Vitamin pernicious anemia

Naturally occurring compounds with carbon-metal bonds are very rare The best example of such an organometallic compound is coenzyme Bi2 which has a carbon-cobalt ct bond (Figure 14 4) Pernicious anemia results from a coenzyme B12 deficiency and can be treated by adding sources of cobalt to the diet One source of cobalt IS vitamin B12 a compound structurally related to but not identical with coen zyme B12... 

Fohc acid is safe, even at levels of daily oral supplementation up to 5—10 mg (97). Gastrointestinal upset and an altered sleep pattern have been reported at 15 mg/day (98). A high intake of foHc acid can mask the clinical signs of pernicious anemia which results from vitamin deficiency and recurrence of epilepsy in epileptics treated with dmgs with antifolate activity (99). The acute toxicity (LD q) is approximately 500 and 600 mg per kg body weight for rats and mice, respectively (100). 

In 1929, Castie (7) tied the work of Combe and Addison with that of Whipple, Miaot, and Murphy by ptoposiag that both an extrinsic factor and an intrinsic factor ate iavolved ia the coatrol of pernicious anemia. The extrinsic factor, from food, is vitamin 2- Th intrinsic factor is a specific B22-biading protein secreted by the stomach. This protein is requited for vitamin B 2 absorption. 

Parallel to the activities in the treatment of pernicious anemia were observations in the 1930s that most farm animals had a requirement for an unknown factor beyond the vitamins then known. The lack of this factor became apparent, eg, when chicks or pigs fed a diet with only vegetable protein evidenced slow growth rate and high mortahty. It became apparent that the requited factor, termed animal protein factor, was present in animal sources such as meat and tissue extracts, milk whey, and cow manure. Subsequent to its isolation, it was rapidly shown that vitamin B 2 is the same as animal protein factor. 

Smaller pool sizes with normal semm B 2 levels may be maintained with dietary intakes below 1 pg. However, more substantial pool sizes are considered advantageous as protection against the development of pernicious anemia, which may occur in advanced age achlorhydria becomes more common after age 60, resulting in compromised absorption of vitamin 2-... 

Cobalt is one of twenty-seven known elements essential to humans (28) (see Mineral NUTRIENTS). It is an integral part of the cyanocobalamin [68-19-9] molecule, ie, vitamin B 2> only documented biochemically active cobalt component in humans (29,30) (see Vitamins, VITAMIN Vitamin B 2 is not synthesized by animals or higher plants, rather the primary source is bacterial flora in the digestive system of sheep and cattle (8). Except for humans, nonmminants do not appear to requite cobalt. Humans have between 2 and 5 mg of vitamin B22, and deficiency results in the development of pernicious anemia. The wasting disease in sheep and cattle is known as bush sickness in New Zealand, salt sickness in Florida, pine sickness in Scotland, and coast disease in AustraUa. These are essentially the same symptomatically, and are caused by cobalt deficiency. Symptoms include initial lack of appetite followed by scaliness of skin, lack of coordination, loss of flesh, pale mucous membranes, and retarded growth. The total laboratory synthesis of vitamin B 2 was completed in 65—70 steps over a period of eleven years (31). The complex stmcture was reported by Dorothy Crowfoot-Hodgkin in 1961 (32) for which she was awarded a Nobel prize in 1964. 

The nutritional requirement for vitamin Bjg is low. Adult humans require only about 3 micrograms per day, an amount easily acquired with normal eating habits. However, because plants do not synthesize vitamin Bjg, pernicious anemia symptoms are sometimes observed in strict vegetarians. 

Pernicious anemia Anemia resulting from lack of secretions by the gastric mucosa of the intrinsic fador essential to the formation of RBCS and the absorption of vitamin B ... 

Vitamin B12 is essential to growth, cell reproduction, the manufacture of myelin (which surrounds some nerve fibers), and blood cell manufacture. The intrinsic factor, which is produced by cells in the stomach, is necessary for the absorption of vitamin B12 in the intestine A deficiency of the intrinsic factor results in abnormal formation of erythrocytes because of the body s failure to absorb vitamin B12, a necessary component for blood cell formation. The resulting anemia is a type of megaloblastic anemia called pernicious anemia. 

Vitamin B12 is also used to perform the Schilling test, which is used to diagnose pernicious anemia. 

Pernicious anemia must be diagnosed and treated as soon as possbte because vitamin B12 deficiency that is allowed to progress for more than 3 months may result in degenerative lesions of the spinal cord. 

VITAMIN S12. Fhtients with pernicious anemia are treated with vitamin B12 by tiie parenteral route (IM) weekly stabilized. The parenteral route is used because tiie vitamin is ineffective orally due to the absence of tiie intrinsic factor in tiie stomach, which is necessary for utilization of vitamin B12. After stabilization, maintenance (usually monthly) injections are necessary for life... 

When teaching a patient about the use of vitamin B12 for pernicious anemia, the nurse would include which of the following statements ... 

A person with pernicious anemia lacks intrinsic factor, a compound required for the absorption of vitamin B12 and its storage in the liver. The diagnosis is confirmed... 

The water-soluble vitamins comprise the B complex and vitamin C and function as enzyme cofactors. Fofic acid acts as a carrier of one-carbon units. Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states. Nevertheless, specific syndromes are characteristic of deficiencies of individual vitamins, eg, beriberi (thiamin) cheilosis, glossitis, seborrhea (riboflavin) pellagra (niacin) peripheral neuritis (pyridoxine) megaloblastic anemia, methyhnalonic aciduria, and pernicious anemia (vitamin Bjj) and megaloblastic anemia (folic acid). Vitamin C deficiency leads to scurvy. 

Pernicious anemia arises when vitamin B,2 deficiency blocks the metabohsm of folic acid, leading to functional folate deficiency. This impairs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The commonest cause of pernicious anemia is failure of the absorption of vitamin B,2 rather than dietary deficiency. This can be due to failure of intrinsic factor secretion caused by autoimmune disease of parietal cells or to generation of anti-intrinsic factor antibodies. 

Twenty-two years later the isolation of the anti-pernicious anemia factor" was announced independently by Smith (5) and Riches (6). Seven years of chemical studies identified 5,6-dimethylbenzimidazole (7), D-ribose (5) and amino-propanol (9) as components of the anti-pemicious anemia factor", but the tetrapyrroline ring structure containing Co(III) awaited the X-ray crystallographic data on the cyano-derivative by Hodgkin and White (10—15). Once the structure of the antipemicious anemia factor was determined it was called Vitamin B12 (cyanocobal-amin). The recommendations of a number of commissions forms the basis of the present system of nomenclature for this molecule and these are presented in Fig. 1. 

Intrinsic factor is produced by the parietal cells. Within the stomach, it combines with vitamin Bu to form a complex necessary for absorption of this vitamin in the ileum of the small intestine. Vitamin B12 is an essential factor in the formation of red blood cells. Individuals unable to produce intrinsic factor cannot absorb vitamin B12 and red blood cell production is impaired. This condition, referred to as Pernicious anemia, occurs as a result of an autoimmune disorder involving destruction of parietal cells. 

Much of the toxicological interest in cyanide relating to mammals has focused on its rapid lethal action. However, its most widely distributed toxicologic problems are due to its toxicity from dietary, industrial, and environmental factors (Way 1981, 1984 Gee 1987 Marrs and Ballantyne 1987 Eisler 1991). Chronic exposure to cyanide is correlated with specific human diseases Nigerian nutritional neuropathy, Leber s optical atrophy, retrobulbar neuritis, pernicious anemia, tobacco amblyopia, cretinism, and ataxic tropical neuropathy (Towill etal. 1978 Way 1981 Sprine etal. 1982 Beminger et al. 1989 Ukhun and Dibie 1989). The effects of chronic cyanide intoxication are confounded by various nutritional factors, such as dietary deficiencies of sulfur-containing amino acids, proteins, and water-soluble vitamins (Way 1981). 

Oral vitamin B12 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin B12 absorption pathway is independent of intrinsic factor. Oral cobalamin is initiated at 1 to 2 mg daily for 1 to 2 weeks, followed by 1 mg daily. 

The chemistry, metabolism, and clinical importance of folic acid have been the subject of many excellent reviews (A7, Gil, H14, H20, Rl). Folic acid deficiency leads to a macrocytic anemia and leucopenia. These symptoms are due to inadequate synthesis of nucleic acid. The synthesis of purine bases and of thymine, required for nucleic acid synthesis, is impaired in folic acid deficiency. Detection of folic acid activity in biologic fluids and tissues is of the utmost importance it distinguishes between the various anemias, e.g., those due to vitamin Bi2 or folic acid deficiency. Because morphology of the abnormal red cell does not help in diagnosing vitamin deficiency, one must rely on assay methods for differential diagnosis. Treatment of pernicious anemia with folic acid has led to subacute combined degeneration of the spinal cord despite... 

There is, moreover, the field of hypervitaminoses, which has been explored for the fat-soluble vitamins, but hardly touched in the water-soluble vitamins. The production of combined system disease by folic acid therapy of pernicious anemia belongs to this group, but many more instances wait to be recognized. The indiscriminate use of polyvitamin preparations by poorly informed clinicians is bound to mask such states and to delay their discovery. Also, the use of flushing doses of vitamins in diagnostic tests may cause acute hypervitaminoses. 

Permonosulfuric acid (PMS), 26 392 Permselective diaphragms, 9 656-657 Permutations, in Latin hypercube sampling, 26 1009-1010 Pernicious anemia, vitamin B12 and, 25 804 Perovskite carbides, 4 692 Perovskite ferrites, 22 55, 56t, 57 Perovskite material, mercury-base superconducting, 23 801 Perovskites, 5 590-591 22 94-96, 97 ... 

The most likely reason for cobalamin deficiency is pernicious anemia (failure to absorb vitamin B 2 in the absence of intrinsic factor from parietal cells). Vitamin Bjj absorption also decreases with aging and in individuals with chronic pancreatitis. Less common reasons for Bjj deficiency include a long-term completely vegetarian diet (plants don t contain vitamin Bjj) and infection with Diphyllobothrium latum, a parasite found in raw fish. Excess vitamin B,2 is stored in the body, so deficiencies develop slowly. 

Cobalt occurs in vitamin B12. This vitamin is very complex and is required for some exotic reactions of metabolism. A deficiency of vitamin B12 results in pernicious anemia. More about this vitamin follows in chapter 15. 

Nothing about vitamin B12 has come easily. Vitamin B12 activity was initially discovered in 1926 when it was observed that liver contains a nutrient factor required for the cure of pernicious anemia. This observation was a boon to victims of... 

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