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  1. 1. Irritable BowelSyndromeDr.Chakravarthy,P.SPG in GatroenterologyAMC/KGH
  2. 2. DefinitionIrritable bowel syndrome (IBS) is a functionalbowel disorder in which abdominal pain ordiscomfort is associated with defecation or achange in bowel habit.Bloating, distension, and disordered defecation arecommonly associated features.WGO Practice Guidelines 2009
  3. 3. Global Prevalence
  4. 4. Epidemiology• Mainly occurs between the ages of 15 and 65• First presentation to physician - 30–50 yrs• Prevalence is greater in women (except in India)• Prevalence in children is similar to that in adults
  5. 5. IBS demographicsStudies in non-Western countries• Lack of female predominance• Greater frequency of upper abdominal pain• Lower impact of defecatory symptoms on apatient’s daily life• Stool frequency - greater in the India as awhole(99% )
  6. 6. IBS demographics• Clinical overlap between functional dyspepsia andIBS- very common in China• In Latin America- constipation predominance ismore frequent than diarrhea predominance
  7. 7. Pathophysiology
  8. 8. PathophysiologyALTERED COLONIC AND SMALL BOWELMOTILITY :• High-amplitude propagated contractions(HAPCs)• Enhanced gastrocolic response• Rectal hypersensitivityDiarrhoea
  9. 9. Pathophysiology• Increased segmental (nonpropulsive) contractions• Decreased HAPCs• Reduced rectal sensationConstipation
  10. 10. ? Precipitating factors of increased colonic &small bowel motility- distension, fatty meal, cholecystokinin,- stress, anger, deoxycholic acid- Autonomic dysfunction- administration of corticotropin releasinghormone (CRH)
  11. 11. • No consensus on the exact patterns of motorderangement that induce constipation ordiarrhea.• Motor abnormalities observed in IBS??? Secondary than primary
  12. 12. VISCERAL HYPERSENSITIVITY :• Balloon distension of rectum (1970)• Found in 60% patients• IBS pts more aware of intestinal gas/contractions• Abnormal sensitization within the dorsal horn ofthe spinal cord or higher up in the central nervoussystem.
  13. 13. • Neurotransmitters - serotonin, neurokinins,calcitonin gene-related peptide• Capsaicin (redpepper) receptor on nerve fibersincreased in the rectosigmoid colon in IBS -mediate visceral pain• N-methyl-d-aspartate (NMDA) receptormodulates central (spinal cord) neuronalexcitability
  14. 14. • Significant increase in serine proteases inthe stools of patients with IBS-D• Serine proteases  ?? damage tightjunctions  increase intestinal permeability• Inflammation is responsible for thesensitization
  15. 15. ABNORMAL GAS PROPULSION ANDEXPULSION• Retention of gas following gas infusion into thesmall intestine is greater in patients with IBS• Intestinal gas infusion - more discomfort thancontrols• ??? Involuntary suppression of abd.wall musclecontraction during gas infusion  more distension• ??? SIBO contribute to bloating…..uncertain
  16. 16. LOCAL INFLAMMATION• Increased mast cells and activated T- lymphocytes abovenormal in the mucosa in patients with IBS• Lymphocytic infiltration of the myenteric plexus withneuron degeneration - in severe IBS• Recovery from a proved episode of bacterial enteritis in 7-30% patients( illness lasting > 3wks or caused by toxigenicorganisms)• A central role of mast cells ???  abd.pain
  17. 17. Mediators  5-hydroxytryptamine(5-HT)(?? Central role in inflammation)prostaglandins, bradykinins,adenosine, nerve growth factors
  18. 18. ROLE OF FOOD• Wheat, dairy products, citrus fruits, potatoes, onions, andchocolate• 50% patients showed symptomatic improvement onelimination of pptating diets – uncontrolled trial• ?? Subtle forms of gluten intolerance in IBS-D patients( symptomatic improvement in 70% IBS-D patients withpositive HLA-DQ2 status with gluten restricted diet)
  19. 19. • Fructose & sorbitolmalabsorption contributesto IBS ??( no difference fromcontrols on double blindedtrial)
  20. 20. ABNORMAL COLONIC FLORA AND SMALLINTESTINAL BACTERIAL OVERGROWTH• Increased colonic fermentation, production of excess gassymptoms  ?? Role of probiotics• High prevalance of SIBO in IBS(based on H2 breath tests & clinical response to non-absorbable antobiotics)
  21. 21. CENTRAL DYSREGULATION• Alterations in the brain response to visceral stimuli in IBS( functional MRI & PET)• Greater activation of the mid-cingular cortex followingdelivered or anticipated rectal distention(explains why anxiety or stress can enhance perception ofvisceral pain, whereas relaxation or distraction decreasespain in IBS)
  22. 22. PSYCHOLOGICAL FACTORS• Depression, anxiety, and somatization are the mostcommon coexistants in IBS (40% to 94% of patients)• H/O sexual, physical, or emotional abuse - more often( abuse  ?? Alters brain response to visceral pain)• Childhood stress – gastric suction– 3times more risk• Anxiety secondary to intestinal inflammation (?TNF-alfa)
  23. 23. GENETIC FACTORS• Familial clustering• Greater concordance in monozygotic twins• Potential genes :a) lower expression of IL-10 geneb) sodium channel mutation (SCN5)c) serotonin type III receptor gene – functional varient
  24. 24. Clinical featuresSymptoms• Bloating• Abnormal stool form (hardand/or loose)• Abnormal stool frequency (lessthan three times per week orover three times per day)• Straining at defecation• Urgency• Feeling of incompleteevacuation• The passage of mucus perrectum
  25. 25. Behavioral features• Symptoms present for > 6 months• Stress aggravates symptoms• Frequent consultations for nongastrointestinal symptoms• History of previous medically unexplained symptoms• Aggravation after meals• Associated anxiety and/or depression
  26. 26. Non-colonic symptoms• Dyspepsia— in 42–87% patients• Nausea• Heartburn
  27. 27. Non-GI symptoms• Lethargy• Backache and other muscle and joint pains• Headache• Urinary symptoms: — Nocturia — Frequency andurgency of micturition — Incomplete bladder emptying• Dyspareunia, in women• Insomnia• Low tolerance to medication
  28. 28. Alarming featuresHistory• Blood in the stool• Family H/O coloncancer, IBD, celiac disease• Fever• Onset after age 50 years• Nocturnal symptoms (awakeningthe patient from sleep)• Chronic diarrhea• Progressive dysphagia• Recurrent vomiting• Severe chronic constipation• Short history of symptoms• Travel history to locations endemicfor parasitic diseases• Weight loss
  29. 29. Alarming featuresPhysical Examination• Abdominal mass• Arthritis (active)• Dermatitis herpetiformis orpyoderma gangrenosum• Occult or overt blood on rectalexamination• Signs of anemia• Signs of intestinal obstruction• Signs of intestinalmalabsorption• Signs of thyroid dysfunction
  30. 30. Diagnosis• Based on history & clinical examination• Matching patient’s profile to clinical criteria
  31. 31. Diagnostic algorithm(WGO practice guidelines,2009)
  32. 32. IBS diagnostic cascadeLevel 1• History, physical examination, exclusion of alarmsymptoms, consideration of psychological factors• Blood counts, ESR or C-reactive protein, stool studies(white blood cells, ova, parasites, occult blood)• Thyroid function, tissue transglutaminase (TTG) antibody• Colonoscopy and biopsy• Fecal inflammation marker (e.g., calprotectin)WGO practice guidelines 2009
  33. 33. IBS diagnostic cascadeLevel 2Level 1 with sigmoidoscopyLevel 3Level 1 with stool studiesWGO practice guidelines 2009
  34. 34. Differential Diagnosis• Celiac sprue/ gluten enteropathy• Lactose intolerance• Inflammatory bowel disease• Colorectal carcinoma• Acute diarrhea ( protozoal / bacterial)• Small-intestinal bacterial overgrowth (SIBO)• Diverticulitis• Pelvic inflammatory disease /Endometriosis
  35. 35. Severity of diseaseRome foundation working team report,2011,Am J GE,July,2011
  36. 36. Management• EDUCATION AND SUPPORT• DIET• MEDICATION –laxatives,antispasmodics,antidiarrheals,serotonin receptor drugs,antideprssants,antibiotics,probiotics
  37. 37. Antispasmodics• Anticholinergics –dicyclomine,propanthelene,hyoscyamine• Non-anticholinergics- imetropium,pinaverium• Peppermint oil- 0.2ml TID 30 min before foodLaxatives• Osmotic laxatives may aggravate bloating & pain• Stimulant laxatives – safer• Lubiprostone – 24 micgm BIDWGO practice guidelines 2009
  38. 38. Antispasmodics (Ali Phar Ther,Aug.2004,1253-1269)
  39. 39. Laxatives (Ali Phar Ther,Aug.2004,1253-1269)
  40. 40. Antidiarrheals• Loperamide – effective when used prophylactically2-16mg/d• Cholestyramine• Bismuth subsalicylateSerotonin-Receptor Drugs• Alosetron ( 5-HT3 antagonist) efficacious in severe IBS-D• Starting dose – 0.5 to 1 mg/d• Can be escalated upto 1mg BID in absence of side effects• Adverse effects – ischemic colitis (0.1% pts), constipation(33%)WGO practice guidelines 2009
  41. 41. Alosetron (Ali Phar Ther,Aug.2004,1253-1269)
  42. 42. Antidepressants and AnxiolyticsTricyclic antidepressants(TCAs) - might improve globalwell-being more than symptoms• Start at a low dose (e.g., 10 to 25 mg of desipramine ornortriptyline) and increase the dose by 10 to 25 mgweekly, aiming for a dose of 75 mg initially• Most beneficial in IBS-DSelective serotonin reuptake inhibitors (SSRIs)• Fewer side effects• More beneficial in IBS-CWGO practice guidelines 2009
  43. 43. Anti depressants (Ali Phar Ther,Aug.2004,1253-1269)
  44. 44. Antibiotics• Nonabsorbable antibiotics – rifaximin(400mg TID for10days)• Treating a recurrence - not recommendedProbiotics• Bifidobacterium lactis DN-173 010• Bifidobacterium infantis 35624
  45. 45. Other Drugs• Gabapentin,Pregabalin• Leuprolide (GRH analogue)• Colchicine ,Misoprostol - ?? Role in refractoryconstipation• Domperidone and erythromycin – prokinetic role• Octreotide
  46. 46. Nonpharmacological methods• Aim to reduce avoidance behavior• Regular mealtimes, the intake of sufficient fluids, andsufficient physical activity• Cognitive/behavioral therapy• Behavioral techniques- Relaxation techniques/ Contingency management• Hypnosis
  47. 47. Lubiprostone (Aliment Pharmacol TherNov.2008,vol.29, 329–341)
  48. 48. ManagementSTEP SEVERITY LEVEL OFCAREMANAGEMENT1 Mild Primary Diagnosis,explanation,reassurance,follow-up2 Moderate Secondary Reinforce step 13 Severe Tertiary Avoid over-testing,addTCA/SSRI,alosetron forseverediarrhea;treatanxiety/depression;refer to pain clinic
  49. 49. Choice of treatmentPredominant symptom First step Second stepBloating Adjust, Treat constipation Probiotic,antibiotic,TCA,SSRIsConstipation Fibre supple./ Polyethylene glycolLubiprostoneDiarrhea Loperamaide AlosetronAbdominal pain Antispasmodic,peppermint oilTCAs,SSRIs,Psychotherapy
  50. 50. What’s new ???IBS-C• 5-HT4 receptor agonists-Tegaserod (withdrawn d/t cardiac events)Prucalopride,Naronapride,Velusetrag(no cardiac risk & more efficacy in early studies)• Guanylate cyclase C agonistsLinaclotide -Chey et al(2012)- 46% pts improvedapproved for use in the USA by the FDA in August2012 for adults
  51. 51. Adsorbents• AST 120, a carbon-based adsorbent(absorption of histamine, serotonin, bacterial products andbile acids )32% pts improved in priliminary studies5-HT3 receptor antagonist – Ramosetron( RC trial – 343 patients, no significant benefit)
  52. 52. Futuristic therapiesNat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)
  53. 53. Futuristic therapiesNat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)
  54. 54. Futuristic therapiesNat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)
  55. 55. Prognosis• Relapses are common• 9-10% develop organic disease a median of 15years after diagnosis• Poor prognosisexcessive psychological distressanxiety, long duration of complaints
  56. 56. Take Home Message• No more a vague symptom complex• Pathophysiology ???• History & examination is of prime importance• Always R/O organic disease before diagnosis• Treatment – predominantly symptomatic• Behavioral therapy is important• Newer drugs in pipeline
  57. 57. THANK YOU
  58. 58. References• Sleisenger’s text book of GI diseases,9th edition• WGO practice guidelines,2009• Cochrane database• Alimentary phar & therapeutics,reviews 2004-06• Nat. Rev. Gastroenterol. Hepatol. 10, 13–23 (2013)