Pathogenesis of Infectious Diarrhea

Abstract

A brief overview of some of the main features involved in normal physiological bi-directional absorption and secretion of fluid in the gut is given, including the nature and cellular location of key enzymes, ion pumps, symports, antiports and diffusion channels; the microanatomy of intestinal villous vasculature and the dynamics of villus blood flow, which together generate hypertonic zones in villus tip regions; and the production, differentiation, escalator movement (from crypt to villus tip) and subsequent shedding of intestinal epithelial cells. (Neural and hormonal mechanisms that regulate normal mucosal ion transport are not discussed.) The manner in which Vibrio cholerae, several pathotypes of Escherichia coli, several Salmonella serotypes, rotavirus, Campylobacter species, Shigella dysenteriae, Yersinia species and Clostridium difficile perturb these mechanisms and cause diarrhea, is discussed. Throughout the article, the main emphasis is on experimental studies designed to elucidate biological mechanisms and (where relevant) the microbial determinants responsible for diarrheal disease. Allusions are also made to the involvement of host responses such as the inflammatory response, the production and release of potent cytokines and accelerated homeostatic responses (such as increased rates of crypt cell division seen in some infections), and the role that they play in pathophysiological fluid secretion.

Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

“…Bacteria that are associated with secretory diarrhea include Vibrio cholerae and enterotoxigenic, enteroaggregative, or enteropathogenic pathotypes of Escherichia coli (2,(4)(5)(6). Diarrheal disease is typically associated with the interaction of the bacterial toxins with the host epithelium, leading to disruption of ion transport systems and subsequent fluid secretion that is the hallmark of diarrhea (7).…”

A major role for proteolytic activity and proteinase-activated receptor-2 in the pathogenesis of infectious colitis

“…Apart from an understanding of the mechanisms by which pathogens infect the hosts, a growing body of evidence suggests that disease symptoms are largely due to pathogen-induced host inflammatory and immune responses (10)(11)(12). An understanding of the mechanisms by which the host immune system is activated by these enteric pathogens is essential for the development of new therapeutic modalities for treating infectious colitis.…”

Rotavirus Infection Stimulates the Cl−Reabsorption Process across the Intestinal Brush-Border Membrane of Young Rabbits

“…The virus infects the mature enterocytes in the upper two-thirds of villus epithelia (28,35), and the idea is now gaining ground that diarrhea is not necessarily a consequence of any physical lesion but can precede it, as if cell dysfunction were the cause rather than the consequence of the histological damage (10,14,21,28,30).…”