Pathophysiology of Crohns Disease
05.28.10
Crohns disease begins with crypt inflammation and abscesses, which progress to tiny focal aphthoid ulcers. These mucosal lesions may develop into deep longitudinal and transverse ulcers with intervening mucosal edema, creating a characteristic cobblestoned appearance to the bowel.
Transmural spread of inflammation leads to lymphedema and thickening of the bowel wall and mesentery. Mesenteric fat typically extends onto the serosal surface of the bowel. Mesenteric lymph nodes often enlarge.
Extensive inflammation may result in hypertrophy of the muscularis mucosae, fibrosis, and stricture formation, which can lead to bowel obstruction. Abscesses are common, and fistulas often penetrate into adjoining structures, including other loops of bowel, the bladder, or psoas muscle.
Fistulas may even extend to the skin of the anterior abdomen or flanks. Independently of intra-abdominal disease activity, perianal fistulas and abscesses occur in 25 to 33% of cases; these complications are frequently the most troublesome aspects of Crohns disease.
Noncaseating granulomas can occur in lymph nodes, peritoneum, the liver, and all layers of the bowel wall. Although pathognomonic when present, granulomas are not detected in about half of patients with Crohns disease.
The presence of granulomas does not seem to be related to the clinical course.Segments of diseased bowel are sharply demarcated from adjacent normal bowel (“skip areas”); hence, the name regional enteritis. About 35% of Crohns disease cases involve the ileum alone (ileitis); about 45% involve the ileum and colon (ileocolitis), with a predilection for the right side of the colon; and about 20% involve the colon alone (granulomatous colitis), most of which, unlike ulcerative colitis (UC), spare the rectum.
Occasionally, the entire small bowel is involved (jejunoileitis). The stomach, duodenum, or esophagus is clinically involved only rarely, although microscopic evidence of disease is often detectable in the gastric antrum, especially in younger patients. In the absence of surgical intervention, the disease almost never extends into areas of small bowel that are not involved at first diagnosis.
There is an increased risk of cancer in affected small-bowel segments. Patients with colonic involvement have a long-term risk of colorectal cancer equal to that of UC, given the same extent and duration of disease.
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