Pathogenesis of infectious diarrhea: GUT PHYSIOLOGY Part 12

DNAThe main conclusions of these integrated studies may be summarized as follows. First, the rapid onset of ischemia (triggered by an unknown mechanism) after initial entry of the virus causes hypoxia, cytopathic changes in enterocytes and hence atrophy of villi. These are precisely the kinds of changes induced by experimental ischemia. The ensuing increased rate of cell division, necessary for the reconstitution of villi, results in transient accumulation of high levels of sodium chloride in a population of villus base cells; a similar phenomenon was seen in dividing HeLa cells. (The phenomenon of villus shortening is often reported in histological analyses of ileal epithelia infected with a variety of pathogens. A corollary to this finding would be that resynthesis of truncated villi would be accompanied by the kind of elemental changes seen in the rotavirus-infected mice during the peak period of diarrhea. It is possible to infer that this actually happens in Salmonella-infected rabbits. Treatment with nitrogen mustard before infection, ostensibly to inhibit PMN influxes, resulted in massive invasion by Salmonella and damage to the epithelial tissue, but no fluid secretion. This result was interpreted in terms of the alkylating effect of nitrogen mustard on DNA and, hence, interference with crypt cell regeneration). asthma inhalers

The loss of excess sodium chloride into the lumen induces hypersecretion of fluid. The rise in sodium and fall in chloride ion levels in the tip cells occurred when villi were ischemic and hence hypoxic. Hypoxia induces a switch to anaerobic/glycolytic-type metabolism, with a predictable rise in intracellular hydrogen ion concentration and a decrease in bicarbonate ion concentration, resulting from perturbation of the carbonic acid dissociation equilibrium. The ensuing imbalance in sodium/hydrogen, chloride/bicarbonate antiports would in turn imbalance the uptake of sodium and chloride ions; predictably, the intracellular sodium ion concentration would rise and the chloride ion concentration would fall. From this analysis, it would follow that the hypoxic state of the upper parts of newly synthesized villi is the reason for lack of absorption and not ‘immature’ enterocytes, and that the prolongation of diarrhea is associated with an intermediate hyperemic state. Only when blood flow had returned to normal did the tip hyperosmotic zone become re-established and diarrhea stopped.

This entry was posted in Diarrhea and tagged Bibrio cholerae, Clostridium difficile, Diarrhea, Escherichia coli, Shigella dysenteri.