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Irritable Bowel Syndrome (IBS)

Irritable Bowel Syndrome (IBS). Presented by: Dr . Nasser Ebrahimi Daryani Professor of Gastroenterology Tehran University of Medical Sciences. Rome II Functional GI Disorders. Esophageal Biliary Gastroduodenal Bowel Anorectal / pelvic floor. Functional GI Disorders -(Rome II).

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Irritable Bowel Syndrome (IBS)

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  1. Irritable Bowel Syndrome (IBS) Presented by: Dr. Nasser EbrahimiDaryani Professor of Gastroenterology Tehran University of Medical Sciences

  2. Rome II Functional GI Disorders Esophageal Biliary Gastroduodenal Bowel Anorectal / pelvic floor Functional GI Disorders -(Rome II) Drossman DA, et al., Gut 1999; 45:II1

  3. Rome III Diagnostic Questionnaire Functional Abdominal Pain Functional Esophageal Functional Gastroduodenal IBS & Functional Bowel Functional Billiary Functional Anorectal

  4. Introduction • A functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits in the absence of detectable structural abnormalities • Throughout the world,10–20% of adults and adolescents have symptoms consistent with IBS • Most studies show a female predominance

  5. Epidemiology Summary IBS - Epidemiology Drossman DA, et al., Gastroenterology 1997; 112:2137

  6. Rome III criteria • Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis • In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 days a week during screening evaluation is required for subject eligibility

  7. Rome III Criteria* – Irritable Bowel Syndrome Recurrent abdominal pain or discomfort at least 3 days/month In the last 3 months associated with 2 or more : Improvement with defecation Onset associated with a change in form (appearance) of stool Onset associated with a change in frequency of stool and and * Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. Longstreth GF, Gastroenterology 2006 1782

  8. IBS Classification IBS Symptom-based JKM 2006

  9. Clinical Features • Most pts have their first symptoms before age 45 • Women are diagnosed with IBS two to three times as often as men • Painless diarrhea or constipation does not fulfill the diagnostic criteria to be classified as IBS

  10. Abdominal Pain • abdominal pain or discomfort is a prerequisite clinical feature of IBS • Frequently episodic and crampy, but it may be superimposed on a background of constant ache • Malnutrition due to inadequate caloric intake is exceedingly rare with IBS • Sleep deprivation is also unusual because abdominal pain is almost present only during waking hours

  11. Pts with severe IBS frequently wake repeatedly during the night • Nocturnal pain is a poor discriminating factor between organic and functional bowel disease • Pain is often exacerbated by eating or emotional stress and improved by passage of flatus or stools • Female IBS pts report worsening symptoms during the premenstrual and menstrual phases

  12. Altered Bowel Habits • The most consistent clinical feature in IBS • Most common pattern is constipation alternating with diarrhea • Pats whose predominant symptom is constipation may have weeks or months of constipation interrupted with brief periods of diarrhea • Nocturnal diarrhea does not occur in IBS

  13. Diarrhea may be aggravated by emotional stress or eating • Stool may be accompanied by passage of mucus • Bleeding is not a feature of IBS unless hemorrhoids are present • Malabsorption or weight loss does not occur

  14. Gas and Flatulence • Quantitative measurements reveal that most pts who complain of increased gas generate no more than a normal amount of intestinal gas • Pts with IBS tend to reflux gas from the distal to the more proximal intestine, which may explain the belching • Bloating & visible distention are more common among female pts

  15. Overlap Among GI Disorders Bloating • 29% with GERD have chronic constipation* • Diagnoses can shift over time† • May share common patho-physiology†‡ Constipation Chronic Constipation Belching Dyspepsia IBS Discomfort Abdominal Pain GERD Regurgitation Heartburn *Locke GR. Neurogastroenterol Motil. 2004;16:1†Corazziari E. Best Prac Res Clin Gastroenterol. 2004;18:613‡Talley NJ. Am J Gastroenterol 2003;98:2454

  16. Upper Gastrointestinal Symptoms • 25-50% of pts with IBS complain of dyspepsia, heartburn, nausea, and vomiting • Prevalence of IBS is higher among pts with dyspepsia (31.7%) than among those who reported no symptoms of dyspepsia (7.9%) • Among pts with IBS, 55.6% reported symptoms of dyspepsia

  17. Pathophysiology of IBS

  18. Gastrointestinal Motor Abnormalities • Colonic motor abnormalities are more prominent under stimulated conditions in IBS • IBS pts may exhibit increased rectosigmoid motor activity for up to 3 h after eating • Motility index and peak amplitude of high-amplitude propagating contractions (HAPCs) in diarrhea-prone IBS pts were greatly increased compared to those in healthy subjects

  19. Visceral Hypersensitivity • IBS patients frequently exhibit exaggerated sensory responses to visceral stimulation • Postprandial pain related to entry of the food bolus into the cecum in 74% of pts • IBS pts do not exhibit heightened sensitivity elsewhere in the body

  20. Central Neural Dysregulation • Functional brain imaging (MRI) have shown that in response to distal colonic stimulation, the mid-cingulate cortex—a brain region concerned with attention processes and response selection—shows greater activation in IBS pts

  21. Abnormal Psychological Features • Recorded in up to 80% of IBS pts • An association between prior sexual or physical abuse and development of IBS has been reported • Abuse is associated with greater pain reporting, psychological distress, and poor health outcome

  22. Pathogenesis of IBS: 5HT Kellow JE. Gastroenterology 2006;130:1412 JKM 2006

  23. Pathogenesis of IBS “Sporadic” JKM 2006

  24. Psychologic distress Younger age Factors Predicting GI Symptoms Females Duration of diarrhea Duration of abdominal pain

  25. Post Infectious IBS Psychological Distress Mucosal Inflammation IBS Symptoms Visceral Sensitivity Acute Infection trigger Dysmotility secretion

  26. Risk factors for developing post-infectious IBS include (in order of importance): - Prolonged duration of initial illness - Toxicity of infecting bacterial strain - Smoking - Mucosal markers of inflammation - Female gender - Depression - Hypochondriasis - Adverse-life events in the preceding 3 months

  27. Potential Risk Factorsfor PI-IBS: • Demographics: • Female • Age < 60 • Acute illness: • Absence of emesis • Fever • Severe diarrhea • “Virulent” organism • Psychology: • Anxiety, neurosis, somatization • Stressful life events prior to infection JKM 2006

  28. Immune Activation and Mucosal Inflammation • Pts with IBS display persistent signs of mucosal inflammation with activated lymphocytes, mast cells & expression of proinflammatory cytokines • Clinical studies shown increased intestinal permeability in pts with IBS-D

  29. Altered Gut Flora • High prevalence of small intestinal bacterial overgrowth in IBS pts noted based on positive lactulose hydrogen breath test • Bacterial genera with Lactobacillus sequence appear to be absent in IBS,& Collinsella sequences were greatly reduced in these pts

  30. Abnormal Serotonin Pathways • 5HT-containing enterochromaffin cells in the colon are increased in a subset of IBS-D pts compared to healthy individuals • Postprandial plasma 5HT levels were significantly higher in this group of pts

  31. Approach to the Patient

  32. A careful history and Ph/Ex are frequently helpful in establishing the diagnosis • Clinical features suggestive of IBS include: - Recurrence of lower abdominal pain with altered bowel habits - Onset of symptoms during periods of stress or emotional upset - Absence of other systemic symptoms such as fever and weight loss - Small-volume stool without any evidence of blood

  33. Laboratory ↓ Hemoglobin ↑ WBC count Positive FOBT ↑ ESR ↑ CRP History Onset after age 50 Family history of colon cancer or inflammatory bowel disease Unintentional weight loss Hematochezia Symptoms of underlying disorder (e.g. hypothyroidism) Common “Red Flags” • Physical • Fever • Abnormal rectal examination • Abdominal mass Drossman DA et al. Gastroenterology. 1997;112:2120-2137. Paterson WG et al. CMAJ. 1999;161:154-160. Camilleri M, Choi MG. AlimentPharmacolTher. 1997;11:3-15. Frissora CL, Harris LA. Emerg Med. 2001;Apr:57-64.

  34. Evaluation • Colonoscopy is recommended : • Over age 50 • In younger patients, is determined by clinical features suggestive of disease (eg, if there is significant diarrhea) • AEA • AGA

  35. In pts with postprandial RUQ pain,ultrasonogram of the gallbladder should be obtained • Laboratory features that argue against IBS: - Evidence of anemia - Elevated sedimentation rate - Presence of leukocytes or blood in stool - Stool volume >200–300 ml/d

  36. In those aged >40 yrs, an air-contrast barium enema or colonoscopy should also be performed • If the main symptoms are diarrhea and increased gas, lactase deficiency should be ruled out with a hydrogen breath test or with evaluation after a 3-week lactose-free diet • In pts with concurrent symptoms of dyspepsia, upper GI radiographs or EGD is advisable

  37. Treatment

  38. Patient Counseling and Dietary Alterations • Reassurance and careful explanation of the functional nature of the disorder are important first steps • Excessive fructose and artificial sweeteners (sorbitol or mannitol) cause diarrhea, bloating, cramping or flatulence • Pts with IBS-D anecdotally report symptom improvement after initiating a low-carbohydrate diet

  39. Stool-Bulking Agents • Fiber speeds up colonic transit in most persons • In diarrhea-prone pts, whole-colonic transit is faster than average; • Most investigations report increases in stool weight, decreases in colonic transit times, and improvement in constipation • Most gastroenterologists consider stool-bulking agents worth trying in patients with IBS-C

  40. Antispasmodics • Anticholinergic drugs may provide temporary relief for symptoms such as painful cramps • Drugs are most effective when prescribed in anticipation of predictable pain • Most anticholinergics contain belladonna alkaloids, which may cause xerostomia, urinary hesitancy and retention, blurred vision, and drowsiness

  41. Antidiarrheal Agents • Peripherally acting opiate-based agents are the initial therapy of choice for IBS-D • Small doses of loperamide, 2–4 mg every 4–6 h up to a maximum of 12 g/d, can be prescribed • high dose of loperamide cause cramping because of increases in segmenting colonic contractions • Another anti-diarrhea agent in IBS pts is the bile acid binder cholestyramine resin

  42. Antidepressant Drugs • In IBS-D pts, the TCA, imipramine slows jejunal migrating motor complex transit propagation and delays orocecal and whole-gut transit • Beneficial effects of TCA in IBS appear to be independent of their effects on depression • Paroxetine (SSRI) accelerates orocecal transit, useful in IBS-C pts • A placebo-controlled study of citalopram in IBS pts reported reductions in pain

  43. Antiflatulence Therapy • Antibiotics may help in a subgroup of IBS pts with predominant symptoms of bloating • Beano, an oral -glycosidase solution, reduce rectal passage of gas without decreasing bloating and pain • Pancreatic enzymes reduce bloating, gas, and fullness during and after high-calorie, high-fat meal ingestion

  44. Modulation of Gut Flora • Pts receiving rifaximin at a dose of 400 mg/TDS experienced substantial improvement of global IBS symptoms over placebo • Currently there is still insufficient data to recommend routine use of this antibiotic in IBS • Bifidobacteriuminfantis 35624 (probiotic) showed significant improvement in the composite score for abdominal pain, bloating/distention, and/or bowel movement compared with placebo

  45. Serotonin Receptor Agonist & Antagonists • a 5-HT3 receptor antagonist such as alosetron reduces perception of painful visceral stimulation in IBS • These agents are more likely to cause constipation in IBS pts with diarrhea alternating with constipation • 0.2% of pts using 5HT3 antagonist developed ischemic colitis versus none in the control group

  46. In IBS pts with constipation, tegaserod (5-HT4 receptor agonist) accelerated intestinal and ascending colon transit • Diarrhea is the major side effect • Tegaserod has been withdrawn from the market; a meta-analysis revealed an increase in serious cardiovascular events

  47. Chloride Channel Activators • Lubiprostoneis a bicyclic fatty acid that stimulates chloride channels in the apical membrane of intestinal epithelial cells • Oral lubiprostone was effective in the treatment of pts with constipation-predominant IBS • Responses were significantly greater in pts receiving lubiprostone 8 g/tds for 3 months • The major side effects are nausea and diarrhea

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