CLASSIFICATION AND PATHOPHYSIOLOGY



Diarrhea may result if one or more of the fol­lowing occur: (1) decreased normal solute and water absorption; (2) increased electrolyte secre­tion; (3) presence of poorly absorbed, osmotically active solutes in the gut lumen; (4) abnormal in­testinal motility; and (5) inflammation with ex­udation of mucus, blood, or pus.

Secretory Diarrhea. Secretory diarrhea, usu­ally due to abnormalities in both absorption and secretion of electrolytes, is a common cause of wa­tery diarrhea . For many of the dis­orders listed here, the ultimate cause of intestinal secretion is an increase in cellular cyclic AMP (cAMP) levels. As shown in Figure 36-4, cAMP has two effects: it inhibits neutral NaCl absorption and stimulates chloride secretion without altering other solute transport mechanisms. For example, cholera, the archetypal secretory diarrhea, is due solely to the action of a small, heat-labile toxin that binds to intestinal mucosal cells and specif­ically stimulates the enzyme adenylate cyclase to produce cAMP. Since other sodium-coupled transport mechanisms function normally, hydra­tion can be maintained by oral administration of sodium-glucose solutions.

Other causes of secretory diarrhea exist but re­main poorly understood. Ion secretion in some cases may be due to increases in intracellular cal­cium or other cyclic nucleotides (cGMP). Small bowel disorders that produce villus atrophy (”flatgut”), such as celiac disease, are often associated with electrolyte secretion, probably due to un­opposed secretion from the remaining crypt cells. Finally, disorders that cause malabsorption (see Section C of this chapter) and osmotic diarrhea (see below) may also be associated with secretory diarrhea. Nonabsorbed bile acids and fatty acids may stimulate ion secretion by colonic mucosal cells.
Secretory diarrhea usually presents as copious watery diarrhea that persists during a two-day fast. Because the diarrheal fluid is composed of elec­trolytes and water, fecal osmolality can be entirely accounted for by the usual cations and anions (Na+, K+, CI-, HC03~, and organic anions) and there is little or no fecal solute gap [solute gap = fecal or plasma osmolality - 2(Na + + K + )]. The factor of 2 is to account for the anions in stool.

Osmotic Diarrhea. Osmotic diarrhea is due to the accumulation of poorly absorbed solutes in the gut lumen. This may occur by (1) ingestion of poorly absorbed solutes such as lactulose, Mg + 2, S04-2, or P04~2; (2) generalized malabsorption; or (3) failure to absorb a specific dietary compo­nent such as lactose. Examples of osmotic diar­rhea are listed in Table 36-9.

Osmotic diarrhea typically stops when the pa­tient fasts (or stops ingesting the responsible sol­ute). Because osmotic diarrhea is due to the pres­ence of poorly absorbed, unmeasured solutes, fecal fluid exhibits a large solute gap (>50 mOsm-L”"1). In this case, the measured stool elec­trolytes [2(Na+ + K +)] usually do not account for all of fecal fluid osmolality. However, in the case of ingestion of anions such as S04~2 or P04-2, the fecal solute gap will be low (normal) and spe­cific measurement of stool S04 ~2 and P04 ~ 2 must be performed. In individuals with carbohydrate malabsorption, stool pH is acidic owing to prod­ucts of fermentation, and reducing substances are . r readily measured in the stool.

Abnormal Intestinal Motility. At least three types of motility disorders may result in diarrhea: (1) reduced peristalsis leading to bacterial over growth (see Section C of this chapter); (2) in­creased small bowel motility leading to decreased contact time between small bowel mucosa and in­testinal contents and thus delivery of increased volume to the colon; and (3) increased colonic 3glemptying with decreased contact time and in­creased stool liquidity. Diarrhea due mainly or in part to motility disorders includes that associated with irritable bowel syndrome, postvagotomy and postgastrectomy syndromes, diabetic neuropathy, scleroderma, and thyrotoxicosis.