Clinical Note

Diarrhea

Diarrhea is the main cause of death or disability in the world today, afflicting individuals of all ages. Death is the direct or indirect result of hypovo-lemia and circulatory collapse compounded by hypokalemia and metabolic acidosis.

The etiology of diarrheas can be subdivided into three broad categories:

1. Diarrhea due to impaired absorption by the small or large intestines. This can result from infection, inflammation, or anything that leads to a reduction of total effective absorptive surface.

2. Osmotic diarrhea due to the accumulation within the small intestine of nonreabsorbable solutes. As discussed earlier, because the small intestine is very leaky to water, the luminal contents are always isotonic with the plasma. It follows that the accumulation of nonreabsorb-able, osmotically active solutes in the lumen will generate an osmotic pressure difference that draws fluid into the lumen. For example, in the condition of glucose-galactose malabsorption mentioned in Chapter 39, the accumulation of these solutes in the small intestine results in an osmotic diarrhea. This problem may be compounded by the intraluminal accumulation of osmoti-cally active breakdown products of bacterial metabolism.

3. Secretory diarrheas resulting from excessive stimulation of the secretory cells present in the crypts of the small intestine and colon. These are among the most prevalent afflictions of mankind.

In some instances, they are caused by excessively high blood levels of normal secretagogues that may result, for example, from functional tumors of endocrine cells. But by far the greatest cause of secretory diarrheas is infestation of the small intestine with enteropathic bacteria such as Vibrio cholerae or certain strains of Escherichia coli. These organisms secrete enterotoxins that bind to receptors on the apical membranes of the crypt cells and result in the stimulation of the adenylate cyclase activity located on their basolateral membranes. Adenylate cyclase activity is maximally and permanently stimulated for the life of the cell, causing maximal secretion by these cells that may result in salt and water losses of many liters per day despite the considerable absorptive reserve capacity of the colon. Secretory diarrheas can also be induced by excessive secretion of endogenous secretagogues. For example, prostaglandins, leukotrienes, histamine, and bradykinin released in immune and/or inflammatory reactions interact with receptors on the basolateral membranes and result in elevations in cell cAMP and/or Ca2+ and, in turn, activation of apical membrane Cl~ channels. Also, certain tumors called carcino-ids secrete serotonin, which brings about an elevation of cell Ca2+ and may result in watery diarrhea.

In short, whereas intestinal secretion is a normal and essential process, overstimulation of the underlying physiologic mechanisms can result in severe disability and death.

36. Intestinal Electrolyte and Water Transport

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