Small bowel bile acids

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

Gallbladder contraction ejects a bolus of bile acids into the small bowel where they participate in fat digestion. 

Bile acids have long been known to aid digestion of dietary fats, but are not essential. Some 50% of dietary fats are absorbed in rats where bile acids are diverted by biliary fistula.Similar results were found in man. This suggested that the micellar phase isolated by ultracentrifugation of duodenal contents was in fact composed of both bile-acid micelles and vesicles, a suggestion supported by a systematic study of the physical chemistry of fat digestion in human small bowel. 

Unconjugated bile acids have pK values of around 6, which means they will be un-ionised in the intestinal lumen and may be passively absorbed. However, conjugated bile acids are ionised and require transporters to cross the enter-ocyte in much the same way as found in the hepatocyte. Although OATP2 is not expressed in small bowel a sodium-independent transporter is present in the... 

Holtmann G, Kelly DG, et al. Survival of human pancreatic enzymes during small bowel transit effect of nutrients, bile acids, and enzymes. Am/ Physiol 273 G553-G558,1997. 

Secretin Enteroendocrine S cells in upper small bowel 1. Stimulates pancreatic and biliary bicarbonate and water secretion 2. Regulates pancreatic enzyme secretion 3. Inhibits postprandial gastric emptying, gastrin release, and gastric acid secretion 1. Gastric acid, bile salts, fatty acids, peptides, and ethanol 2. Somatostatin inhibits secretion... 

Bicarbonate has been shown to compete in vitro with bile acids for binding sites on the colestyramine resin. The chloride ions in the colestyramine resin may cause an anion exchange of not only the bile salts, as is the intention, but also bicarbonate in the small bowel. This removal of bicarbonate from the body can predispose to the development of a hyperchloraemic metabolic acidosis and hyperkalaemia. This might be exacerbated by the bicarbonate-losing and hyperkalaemic effects of spironolactone. 

Fig. 3. Transport of various bile acids by everted gut sacs of guinea pig small bowel. Values are means of three to six sacs. The range of values is given in parentheses. From Lack and Weiner (22).

No information is available at present on the effects of the many other secondary bile acids present in feces in small concentrations on water and electrolyte movement in the colon. In addition, no information is available on the role of bile acids in constipation, irritable bowel syndrome, nonspecific diarrhea, antibiotic diarrhea, or the diarrhea of the germ-free animal. Of interest is the response of the diarrhea of the germ-free animal to an anion exchange resin similar to cholestyramine (112). Studies are needed to define the structure-activity relationships for bile acids and the induction of water and sodium secretion by the colon. In addition, information is needed on the composition, concentration, and physical state of bile acids in colonic contents and feces in health and disease. 

The observations on small intestinal responses to bile acid cited above have been extended to include responses of the large bowel to altered bile acid concentrations and compositions. Increased concentrations of bile acids in the colon cause abnor-... 

The remaining 59 patients, with relatively low serum bile acid concentrations (SGLC = 2.2 0.3,GC = 2.2 0.3, 3a-hydroxy bile acids = 10.3 0.9), included patients with mild liver disease, intestinal dysfunctions such as Crohn s disease, coeliac disease and gastroenteritis, acute lymphatic leukemia treated with methotrexate, contaminated small bowel syndrome and three patients with benign recurrent intrahepatic cholestasis (BRIC). 

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