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肠易激综合征的新概念 Newest concepts in irritable bowel syndrome IBS

肠易激综合征的新概念 Newest concepts in irritable bowel syndrome IBS. 张虎 华西医院消化科. 旧概念 ： 过敏性结肠炎 易激结肠 或黏液性结肠炎. 新概念 ：一种以腹痛或腹部不适伴排便习惯改变为特征的功能性肠病

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肠易激综合征的新概念 Newest concepts in irritable bowel syndrome IBS

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  1. 肠易激综合征的新概念Newest concepts in irritable bowel syndromeIBS 张虎 华西医院消化科

  2. 旧概念： 过敏性结肠炎 易激结肠 或黏液性结肠炎

  3. 新概念：一种以腹痛或腹部不适伴排便习惯改变为特征的功能性肠病新概念：一种以腹痛或腹部不适伴排便习惯改变为特征的功能性肠病 …a group of functional bowel disorders in which discomfort or pain is associated with defecation or a change in bowel habit , and with features of disordered defecation.

  4. 该病缺乏可解释症状的形态学改变和生化异常

  5. IBS - Psychosocial IBS Non-patients normal • Psychologic disturbance relates to patients who see physicians • Psychosocial factors influence health care seeking Psychologic disturbance IBS patients

  6. 流行病学研究 西方国家 患病率 5---24% 美国 人群 10-20% 就诊率 30％ $80亿 国内 北京 潘国宗 7.26％ 广州 陈旻湖 5.6％ 就诊率 22.4％

  7. What causes IBS ?

  8. Development of IBS pathophysiology • ｛ • inflammation • 5-HT mediated hypersensitivity • and gut motility • Brain-gut interaction • Visceral hypersensitivity • Abnormal motor function • 1950 1960 1970 1980 1990 2000 Abnormal network regulation Of nerve-immune-endocrine IBS molecular biology …….

  9. IBS发病机制的认识 • 临床症状 • 腹痛、不适 • 大便异常， • 流行病学等 • 第一阶段

  10. IBS发病机制的认识 • 临床症状 运动异常 • 感觉异常 • 社会心理致病 • 腹痛、不适 压力、电活动 • 大便异常， 敏感性、 5-HT • 流行病学等 炎症、脑肠交流 • 第一阶段 第二阶段

  11. Endogenous Modulation .cortex .Brainstem End organ sensitivity.silentnociceptors Visceral Hypersensitivity hyperalgesia allodynia Spinal Hyperexcitability .Nitric oxide Activation Long-term Hyperalgesia .tonic cortical regulation .Neuroplasticity

  12. IBS发病机制的认识 • 临床症状 运动异常 • 感觉异常 • 社会心理致病 • 腹痛、不适 压力、电活动 • 大便异常， 敏感性、 5-HT • 流行病学等 炎症、脑肠交流 • 第一阶段 第二阶段

  13. Serotonin(5-HT) in the human gut 5-HT1 5-HT3 5-HT4 Gastric accommodation ↑ ↑ Transit ↓ ↑ ↑ Colonic tone ↓ ↑ Sensation ↑ ? Secretion ↑

  14. IBS发病机制的认识 • 临床症状 运动异常 • 感觉异常 • 社会心理致病 • 腹痛、不适 压力、电活动 • 大便异常， 敏感性、 5-HT • 流行病学等 炎症、脑肠交流 • 第一阶段 第二阶段

  15. IBS - Post Infectious Psychologic distress Factors Predicting GI Symptoms Younger age Females Duration of diarrhea Duration of abdominal pain

  16. IBS发病机制的认识 • 临床症状 运动异常 • 感觉异常 • 社会心理致病 • 腹痛、不适 压力、电活动 • 大便异常， 敏感性、 5-HT • 流行病学等 炎症、脑肠交流 • 第一阶段 第二阶段

  17. Mechanosensitive afferent Sensitized spinal circuits Repeated stimulation Dorsal root ganglion

  18. Descending Visceral Pain Pathway Thalamus PAG Locus coeruleus Caudal raphe nucleus Amygdala Noradrenergic Rostral ventral medulla Serotonergic Opioidergic Colon

  19. Input Integration Effect Cognition Affect Motility Secretion Blood Flow Inflammation Sight Sound Smell Somatosensory Viscerosensory

  20. IBS发病机制的认识 • 临床症状 运动异常 分子生物学阶段 • 感觉异常 网络调控 • 社会心理致病 • 腹痛、不适 压力、电活动 • 大便异常， 炎症、敏感性 • 流行病学等 5-HT、脑肠交流 • 第一阶段 第二阶段 第三阶段 一氧化氮 5－HT及受体 多巴胺及受体 胃肠道激素及受体 细胞因子及受体 细胞信号转导蛋白 离子及离子通道 ● ● ●

  21. Extracellular network regulation Nerve cells Cytokine, receptor, peptide, 5-HT Immune cells Endocrine cells

  22. How to develop in a person?

  23. Psycho- Physiological triggers Predisposing factors Concurrent modifiers Brain-gut dysregulation Early life Genetic vulnerability, Enviromnent eg illness Behavior reinforcement, abuse

  24. Psycho- Physiological triggers Predisposing factors Concurrent modifiers Brain-gut dysregulation ↑↓ Chronic threat & prolonged effortful coping Early life Enteric Infection/ Inflammation/ toxins Genetic Environment

  25. Predisposing factors Psycho- Physiological triggers Concurrent modifiers Brain-gut dysregulation Stress-response neuromodulation ↓ Chronic threat & prolonged effortful coping Personality, emotional Support, age, gender, Sleep dysfunction Early life ↑ Life event stress, Food allergens, Altered bowel flora Genetic Environment Enteric Infection/ Inflammation/ toxins Post-infective neuromodulation

  26. Psycho- Physiological triggers Predisposing factors Concurrent modifiers Brain-gut dysregulation ↓ Cortical Arousal (anxiety)) Stress-response neuromodulation Prolonged threat &effortful coping CNS Personality, emotional Support, age, gender, Sleep dysfunction ↑ Early life Visceral hypersensitivity Life event stress, Food allergens, Altered bowel flora Enteric infection Inflammation, trauma ENS Altered Epithelial permeability Post-infective neuromodulation GI symptoms Dysmotility IBS EI symptoms

  27. How to diagnose ？

  28. 诊断 • 以症状为基础

  29. 诊断标准 • Manning标准 1978年 • Rome I 1992年 • Rome II 1999年 • Rome III 2006年 ? • 2003年三月 广州首届全国IBS会议 决定采用国际认同的Rome II 诊断标准

  30. Rome I Criteria Rome II Criteria ● At least 3 months continuous / recurrent symptoms of the following -Abdominal pain or discomfort that is -associated with a change in frequency of stool and/or -associated with a change in consistency of stool; and ●Two or more of the following at least 25% of the time altered stool frequency (>3/day or < 3/week) altered stool passage (straining, urgency) passage of mucus bloating or feeling of abdominal distention ● at least 12 weeks, which need not be consecutive, in the past 12 months, of abdominal discomfort or pain that has two of three features -relieved by defecation; and/or -onset associated with a change in frequency of stool; and/or -onset associated with a change in form(appearance) of stool

  31. The Rome II criteria at least 12 weeks, which need not be consecutive, in the past 12 months, of abdominal discomfort or pain that has two of three features onset associated with change in form (appearance) Relieved by defecation onset associated with change in frequency And/or And/or

  32. 支持IBS诊断的症状累积 • 大便频率异常（异常定义为排便每天多于三次及每周少于三次） • 大便性状异常（粗、硬便或稀、水便） • 排便过程异常（摒力、便急或排便不急感） • 粘液便 • 气胀或腹胀感 功能性肠病的诊断均假设症状没有结构性和生化性解释

  33. 该诊断的体现的几个重要原则 • 诊断应建立在排除器质性疾病的基础上 • IBS属于肠道功能性疾病 • 强调腹痛或腹部不适与排便的关系，体现IBS作为一个特定的症候群有别于其他肠道功能行疾病（如功能性腹泻、功能性便秘、功能性腹痛等） • 该诊断标准将判断的时间延长至12个月，规定其间至少有12周时间有症状，但可以不连续，反应了本病慢性、反复发作的特点，可使器质性疾病特别是肠道肿瘤的漏诊几率降低 • 该诊断标准在必备条件中没有对排便次数和粪便性状作硬性规定，只强调腹痛或腹部不适伴有排便次数和粪便性状的改变，可使更多病例得到诊断，提高诊断的敏感性。

  34. 表现分型 分型依据的症状： ①每周排便<3次； ② 每天排便>3次； ③块状或硬便； ④稀烂便或水样便； ⑤排便费力； ⑥排便急迫感。

  35. 表现分型 ●分型依据的症状： ①每周排便<3次； ② 每天排便>3次； ③块状或硬便； ④稀烂便或水样便； ⑤排便费力； ⑥排便急迫感。 ●便秘为主型 ① ③ ⑤ 项中之一项或以上，而无 ② ④ ⑥项 或 ① ③ ⑤ 项中之二项或以上，可伴有② ④ ⑥ 中之一项

  36. 表现分型 ●分型依据的症状： ①每周排便<3次； ② 每天排便>3次； ③块状或硬便； ④稀烂便或水样便； ⑤排便费力； ⑥排便急迫感。 ●腹泻为主型 ② ④ ⑥项中之一项或以上，而无 ① ③ ⑤ 项 或 ② ④ ⑥项中之二项或以上，可伴有① ⑤中一项，但无③项

  37. 表现分型 ●分型依据的症状： ①每周排便<3次； ② 每天排便>3次； ③块状或硬便； ④稀烂便或水样便； ⑤排便费力； ⑥排便急迫感。 ●腹泻便秘交替型 ① ② ③ ④ ⑤ ⑥

  38. 诊断流程 问诊＋查体 发热、消瘦、便血、腹部包块

  39. 诊断流程 问诊＋查体 发热、消瘦、便血、腹部包块 有 无 彻底检查 近期排便习惯改变、肿瘤家族史、>40岁

  40. 诊断流程 问诊＋查体 发热、消瘦、便血、腹部包块 有 无 彻底检查 近期排便习惯改变、肿瘤家族史、>40岁 是 否 肠镜或钡灌肠 大便常规＋OB

  41. What is the best management approach?

  42. 治疗 个体化、综合治疗

  43. 治疗原则 A comprehensive multicomponent approach Treatment program is based on dominant symptom and their severity, and on psychosocial factors , and etiological factors

  44. Drugs for dominant in IBS Antispasmodics Tricyclic Antidepressants SSRI Abdominal pain Constipation Fiber Osmotic laxatives Tegaserod PEG solution Diarrhea Loperamide Cholestyramine Diphenoxylate

  45. 治疗原则 A comprehensive multicomponent approach Treatment program is based on dominant symptom and their severity, and on psychosocial factors , and etiological factors

  46. Severe Realistic goalsAntidepressants Referral for pain management Moderate Gut acting agents Psychologic (motility/sensation) treatments Mild Lifestyle and dietary modification All Therapeutic relationship/continuity of care education/reassurance

  47. 治疗原则 A comprehensive multicomponent approach Treatment program is based on dominant symptom and their severity, and on psychosocial factors , and etiological factors

  48. 心理治疗 What can we do? How to do?

  49. 心理治疗 第一层次：一般性心理治疗或支持性心理治疗（supportive psychotherapy） 第二层次：心理治疗干预(psychotherapeutic intervention)

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