Cholestatic liver disease bile acid synthesis

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). 

Diagnosis of the 4 inborn errors of bile acid synthesis discussed in this chapter is important because three are treatable by oral bile acid supplementation (such treatment was not successful in the single reported case of oxysterol 7a-hydroxylase deficiency). Liquid secondary ion mass spectrometry (LSI-MS) is a simple and rapid method which can be used to screen urine samples for abnormal cholanoids (bile acids and bile alchohols). It should be applied to neonates with unexplained cholestatic liver disease, particularly if familial and associated with steatorrhoea and fat-soluble vitamin malabsorption, to infants and children with developmental delay whether or not this is associated with specific features suggestive of a peroxisomal disorder (e.g. hypotonia, seizures, dysmorphic features, ocular and auditory abnormalities and hepatic dysfunction) or CTX (e.g. juvenile cataracts). 

The Increase In AP activity is stimulated by bile acids. A rise in bile acids, which is considered to be the most sensitive and earliest marker of cholestasis, precedes any elevation in AP. The latter derives from enzyme synthesis with increased secretion into the blood. Under pathological conditions, bile duct AP is formed, which is a sensitive marker for hepatobiliary diseases, cholestasis and space-occupying lesions of the liver. The sensitivity is 80-100% in cholestatic diseases. AP activity is usually higher in obstructive jaundice and cholangitis than in intrahepatic obstructions, and it is highest in the vanishing bile duct disease or in complete obstruction. (13, 39, 41) (s. tabs. 5.9 13.2-13.4)... 

The liver synthesizes fibrinogen factors V, VIII, XI, and XII, and the vitamin K-dependent factors II, VII, IX, and X. Furthermore the liver plays an important role in platelet growth and function. The vitamin K-dependent proteins contain y-carboxy-glutamic acid. Vitamin K is necessary for the carboxylation of these proteins, which facilitate the conversion of prothrombin to thrombin. Patients with severe hepatocellular disease have decreased synthesis of the vitamin K-dependent clotting factors, especially factor VII. Furthermore, patients with cholestatic disease have decreased bile salt secretion, which is necessary for the absorption of vitamin K, leading to failure of activation of factors II, VII, IX, and X. In these patients, unlike those with hepatocellular disease, the prothrombin time can be corrected with an injection of vitamin K. 

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