity": "肌酸", "start_idx": 7, "type": "bod" } ]
正常儿童尿中肌酐排出量约为[15+0.5×年龄(岁)]mg/(kg•24h),由肾小球滤过后,既不为肾小管回吸收,也不为肾脏代谢,但可由近曲小管少量分泌。
[ { "end_idx": 4, "entity": "尿", "start_idx": 4, "type": "bod" }, { "end_idx": 7, "entity": "肌酐", "start_idx": 6, "type": "bod" }, { "end_idx": 42, "entity": "肾小球", "start_idx": 40, "type": "bod" }, { "end_idx": 52, "entity": "肾小管", "start_idx": 50, "type": "bod" }, { "end_idx": 61, "entity": "肾脏", "start_idx": 60, "type": "bod" }, { "end_idx": 71, "entity": "近曲小管", "start_idx": 68, "type": "bod" } ]
因而,正常人肌酐排泄量超过滤过量的10%~20%。
[ { "end_idx": 10, "entity": "肌酐排泄量", "start_idx": 6, "type": "ite" } ]
但在血浆中也有10%~20%非肌酐的色素物质可与肌酐一起用苦味酸比色法测出,故恰与尿中多出的抵消。
[ { "end_idx": 3, "entity": "血浆", "start_idx": 2, "type": "bod" }, { "end_idx": 21, "entity": "非肌酐的色素物质", "start_idx": 14, "type": "bod" }, { "end_idx": 25, "entity": "肌酐", "start_idx": 24, "type": "bod" }, { "end_idx": 34, "entity": "苦味酸比色法", "start_idx": 29, "type": "pro" }, { "end_idx": 41, "entity": "尿", "start_idx": 41, "type": "bod" } ]
因此,肌酐廓清率可准确反映肾小球滤过率(GFR)。
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GFR下降至<40ml/(min•1.73m2</sup>)时,滤过的肌酐减少,肾小管分泌的增加,此时Ccr将比实际GFR高出10%~40%。
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肌酐廓清率的测定方法是测定同一时间内血及尿中的肌酐浓度,并准确测定尿量(留4小时或12小时尿),计算出肾脏每分钟清除血浆中肌酐的毫升数,再用患儿体表面积矫正即得出矫正肌酐廓清率:矫正廓清率=内生肌酐廓清率×1.73(m2</sup>)/小儿实际体表面积(m2</sup>)正常新生儿为25~27ml/(min•1.73m2</sup>),婴儿期60~80ml/(min1.73m2</sup>),2岁以后的小儿矫正内生肌酐廓清率为80~120ml/(min•1.73m2</sup>)。
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由于血肌酐浓度十分恒定,其变化与肾小球滤过率高低十分密切。
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因此不少人试图以血肌酐来拟算肾小球滤过率。
[ { "end_idx": 10, "entity": "血肌酐", "start_idx": 8, "type": "ite" }, { "end_idx": 19, "entity": "肾小球滤过率", "start_idx": 14, "type": "ite" } ]
Schwartz等研究Scr/GFR和身长间的关系,得出公式为:矫正Ccr=K×身长(cm)/Scr(mg/dl)式中K为单位体重排肌酐的常数,2~12岁小儿为0.55,≤1岁婴儿为0.45,≤1岁的低体重儿为0.33。
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第十章小儿腹泻病在未明确病因前,大便性状改变与大便次数比平时增多,统称为腹泻病(diarrhealdisease)。
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全球大约每年至少10亿人次发生腹泻,根据世界卫生组织调查,每天大约1万人死于腹泻。
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在我国,腹泻病同样是儿童的常见病,据有关资料,我国5岁以下儿童腹泻病的年发病率为201%,平均每年每个儿童年发病3.5次,其死亡率为0.51%。
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因此,对小儿腹泻病的防治十分重要。
[ { "end_idx": 8, "entity": "小儿腹泻病", "start_idx": 4, "type": "dis" } ]
根据病程腹泻病分为:急性腹泻病(acutediarrhealdisease)病程在2周以内;迁延性腹泻病(persistentdiarrhealdisease)病程在2周~2个月;慢性腹泻病(chronicdiarrhealdisease)病程在2个月以上。
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按病情分为:轻型:无脱水,无中毒症状;中型:轻度至中度脱水或有中毒症状;重型:重度脱水或有明显中毒症状(烦躁、精神萎靡、嗜睡、面色苍白。
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高热或体温不升以及白细胞计数明显增高痢疾、霍乱、病毒及其他感染性腹泻等;非感染性,包括食饵性(饮食性)腹泻;症状性腹泻,如过敏性腹泻;其他腹泻病如乳糖不耐症及糖原性腹泻等。
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(一)内在因素1.消化系统发育不成熟婴幼儿时期,胃酸及消化酶分泌不足,消化酶的活性较低,神经系统对胃肠道调节功能较差,不易适应食物的质和量,且生长发育快,营养物质的需要相对较多,胃肠道负担较大,消化功能经常处于紧张状态,易发生消化功能紊乱。
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2.机体防御功能较差婴幼儿时期免疫功能相对不够成熟,血液中的免疫球蛋白和胃肠道sIgA均较低,胃肠屏障功能较弱,胃酸分泌量少,胃肠排空较快,对感染因素防御功能差。
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另外,新生儿,出生后尚未建立完善的肠道正常菌群,对侵入肠道的病原微生物拮抗能力弱,人工喂养者食物中缺乏母乳含有的大量免疫物质,且食物和食具污染机会较多,肠道感染的发生率明显高于母乳喂养儿。
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3.体液分布特点婴儿细胞间质液较多,且水代谢旺盛,肾功能调节差,易发生体液紊乱。
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(二)感染因素1.肠道感染主要由细菌和病毒引起。
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(1)细菌:除法定传染病外。
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①大肠杆菌(Escherichiacoli,E.Coli):按其致病机制分类为致病性大肠杆菌(Entero-pathogenicE.Coli,EPEC)、产毒素性大肠杆菌(EnterotoxigenicE.Coli,ETEC)、侵袭性大肠杆菌(EnteroinvasiveE.Coli,EIEC)、出血性大肠杆菌(EnterohemorrhagicE.Coli,EHEC)以及黏附性大肠杆菌(EnteroadhesiveE.Coli,EAEC);②空肠弯曲菌(Campylobacterjejuni);③耶尔森菌(Yersiniaentero-colitica);④其他:鼠伤寒沙门菌(Salmonellatyphimurium)、变形杆菌(proteus)、铜绿假单胞菌(Pseudomonasaeruginosa)、克雷伯菌(Klebsiella)、金黄色葡萄球菌(Staphlococcusaureus)以及难辨梭状芽胞杆菌(Clostridiumdifficile)等。
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(2)病毒:①轮状病毒(humanrotavirus),是引起婴幼儿腹泻的主要病原;②诺如病毒(Norovirus);③肠道腺病毒(adenovirus);④其他,如星状病毒(astrovirus)、杯状病毒(calicivirus)及冠状病毒(coronavirus)等。
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(3)真菌和原虫:真菌感染主要为白色念珠菌(Candidaalbicans),一些原虫的感染如蓝氏贾第鞭毛虫(Giardialam-blia)、结肠小袋虫(Balantidiumcoli)、隐孢子虫(Cryptosporidi-um)及阿米巴原虫(Entamoebahistolytica)等。
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2.肠道外感染小儿患上呼吸道感染、肺炎、肾盂肾炎、中耳炎、皮肤感染及其他急性感染性疾病时可伴有腹泻。
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这是由于发热及病原体毒素的影响,使消化功能紊乱,酶分泌减少肠蠕动增加。
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腹泻的主要原因之一。
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过多过早喂哺大量淀粉类、脂肪类食物,突然改变食物品种和断奶等均可导致腹泻。
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气候的突然变化,使肠蠕动增加,消化酶和胃酸分泌减少,可诱发腹泻。
[ { "end_idx": 9, "entity": "肠", "start_idx": 9, "type": "bod" }, { "end_idx": 17, "entity": "消化酶", "start_idx": 15, "type": "bod" }, { "end_idx": 20, "entity": "胃酸", "start_idx": 19, "type": "bod" }, { "end_idx": 30, "entity": "腹泻", "start_idx": 29, "type": "dis" } ]
一些吸收不良综合征如乳糖不耐受症、糖原性腹泻、先天性氯化物性腹泻、遗传性果糖不耐受症、胰腺囊性纤维性变以及原发性肠吸收不良等都可引起腹泻。
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牛奶蛋白过敏者,吃牛乳后48小时发生水样泻。
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【发病机制】不同病因引起腹泻的机制不同,可通过以下几种机制致病。
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(一)非感染因素主要是饮食的量和质不恰当,使婴儿消化道功能发生障碍,食物不能充分消化和吸收,积滞于肠道上部,同时酸度下降,有利于肠道下部细菌上移繁殖,使消化功能紊乱。
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肠道内产生大量的乳酸、乙酸等有机酸,使肠腔渗透压增强,引起腹泻。
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(二)感染因素病原微生物能否引起肠道感染,取决于宿主防御功能的强弱、感染量的大小以及微生物毒力(黏附性、产毒性及侵袭性)、细胞毒性,其中微生物的黏附能力对于肠道感染至关重要。
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1.细菌性肠炎主要通过细菌产生毒素作用及细菌侵袭性作用为主要发病机制。
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(1)肠毒素性肠炎:病原菌不侵入肠黏膜,不引起病理形态学上的变化,仅附着于完整的肠绒毛上,通过产生肠毒素致病。
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典型的细菌为ETEC和霍乱弧菌。
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其他细菌也可产生肠毒素,如耶尔森菌、鼠伤寒沙门菌、金黄色葡萄球菌、变形杆菌及空肠弯曲菌等。
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以ETEC为例,通过其菌毛黏附在小肠微绒毛上,生长繁殖,产生大量肠毒素。
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肠毒素有两种,即不耐热毒素(heatliabletoxin,LT)和耐热毒素(heatstabletoxin,ST)。
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LT的理化性质、免疫状态及作用机制与霍乱毒素相同。
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LT与小肠上皮细胞上的受体神经节苷脂结合,激活腺苷酸环化酶,使肠上皮细胞内三磷酸腺苷(ATP)转化为环磷酸腺苷(cAMP)。
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ST通过激活鸟苷酸环化酶使三磷酸鸟苷(GTP)转化为环磷酸鸟苷(cGMP)。
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二者均抑制肠黏膜对钠(同时对氯和水)的吸收,促进氯(同时对钠和水)的分泌。
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使水向肠腔内渗透,液体积聚于肠道,引起腹泻。
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(2)侵袭性肠炎:病原侵入肠黏膜固有层,引起充血、水肿、炎症细胞浸润、渗出性炎症病变、糜烂及溃疡等,造成腹泻。
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由各种侵袭性细菌所致,如志贺菌、沙门菌、EIEC、空肠弯曲菌、耶尔森菌和金黄色葡萄球菌等。
[ { "end_idx": 7, "entity": "侵袭性细菌", "start_idx": 3, "type": "mic" }, { "end_idx": 14, "entity": "志贺菌", "start_idx": 12, "type": "mic" }, { "end_idx": 18, "entity": "沙门菌", "start_idx": 16, "type": "mic" }, { "end_idx": 23, "entity": "EIEC", "start_idx": 20, "type": "mic" }, { "end_idx": 29, "entity": "空肠弯曲菌", "start_idx": 25, "type": "mic" }, { "end_idx": 34, "entity": "耶尔森菌", "start_idx": 31, "type": "mic" }, { "end_idx": 42, "entity": "金黄色葡萄球菌", "start_idx": 36, "type": "mic" } ]
志贺菌、EIEC和金黄色葡萄球菌主要侵犯结肠;空肠弯曲菌主要病变在空肠和回肠,也可累及结肠;耶尔森菌多累及回肠;鼠伤寒沙门菌主要累及回肠和结肠。
[ { "end_idx": 2, "entity": "志贺菌", "start_idx": 0, "type": "mic" }, { "end_idx": 7, "entity": "EIEC", "start_idx": 4, "type": "mic" }, { "end_idx": 15, "entity": "金黄色葡萄球菌", "start_idx": 9, "type": "mic" }, { "end_idx": 27, "entity": "空肠弯曲菌", "start_idx": 23, "type": "mic" }, { "end_idx": 37, "entity": "回肠", "start_idx": 36, "type": "bod" }, { "end_idx": 49, "entity": "耶尔森菌", "start_idx": 46, "type": "mic" }, { "end_idx": 54, "entity": "回肠", "start_idx": 53, "type": "bod" }, { "end_idx": 61, "entity": "鼠伤寒沙门菌", "start_idx": 56, "type": "mic" }, { "end_idx": 70, "entity": "结肠", "start_idx": 69, "type": "bod" } ]
这类病原菌均能引起痢疾样症状,粪便水分不多有脓血黏液痉挛样腹痛;同时具肠毒素作用和侵袭作用的菌株则可引起毒素性水样腹泻和痢疾样症状。
[ { "end_idx": 4, "entity": "病原菌", "start_idx": 2, "type": "mic" }, { "end_idx": 16, "entity": "粪便", "start_idx": 15, "type": "bod" }, { "end_idx": 20, "entity": "粪便水分不多", "start_idx": 15, "type": "sym" }, { "end_idx": 25, "entity": "脓血黏液", "start_idx": 22, "type": "bod" }, { "end_idx": 25, "entity": "有脓血黏液", "start_idx": 21, "type": "sym" }, { "end_idx": 30, "entity": "痉挛样腹痛", "start_idx": 26, "type": "sym" }, { "end_idx": 37, "entity": "肠毒素", "start_idx": 35, "type": "mic" }, { "end_idx": 47, "entity": "菌株", "start_idx": 46, "type": "mic" }, { "end_idx": 58, "entity": "毒素性水样腹泻", "start_idx": 52, "type": "dis" } ]
2.病毒性肠炎(viralenteritis)目前对轮状病毒(rotavirus)研究较多。
[ { "end_idx": 6, "entity": "病毒性肠炎", "start_idx": 2, "type": "dis" }, { "end_idx": 21, "entity": "viralenteritis", "start_idx": 8, "type": "dis" }, { "end_idx": 29, "entity": "轮状病毒", "start_idx": 26, "type": "mic" }, { "end_idx": 39, "entity": "rotavirus", "start_idx": 31, "type": "mic" } ]