Cholestasis malabsorption

Trace elements are essential cofactors for numerous biochemical processes. Trace elements that are added routinely to PN include zinc, selenium, copper, manganese, and chromium. There are various commercial parenteral trace element formulations that can be added to PN admixtures (e.g., MTE-5 ). Zinc is important for wound healing, and patients with high-output fistulas, diarrhea, burns, and large open wounds may require additional zinc supplementation. Patients may lose as much as 12 to 17 mg zinc per liter of gastrointestinal (GI) output (e.g., from diarrhea or enterocutaneous fistula losses) however, others have demonstrated that 12 mg/day may be adequate to maintain these patients in positive zinc balance.18 Patients with chronic diarrhea, malabsorption, and short-gut syndrome may have increased selenium losses and may require additional selenium supplementation. Patients with severe cholestasis should have copper and manganese... 

Pregnant or lactating women should not take orlistat because no data exist to establish safety. Orlistat is contraindicated in patients with chronic malabsorption syndrome or cholestasis.31... 

Chronic malabsorption syndrome or cholestasis hypersensitivity to orlistat or to any component of this product. 

In patients who have preexisting bowel disease or cholestasis, steatorrhea may occur. Malabsorption of vitamin occurs rarely, leading to hypoprothrombinemia. Prothrombin time should be measured frequently in patients who are taking resins and anticoagulants. Malabsorption of folic acid has been reported rarely. Increased formation of gallstones, particularly in obese persons, was an anticipated adverse effect but has rarely occurred in practice. 

Malabsorption has many causes. Some malabsorptive disorders, for example coeliac sprue, impair the absorption of most nutrients, vitamins and trace minerals (global malabsorption) others, for example pernicious anaemia, are more selective. Pancreatic insufficiency causes malabsorption if >90% of function is lost. Increased lumen acidity (e.g. Zollinger-Ellison syndrome) inhibits lipase and fat digestion. Cirrhosis and cholestasis reduce hepatic bile synthesis or delivery of bile salts to the duodenum, causing malabsorption. Some causes are summarised in Table 4.2. 

This chronic cholestatic liver disease affects 1 in 4000 people in the United Kingdom. Pruritus is a common early symptom, and can be helped by colestyramine. Qu-onic cholestasis leads to malabsorption of fat-soluble vitamins, particularly vitamin D, and deficiency of which must be corrected to avoid osteomalacea. 

Adverse effects include flatulence and liquid, oily stools, leading to faecal urgency, abdominal and rectal pain. Symptoms may be reduced by adhering to a reduced-fat diet. Low plasma concentrations of the fat-soluble vitamins A, D and E have been foimd. OrUstat is contraindicated where there is chronic intestinal malabsorption or cholestasis. 

Sokol RJ, Butler-Siraon N, Heubi JE, lannaccone ST, McClung HJ, Accurso F et al. Vitamin E deficiency neuropathy in children with fat malabsorption. Studies in cystic fibrosis and chronic cholestasis. Ann NY Acad Sci 1989 570 156-69. 

Serial PT measurements also can be used to differentiate between cholestasis and severe hepatocellular disease. In practice, PT should be measured again after vitamin K injection, because cholestasis wiD. cause a decrease in PT because of malabsorption of vitamin K. The patient has cholestasis if the PT corrects after vitamin K replacement (10 mg sub-cutaneously or intramuscularly, followed by PT measurement 4 hours later). With time, if the PT does not return to normal, the patient has severe hepatocellular disease. 

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. 

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. 

Extrahepatic biliary obstruction occurs due to a myriad of benign and malignant etiologies. The resulting cholestasis may lead to malabsorption, coagulopathy, pruritus, hepatocellular failure, renal dysfunction. 

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. 

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