Pathogenesis of diarrhea in ulcerative colitis - New views on an old problem

Background: Whereas water movement into the intestinal lumen occurs secondary to Cl- secretion in secretory diarrheal diseases, defects in key transport processes lead to profound decreases in colonic Na+, Cl-, and water absorption in ulcerative colitis. Studies and Results: Recent studies indicate reduced expression/activity of apical Na+ channels and basolateral Na+, K+-ATPase, leading to loss of electrogenic Na+ absorption in the distal colon and rectum. There is also likely to be a decrease in electroneutral NaCl cotransport, which is present throughout the colon. Preliminary work on basolateral K+ channel abundance and activity in colonic epithelial cells suggests that whole-cell K+ conductance is decreased in ulcerative colitis, leading to epithelial cell depolarization, and further limitation of Na absorption. In addition, there is a marked reduction in colonic epithelial resistance, which reflects a decrease in the integrity of intercellular tight junctions and the presence of apoptotic foci. Conclusions: Impaired Na and Cl- transport, combined with enhanced epithelial leakiness, results in a profound decrease in the capacity of the inflamed colon to absorb salt and water. Transport abnormalities in ulcerative colitis may at least partly reflect the effects of proinflammatory cytokines, raising the possibility of novel approaches to the restoration of colonic absorptive capacity in this disease.