Bile acids malabsorption

Oelkers, P., et al. Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). J. Clin. Invest. 1997, 99, 1880-1887. 

The consequence of bacterial bile acid metabolism [66, 74,77] is hardly clinically significant malabsorption [6] in otherwise healthy individuals [32,79], but in predisposed individuals this may be different. Accordingly, omeprazole interferes with the absorption of vitamin B12 [80-83] and protein assimilation [84], The mechanism for altered vitamin B12 absorption is prevention of its cleavage from dietary protein [83], for which the importance of the concurrent bacterial overgrowth has not yet been ruled out. 

Transport by ASBT is electrogenic with a 2 1 ratio of Na rbile acids and membrane potential may regulate transport function. ASBT is essential for the enterohepatic circulation as shown by ASBT gene knockout mice that developed bile-acid malabsorption with no enterohepatic circulation. This is summarised in Figure 2.4. 

Malabsorption Because they sequester bile acids, these resins may interfere with normal fat absorption and digestion and may prevent absorption of fat-soluble vitamins such as A, D, E, and K. 

In addition symptomatic treatment with opiates, with bile acid binding resins in those with bile acid malabsorption, with milk free diets in those who are lactose intolerant, and with low fat diets may materially help relevant symptoms. 

Porter JL, Fordtran JS, Santa Ana CA, Emmett M, Hagey LR, Macdonald EA, Hofmann AF (2003) Accurate enzymatic measurement of fecal bile acids in patients with malabsorption. J Lab Clin Med 141 411-418... 

If more cholesterol enters the bile than can be solubilized by the available bile salts and phosphatidylcholine, cholesterol gallstone disease (cholelithiasis) can occur. This is generally caused by gross malabsorption of bile acids from the intestine, obstruction of the biliary tract, or severe hepatic dysfunction, leading to abnormalities in bile or bile salt production. 

Conjugated bile salts are normally absorbed in the terminal ileum. Disease of the terminal ileum (eg, Crohn s disease) or surgical resection leads to malabsorption of bile salts, which may cause colonic secretory diarrhea. The bile salt binding resins cholestyramine or colestipol may decrease diarrhea caused by excess fecal bile acids (see Chapter 35 Agents Used in Hyperlipidemia). The usual dose is 4-5 g one to three times daily before meals. Side effects include bloating, flatulence, constipation, and fecal impaction. In patients with diminished circulating bile acid pools, further removal of bile acids may lead to an exacerbation of fat malabsorption. These agents bind a number... 

T. Nakamura, T. Takeuchi, A. Terada, Y. Tando, and T. Suda, Near-Infrared Spectrometry Analysis of Fat, Neutral Sterols, Bile Acids, and Short-Chain Fatty Acids in the Feces of Patients with Pancreatic Maldigestion and Malabsorption, Int. J. Pancreatol., 23(2), 137-143 (1998). 

Primary bile acid malabsorption (absent or inefficient ileal active transport)... 

Bile acid malabsorption leading to chronic diarrhea occurs when there is ileal disease (e.g., Crohn s disease), or after resection of the terminal deum it may also occur following cholecystectomy and in some patients with irritable bowel syndromed The malabsorption of bile salts produces diarrhea by two different mechanisms. When significant bile salt depletion occurs, the deficiency of intraluminal bile salts leads to fat malabsorption and steatorrhea. More commonly, malabsorption of bile salts in the ileum leads to increased concentrations of bile salts in the colon where they alter water and electrolyte absorption. This leads to net secretion of water into the lumen and diarrhea. Bile salt malabsorption is probably an underdiagnosed condition and should be suspected in patients with unexplained chronic diarrhea. 

Serum 7a-hydroxy-4-cholesten 3-one concentrations in the evaluation of bile acid malabsorption in patients with diarrhoea correlation to the SeHCAT test. Gut 1993 34 698-701. 

Sauter GH, Munzing W, von Ritter C, Pamngartner G. Bile acid malabsorption as a cause of chronic diarrhea diagnostic value of 7a-hydroxy-4-cholesten-3-one in serum. Dig Dis Sci 1999 44 14-9. 

Smith MJ, Cherian P, Raju GS, Dawson BF, Mahon S, Bardhan KD. Bile acid malabsorption in persistent diarrhoea. J R Coll Physicians Lond 2000 34 448-51. 

WiUiams AJK, Merrick MV, Eastwood MA. Idiopathic bile acid malabsorption—a review of clinical presentation, diagnosis and response to treatment. Gut 1991 32 1004-6. 

Drugs Alcohol, estrogens, isotretinoin, beta blockers, glucocorticoids, bile-acid resins, thiazides asparaginase, interferons, azole antifungals, mirtazapine, anabolic steroids, sirolimus, bexarotene Malnutrition Malabsorption Myeloproliferative diseases Chronic infectiousdiseases AIDS, tuberculosis Monoclonal gammopathy Chronic liver disease Malnutrition Obesity... 

Systemic complications of Crohn s disease are common, and similar to those found with ulcerative colitis. Arthritis, iritis, skin lesions, and liver disease often accompany Crohn s disease. Renal stones occur in up to 10% of patients with Crohn s disease (less frequently with ulcerative colitis) and are caused by fat malabsorption, which allows for greater oxalate absorption and formation of calcium oxalate stones. Gallstones also occur with greater frequency in patients with ileitis, possibly because of bile acid malabsorption at the terminal ileum. 

Herbal medicines or teas often contain senna, which may produce diarrhea. In patients with disease persistence following dietary modification, loperamide may be used for episodic management of urgent diarrhea, or in situations in which the patient wishes to avoid the possibility of an acute onset of symptoms. This drug decreases intestinal transit, enhances water and electrolyte absorption, and strengthens rectal sphincter tone. Some patients may require continuous therapy, and careful dosage titration can usually be undertaken to prevent the development of constipation. Cholestyramine may be useful in patients with diarrhea related to idiopathic bile acid malabsorption or following cholecystectomy. ... 

Vitamin K absorption depends on both bile acids and pancreatic enzymes to create micelles. Malabsorption resulting from diseases of the small intestine or pancreas—such as cystic fibrosis, Crohn s... 

Diarrhea and steatorrhea are common in patients with hepatic cholestasis because of intestinal malabsorption (due in part to mucosal edema from hypoalbuminemia), inadequate bile acid delivery to the duodenum, and pancreatic dysfunction with decreased secretion of hpase. Micelle formation is impeded, and thus the long-chain fatty acids pass through the colon, resulting in a foul-smelling, soapy diarrhea. 

---