Possible Role of Pancreatic Enzymes in the Etiology of Ulcerative Colitis

Abstract

It is a common observation that patients with ulcerative colitis frequently exhibit remarkable clinical improvement following ileostomy. Weight gains of fifty pounds or more have been recorded. Since ileostomy diverts the fecal stream from the colon, perhaps some substance in the upper gastrointestinal tract initiates or aggravates the symptoms of this disease. Portis, Block and Necheles1 succeeded, by perfusing the colons of dogs with 1 to 2% trypsin solutions, in both acute and chronic experiments, in damaging the colonic mucosa. This was manifested by hyperemia, capillary hemorrhages, extensive hemorrhages of the mucosa, and surface necrosis of the mucosa. Ivy and Clarke2, however, did not succeed in producing any mucosal changes in six dogs by diverting the upper jejunal contents to the appendix. They state that their experiments did not rule out the possibility that the quantity or activity of the proteolytic enzymes of the upper intestine may be greater than normal in ulcerative colitis, or that the colon may be more susceptible in this disease. To investigate the first possibility, we studied the external secretion of the pancreas in a group of patients with this disease, using intravenous secretin as the stimulus. As a preliminary study, we undertook a series of experiments with dogs. Ten mongrel dogs were used. Under pentothal anesthesia a loop of colon with its intact blood supply was transposed into the duodenum distal to the ampulla of Vater with end to end anastomosis (Figure 1). This colonic segment had of necessity to be from the right side of the colon, inasmuch as the left side of the colon does not lend itself well to transposition because the blood supply to the left side in the dog cannot be interrupted without producing gangrene of the distal segment. These animals died or were sacrificed at intervals of two weeks to ten months (Table 1). In every case except one the colonic segments were intact. In one dog which lived for fourteen weeks there was moderate inflammation with small superficial ulcerations. These experiments confirm the findings of Ivy and Clarke2 that the dog's colonic mucosa can tolerate the bile and pancreatic juice normally present in the duodenum. Meyer and his collaborators3 have shown that the lysozyme content of ileostomy drainage is not abnormally high in this disease. We verified this in two patients.