The Arteriolar Vasodilatation Model of Vibrio cholerae Induced Diarrhoeal Disease

Abstract

Secretory diarrhoeal disease caused by enterotoxins produced by pathogenic bacteria is characterised by severe fluid loss into the intestine. A prevalent explanation for such high rates of loss, such as occur in episodes of cholera, is that intestinal epithelial cells (enterocytes) actively secrete chloride ion into the lumen. Fluid is drawn into the lumen because of the osmotic pressure difference that is created across the mucosa. Widely proposed as the cause of many forms of secretory diarrhoea, the enterocyte based paradigm displaced an earlier model of secretion i.e. fluid filtration caused by increased capillary hydrostatic pressure, possibly coupled with increased hydraulic conductivity. This would be aggravated by any concurrent inhibition of fluid absorption if it occurred. In the earlier and alternative paradigm, pathophysiological reductions in smooth muscle tone elevate capillary pressure, thereby increasing the hydrostatic pressure gradient that forces fluid from the capillary into the interstitial space and thence into the lumen. In this review, the present and historical evidence for the vasodilatation view of secretory diarrhoeal disease is presented, together with past challenges of this concept, particularly those involving the erroneous equating of solute permeability with hydraulic conductivity. It can be seen that the physical forces model of altered Starling forces combined with enhanced fluid permeation explains more experimental findings than the cellular based enterocyte model can. Several key past papers advocating enterocyte secretion in which the capillary vasodilatation model was also discounted, were examined for the inherent fallacies within the arguments that were proposed. Where possible, quantitative arguments are proposed that indicate that is it the combination of capillary vasodilatation combined with increased tight junctional hydraulic conductivity that causes profuse secretion, made worse by any concurrent inability to absorb fluid. To assist the general physiological reader, an appendix reviews Bernoulli’s principle of flow within tubes and explains the arguably counter-intuitive phenomenon that vasodilatation increases capillary pressure because of a velocity reduction within a dilated segment.