Crohn's Disease - Causes and Pathogenesis

The cause of Crohn's disease

The causes of Crohn's disease are unknown. The infectious nature of the disease is most widely discussed. It is assumed that Crohn's disease is associated with viruses, chlamydia, yersinia, and intestinal microbiocenosis disorders (a decrease in the number of bifidobacteria with a simultaneous increase in the number of pathogenic enterobacteria, anaerobic microorganisms, and potentially pathogenic strains of E. coli). However, the primary role of any infectious factor in the development of Crohn's disease remains unproven at present. Recently, much attention has been paid to the development of the disease due to nutritional factors (insufficient fiber in the diet and frequent use of chemical preservatives and dyes). Genetic factors play a certain role. In approximately 17% of cases, Crohn's disease is detected among the patient's closest relatives.

Pathogenesis of Crohn's disease

Autoimmune mechanisms play a leading role in the pathogenesis of Crohn's disease. It is assumed that this disease is characterized by the development of an autoimmune process, the production of IgG antibodies to the gastrointestinal tract (primarily to the large intestine), and the appearance of lymphocytes sensitized to the antigens of the colon mucosa. As a result, an inflammatory process develops in the digestive tract with the appearance of ulcers, necrosis, severe intoxication, intestinal bleeding, and other symptoms of the disease. Crohn's disease is also characterized by frequent extraintestinal manifestations caused by autoimmune mechanisms. A deficiency of secretory IgA in the intestine also plays a major role in the development of Crohn's disease.

Pathomorphology

In Crohn's disease, any part of the gastrointestinal tract may be involved in the pathological process. The terminal section of the ileum is most often affected (85-90%). In approximately 45-50% of patients, the inflammatory process is localized simultaneously in the ileum and ascending colon; the rectum is affected in 20% of cases; only the colon - in 20% (granulomatous colitis). Very rarely, the esophagus is involved in the pathological process (in 0.5% of patients), the stomach (in 6% of cases).

The first macroscopic signs of Crohn's disease are small focal "aphthous" ulcerations of the mucous membrane. Later, the inflammatory process progresses and involves all layers of the intestinal wall (transmural inflammation), the affected intestinal wall becomes edematous and thickens significantly. Deep convoluted and linear ulcerations appear on the mucous membrane of the affected intestine. The presence of multiple ulcerations with edema of the mucous membrane between them creates a characteristic "cobblestone" picture, which is clearly visible during endoscopic examination. The corresponding parts of the mesentery are also involved in the pathological process, it thickens significantly, its fatty tissue spreads to the serous surface of the intestine. An increase in mesenteric lymph nodes is characteristic.

Transmural inflammation of the intestine, deep ulcers, edema, fibrosis cause local complications of Crohn's disease - obstruction, external and internal fistulas, mesenteric abscesses.

Characteristic microscopic manifestations of Crohn's disease are:

• damage to all layers of the intestinal wall;
• swelling and infiltration of the submucosal layer with lymphocytes and plasma cells;
• hyperplasia of lymphatic follicles, Peyer's patches;
• granulomas consisting of large epithelial cells, multinucleated Langhans cells without signs of caseous decay (sarcoid-like granulomas).

In Crohn's disease, affected areas of the intestine alternate with normal areas.