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新生儿坏死性小肠结肠炎课件_3

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新生儿坏死性小肠结肠炎ppt 新生儿坏死性小肠结肠炎 新生儿坏死性 小肠结肠炎 新生儿坏死性 新生儿坏死性小肠结肠炎ppt课件新生儿
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单击此处编辑母版标题样 式 单击此处编辑母版副标题样式 1 1 * * 新生儿坏死性小肠结肠炎 (Necrotizing Enterocolitis,NEC) • 暨南大学医学院一附院儿科 • 柳国胜 主讲 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 一般概况 • 于1964年首次发现其具有独特的临床和放射表现 • 发病机制尚未完全明了的严重胃肠道疾病 • 流行病学的观察到感染、肠道喂养及胃肠道局部缺血 性损害在这一疾病发生中的潜在作用 • 在所有NICU的病婴中NEC的总的发生率在1%-5%之间, 其中62%-94%的患者是早产儿,胎龄越小,NEC的发生 率越高,占极低出生体重儿(VLBW )的存活者 5-10% • 通常发生在生后3-10天,范围是从生后24小时至3个月 • VLBW 的NEC死亡率可高达 50% With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 一般概况 • 在美国,新生儿坏死性小肠结肠炎发生率约 为1~3/ 1000 • 每年新增患儿3 000 余例,死亡近1 000 例 • 占新生儿死亡病例的50 % • 所以美国国立卫生研究院投入巨资对该病 进行研究, 形成了多个研究中心 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 病因及发病机制 • NEC最一致的流行病学危险因素:早产、肠 道喂养、细菌定植 • 其他危险因素:窒息、先天性心脏病(CHD )、红细胞增多症、脐动静脉置管、使用 消炎痛及甲基黄嘌呤 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 胃肠道功能不成熟 • NEC主要发生于早产儿及低体重儿,使人们自然想 到胃肠道功能不成熟是该病的原因 • 发育未成熟的胃肠道分泌胃液及胰液的能力降低, 使得细菌易于在胃肠道内繁殖 • 杯状细胞分泌粘液的能力不足而肠上皮细胞间的 连接松弛,从而产生细菌移位, 触发炎症反应而引 起NEC • 早产儿肠蠕动减慢又延长了细菌在肠道内存留的 时间,加重了细菌感染引发的炎症反应 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 胃肠道功能不成熟 结构屏障 • 临床和动物实验都证实发生NEC时,肠道渗 透性显著增加,同时伴随有上皮层的破坏 • 肠完整性可能受前列腺素、NO、表皮生长 因子的调控 • 目前认为前列腺素通过增加紧密连接帮助 屏障作用修复,这正好可以解释消炎痛-前 列腺素抑制剂,与自发性肠穿孔的关系 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 胃肠道功能不成熟 生物化学屏障 • Paneth cells :被发现在肠腺底部,分泌溶菌酶 ,磷脂酶A2和小的抗微生物肽,可以调节细菌群 体的组成和分布。 • Paneth cells和其它肠上皮细胞分泌防御素,通 过扩大促炎症反应和促分泌反应从而促进宿主防 御反应。 • 肠道屏障发育异常和结构不成熟,都容易造成肠 道的损伤 早产儿不论是结构屏障还是生物化学屏障都发育不 成熟 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 缺氧缺血性损伤 • 选择性的内脏缺血 • 低血压 • 低体温 • 缺氧 • 喂养 • 贫血 • 脐导管插入术 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 缺氧缺血性损伤 • 窒息缺氧时,肠壁血流可减少到正常的 35%-50%,末端回肠、升结肠可减少到 正常的10%-30%,因而导致肠粘膜缺血 损伤。 • 氧自由基、血管运动肠多肽、炎性介质 均被认为是粘膜损伤的中介物 • 近年来的研究否认了单纯缺氧在N EC 发 生中的作用 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 缺氧缺血性损伤 • 肠道循环取决于血管舒张和血管收缩之间 的动态平衡 • 静息状态下,由于NO产物的增加使血管舒 张占优势,从而增加血流速度及氧供满足 肠道生长发育及消化营养所需 • 病理状态下,血管收缩占优势,从而导致 肠道缺血性损伤: 炎性介质上调了内皮素 -1和内皮素-A; IL-1β在血管收缩方面起 辅助性作用 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 缺氧缺血性损伤 • 有许多关于肠道血流和NEC之间关系的研究 • 近年来,已经证实以下因子会引起肠系膜 血流的减少,如使用咖啡因,临床症状表 现严重的PDA,使用消炎痛治疗PDA,高营 养素,使用CPAP • 暂时还没有明确的证据表明以上这些情况 与NEC直接相关 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 缺氧缺血性损伤 • 已经证实早期耐受肠道喂养与肠系膜上动 脉的血流增加有显著的相关性 • 通过超声发现肠道动力的改变及随后的喂 养不耐受与肠系膜上动脉血流的异常相关 • 有研究表明,新生儿生后第1天肠系膜上动 脉高阻力血流模式往往导致NEC的发生 • 因此,可以推测早产儿肠道循环状态使得 这些婴儿更容易发生NEC With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 胃肠道营养 所有发生NEC的婴儿中90%~95%是胃肠道喂 养,故胃肠道营养也被认为起主要作用。 • 未经消化的配方乳为细菌的繁殖提供了底物 • 营养的吸收期间肠对氧的需求增加 • 不成熟的免疫系统 • 胃肠道运动障碍或静止 • 肠系膜血管调节能力不成熟或缺乏 • 缺氧或感染的应激 • 代谢需求增加可以导致组织缺氧 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 喂养与NEC • 提供基质(CH2O)予细菌生长 • 过早过量喂养 吸收不良 碳水化合物的发酵 气胀 肠腔内压增加 危及血管 * 90% NEC于进食后出现 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 胃肠道营养 • 尽管知道肠道营养有上述不利,但大多数肠道喂 养的早产儿并没有发生NEC • 胃肠道营养同胃肠道外营养比较起来更容易管理 ,对粘膜产生有益的营养作用 • 导管相关的败血症、高糖血症、胆汁淤积及佝偻 病是早产儿使用胃肠道外营养的并发症 • 力图预防NEC发生而作出停止牛乳喂养的决定应 该仔细权衡 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 胃肠道营养 • 母乳的一项有益的作用即防止NEC的发生 已经被提出 • 母乳中潜在的保护性因子包括大量的乳酸 杆菌,抗葡萄球菌介质,免疫球蛋白,补 体组成成份,溶菌酶、乳酸过氧化物酶, 乳铁蛋白,巨噬细胞及淋巴细胞 • 母乳喂养的婴儿也确实发生了NEC,这表 明其它一些因素超过母乳的保护性作用 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 营养喂养时间和份量可能是可改变的早产儿NEC 风险因素Henderson et al: Arch Dis Child 2009;94:F120-3 • 多中心组群研究 • 53例NEC vs 年龄配对对照 • 与对照比较,NEC病例有 –较少母乳喂哺 –营养喂养时间短 –达到完全喂哺的过程快 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 感染性疾病 • 只有30%的NEC患儿血培养阳性,而目前许多报 道仍认为感染是NEC的重要发病因素,NEC可集 中发病,采取严格感染控制措施后可减少NEC的 发生,甚至消失 • 发生发展有类似于败血症和感染性休克样的临床 表现,可出现多脏器功能衰竭 • 有作者认为NEC是胃肠功能衰竭在新生儿期的一 种特殊表现,严重时常伴多功能衰竭、呼衰( 91%)、肾衰(85%)、心衰(33%)和肝衰( 15%) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society •心率180 超过 6 小時 •MBP 0.4方能维持 PaO250mmHg •尿量103umol/L •結合膽紅素25umol/L •微循環情況 •CRT(毛細血長再充盈 時間)3 sec •皮下水腫 •FDP 32 ug/ml •PT 150 秒 新生儿多脏器衰竭 Morecroft: Acta Paediatr 1994 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society • TNF和PAF可诱导NEC的发生 • 免疫球蛋白能有预防NEC的发生 提示:NEC与感染的关系非常密切 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 遗传倾向 • 越来越多的遗传学证据表明遗传多态性与早产, RDS,BPD,败血症,ROP及其他新生儿疾病的发生 有相关性。 • NEC的发生及严重性似乎有相同的遗传倾向 • 不成熟的循环应答也可能与VEGF和CPS-1基因的改 变有关, VEGF在血管生成和血管舒张方面起重要 作用。 • 氨甲酰磷酸合成酶-1是一种限速酶,是精氨酸的 产物, 是NO的前体。 • 其他遗传学变化可能影响炎性信号识别受体模式 或细胞因子编码基因,从而引发炎性瀑布样表达 。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 危险因素 •早产 •围产期窒息 •呼吸窘迫综合征 •脐插管术 •低体温 •休克 •缺氧 •动脉导管未闭 •青紫型先天性心脏病 •红细胞增多症 •血小板增多症 • 贫血 • 交换输血 • 先天性胃肠道畸形 • 慢性腹泻 • 非母乳的配方乳 • 鼻-空肠喂养 • 高渗配方乳 • 喂养量过多增加过快 • 流行期间住院 • 坏死性细菌的肠道移位 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 临床表现 • NEC相关的症状和体征 • 突发性NEC与隐匿性NEC的比较 • 不同病区NEC的表现 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 扩张(固定)肠回 •患儿WCK, •孕32周出生 •出生体重1380g, 19天大 –腹胀 –体温不稳定 –精神萎靡 –呼吸暂停 –皮肤苍白, 发花 –DIC 代谢性酸 中毒, 休克 –粪便含有血丝 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 腹腔积气 肠道气囊肿症 肝门静脉积气 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society NEC相关的症状和体征 胃肠道 •腹胀 •腹部触痛 •喂养不耐受 •胃排空延迟 •呕吐 •潜隐的或肉眼可见的便血 •大便性状改变或腹泻 •腹部团块 •腹壁红斑 全身症状 •昏睡 •呼吸暂停或呼吸困难 •体征不稳定 •“不对劲” •酸中毒(代谢性或呼吸性) •血糖不稳定 •灌注不足或休克 •弥漫的血管内凝血(DIC) •血糖呈阳性 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 突发性NEC与隐匿性NEC的比较 突发的NEC • 足月儿或早产儿 • 急性灾难性的病情恶化 • 呼吸困难 • 休克或酸中毒 • 明显腹胀 • 血培养阳性 隐匿的NEC • 通常为早产儿 • 1~2天的渐进期 • 喂养不耐受 • 大便性状改变 • 间歇性腹胀 • 大便潜血 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 不同病区NEC的表现 一般病房 • 逐渐康复的足月儿或早产 儿 • 不存在危险因素的早产儿 • 发作的年龄与胎龄成反比 • 喂养紊乱是重要的临床特 征 • 渐进或爆发发作 重症监护病房 • 生后的足月儿或早产儿 • 其它持续的医学问题/危 险因素 • 生后一周发作 • 喂养紊乱不常见 • 通过ICU的护理,症状和 体征可能不典型 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 临床分期 贝尔等设计的NEC的临床分期系统 • IA期-可疑NEC • IB期-临床NEC • ⅡA期-确诊NEC(轻度) • ⅡB期-确诊NEC(中度) • ⅢA期-进展期NEC(重度,肠完整无损) • ⅢB期-进展期NEC(重度,肠穿孔) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society IA期-可疑NEC • 全身症状 :体温不稳定、呼吸暂停、心率减慢、 嗜睡 • 肠道症状:饲喂前胃潴留增加、轻度腹胀、呕吐 、大便潜血(+) • 放射线的症状:正常或肠扩张,轻度肠梗阻 • 治疗:NPO,在培养之前使用抗生素三天. With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society IB期-临床NEC • 全身症状:同IA期 • 肠道症状:直肠中排出鲜血 • 放射前症状:同IA期 • 治疗:同IA期 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ⅡA期-确诊NEC(轻度) • 全身症状:同IA期 • 肠道症状:同IA期,加上肠鸣音消失,腹部压痛 +/- • 放射学症状:肠扩张,肠梗阻,肠积气征 • 治疗:NPO,在24~48小时内如果检查是正常的 ,抗生素使用7~10天 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ⅡB期-确诊NEC(中度) • 全身症状:同ⅡA期,加上轻度代谢性酸中毒, 轻度血小板减少症 • 肠道症状:同ⅡA期,加上肠鸣音消失,明确的 腹部触痛,+/-腹部蜂窝织炎或右下1/4肿块 • 放射学症状:同ⅡA期,加上门静脉积气,+/-腹 水 • 治疗:NPO,抗生素使用14天,碳酸氢盐纠正的 中毒 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ⅢA期-进展期NEC • 全身症状:同ⅡB期,加上低血压,心率慢,严 重的呼吸暂停,混合性酸中毒,DIC,中性粒细 胞减少症 • 肠道症状:同ⅡB期,加上腹膜炎的症状,明显 的触痛,及腹胀 • 放射学症状:同ⅡB期,加上明确的腹水表现 • 治疗:同ⅡB期,加上200ml/kg液体,正性肌力 的药物应用,机械通气治疗,放液性腹穿刺术。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ⅢB期-进展期NEC • 全身症状:同ⅢA期 • 肠道症状:同ⅢA期 • 放射学症状:同ⅡB期,加上气腹 • 治疗:同上,加上外科干预 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 辅助诊断 • 实验室数据 :白细胞增多、血小板减少、电 解质失衡、酸中毒等 • X线腹部平片 :肠积气征 ,气腹 ,门静 脉系统内出现气体(PVA) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗 • 内科治疗 –足量的静脉内液体补充 –血红细胞比积的校正 –鼻胃管减压使肠道休息 –纠正血小板减少 –急性期每6小时摄一次腹部X线平片用于监测穿孔 – 如果患儿有呼吸暂停和心律减慢,需要气管插管及机械通气 – 禁食并胃肠道外全营养 (TPN) –抗生素治疗10~14天 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society • 外科治疗 – 高度特异的征象: 气腹、阳性穿刺术、一系 列X光片上固定的肠襻、腹部团块、门静脉积 气 – 非特异性的支持性的表现:腹部触痛、持续的 血小板减少(5 days)可能更容易导致NEC 的发生或死亡。因此认为长时间使用抗生素增加 NEC的风险。建议早产儿一旦怀疑败血症应尽早使 用抗生素,一旦败血症被排除尽早停抗生素 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 预防 • 预防NEC的关键在于易患人群中使多种起作用的 因素减到最小 • 在开始肠道喂养之前纠正低血容量和高粘滞血症 以及给予足够的时间使机体自稳定机制成熟都是 很重要的 • 喂养最初应该从慢慢给予少量的奶开始 • 有无喂养不耐受的症状,有无胃残留物增加,有 无腹胀及大便潜血阳性 • 有胃肠功能障碍的证据,意味着要密切观察及可 能需要重建静脉内营养支持和肠道减压 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 预防 • 产前使用类固醇的多中心,随机的双音研 究中,治疗组与对照组比较,NEC的发生 有显著的下降 • 当两组病例在年龄及体重方面有可比性并 且也考虑到并发症的时候,类固醇的有效 作用已经被证明 • 有一些其他的研究也得出了相同的结论, 这些研究支持早期分娩的妇女在产前使用 类固醇 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 限制液量 • Cochrane数据库2000 • 4个随机对照研究 • 限制液量 –减少动脉导管未闭的发生 –减少NEC的发生 –减少死亡率 –倾向减低肺支气管发育不良 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 预防 • 母乳中富含免疫保护因子,如分泌型IgA和非分泌 型IgA、IgG、IgM,溶菌酶,乳酸过氧化物酶, 乳铁蛋白,干扰素,双歧因子,以及细胞组成成 分如巨噬细胞,淋巴细胞和中性粒细胞 • 母乳中还含有血小板活化因子乙酰水解酶(PAF- AH),是一种可以修复PAF活性的酶,也是NEC 的一种潜在媒介物 • 已有证据表明供给一部分挤出的母乳及完全给予 挤出的母乳喂养与NEC发生率降低有一定的相关 性 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 母乳 • Lucas et al: Lancet 1990 • 926名早产儿 • 只用配方奶喂养:NEC的发病率 –比母乳喂养多6-10倍 –比混合喂养多3倍 –孕周30周的比其它高20倍 • 然而, 随机对照研究并无发现任何分别(3/83比6/76) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 预防 • 关于摄入口服的免疫球蛋白的几项研究显 示它可以降低肠道感染的严重性或发生率 • 静脉用丙种球蛋白预防新生儿感染的一项 多中心试验没有显示它有预防NEC的保护 作用 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 预防 • 益生菌(probiotics)预防NEC的发生也是近年来研 究的热点 • 双
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