Mechanism of diarrhea in collagenous colitis

Abstract

Dear Sir: We read with interest the article by Burgel et al.1Burgel N. Bojarski C. Mankertz J. Zeitz M. Fromm M. Schulzke J.-D. Mechanisms of diarrhea on collagenous colitis.Gastroenterology. 2002; 123: 433-443Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar on mechanisms of diarrhea on collagenous colitis. To estimate epithelial barrier function, they concentrated on tight junction proteins such as occcludin and several members of the claudin transmembrane family. The authors found that the reduced net Na+ and CL-absorption is the predominant diarrheal mechanism in collagenous colitis (CC), accompanied by secretory component of active electrogenic chloride secretion. Burgel et al.1Burgel N. Bojarski C. Mankertz J. Zeitz M. Fromm M. Schulzke J.-D. Mechanisms of diarrhea on collagenous colitis.Gastroenterology. 2002; 123: 433-443Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar found that the subepithelial collagenous band as a significant diffusion barrier is a cofactor, and conclude that down-regulation of tight junction molecules but no epithelial apoptoses is a structural correlate of barrier dysfunction contributing to diarrhea by a leak flux mechanism. They postulated that except for motility diarrhea, all other forms of diarrhea are driven by osmotic forces. The cause for diarrhea in CC patients remains controversial. Some authors2Giardello F. Lazemby A. The atypical colitides.Gastroenterol Clin North Am. 1999; 28: 479-490Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar found that diarrhea in CC patients persisted in the face of fasting and that the stool osmotic gap was consistent with a secretory mechanism. PGE2 levels were markedly elevated in jejunal aspirates and in stools from patients with CC, raising speculation that prostaglandins may mediate active anion secretion. Other authors believe that the collagen band may be directly responsible for the watery diarrhea associated with that syndrome. The histological diagnosis of CC is based on the microscopic demonstration of a thick amorphous table underneath the surface epithelium of the colon (and sometimes of the rectum).3Rask-Madsen J. Grove O. Hansen M. et al.Colonic transport of water and electrolytes in a patient with secretory diarrhea due to collagenous colitis.Dig Dis Sci. 1983; 28: 1141-1146Crossref PubMed Scopus (85) Google Scholar Despite the presence of other histological findings, the thickness of that subepithelial amorphous band is the most important single microscopic parameter in the diagnosis of CC.4Rubio C.A. A simple method to evaluate the thickness of collagen in collagenous colitis.Scand J Gastroenterol. 2000; 35: 223-224Crossref PubMed Scopus (10) Google Scholar It is common, however, that the cells of the surface epithelium are morphologically distorted in that disease; they are often flattened, sometimes in syncytial arrangement and even have a tendency to detach from the underlying subepithelial collagen band. Total epithelial denudation may be seen in some areas.5Rubio C.A. Slezak P. The subepithelial band in collagenous colitis is autofluorescent A study in H&E stained sections.In Vivo. 2002; 16: 123-126PubMed Google Scholar Recent developments indicate that in the normal colonic mucosa, the columnar cells between the crypts strongly express Aquaporin 86, a specific water-selective channel protein that regulates water absorption in the human colonic and other cells. The question arises as to whether the deranged surface epithelium in CC, often showing syncytial arrangement, flattened or even detached epithelial cells, is able to continue synthesizing normal amounts of Aquaporin. The production of Aquaporin should obviously cease in areas with total epithelial denudation. Under those circumstances the water absorptive mechanism in CC may be abrogated, water accumulate in the lumen and watery diarrhea may ensue. It is conceivable that the watery diarrhea in CC evolve as a consequence of multifactorial parameters. However, there appears to be sufficient microscopic evidence to explain (at least in part) the cause of the watery diarrhea in CC patients: one is the debatable significance of the thickness of the collagenous band (watery diarrhea occurs even in patients with a collagenous band of “moderate” thickness), and the other is the obvious alteration occurring in the mucosa telescoping from cell distortion to total epithelial denudation. Under those circumstances the production of the cell-bound water channel protein Aquaporin, one of the molecules responsible for water transit homeostasis in the colon, is disturbed or it may even be totally abrogated. 6Fisher H. Stenlig R. Rubio C.A. Lindblom A. Differential expression of Aquaporin 8 in human colonic epithelial cells and colorectal tumors.BMC Physiol. 2001; 1: 1-3Crossref PubMed Scopus (46) Google Scholar