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Inflammatory Bowel Disease, Irritable Bowel Syndrome

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  • 1. Harrisons Club:InflammatoryBowel DiseaseMarica A. Lazo

2. Inflammatory Bowel Disease Immune-mediated chronic intestinal condition 2 major types: Ulcerative colitis (UC) and Crohnsdisease (CD) Highest incidence in Europe, the UnitedKingdom, and North America Urban areas have a higher prevalence of IBDthan rural areas, and high socioeconomic classeshave a higher prevalence than lowersocioeconomic classes 3. Epidemiology 4. Genetic Disorders Associated with IBD 5. Etiology and PathogenesisIn genetically predisposed individuals, exogenous factors (e.g., composition of normal intestinalmicrobiota) + endogenous host factors (e.g., intestinal epithelial cell barrierfunction, innate and adaptive immune function)chronic state of dysregulated mucosal immune function that is further modified by specific environmental factors (e.g.,smoking, enteropathogens) 6. Genetic Considerations The diseases and the genetic risk factors that areshared with IBD include rheumatoid arthritis(TNFAIP3), psoriasis (IL23R,IL12B), ankylosingspondylitis (IL23R), type 1 diabetes mellitus(IL10,PTPN2), asthma (ORMDL3), and systemiclupus erythematosus (TNFAIP3,IL10) 7. Genetic Considerations Defective Immune regulation Suppression of inflammation is altered uncontrolled inflammation Inflammatory cascade Cytokine activity not regulated imbalancebetween proinflammatory and anti-inflammatory mediators Exogenous factors Normal microbiota is perceived inappropriatelyas if it were a pathogen 8. Pathology 9. Ulcerative Colitis Macroscopic Features 10. Crohns Disease Macroscopic Features 11. Macroscopic FeaturesUC CD Rectal involvement Pseudopolyps Toxic megacolon Skip lesions Perirectal fistulas, fissures, abscesses, and anal stenosis Transmural involvement Cobblestone appearance 12. Ulcerative Colitis Microscopic Features 13. Crohns Disease Microscopic Features 14. Only GALS can be Crohns!G GranulomasAL All Layers and All LevelsS Skip lesions 15. Clinical Presentation 16. Clinical Features of UC vs CD 17. Endoscopic and Radiographic Features ofUC vs CD 18. Differential Diagnosis of UCand CD 19. Diseases that Mimic IBD 20. Diseases that Mimic IBD 21. Extraintestinal Manifestations Dermatologic Rheumatologic Ocular Hepatobiliary Urologic Metabolic bone disorders Thromboembolic disorders Others 22. Extraintestinal Manifestations:A PIE SAC Aphthous ulcers Pyoderma gangrenosum Iritis Erythema nodosum Sclerosing cholangitis Arthritis Clubbing of fingertips 23. Treatment of IBD 24. Treatment 5-ASA Agents Mainstay of therapy for mild to moderate UC is Sulfasalazine and other 5-ASA agents. Limited role in inducing remission in CD. 25. Treatment Glucocorticoids For moderate to severe UC and CD Prednisone 4060 mg/d for active UC that isunresponsive to 5-ASA therapy. Parenteral: hydrocortisone, 300 mg/d, ormethylprednisolone, 4060 mg/d. No role in maintenance therapy for both UCand CD 26. Treatment Antibiotics Pouchitis in 1/3 of UC patients post colectomy =responsive to metronidazole and/or ciprofloxacin Metronidazole Effective in active inflammatory, fistulous, and perianal CD and may prevent recurrence after ileal resection. The most effective dose is 1520 mg/kg per day in three divided doses; it is usually continued for several months. 27. Treatment Azathioprine 6-Mercaptopurine Methotrexate Cyclosporine Tacrolimus Biologic therapies Anti-TNF therapies Natalizumab 28. Standard Medical Management of UC 29. Standard Medical Management of CD 30. Indications for Surgery 31. Harrisons Club:Irritable BowelSyndromeMarica A. Lazo 32. Irritable Bowel Syndrome A functional bowel disorder characterized byabdominal pain or discomfort and altered bowelhabits in the absence of detectable structuralabnormalities 10-20% of adults and adolescents havesymptoms c/w IBS, with FEMALE predominance(2-3x as often as men) Commonly first symptoms occur before age 45 33. Diagnostic Criteria for IBS(ROME II Criteria) 34. Clinical Features Abdominal pain/discomfort Prerequisite clinical feature of IBS Variable in intensity and location Exacerbated by eating or emotional stress and improved by passage of flatus or stools Altered bowel habits Most consistent clinical feature in IBS Constipation alternating with diarrhea, usually with one symptom predominating 35. Clinical Features Gas and flatulence Impaired transit and tolerance of intestinalgas loads Reflux gas from distal to proximal intestine -flatulence Upper GI symptoms 25-50% of patients complain of dyspepsia,heartburn, nausea or vomiting 36. Pathophysiology1. Gastrointestinal motor abnormalities Increased rectosigmoid motor activity for upto 3 hours after eating Recordings from the transverse, descendingand sigmoid colon showed that the motilityindex and peak amplitude of high-amplitudepropagating contractions (HAPCs) in IBS-Dwere increased 37. Pathophysiology2. Visceral hypersensitivity Exaggerated sensory responses to visceralstimulation Proposed mechanisms: End-organ sensitivity CNS modulation Long-term hyperalgesia Tonic cortical regulation Neuroplasticity 38. Pathophysiology3. Central Neural Dysregulation Clinical association of emotional disorders and stress with symptom exacerbation and the therapeutic response In response to distal colonic stimulation, the mid-cingulate cortex shows greater activation in IBS patients Preferential activation of the prefrontal lobe increased perception of visceral pain 39. Pathophysiology4. Abnormal Psychological Features Abnormal psychiatric features are present in up to 80% of IBS patients An association between prior sexual or physical abuse and development of IBS has been reported Increased motor reactivity of the colon and small bowel to a variety of stimuli and altered visceral sensation associated with lowered sensation thresholds 40. Therapeutic Targets for IBS 41. Pathophysiology5. Post-Infectious IBS Occurs more commonly in females and affects younger rather than older patients Risk factors: prolonged duration of initial illness, toxicity of bacterial strain, smoking, mucosal markers of inflammation, female gender, depression, hypochondriasis, and adverse-life events in the preceding 3 months Campylobacter, Salmonella and Shigella 42. Pathophysiology6. Immune Activation and Mucosal Inflammation Activated lymphocytes, mast cells, andenhanced expression of proinflammatorycytokines abnormal epithelial secretionand visceral hypersensitivity Psychological stress release ofproinflammatory cytokine alter intestinalpermeability 43. Pathophysiology7. Altered Gut Flora High prevalence of small intestinal bacterial overgrowth in IBS patients (positive lactulose hydrogen breath test) Bacterial genera with Lactobacillus sequence appear to be absent from IBS, and Collinsella sequences were reduced 44. Pathophysiology8. Abnormal Serotonin Pathways Serotonin (5HT)-containing enterochromaffin cells in the colon are increased in a subset of IBS-D patients compared to healthy individuals or patients with ulcerative colitis Increased release of serotonin may contribute to postprandial symptoms and provides a rationale for the use of serotonin antagonists in the treatment of IBS 45. Approach to the Patient with IBSIBS NOT IBS recurrence of lower appearance of the disorderabdominal pain with for the first time in old agealtered bowel habits over a progressive course from timeperiod of time withoutof onset, persistent diarrheaprogressive deterioration after a 48-h fast onset of symptoms during presence of nocturnalperiods of stress diarrhea or steatorrheal absence of other systemic stoolssymptoms such as fever andweight loss small-volume stool withoutany evidence of blood 46. Differentials Lactase deficiency Diverticular disease of Celiac spruethe colon, Side-effects from inflammatory bowelanticholinergic,diseaseantihypertensive, and Giardiaantidepressant meds Laxative abuse Biliary tract disease, Hyperthyroidismintestinal ischemia,peptic ulcer disorders,and carcinoma of thestomach and pancreas 47. Approach to the Patient with IBS Young pxs with mild symptoms require minimaldiagnostic evaluation, while older pxs or thosewith rapidly progressive symptoms shouldundergo a more thorough one CBC and sigmoidoscopic examination, stoolexam In pxs with persistent diarrhea not responding toanti-diarrhea agents, a sigmoid colon biopsyshould be performed to rule out microscopiccolitis 48. Approach to the Patient with IBS In those aged >40 years, an air-contrast bariumenema or colonoscopy should also be performed If the main symptoms are diarrhea andincreased gas, the possibility of lactase deficiencyshould be ruled out with a hydrogen breath testor with evaluation after a 3-week lactose-freediet Lab features that argue against IBS includeanemia, elevated ESR, presence of leukocytes orblood in stool, and stool volume >200300 mL/d 49. Treatment High-fiber diet Anticholinergic drugs inhibit gastrocolic reflex(ipratropium bromide) Anti-diarrheals (loperamide) Anti-depressants TCAs and SSRIs (fluoxetine) Activated charcoal as part of anti-flatulencetherapy Serotonin Receptor Agonist and Antagonists alosetron, tegaserod Chloride Channel Activators lubiprostone 50. Thank you!

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