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Inflammatory bowel disease


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Inflammatory bowel disease

  1. 1. Inflammatory bowel disease intestines.It includes a group of chronic disorders thatcause inflammation or ulceration in large andsmall intestines.
  2. 2. TYPES Crohn’s disease Ulcerative colitis• Extends into the deeper layers of the intestinal wall, • causes ulceration and and may affect the mouth, inflammation of the inner esophagus, stomach, and lining of the colon and small intestine. rectum.• Transmural inflammation and skip lesions. • It is usually in the form of• In 50% cases -ileocolic,30% characteristic ulcers or open ileal and 20% -colic region. sores.• Regional enteritis
  3. 3. Other forms of IBD• Collagenous colitis• Lymphocytic colitis• Ischemic colitis• Behcet’s syndrome• Infective colitis• Intermediate colitis
  4. 4. Epidemiology Ulcerative colitis Crohn’sIncidence / 1 lac. 2.2-14.3 3.1-14.6Age of onset 15-30, 60-80Ethnicity JewishMale: Female 1:1 1.1-1.8 : 1Smoking May prevent CausativeOral contraceptives No risk 1.4 odds ratioAppedicectomy Protective NotMonozygotic 6% 58%Dizygotic 0% 4%
  5. 5. Etiopathogenesis• Exact cause is unknown.• Genetic factors• Immunological factors• Microbial factors• Psychosocial factors
  6. 6. Genetic factors• Ulcerative colitis is more common in DR2-related genes• Crohn’s disease is more common in DR5 DQ1 alleles• 3-20 times higher incidence in first degree relatives
  7. 7. Immunologic factors• Defective regulation of immunesuppresion• Activated CD+4 cells activate other inflammatory cells like macrophages & B-cells or recruit more inflammatory cells by stimulation of homing receptor on leucocytes & vascular epithelium.
  8. 8. Pathogenesis of IBD Tolerance Acute Injury Environmental trigger Normal Complete Healing Gut (Infection, NSAID, other) Genetically Tolerance- Acute Inflammation Susceptible controlled Host ↓ Immunoregulation, inflammation failure of repair or bacterial clearance Chronic InflammationAmerican Gastroenterological Association Institute, Bethesda, MD.Sartor RB. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407.
  9. 9. PathologyMacrocopic features• Ulcerative colitis Usually involves rectum & extends proximally to involve all or part of colon. Spread is in continuity. May be limited colitis( proctitis & proctosigmoiditis) in total colitis there is back wash ileitis (lumpy- bumpy appearance)
  10. 10. • Mild disease- erythema & sand paper appearance(fine granularity)• Moderate-marked erythema,coarse granularity,contact bleeding & no ulceration• Severe- spontaneous bleeding, edematous & ulcerated(collar button ulcer).• Long standing-epithelial regeneration so pseudopolyps , mucosal atrophy & disorientation leads to a precancerous condition.• Eventually can lead to shortening and narrowing of colon.• Fulminant disease-Toxic colitis/megacolon
  11. 11. Ulcerative colitis pseudopolyps Ulcer
  12. 12. Microscopic features Crypts atrophy & irregularity Superficial erosion Diffuse mixed inflammation Basal lymphoplasmacytosis
  13. 13. Diffuseinflammation Crypt distortion
  14. 14. Macroscopic features• Crohn’s diseaseCan affect any part of GITTransmuralSegmental with skip lesionsCobblestone appearanceCreeping fat- adhesions & fistula
  15. 15. Microscopic features• Aphthous ulcerations• Focal crypt abscesses• Granuloma-pathognomic• Submucosal or subserosal lymphoid aggregates• Transmural with fissure formation
  16. 16. Aphthous ulcerGranuloma
  17. 17. Clinical features• Ulcerative colitisDiarrheaRectal bleedingTenesmusPassage of mucusCrampy abdominal pain
  18. 18. • Diarrhea & bleeding blood-intermittent &mild. do not seek medical attention.• Patient with proctatis-pass fresh or blood stained mucus with formed or semi formed stool. They also have tenesmus , urgency with feeling of incomplete evacuation.• With proctosigmoiditis-constipation• Severe disease-liquid stools with blood , pus & fecal matter.
  19. 19. • Physical signsProctitis – Tender anal canal & blood on rectal examinationExtensive disease-tenderness on palpation of colonToxic colitis-severe pain &bleedingIf perforation-signs of peritonitis
  20. 20. Clinical Severity of UC Mild Moderate Severe Fulminant Bowel movement <4 >6 >10 Blood in stool Intermittent Frequent Continuous Temperature Normal >37.5° >37.5° Pulse Normal >90 bpm >90 bpm Intermediate <75% normal Transfusion Hemoglobin Normal rate required ESR <30 mm/hour >30 mm/hour >30 mm/hour Abdominal Abdominal Clinical signs distension and tenderness tenderness1. Truelove SC, et al. Br Med J. 1955;2:1041-1045.2. Sandborn WJ. Curr Treat Options Gastroenterol.1999;2:113-118.
  21. 21. Diagnosis• Laboratory tests• Endoscopy• Radiography• Biopsy
  22. 22. Laboratory tests• HemogramC-reactive protein is increasedESR is increasedPlatelet count-increasedHemoglobin-decreased Fecal Calponectin levels correlate with histological inflammation,predict relapses &detect pouchitis
  23. 23. Bariumenema
  24. 24. Barium enema• Fine mucosal granularity• Superficial ulcers seen• Collar button ulcers• Pipe stem appearance- loss of haustrations• Narrow & short colon- ribbon contour colon
  25. 25. Sigmoidoscopy• Always abnormal• Loss of vascular patterns• Granularity• Friability• ulceration
  26. 26. Extra intestinal manifestations
  27. 27. Clinical features• Ileal Crohn’s DiseaseAbdominal pain Diarrhea Weight lossLow grade fever• Jejunoileitis disease Malabsorption Steatorrhea
  28. 28. Colitis and perianal disease• Bloody diarrohea• Passage of mucus• Lethargy• Malaise• Anorexia• Weight loss
  29. 29. Diagnosis• Laboratory tests• Endoscopy• Radiography• Biopsy• CT enterography
  30. 30. Laboratory tests• CRP-elevated• ESR-elevated• Anemia• Leukocytosis• hypoalbuminemia
  31. 31. Barium enemaStringsign
  32. 32. Colonoscopy
  33. 33. CT enterography• Mural hyperenhancement• Stratification• Engorged vasa recta• Perienteric inflammatory changes
  34. 34. Treatment
  35. 35. Treatment
  36. 36. Lifestyle changes
  37. 37. Drugs• 5-ASA agents• Glucocorticoids• Antibiotics• Immunosuppresants• Biological therapy
  38. 38. 5-ASA Agents•Sulfasalazine (5-aminosalicylicacid and sulfapyridine as carriersubstance)•Mesalazine (5-ASA), e.g. Asacol,Pentasa•Balsalazide (prodrug of 5-ASA)• Olsalazine (5-ASA dimer cleavesin colon)
  39. 39. Topical Action of 5-ASA: Extent of Disease Impacts Formulation Choice Distribution of 5-ASA Preparations Oral • Varies by agent: may be released in the distal/terminal ileum, or colon1 Liquid Enemas • May reach the splenic flexure2-4 • Do not frequently concentrate in the rectum3 Suppositories • Reach the upper rectum2,5 (15-20 cm beyond the anal verge)1. Sandborn WJ, et al. Aliment Pharmacol Ther. 2003;17:29-42; 2. Regueiro M, et al. Inflamm Bowel Dis. 2006;12:972–978; 3. Van Bodegraven AA,et al. Aliment Pharmacol Ther. 1996; 10:327-332; 4. Chapman NJ, et al. Mayo Clin Proc. 1992;62:245-248; 5. Williams CN, et al. Dig Dis Sci. 1987;32:71S-75S.
  40. 40. • Use In mild to moderate UC & crohn’s colitis Maintaining remission May reduce risk of colorectal cancer• Adverse effects Nausea, headache, epigastric pain, diarrhoea, hypersensitivity, pancreatitis Caution in renal impairment, pregnancy, breast feeding
  41. 41. Glucocorticoids• Anti inflammatory agents for moderate to severe relapses.• Inhibition of inflammatory pathways• Budesonide- 9mg/dl used for 2-3 months & then tapered.• Prednisone-40-60mg/day• No role in maintainence therapy
  42. 42. Antibiotics• No role in active/quienscent UC• Metronidazole is effective in active inflammatory,fistulous & perianal CD.• Dose-15-20mg/kg/day in 3 divided doses.• Ciprofloxacin• Rifaximin
  43. 43. Immunosuppresants• ThiopurinesAzathioprine6-mercaptopurin• Methotrexate• Cyclosporine
  44. 44. Cyclosporine• Preventing clonal expansion of T cell subsets• Use Steroid sparing Active and chronic disease• Side effects Tremor, paraesthesiae, malaise, headache, gingival hyperplasia, hirsutism Major: renal impairment, infections, neurotoxicity
  45. 45. Biological therapy• Infliximab Anti TNF monoclonal antibody Infliximab binds to TNF trimers with high affinity, preventing cytokine from binding to its receptors It also binds to membrane-bound TNF- a and neutralizes its activity & also reduces serum TNF levels.• Use Fistulizing CD Severe active CD Refractory/intolerant of steroids or immunosuppression• Side effects Infusion reactions, Sepsis, Reactivation of Tb, Increased risk of Tb
  46. 46. Other medicationsAnti- diarrheals - Loperamide (Imodium)Laxatives - senna, bisacodylPain relievers. acetaminophen (Tylenol).Iron supplements Nutrition
  47. 47. Surgery Ulcerative colitis Indications:• Fulminating disease• Chronic disease with anemia, frequent stools, urgency & tenesmus• Steriod dependant disease• Risk of neoplastic change• Extraintestinal manifestations• Severe hemorrhage or stenosis
  48. 48. Others• Proctocolectomy & ileostomy• Rectal &anal dissection• Colectomy with ileorectal anastomosis• Ileostomy with intraabdominal pouch
  49. 49. Crohn’s disease• Ileocaecal resection• Segmental resection• Colectomy & ileorectal anastamosis• Temporary loop ileostomy• Proctocolectomy• Stricturoplasty
  50. 50. Strictureplasty