Crohn’s disease is an example of inflammatory bowel disease that can manifest anywhere along the digestive tract from the mouth to the anus, with the ileocolon being the most common site of disease. In a typically functioning GI tract, mechanical and chemical digestion begin in the mouth; food is then transported through the esophagus to the stomach where chemical digestion continues. Chyme (partially digested food) moves into the small intestine where major nutrients and water are digested and absorbed by villi. Chyme continues into the large intestine where muscular contraction and relaxation massage the contents, allowing excess water to be absorbed. The fecal mass is passed through the colon via peristaltic movements until it is emptied through the anus.
Crohn’s disease is thought to be an overly aggressive response to normal flora bacteria by the body’s immune system, specifically Th1 cytokines, in individuals with CARD15/NOD2 gene mutations. Th1 cytokines elicit a pro-inflammatory response and perpetuate an autoimmune response resulting in further injury and inflammation. Inflammation begins in the intestinal submucosa, but may extend through the entire intestinal wall. Chronic inflammation leads to ulceration and the formation of cobble-stone appearing granulomas. Patches of disease and inflammation throughout the small and large intestine create the characteristic skip lesions.
The inflamed, thickened, and ulcerated intestinal lining leads to abdominal pain; decreased absorption of water and essential nutrients resulting in diarrhea, weight loss, and hypoalbuminemia; malabsorption of vitamin B12 resulting in anemia; and malabsorption of folic acid and vitamin D, resulting in anemia and bone disease. Complications of Crohn’s disease include obstruction from intestinal inflammation and thickening; fistulae formation from ulcers tunneling through surrounding tissue; abscess formation as neutrophils infiltrate the intestinal glands (crypts of Liebekühn); and chronic blood loss from ulcers.