12. Environment Triggers Immunoregulatory Defects and Microbial Exposure Genetic Factor c)Occupation a)Dysfunctional immune host response to normal luminal components a)Westernization b)Sanitation and exposure to infection d)Diet c)Defective barrier function IBD-1 locus and NOD2/CARD15 gene e)Tobacco smoking b)Infection with a specific pathogen Etiology

28. Pathologic Findings in IBD

32. Endoscopic image of colon cancer identified in the sigmoid colon on screening colonoscopy for Crohn's disease.

33. Crohn's disease can mimic ulcerative colitis on endoscopy. This endoscopic image is of Crohn's colitis showing diffuse loss of mucosal architecture, friability of mucosa in sigmoid colon and exudate on wall, all of which can be found with ulcerative colitis.

34. Section of colectomy showing transmural inflammation

35. Endoscopy image of colon showing serpiginous ulcer, a classic finding in Crohn's disease

37. Endoscopic image of a sigmoid colon afflicted with ulcerative colitis. Note the vascular pattern of the colon granularity and focal friability of the

38. Colonic pseudopolyps of a patient with intractable ulcerative colitis . Colectomy specimen

39. H&E stain of a colonic biopsy showing a crypt abscess, a classic finding in ulcerative colitis

40. Biopsy sample ( H&E stain ) that demonstrates marked lymphocytic infiltration (blue/purple) of the intestinal mucosa and architectural distortion of the crypts.

41. SIGN & SYMPTOM of IBD

42. Inflammatory Bowel Disease Symptoms Because inflammatory bowel disease is a chronic disease (lasting a long time), you will go through periods in which the disease flares up and causes symptoms. These periods are followed by remission, in which symptoms disappear or decrease and good health returns. Symptoms may range from mild to severe and generally depend upon the part of the intestinal tract involved. They include the following :

43. Abdominal cramps and pain Bloody diarrhea Severe urgency to have a bowel movement Fever Loss of appetite Weight loss Anemia (due to blood loss)

44. Other Symptoms of IBD People with IBD may have symptoms outside the digestive tract, such as: Mouth sores and skin problems Arthritis Eye problems that affect vision

45. Symptoms in Crohn's disease vs. ulcerative colitis Crohn's disease Ulcerative colitis Defecation Often porridge-like sometimes steatorrhea Often mucus-like and with blood Tenesmus Less common More common Fever Common Indicates severe disease Fistulae Common Seldom Weight loss Often More seldom

46. Findings in diagnostic workup in Crohn's disease vs. ulcerative colitis Sign Crohn's disease Ulcerative colitis Terminal ileum involvement Commonly Seldom Colon involvement Usually Always Rectum involvement Seldom Usually Involvement around the anus Common Seldom Bile duct involvement No increase in rate of primary sclerosing cholangitis Higher rate

47. Distribution of Disease Patchy areas of inflammation (Skip lesions) Continuous area of inflammation Endoscopy Deep geographic and serpiginous (snake-like) ulcers Continuous ulcer Depth of inflammation May be transmural, deep into tissues Shallow, mucosal Stenosis Common Seldom Granulomas on biopsy May have non-necrotizing non-peri-intestinal crypt granulomas Non-peri-intestinal crypt granulomas not seen Sign Crohn's disease Ulcerative colitis

48. Pathological features of Crohn’s disease Any portion of small bowel: usually ileum may also involve: any segment of digestive tract Early stages: involved small bowel has soggy feeling mucosa: reddish purple may show pinpoint erosions known as ‘aphthoid ulcers’ Later stages: prominent ulceration

50. Fig. 2: Gross appearance of Crohn's disease. The combination of ulceration and elevated remnants of mucosa results in a typical cobblestone appearance. Fig. 3: Gross appearance of Crohn's disease. Another example of cobblestone appearance. Fig. 4: Gross appearance of Crohn's disease. Note the segmental nature of the inflammation, and rigidity of the wall, and flattening of the mucosa are characteristic.

51. Histopathology Submucosal lymphedema: early change accompanied by: lymphoid hyperplasia in lamina propria and submucosa scattering of chronic inflammatory cells, including: plasma cells: including some binucleated forms lymphocytes eosinophils Histiocytes: some containing prominent lysosomal inclusions mast cells Ulcerations: begin at top of lymphoid follicles preceded by patchy epithelial necrosis may have vascular pathogenesis

56. Signs and symptoms Diarrhea- patients often experience frequent loose or watery bowel movements. -stool is occasionally accompanied by thick, dark blood (not bright red smears of blood, which usually result from a bleeding hemorrhoid) -There is less mucus or pus in the stool than in cases of ulcerative colitis.

65. Fig. 2: Ulcerative colitis. Chronic form, showing mucosal ulceration with residual foci of elevated and hyperemic mucosa. Fig. 3: Pseudopolyps in ulcerative colitis. Fig. 4: Pseudopolyps in ulcerative colitis.

72. Fig. 9: Adenocarcinoma with mucinous features arising in a colon affected by ulcerative colitis. This is a common tumor subtype in this particular setting. Fig. 10: Dysplasia in ulcerative colitis. Indefinite for dysplasia. Fig. 11: Dysplasia in ulcerative colitis. Low-grade dysplasia.

73. Fig. 12: Dysplasia in ulcerative colitis. High-grade dysplasia. Fig. 13: Dysplasia in ulcerative colitis. Dysplasia with papillary features.

74. Signs and Symptoms Diarrhea- frequent watery stools are the norm -stools are accompanied by thick blood (not bright red smears of blood, which usually occur from a bleeding hemorrhoid). -Mucus or pus also often passes with the stool. -Individual with ulcerative colitis will have stool of more normal consistency that contains pus or mucus.

80. Fig. 6: Ulcerative colitis. Case complicated with toxic megacolon. Fig. 7: Ulcerative colitis complicated by toxic megacolon.

81. INVESTIGATIONS