Crohn's disease: causes and pathogenesis

The cause of the development of Crohn's disease

The causes of Crohn's disease are unknown. The infectious nature of the disease is most widely discussed. The connection of Crohn's disease with viruses, chlamydia, Yersinia, disturbances of the intestinal microbiocenosis (reduction of the number of bifidobacteria with a simultaneous increase in the number of pathogenic enterobacteria, anaerobic microorganisms, potentially pathogenic strains of Escherichia coli) is suggested. However, the primary cause of any infectious factor in the onset of Crohn's disease remains at present unproven. Recently, much attention has been paid to the development of the disease in nutrition (lack of vegetable fiber in the diet and frequent use of chemical preservatives and dyes). A certain role is played by genetic factors. Approximately 17% of cases of Crohn's disease is detected among the closest relatives of the patient.

Pathogenesis of Crohn's disease

In the pathogenesis of Crohn's disease, the leading role is played by autoimmune mechanisms. It is assumed that this disease develops an autoimmune process, antibodies of IgG class are produced to the gastrointestinal tract (primarily to the large intestine) and lymphocytes are sensitized to antigens of the mucous membrane of the large intestine. As a result, the inflammatory process in the digestive tract develops with the appearance of ulcers, necrosis, severe intoxication, intestinal bleeding and other symptoms of the disease. For Crohn's disease, frequent extraintestinal manifestations due to autoimmune mechanisms are also characteristic. A large role in the development of Crohn's disease is also played by a deficiency in the intestine of secretory IgA.

Pathomorphology

With Crohn's disease, any department of the gastrointestinal tract can be involved in the pathological process. The terminal segment of the ileum is most often affected (85-90%). Approximately in 45-50% of patients the inflammatory process is localized simultaneously in the iliac and ascending colon; defeat of the rectum is observed in 20% of cases; one only colonic - 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 "aphtid" ulceration of the mucosa. Later the inflammatory process progresses and involves all layers of the intestinal wall (transmural inflammation), the affected bowel wall becomes edematous, considerably thickens. Deep, convoluted and linear ulcers appear on the mucosa of the affected bowel. The presence of multiple ulcers with edema of the mucous membrane between them creates a characteristic picture of "cobblestone pavement," which is clearly seen in endoscopic examination. In the pathological process, the corresponding parts of the mesentery are also involved, it thickens considerably, its adipose tissue extends to the serous surface of the intestine. Characteristic increase of mesenteric lymph nodes.

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

The characteristic microscopic manifestations of Crohn's disease are:

• defeat of all layers of the intestinal wall;
• edema and infiltration of lymphocytes and plasma cells of submucosal layer;
• hyperplasia of lymphatic follicles, Peyer's plaques;
• granulomas, consisting of large epithelial cells, multinuclear Langgans cells without evidence of caseous decay (sarcoid granulomas).

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