Deficiency of fat-soluble vitamin

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]. 

In cholestasis, bile salts and bile pigments are retained and appear in the circulation, and steatorrhea and deficiencies of fat-soluble vitamins may occur. These deficiencies are often manifested as hypoprothrombinemia (from lack of vitamin K) and osteomalacia (from lack of vitamin D). The magnitude depends on the degree of obstruction. If blockage is complete, urinary urobilinogen will be absent and the stools will have a pale, clay-like color. 

As patients lose exocrine function of the pancreas, they have decreased ability to absorb lipids and protein ingested with normal dietary intake. Weight loss from nutritional malabsorption is a common symptom of chronic pancreatitis not often seen in acute pancreatitis. Fatty- or protein-containing stools are also common carbohydrate absorption is usually unaffected. Even though patients with chronic pancreatitis have decreased ability to absorb lipid from the gastrointestinal tract, there does not appear to be an increased incidence of fat-soluble vitamin deficiency in these patients.34... 

Vitamin A deficiency is worldwide one of the most prevalent nutrition-dependent deficiency diseases. It leads to changes of the respiratory epithelium, which result in repeated infections of the respiratory tract, the main cause of death in vitamin A-deficient children. The difficulty in supplying the respiratory epithelium with vitamin A is that the affected children frequently suffer as well from infections of the gastrointestinal tract with subsequent reduction of the absorption of fat-soluble vitamins. Nutritargeting can in these cases avoid the problems of malabsorption and ensure the micronutrient supply. 

Use of orlistat could interfere with the body s absorption of fat-soluble vitamins and beta carotene. Long-term use could result in deficiencies of vitamins A, D, E, and K, and beta carotene. Patients are advised to take supplements. Another possible side effect is calcium deficiency. 

Chronic malabsorption does not fully explain the different extents of fat-soluble vitamin deficiencies associated with ABL. More specifically, why are plasma vitamin E levels more severely affected than those of vitamins A or K The answer for this can be traced to apoB lipoprotein biosynthesis and catabolism (Fig. 27-2). Just as observed for lipids, hydrophobic, fat-soluble vitamins require apoB lipoproteins as vehicles for plasma transport. The reliance of each fat-soluble vitamin on apoB lipoproteins varies, and this variable dependency is directly related to the severity of symptoms observed in ABL. 

Cystic fibrosis patients are usually advised to take more than the recommended daily amounts of these vitamins in order to prevent deficiency. A common problem associated with poor absorption of fat-soluble vitamins is deficiency of vitamin K. Vitamin K is required by the liver to produce many blood coagulation factors. Part of the problem for cystic fibrosis patients is their chronic antibiotic therapy, which decreases the bacterial population of the colon colonic bacteria synthesize vitamin K. Vitamin K deficiency leads to prolonged blood-clotting time. Vitamin D deficiency could cause rickets in a child or osteomalacia in adults. Vitamin A deficiency leads to night blindness, skin and other ocular defects. 

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. 

Deficiency of water-soluble vitamins is far less precarious than a deficit of fat-soluble vitamins. While the first condition is generally rare, it can nevertheless often be observed in severe alcoholism. In liver cirrhosis, it was possible to detect a reduced amount of vitamins B2, Bg, Bi2, C and niacin or pantothenic acid in the liver as well as hypofunction of vitamins Bi, B2, Bg, C and folic acid. Hypovitaminosis may develop due to the reduced formation of specific transport proteins or the decreased acti-... 

Table 7.1 Sources, Functions and Deficiency symptoms of Fat Soluble Vitamins...

Blockage of the bile duct caused by problems such as cholesterol-containing gallstones or duodenal or pancreatic tumors can lead to an inadequate concentration of bile salts in the intestine. Digestion and absorption of dietary lipids is diminished. Certain diseases that affect the pancreas can lead to a decrease in bicarbonate and digestive enzymes in the intestinal lumen. (Bicarbonate is required to raise the intestinal pH so that bile salts and digestive enzymes can function.) If dietary fats are not adequately digested, steatorrhea may result. Malabsorption of fats can lead to caloric deficiencies and lack of fat-soluble vitamins and essential fatty acids. 

The answer is a. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287-320.) Vitamins A, D, E, and K are all fat-soluble. The physical characteristics of fat-soluble vitamins derive from the hydrophobic nature of the aliphatic chains composing them. The other vitamins listed are water-soluble, efficiently administered orally, and rapidly absorbed from the intestine. Fat-soluble vitamins must be administered intramuscularly or as oral emulsions (mixtures of oil and water). In intestinal disorders such as chronic diarrhea or malabsorption due to deficient digestive enzymes, fat-soluble vitamins are poorly absorbed and can become deficient. Supplementation of fat-soluble vitamins is thus routine in disorders like cystic fibrosis (219700), a cause of respiratory and intestinal disease that is the likely diagnosis in this child. 

Cholestyramine is another treatment option for cholestasis of pregnancy. It is an oral medication that binds bile salts in the intestine and promotes their excretion in the feces. As this drug is not absorbed, it most likely has little effect on the fetus. Effects on the fetus are stiU under evaluation. However, cholestyramine can interfere with the absorption of fat soluble vitamins, such as vitamins A, D, E, and K. In rare cases, drug-induced vitamin K deficiency is believed to contribute to hemorrhaging during childbirth. 

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. 

Xenobiotic-induced pancreatitis may be accompanied by gross plasma lipid changes that may result from marked changes of carbohydrate metabolism (see Chapter 9). The observation of the presence of gross macroscopic fecal fat content (steatorrhea) can indicate effects on pancreatic function, biliary dysfunction, or intestinal malabsorption. In longer-term studies, malabsorption of fat-soluble vitamins may be reflected by the clinical condition of vitamin-deficient animals. 

Usuki (169) raised rabbits on a diet deficient in fat-soluble vitamins and found a 9% incidence of gallstones after 6-8 weeks. Qualitative analysis revealed that these small sandlike stones contained calcium, bilirubin, and traces of cholesterol. 

May Mellanby, in very careful work well reviewed by Mellanby and King (1039), studied the structural relations of the teeth in children and in experimental work in dogs. The development of enamel hypoplasia as a result of vitamin D deficiency was established. The formation of secondary dentine as a function of the supply of fat-soluble vitamins was also recorded. 

Fiebrich HB, Van Den Berg G, Kema IP, Links TP, Kleibeuker JH, Van Beek AP, Walenkamp AM, Sluiter WJ, De Vries EG. Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue. Aliment Pharmacol Ther 2010 32(11-12) 1398-404. 

In 1913, vitamin A was discovered by Elmer V. McCollum and Marguerite Davis of the University of Wisconsin, and by Thomas 5. Osborne and Lafayette B. Mendel of the Connecticut Experiment Station. Working independently, each research team demonstrated the presence of an essential dietary substance in fatty foods. McCollum and Davis found it in butter-fat and egg yolks Osborne and Mendel discovered it in cod liver oil. These researchers believed that only one factor, which they called fat-soluble A, was needed to supplement purified diets. They described the condition as the "type of nutritive deficiency exemplified in the form of an infectious eye disease prevalent in animals inappropriately fed." In 1915, McCollum and Davis also noted that a deficiency of fat-soluble A caused night blindness. (It is noteworthy that Miss Marguerite Davis, a young biologist who had just obtained her bachelor s degree from the University of California, volunteered to do the rat work for McCollum without salary.)... 

Deficiencies of vitamin K and indeed all the other fat soluble vitamins are more likely to occur as a result of impairment in fat absorption than from dietary insufficiency. This could occur when the secretion of bile salts is restricted (as in biliary obstruction), when sections of the gut have been removed or damaged by surgery or in diseases, such as tropical sprue and cystic fibrosis, that are associated with poor intestinal absorption. Even when normal absorptive mechanisms are functioning well, some fat is necessary in the diet to improve the absorption and utilization of fat soluble vitamins. There is little evidence, however, that, within the normal range of fat intakes, the amount of dietary fat significantly affects the utilization of fat soluble vitamins. 

Bile acid sequestrants may interfere with die digestion of fats and prevent die absorption of die fat-soluble vitamins (vitamins A, D, E, and K) and folic acid. When die bile acid sequestrants are used for long-term therapy, vitamins A and D may be given in a water-soluble form or administered parenterally. If bleedingtendencies occur as die result of vitamin K deficiency, parenteral vitamin K is administered for immediate treatment, and oral vitamin K is given for prevention of a deficiency in the futum... 

Fat-soluble vitamin supplementation is usually required in pancreatic insufficiency. Specially-formulated products for CF patients (ADEKs and Vitamax ) are usually sufficient to attain normal serum vitamin levels at a dose of 1 tablet daily for younger children and 2 tablets daily for teenagers and adults. Additional supplementation may be needed in uncontrolled malabsorption or for replacement of severe vitamin deficiency.5,15 Appetite stimulants such as cyproheptadine may be an option for promoting nutrition and weight gain, but efficacy has not been established. 

Formation of strictures, abscesses, fistulae, and obstructions in patients with CD is possible. Patients with CD may develop significant weight loss or nutritional deficiencies secondary to malabsorption of nutrients in the small intestine, or as a consequence of multiple small- or large-bowel resections. Common nutritional deficiencies encountered in IBD include vitamin B12, fat-soluble vitamins, zinc, folate, and iron. Malabsorption in children with CD may contribute to significant reductions in growth and development. 

No specific dietary restrictions are recommended for patients with IBD, but avoidance of high-residue foods in patients with strictures may help to prevent obstruction. Nutritional strategies in patients with long-standing IBD may include use of vitamin and mineral supplementation. Administration of vitamin B12, folic acid, fat-soluble vitamins, and iron may be needed to prevent or treat deficiencies. In severe cases, enteral or parenteral nutrition maybe needed to achieve adequate caloric intake. 

Water-soluble vitamins removed by hemodialysis (HD) contribute to malnutrition and vitamin deficiency syndromes. Patients receiving HD often require replacement of water-soluble vitamins to prevent adverse effects. The vitamins that may require replacement are ascorbic acid, thiamine, biotin, folic acid, riboflavin, and pyridoxine. Patients receiving HD should receive a multivitamin B complex with vitamin C supplement, but should not take supplements that include fat-soluble vitamins, such as vitamins A, E, or K, which can accumulate in patients with renal failure. 

Vitamin K is a fat-soluble vitamin cofactor for the activation of factors II, VII, IX, and X in the liver. Almost all neonates are vitamin K-deficient at as a result of (1) insignificant transplacental vitamin K crossover, (2) lack of colonization of the colon by vitamin K-producing bacteria, and (3) inadequate dietary vitamin K intake (especially in breast-fed infants because human milk contains less vitamin K than infant formula or cow s milk). Vitamin K-deficiency bleeding (VKDB) refers to bleeding attributable to vitamin K deficiency within first 6 months of life. It occurs in three general time frames early (0-24 hours), classic (1-7 days), and late (2-12 weeks). Early onset occurs rarely and usually is associated with maternal ingestion of anticonvulsants, rifampin, isoniazid, and warfarin. Classic vitamin K-dependent bleeding usually results from the lack of prophylactic vitamin K administration in... 

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. 

Consequences may include fluid and electrolyte imbalance and hypokalaemia, calorie deficit, deficiencies of haematinics (iron, folate and vitamin B12) and vitamin deficiencies particularly fat-soluble (A, D and K). 

Itching associated with retention of bile acids is ameliorated by treatment with the bile acid binding resin cholestyramine. Fat soluble vitamin (A, D and K) deficiency may require administration of supplements. Direct toxic effects of alcohol associated with dietary deficiency may require soluble B vitamin administration. 

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. 

Vitamin K is a fat soluble vitamin found primarily in leafy green vegetables. There are two normal forms exist, Kj found in food (called phytona-dione), found in human tissue (synthesized by intestinal bacteria) known as menaquinone. The synthetic compound is known as Kg. Synthetic analogues of natural vitamin also show biological activity. Most of the vitamin K is synthesized by intestinal microorganisms and there is a risk of vitamin K deficiency in new born infants. 

Vitamin A is necessary for growth and reproduction, resistance to infection, maintenance and differentiation of epithelial tissues, stability and integrity of membrane structures, and the process of vision. In terms of the last function, vitamin A is a component of rhodopsin or visual purple, a photosensitive pigment in the eye that is needed for vision in dim light. An early mild clinical symptom of vitamin A deficiency is night blindness a severe deficiency of this fat-soluble vitamin results in xerophthalmia, an eye condition leading to blindness. 

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