Bile salt diarrhea

Bile salt diarrhea: Description, Causes and Risk Factors:Bile is a thick yellow fluid secreted by the liver, that helps in fat digestion. During the meals, this liver bile is stored in the gallbladder, a small sac underneath the liver which squeezes and releases these stored bile salts in to the small intestine that aids in digestion. Bile acids and bile salts have essential functions in the liver and in the small intestine. Their synthesis in the liver provides a metabolic pathway for the catabolism of cholesterol and their detergent properties promote the solubilisation of essential nutrients and vitamins in the small intestine. These disorders generally lead to severe human liver disease, underscoring the essential role of bile acids in metabolism. Recent advances in the elucidation of gene defects underlying familial cholestasis syndromes has greatly increased knowledge about the process of bile flow. The expression of key proteins involved in bile flow is tightly regulated by transcription factors of the nuclear hormone receptor family, which function as sensors of bile acids and cholesterol.When the gallbladder is surgically removed, the liver has to secrete more bile salts, and more salts are released between meals since there is no place to store them. This increased amount of bile salts can sometimes overwhelm or overpower the small intestines' capacity to reabsorb them. The excess spills over into the large intestine, or colon, where bile acts somewhat like a laxative, which eventually causes bile salt diarrhea and abnormal bile bowel movements.Every day normal adults put - 30 g of conjugated bile salts into their intestines. Most are incorporated into micelles and large vesicles that also contain cholesterol and lecithin, but a small fraction are present as monomers in solution. In the gut lumen, these micelles and vesicles also take up fatty acids and monoglycerides. The chemical activity of the free bile salt monomers is far less in the presence of lipid-rich mixed micelles than in the presence of pure bile salt micelles. As these lipid-rich micelles and vesicles travel down the small intestine, the contained lipids are absorbed, increasing the activity of the dissolved bile salt monomers. The distal ileum keeps this activity low by quickly absorbing the monomers via a sodium-dependent active transport process that is so efficient that normally almost no bile acids reach the colon. If the ileum is diseased or has been resected, however, significant quantities of bile acids do reach the colon, and there, in the absence of protective lipids, the chemical activities of the dissolved bile acid anions reach levels that affect colonic ion transport. Specifically, they stimulate the secretion of electrolytes and water, causing diarrhea. Not all bile acids have this effect. Dihydroxy bile acids with both hydroxy groups in the alpha configuration (this does not include ursodeoxycholic acid, which has one of its hydroxys in the beta configuration) do; the more hydrophilic trihydroxy bile acids do not. Deconjugation of the bile acids by colonic bacteria further enhances their secretory potency.Bile saltSome years ago, dihydroxy bile salts were shown to increase colonic mucosal cAMP levels and adenylyl cyclase activity. Subsequent studies suggest, however, that this is an indirect effect of bile salts mediated by prostaglandins and other compounds released from affected leukocytes and fibroblasts in the lamina propria.In 1989 researchers identified Ca2+ as the intracellular mediator for the action of bile salts on colonic epithelial cells. They showed that taurodeoxycholate (TDC), when applied to confluent monolayers of T84 cells (a colon cancer cell line that actively secretes Cl- in response to a variety of stimuli), stimulates net Cl- secretion, increases cytosolic Ca2+, but does not alter the level of cAMP or cGMP. They also found that TDC was more potent on the basolateral side of the monolayer than on the apical side. Apical TDC stimulated secretion only at concentrations that markedly increased the conductance of the monolayer, suggesting bile salt-induced leakage of bile salts to the basolateral side.How do bile salts increase cytosolic Ca2+" in colonic epithelial cells, and is the Ca2+" responsible for the associated secretion. In this issue researchers showed that application of TDC to isolated T84 cells activates three conductances, one for K+, one for Cl- (both are necessary for secretion), and a nonselective cation conductance, and causes both a 10-fold increase in cytosolic Ca2+ and an accumulation of inositol monophosphate, reflecting production of inositol 1,4,5-triphosphate (IP3). In clever and persuasive ways, they show that the increase in Ca2+ is responsible for the activation of K+ and Cl- conductances (but not the nonspecific cation conductance) and that IP3 is responsible for the increase in Ca2+. TDC's effect on the T84 cell plasma membrane is quite subtle: in the time intervals between discrete channel openings, the membrane resistance is as high as ever. Its effects are strikingly similar to those of the muscarinic cholinergic agonist, carbachol.How does TDC stimulate polyphosphoinositide turnover in the basolateral membrane of T84 cells?
  • Is there a specific receptor for TDC coupled to a G protein that, in turn, activates phospholipase C (PLC)?
  • Does TDC more directly activate PLC? Or does TDC disrupt the membrane structure sufficiently to make otherwise unavailable polyphosphoinositides available for degredation by PLC?
The authors raise these interesting questions but have no answers. This is a fruitful area for future research.Symptoms:Although the symptoms may vary, quite often many patients suffer persistent diarrhea after their gallbladder removal. The condition is so worse, that the patient experiences an urgency and watery diarrhea instantly after having meals. The condition can be extremely embarrassing especially at work or while dining with friends, as the person may have to stop and head for the closet bathroom before finishing the meal. Hence, making people reluctant to have meals away from their home.Diagnosis:Since there is no specific diagnostic test for this condition, your doctor must confirm his suspicion that bile salt diarrhea is the culprit by ruling out other possible causes of diarrhea such as infection, colitis, cancer, and others. To do so the doctor will ask questions about your health history in general and specifically about the change in bowel habits. A physical examination is then performed. Special tests of blood and stool samples may be requested. In most cases, the doctor will need to examine the lining of the colon with a "scope" test such as colonoscopy to be sure that colitis and cancer are not present. Every case is a little different and it is the doctor's job to determine which tests are necessary to confirm the diagnosis.Treatment:There is no known cure for this problem, but treatment is available. Once it has been established that bile salt diarrhea is the problem, treatment is usually prescribed to lessen the symptoms of diarrhea and urgency. The mainstay of treatment is a powder called cholestyramine resin. This medication is primarily marketed as a drug for patients with high blood cholesterol. It comes as a powder that is mixed with about 6 ounces of water. Several formulations are available such as LoCHOLEST, Locholest Light, Prevalite, Questran, Questran Light. It also comes in a tablet form called Colestid. Much like a chemical "sponge," this medicine lowers blood cholesterol by trapping and inactivating bile salts in the intestine, preventing their reabsorption. By trapping bile salts, cholestyramine also helps patients with bile salt diarrhea. The dose required to treat this condition is usually only once daily.NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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