Fat, malabsorption

In experimental animals, vitamin E deficiency results in resorption of femses and testicular atrophy. Dietary deficiency of vitamin E in humans is unknown, though patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic fiver disease suffer deficiency because they are unable to absorb the vitamin or transport it, exhibiting nerve and muscle membrane damage. Premamre infants are born with inadequate reserves of the vitamin. Their erythrocyte membranes are abnormally fragile as a result of peroxidation, which leads to hemolytic anemia. 

Shindo K, Machida M, Miyakawa K, Fukumura M A syndrome of cirrhosis, achlorhydria, small intestinal bacterial overgrowth, and fat malabsorption. Am J Gastroenterol 1993 88 2084-2091. 

Essential fatty acid deficiency is rare but can occur with prolonged lipid-free parenteral nutrition, very low fat enteral formulas, severe fat malabsorption, or severe malnutrition. The body can synthesize all fatty acids except for linoleic and linolenic acid, which should constitute approximately 2% to 4% of total calorie intake. 

Associated with Fat malabsorption Long-term antibiotic fllerapy Breast-fed newborns Infrmt whose mother was taking anticonvulsant therapy during pr nancy Associated with Diet deficient in citrus fruit, green vegetables... 

FIGURE 5.3 Inhalation of vitamin A improves vitamin A deficiency in Ethiopian children with severe fat malabsorption. 

A major symptom of fat malabsorption is steatorrhea, production of bulky, foul-smelling feces that float due to high fat content, which may be accompanied by diarrhea and abdominal pain, and if sustained for a period of days or weeks, lead to deficiencies of the fat-soluble vitamins. 

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. 

Deficiencies characterized by excessive bleeding may occur in infants due to their lack of intestinal bacteria or In adults having fat malabsorption disorders, such as cystic fibrosis, which result in insufficiency of pancreatic lipase secretion. 

Orlistat, a semisynthetic derivative of lipstatin, is a potent and selective inhibitor of pancreatic lipases. It was designed to treat obesity. Orlistat prevents approximately 25% of dietary fat from being absorbed. Very little of the drug itself is absorbed. Its adverse effects are therefore restricted to those related to fat malabsorption, with potential losses of fat-soluble vitamins. It has a relatively small effect on body mass, but enough to realise in one study a 37% reduction in the incidence of type 2 diabetes. 

That initial assessment should consider whether diarrhoea is watery, or sugar or fat malabsorptive, or whether there is active bleeding or significant abdominal pain suggesting inflammatory disease. In the elderly constipation with overflow may be the real problem, and the possibilities of partial mechanical obstruction and neoplasia must be born in mind. 

Dietary causes of vitamin D deficiency are unusual except among the poor and malnourished, and in those with fat malabsorption. Reduced exposure to sunlight may then become a critical factor. Renal failure can impair 1-hydroxylation of cholecalciferol, and chronic liver disease can reduce 25-hydroxylation as well as contributing to malabsorption. 

Since vitamin A is a fat-soluble vitamin, any disease that results in fat malabsorption and impaired liver storage brings with it the risk of vitamin A deficiency these conditions include biliary tract disease, pancreatic disease, sprue, and hepatic cirrhosis. One group at great risk are children from low-income families, who are likely to lack fresh vegetables (carotene) and dairy products (vitamin A) in the diet. 

L B. Supplement with vitamin A. Vitamin A deficiency symptoms include night blindness that can lead to corneal ulceration. This deficiency can occur in patients with impaired liver storage or fat malabsorption. Dairy products, such as milk, are a good source of vitamin A. (3-Carotene, a vitamin A precursor, is found in pigmented vegetables, such as carrots. When a deficiency is diagnosed, it is appropriate to treat the patient with a supplement rather than to rely on increased consumption of vitamin A-rich foods. A patient with pancreatic disease and malabsorption syndrome will need parenteral supplementation. 

In chylomicron retention disease (Anderson s disease) the secretory defect is restricted to intestinal apoB-containing lipoproteins (i.e., chylomicrons). This very rare recessively inherited disorder results from defects in a GTPase, Sarlb, which plays a critical role in the intracellular assembly and trafficking of chylomicrons. The affected patients present with fat malabsorption resulting in steatorrhea and deficiency of fat-soluble vitamins [46, 52, 54]. 

Vitamin E deficiency is normally associated with diseases of fat malabsorption and is rare in humans. Deficiency is characterized by erythrocyte haemolysis and prolonged deficiency can cause neuromuscular dysfunction. Hypervitaminosis E is not common, despite an increased intake of vitamin E supplements. Extremely high doses of the vitamin may interfere with the blood clotting process. 

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... 

It should be noted that deficiency states for some vitamins (e.g., pantothenic acid) are practically unknown in human beings. In such cases, deficiency states may be simulated by feeding the subject an appropriate vitamin antagonist. In another series of situations, vitamin deficiencies can be brought about by interfering with their absorption intentionally or may be the result of a disease process. Thus, fat-soluble vitamin deficiency may develop in cases of fat malabsorption syndromes (steatorrhea) sprue, pancreatic insufficiency, and bile duct obstruction. 

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. 

Steatorrhea, the clinical result of insufficient intraluminal lipid hydrolysis, is the most important digestive malfunction in pancreatic exocrine insufficiency. As a rule, concomitant malabsorption of the lipid-soluble vitamins A, D, E, and K must be suspected in these patients. Naturally, potential differential diagnoses have to be considered in patients who present with steatorrhea (Table 26-1). The pivotal role of fat malabsorption in chronic pancreatitis is due to several interacting mechanisms ... 

Abetalipoproteinemia (ABL) is a rare, autosomal recessive disease first described by Bassen and Kornsweig in 1950. It is characterized by the absence of plasma apoB lipoproteins, fat-soluble vitamin deficiencies (A, E, and K), and the presence of acanthocytosis (Table 27-1). Other signs include fat malabsorption presenting as steatorrhea, flatus, abdominal discomfort, and progressive ataxic neuropathy. The key diagnostic feature is an extremely low plasma total cholesterol and absence of all apoB lipoproteins (chylomicrons, VLDL, and LDL). 

In ABL, fat malabsorption is responsible for the diarrhea and flatus. Symptoms are prominent in affected newborns with the severity coupled to their lipid-rich diets. Chronic diarrhea results in nutrient wasting and, in some cases, failure to thrive. Since fat malabsorption is responsible for the initial gastrointestinal symptoms, it is not uncommon for affected individuals to restrict dietary fat independent of medical advice, alleviating the frequency of diarrhea and flatus. Occasional exacerbations still occur, but not serious enough to provoke a clinical visit. As a result, affected individuals often develop normally, unaware of their disease, until a gross secondary neuropathy becomes symptomatic toward the third decade of life or even earlier. 

Abetalipoproteinemia mttp/ Biosynthesis of apoB Fat malabsorption, Absence of all... 

In the absence of inadequate endogenous synthesis, vitamin D must be obtained from dietary sources or from supplements. Few foods contain vitamin D except for the flesh of fatty fish (salmon, mackerel, sardines), fish liver oils, and eggs from hens fed feed enriched with vitamin D. In the United States, all commercially produced milk is fortified with vitamin D2 at a level of 400 IU/L (1 IU = 0.025 fig of vitamin D3). Therefore, in the United States (and other economically advanced countries) most dietary vitamin D is obtained from milk and other vitamin D2-fortified foods. Both vitamin D2 and vitamin D3 are converted at the same rate to 25-hydroxyvitamin D by a hydroxylase in the liver and are equally active as a prohormone. Because dietary uptake of vitamin D is dependent on normal fat absorption, conditions in which fat malabsorption is present can result in vitamin D deficiency. Because breast milk contains little vitamin D, vitamin D deficiency can occur in infants who are solely breastfed, are not exposed to adequate sunlight, and are not receiving vitamin D supplements. The adequate intake of vitamin D for children is 5 pg/day (200 IU/day) (Table 30-2). 

Deficiency develops in patients with severe fat malabsorption, cystic fibrosis, chronic cholestatic hepatobiliary disease, and in two rare groups of patients with genetic diseases ... 

Since vitamin E is absorbed from the intestines in chylomicrons, any fat malabsorption diseases can lead to deficiencies in vitamin E intake. Neurological disorders have been associated with vitamin E deficiencies associated with fat malabsorptive disorders. 

Naturally occurring vitamin K is absorbed from the intestines only in the presence of bile salts and other lipids through interaction with chylomicrons. Therefore, fat malabsorptive diseases can result in vitamin K deficiency. 

Fal malabsorption syndromes Fat malabsorption syndromes such as cystic fibrosis and cholestatic liver diseases (lack of bile salts) can impair the absorption of vitamin D. 

Persons at risk for EFA deficiency tend to be the same as those at risk for vitamin E deficiency. Some signs are shared by both defidencies. Premature infants may be at risk for EFA deficiency because of their low stores of lipids and their rapid growth, especially when they are fed diets that do not contain EFAs. For example, fats have been omitted from diets used to feed preterm infants (to avoid a variety of complications). EFA deficiency may develop later in life with fat malabsorption syndromes, EFA deficiency has presented in adults fed by total parenteral nutrition for longer periods, where EFAs had not been included in the liquid diet. 

Filer, L. J. (1971). Vitamin K supplementation for irdants receiving milk substitute infant formulas and for those with fat malabsorption. Pediatrics 48,483-487. 

The effect of oral pancreatic enzyme supplementation (Creon 10 000 in a dose of 1000 units of lipase per gram of ingested dietary fat) on fat malabsorption has been evaluated in an open study in 24 patients with HIV infection (1). Pancreatic enzyme supplementation was highly effective in reducing fecal fat loss. There were no clinical adverse effects or changes in serum biochemistry attributable to the drug. 

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