Bile salt deficiency

Bile salt deficiency must also be directly studied. It may occur in the absence of obstruction or obvious liver disease (R7). The majority of patients with one form or another of the sprue syndrome will be found to have pancreatic enzymes and bile salts within the normal range. Pancreatic enzymes are absent or markedly deficient in patients with pancreatogenous malabsorption syndrome (B17, F13). It is surprising how frequently this necessary step in differential diagnosis is omitted. 

Steatorrhoea is excess fat in the stool, otherwise known as fatty stools. In cholestasis and bile salt disease this is due to a bile salt deficiency... 

Proper nutritional support is an important aspect of the treatment of patients with IBD, not because specific types of diets are useful in alleviating the inflammatory conditions, but because patients with moderate to severe disease are often malnourished either because the inflammatory process results in significant malabsorption or maldigestion, or because of the catabolic effects of the disease process. Malabsorption may occur in the patient with Crohn s disease with inflammatory involvement of the small bowel, where many nutrients are absorbed, as well as in patients who have undergone multiple small bowel resections with subsequent reduction in absorptive surface ( short gut ). Maldigestion can occur if there is a bile salt deficiency in the gut. 

Many studies report decreased mucosal levels of di- and triglycerides with increased concentrations of unesterified fatty acids in bile salt deficiency [8]. One possible explanation for this could be diminished monoglyceride solubilization and absorption and a consequent reduction in available monoglyceride for esterification. However, a reduced esterifying capacity is also possible. This could be the result of lack of activation of pre-existing enzymes in the mucosa by bile salts or a lack of... 

Like cholesterol, fat-soluble vitamins are strongly dependent on the presence of bile salts in the intestinal lumen for their absorption. Using thoracic duct lymph samples to estimate their absorption, Forsgren [98] showed marked depression of absorption of radiolabeled vitamins A, D, E and K in patients with total biliary obstruction. Intraluminal bile salt deficiency probably also contributes to impaired vitamin D absorption in primary biliary cirrhosis [99]. When exocrine pancreatic insufficiency is also present, absorption of vitamin K is even more markedly impaired [98]. More polar subspecies of the fat-soluble vitamins such as vitamin K3 [100] and 25-hydroxyvitamin D, [101] depend much less on bile salts for their absorption. 

In clinical terms, intraluminal bile salt deficiency such as occurs in various forms of cholestasis, can clearly lead to impaired assimilation of fat-soluble vitamins. When the bile-salt-binding resin cholestyramine is given on a long-term basis in the treatment of hypercholesterolemia there is some risk of malabsorption of fat-soluble vitamins though in clinical practice this is not common. 

Medium-chain triglycerides (MCT) are important components of nutritional supplements used in patients with digestive disorders. They therefore can be employed as an easily absorbed source of calories in patients who have a gastrointestinal (Gl) disorder that may result in malabsorption of nutrients. These diseases include pancreatic insufficiency, intraluminal bile salt deficiency due to cholestatic liver disease, biliary obstruction, ileal disease or resection, and disease causing obstruction of intestinal lymphatics. Remember, however, that MCT do not contain polyunsaturated fatty acids that can be used for synthesis of eicosanoids (see Chapter 35). 

Bile acids have two major functions in man (a) they form a catabolic pathway of cholesterol metabolism, and (b) they play an essential role in intestinal absorption of fat, cholesterol, and fat-soluble vitamins. These functions may be so vital that a genetic mutant with absence of bile acids, if at all developed, is obviously incapable of life, and therefore this type of inborn error of metabolism is not yet known clinically. A slightly decreased bile acid production, i.e., reduced cholesterol catabolism, as a primary phenomenon can lead to hypercholesterolemia without fat malabsorption, as has been suggested to be the case in familial hypercholesterolemia. A relative defect in bile salt production may lead to gallstone formation. A more severe defect in bile acid synthesis and biliary excretion found secondarily in liver disease causes fat malabsorption. This may be associated with hypercholesterolemia according to whether the bile salt deficiency is due to decreased function of parenchymal cells, as in liver cirrhosis, or whether the biliary excretory function is predominantly disturbed, as in biliary cirrhosis or extrahepatic biliary occlusion. Finally, an augmented cholesterol production in obesity is partially balanced by increased cholesterol catabolism via bile acids, while interruption of the enterohepatic circulation by ileal dysfunction or cholestyramine leads to intestinal bile salt deficiency despite an up to twentyfold increase in bile salt synthesis, to fat malabsorption, and to a fall in serum cholesterol. 

Cholesterol and fat-soluble vitamins require bile acid induced micellar solubilization for absorption, which takes place in the upper small intestine (c/. 32,116-118). Accordingly, in bile salt deficiency states, cholesterol absorption should be markedly impaired and fecal neutral sterol excretion increased. The fact that fecal neutral steroid excretion on a low-cholesterol diet is actually normal, as after ileal resection, ileal bypass, and cholestyramine treatment, or even decreased, as in cirrhosis of the liver or biliary occlusion (11), is due to a markedly reduced biliary secretion of cholesterol. In gluten enteropathy, in which no excessive bile salt loss usually exists, fecal neutral sterol excretion is markedly augmented (119). However, in occasional cases in which fecal bile salt elimination is markedly enhanced, the fecal neutral steroid excretion is quite normal, probably owing to decreased biliary cholesterol secretion as a consequence of low biliary bile salt secretion. Detailed information on the role of bile salts in both intraluminal and mucosal phases of fat and sterol absorption is presented in many recent reviews (6,10,113,114,117). 

Intestinal bile salt deficiency associated with impaired gallbladder contraction and slightly augmented fecal bile salt excretion during hypocalcemic steatorrhea of patients with primary hypoparathyroidism (84) will be discussed later (see Section VIIE2a). 

Bile salt deficiency as a result of a marked fecal loss of bile acids was... 

Studies with radioactive glycocholate or taurocholate demonstrated a virtual absence of the enterohepatic circulation of bile acids in patients with jejunotransversocolostomy (77). The small amount of absorbed bile acids contained some deconjugated cholate and deoxycholate (which had been reconjugated in the liver), indicating a rapid bacterial action during an apparently fast intestinal passage. Under these conditions, steatorrhea is apparently not solely due to bile salt deficiency induced impairment of micelle formation, but reduced absorptive area may play an important contributory role. No direct measurement of bile acid synthesis by fecal determination has been performed in this condition. 

Infants with severe cholestasis due to 3jff-HSDH deficiency may have hypo-calcaemia due to malabsorption of vitamin D or severely deranged clotting due to malabsorption of vitamin K. Vitamins D and K should be given either parenterally or orally in a form that is absorbed despite intestinal bile salt deficiency (e.g. la-hydroxy-cholecalciferol or 1,25-dihydroxy-chole-calciferol). Fresh frozen plasma and intravenous calcium supplement may occasionally be required. 

Clinical stresses which interfere with vitamin metabohsm, can result in calcium deficiency leading to osteomalacia and osteoporosis (secondary vitamin D deficiency). These stresses include intestinal malabsorption (lack of bile salts) stomach bypass surgery obstmctive jaundice alcoholism Hver or kidney failure decreasing hydroxylation of vitamin to active forms inborn error of metabohsm and use of anticonverdiants that may lead to increased requirement. 

The risk of colon cancer appears to be inversely related to calcium and folate intake. Calciums protective effect may be related to a reduction in mucosal cell proliferation rates or through its binding to bile salts in the intestine, whereas dietary folate helps in maintaining normal bowel mucosa. Additional micronutrient deficiencies have been demonstrated through several studies to increase colorectal cancer risk and include selenium, vitamin C, vitamin D, vitamin E, and 3-carotene however, the benefit of dietary supplementation does not appear to be substantial.11... 

Jansen PL, Strautnieks SS, Jacquemin E, Hadchouel M, Sokal EM, Hooiveld GJ et al. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 1999 117(6) 1370— 1379. 

Patients suffering from obstruction of the bile duct fail to digest fat, due to a deficiency of bile salts to maintain an effective emulsion of fat. 

Ora/. Anticoagulant-induced prothrombin deficiency (see Warnings) hypoprothrombinemia secondary to salicylates or antibacterial therapy hypoprothrombinemia secondary to obstructive jaundice and biliary fistulas, but only if bile salts are administered concomitantly with phytonadione. 

Hypoprothrombinemia due to other causes in adults 2.5 to 25 mg (rarely, up to 50 mg) amount and route of administration depends on severity of condition and response obtained. Avoid oral route when clinical disorder would prevent proper absorption. Give bile salts with tablets when endogenous supply of bile to Gl tract is deficient. 

Strautnieks, S.S. et al (2008) Severe bile salt e5qx)rt pump deficiency 82 different ABCBll mutations in 109 families. Gastroenterology, 134 (4), 1203—1214. 

The answer is B. This patient s greasy, foul-smelling stools indicate steatorrhea. Her vision problems may be a manifestation of vitamin A deficiency due to fat malabsorption. The most likely explanation is biliary insufficiency, ie, decreased bile salt production leading to poor emulsification of dietary fats. Active ileal disease is a possibility, but the WBC count would likely be elevated unless her condition was in remission. Infection with Giardia is less likely due to the absence of pathogenic organisms in her stool. Lactose intolerance can produce diarrhea but not steatorrhea. 

Mechanism of Action An antioxidant that prevents oxidation of vitamins A and C, protects fatty acids from aff ack by free radicals, and protects RBCs from hemolysis by oxidizing agents. Therapeutic Effect Prevents and treats vitamin E deficiency. Pharmacokinetics Variably absorbed from the GI tract (requires bile salts, dietary fat, and normal pancreatic function). Primarily concentrated in adipose tissue. Metabolized in the liver. Primarily eliminated by biliary system. 

Vitamins Ki and K2 require bile salts for absorption from the intestinal tract. Vitamin Kl is available clinically in oral and parenteral forms. Onset of effect is delayed for 6 hours but the effect is complete by 24 hours when treating depression of prothrombin activity by excess warfarin or vitamin deficiency. Intravenous administration of vitamin Ki should be slow, because rapid infusion can produce dyspnea, chest and back pain, and even death. Vitamin repletion is best achieved with intravenous or oral administration, because its bioavailability after subcutaneous administration is erratic. Vitamin Ki is... 

Normally there is very little fat in the feces. However, fat content in stools may increase because of various fat malabsorption syndromes. Such increased fat excretion is steatorrhea. Decreased fat absorption may be the result of failure to emulsify food contents because of a deficiency in bile salts, as in liver disease or bile duct obstruction (stone or tumor). Pancreatic insufficiency may result in an inadequate pancreatic lipase supply. Finally, absorption itself may be faulty because of damage to intestinal mucosal cells through allergy or infection. An example of allergy-based malabsorption is celiac disease, which is usually associated with gluten intolerance. Gluten is a wheat protein. An example of intestinal infection is tropical sprue, which is often curable with tetracycline. Various vitamin deficiencies may accompany fat malabsorption syndromes. 

Malabsorption is defined as an inadequate assimilation of dietary substances due to defects in digestion, absorption or transport. Malabsorption can affect macronutrients (proteins, carbohydrates, fats), micronutrients (vitamins, minerals) or both, causing excessive faecal excretion and producing nutritional deficiencies and GI symptoms. Digestion and absorption occur in three phases, namely (i) the intra-lumen hydrolysis of fats, proteins and carbohydrates by enzymes, and emulsification by bile salts, (ii) digestion by brush-border enzymes and uptake of end-products and (iii) lymphatic transport of nutrients. Malabsorption can occur when any of these phases is impaired. 

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