The Pathophysiology of Irritable Bowel SyndromeCME - Medscape

The Pathophysiology of Irritable Bowel Syndrome CMEImportant cellular mechanisms present in the small intestine and colon -- goblet cells, enterocytes, and enteroendocrine cells -- workin unison to change fluid and electrolyte movement through the epithelium. For example, goblet cells produce not only mucins,but also secrete guanylin, and uroguanylin which activate the guanylate cyclase C receptor to induce chloride secretion from theenterocytes. Similarly, enteroendocrine cells produce transmitters, such as 5-hydroxytryptamine, which then stimulate either thesubmucosal neuron to evoke secretion, or directly stimulate the enterocytes to produce chloride secretion and thereby drag waterand sodium into the lumen.Different mechanisms may be involved in the pathophysiology of IBS, but more importantly, perhaps, is that these mechanismsprovide a means to treat IBS-C. For example, drugs that activate the chloride channel directly, and drugs that bind to theguanylate cyclase C receptor to induce chloride secretion, help to manage constipation in IBS-C.Rectal hypersensitivity had previously been thought to be associated with IBS, but it is now apparent that not all patients withIBS have evidence of hypersensitivity of the rectum or the intestines. IBS is not all about sensation, and we need to consider othermechanisms for IBS.Slide 9.One of those mechanisms is a change in the barrier function in the small intestine and in the colon, which we term mucosalpermeability. [4] Increased permeability with alteration of the expression of the tight junction proteins may occur as the result ofprior gastroenteritis, atopy, or food intolerance. These may occur, for example, with gluten intake or ingestion of fermentableoligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), the sugar entities that alter barrier function of theintestine. Stress also is known to make the mucosa leaky (more permeable) and allow antigens or other chemicals in the lumenaccess to the surface epithelial cells and to nerve cells below that level. Typically, changes in permeability results in IBS-D, withfluid secretion or activation of those sensory mechanisms that ultimately become expressed as pain.Pg.10