Vitamin B12 deficiency anemia

Macrocytic anemias Megaloblastic anemias Vitamin B12 deficiency Folic acid deficiency anemia Microcytic hypochromic anemias Iron-deficiency anemia Genetic anomaly Sickle cell anemia Thalassemia... 

Except for the rare patient with an undiagnosed pernicious anemia, vitamin B12 deficiency is unusual in pregnant women consuming a normal ... 

Pernicious Anemia Vitamin B12 deficiency can arise from a few rare genetic diseases that lead to low B12 levels despite a normal diet that includes B12-rich meat and dairy sources. These conditions cannot be treated with dietary B12 supplements. Explain. 

Breakdown of isoleucine, valine, threonine, and methionine results in the production of propionyl-CoA. Propionyl-CoA, in turn, is catabolized to succinyl-CoA via the intermediate methylmalonyl-CoA. Methylmalonyl-CoA is a compoimd of imusual interest to nutritional scientists. This compound accumulates in the cell during a vitamin B12 deficiency. Vitamin B12 deficiency is not a rare disease, as it appears in a common autoimmune disease called pernicious anemia. Vitamin B12 deficiency also occurs in strict vegetarians who avoid meat, fish, poultry, and dairy products. Methylmalonyl-CoA can also build up with rare genetic diseases that involve the production of defective, mutant forms of methylmalonyl-CoAmutase. Most of the methylmalonyl-CoAthat accumulates to abnormally high levels in the cell is hydrolyzed to methylmalonic acid (MMA), which leaves the cell for the bloodstream and eventual excretion in the urine. Some of the MMA is converted back to propionyl-CoA, resulting in the production and accumulation of propionic acid in the cell. The measurement of plasma and urinary MMA has proven to be a method of choice for the diagnosis of vitamin B12 deficiency, whether induced by pernicious anemia or by dietary deficiency. 

Macrocytic or magaloblastic anemia is caused by disturbances of DNA synthesis. It occurs, for example, in both folic acid and vitamin B12 deficiencies. Hematopoesis is slowed down due to reduced DNA synthesis and a reduced number of abnormally large (macrocytic) and hemaglobin-rich (hyperchromic) erythrocytes is released. 

It is recommended that women of childbearing age take 400 pg/d synthetic folic acid as a supplement in order to reduce the risk of neural tube defects of the embryo when they later become pregnant (periconcep-tional folic acid supplementation) [2]. When supplementing folic acid, it should be considered that this vitamin can mask the simultaneous presence of vitamin B12 deficiency. The typical symptom of vitamin B12 deficiency, megaloblastic (= macrocytic) anemia, will be reduced by high doses of folic acid, yet the nervous system will - in the long run - be irreversibly damaged (= funicular myelitis) when vitamin B12 is not provided as well. 

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. 

The underlying cause of anemia (e.g., blood loss iron, folic acid, or vitamin B12 deficiency or chronic disease) must be determined and used to guide therapy. As discussed previously, patients should be evaluated initially based on laboratory parameters to determine the etiology of the anemia (see Fig. 63-3). Subsequently, the appropriate pharmacologic treatment should be initiated based on the cause of anemia. 

Vitamin B12 (cyanocobalmin) administered both orally and parenterally is equally effective in treating anemia from vitamin B12 deficiency. However, use of parenteral cyanacobalamin is the most common method of vitamin B12 replacement because it may be more reliable and practical. Subcutaneous or intramuscular administration is appropriate. Vitamin B12 is absorbed completely following parenteral administration, whereas oral vitamin B12 is absorbed poorly via the GI tract. Furthermore, use of parenteral vitamin B12 to treat megaloblastic anemia may circumvent the need to perform a Schilling test to diagnose lack of intrinsic factor. 

Macrocytic anemias are characterized by increased mean corpuscular volume (110 to 140 fL). One of the earliest and most specific indications of macrocytic anemia is hypersegmented polymorphonuclear leukocytes on the peripheral blood smear. Vitamin B12 and folate concentrations can be measured to differentiate between the two deficiency anemias. A vitamin B12 value of less than 150 pg/mL, together with appropriate peripheral smear and clinical symptoms, is diagnostic of vitamin B12-deficiency anemia. A decreased RBC folate concentration (less than 150 ng/mL) appears to be a better indicator of folate-deficiency anemia than a decreased serum folate concentration (less than 3 ng/mL). 

Vitamin B12 is a very complex molecule that contains an atom of cobalt. Pernicious anemia is a vitamin B12 deficiency disease. Vitamin B12 is a... 

A frequent cause of vitamin B12 deficiency is atrophic gastritis leading to a lack of intrinsic factor. Besides megaloblastic anemia, damage to mucosal linings and degeneration of myelin sheaths with neurological sequelae will occur (pernicious anemia). 

Administration of FA can mask a vitamin B12 deficiency. Vitamin B12 is required for the conversion of methyltet-rahydro-FA to tetrahydro-FA, which is important for DNA synthesis (B). Inhibition of this reaction due to B12 deficiency can be compensated by increased FA intake. The anemia is readily corrected however, nerve degeneration progresses unchecked and its cause is made more difficult to diagnose by the absence of hematological changes. Indiscriminate use of FA-containing multivitamin preparations can, therefore, be harmful... 

Cobalamine can only be resorbed in the small intestine when the gastric mucosa secretes what is known as intrinsic factor—a glycoprotein that binds cobalamine (the extrinsic factor) and thereby protects it from degradation. In the blood, the vitamin is bound to a special protein known as trans-cobalamin. The liver is able to store vitamin Bi2 in amounts suf cient to last for several months. Vitamin B12 deficiency is usually due to an absence of intrinsic factor and the resulting resorption disturbance. This leads to a disturbance in blood formation known as pernicious anemia. 

The main causes for vitamin B12 deficiency are impaired absorption due to a lack of gastric intrinsic factor (e.g. pernicious anemia), ileal abnormalities, or it can be the result of a strictly vegetarian diet. 

Cyanocobalamin and the derivative hydroxo-cobalamin, given IM or deep subcutaneously, are indicated for treating vitamin B12 deficiency. Only in strict vegetarians oral preparations may be effective. Oral preparations with added intrinsic factor mostly are not reliably in patients with pernicious anemia. More than half the dose of cyanocobalamin injected is excreted in the urine within 48 hours and the therapeutic advantages of doses higher than 100 pg are questionable because of this rapid eiimination. As... 

Cyanocobalamin, or vitamin B12, is in small amounts required for red blood cell production and for the formation of nucleoproteins and proteins. It is also needed for the proper functioning of the nervous system. Folic acid supplements can correct the anemia associated with vitamin B12 deflciency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B12 deficiency. Vitamin B12 is only found in animal sources such as liver and other organs. Some vitamin B12 is obtained from fish, eggs and milk. Folic acid and cyanocobalamin have been discussed in more detail in Chapter 22. 

Severe cyanocobalamin (vitamin B12) deficiency results in pernicious anemia that is characterized by megaloblastic anemia and neuropathies. The symptoms of this deficiency can be masked by high intake of folate. Vitamin B12 is recycled by an effective enterohep-atic circulation and thus has a very long half-hfe. Absorption of vitamin B12 from the gastrointestinal tract requires the presence of gastric intrinsic factor. This factor binds to the vitamin, forming a complex that... 

Megaloblastic anemia is characterized by the appearance of large cells in the bone marrow and blood due to defective maturation of hematopoietic cells. Folic acid or vitamin B12 deficiency will result in this type of anemia. Malabsorption, impaired use, chronic infections, and drugs can lead to folic acid or vitamin B12 deficiency. 

Vitamin B12 is used to treat or prevent deficiency. The most characteristic clinical manifestation of vitamin B12 deficiency is megaloblastic, macrocytic anemia (Table 33-2), often with associated mild or moderate leukopenia or thrombocytopenia (or both), and a characteristic hypercellular bone marrow with an accumulation of megaloblastic erythroid and other precursor cells. The neurologic syndrome associated with vitamin Bi2 deficiency usually begins with paresthesias in... 

The most common causes of vitamin B12 deficiency are pernicious anemia, partial or total gastrectomy, and conditions that affect the distal ileum, such as malabsorption syndromes, inflammatory bowel disease, or small bowel resection. 

Folate deficiency results in a megaloblastic anemia that is microscopically indistinguishable from the anemia caused by vitamin B12 deficiency (see above). However, folate deficiency does not cause the characteristic neurologic syndrome seen in vitamin B12 deficiency. In patients with megaloblastic anemia, folate status is assessed with assays for serum... 

Folic acid deficiency, unlike vitamin B12 deficiency, is often caused by inadequate dietary intake of folates. Patients with alcohol dependence and patients with liver disease can develop folic acid deficiency because of poor diet and diminished hepatic storage of folates. Pregnant women and patients with hemolytic anemia have increased folate requirements and may become folic acid-deficient, especially if their diets are marginal. Evidence implicates maternal folic acid deficiency in the occurrence of fetal neural tube defects, eg, spina bifida. (See Folic Acid Supplementation A Public Health Dilemma.) Patients with malabsorption syndromes also frequently develop folic acid deficiency. Patients who require renal dialysis develop folic acid deficiency because folates are removed from the plasma during the dialysis procedure. 

Cyanocobalamin A cofactor required for essential enzymatic reactions that form tetrahydrofolate, convert homocysteine to methionine, and metabolize l-methylmalonyl-CoA Adequate supplies are required for amino acid and fatty acid metabolism, and DNA synthesis Treatment of vitamin B12 deficiency, which manifests as megaloblastic anemia and is the basis of pernicious anemia Parenteral vitamin B12 is required for pernicious anemia and other malabsorption syndromes Toxicity No toxicity associated with excess vitamin B12... 

The effects of cobalamin deficiency are most pronounced in rapidy dividing cells, such as the erythropoietic tissue of bone marrow and the mucosal cells of the intestine. Such tissues need both Die N5-N10-methylene and N10-formyl forms of tetrahydrofolate for Ihe synthesis of nucleotides required for DNA replication (see pp. 291, 301). However, in vitamin B12 deficiency, the N5-methyl form of tetrahydrofolate is not efficiently used. Because the methylated fonn cannot be converted directly to other forms of tetrahydrofolate, tie Ns-methyl form accumulates, whereas the levels of the other forms decrease. Thus, cobalamin deficiency is hypothesized to lead to a deficiency of the tetrahydrofolate forms needed in purine and thymine synthesis, resulting in the symptoms of megaloblastic anemia. 

Megaloblastic anemia Neural tube delects Anemia Birth delects None A n.w Administration of high levels of folate can I mask vitamin B12 deficiency. 

Intramuscular injection of as little as 3-6 pg of crystalline vitamin B12 is sufficient to bring about a remission of pernicious anemia and 1 pg daily provides a suitable maintenance dose (often administered as hydroxocobalamin injected once every 2 weeks). For a normal person a dietary intake of 2-5 pg / day is adequate. There is rarely any difficulty in meeting this requirement from ordinary diets. Vitamin B12 has the distinction of being synthesized only by bacteria, and plants apparently contain none. Consequently, strict vegetarians sometimes have symptoms of vitamin B12 deficiency. 

Fujita H, Narita T, Yoshioka N, Hosoba M, Ito S. A case of megaloblastic anemia due to vitamin B12 deficiency precipitated in a totally gastrectomized type II diabetic patient following the introduction of metformin therapy. Endocr J 2003 50 483 1. 

Folic acid Men women 400 MQ/d Coenzyme in the metabolism of nucleic acids and amino acids prevents megaloblastic anemia Adverse effects have not been documented, but high doses may mask neurological complications in people with Vitamin B12 deficiency... 

Pernicious anemia associated with gastric atrophy is the most common cause of clinically apparent vitamin B12 deficiency in North American and European populations. 

Megaloblastic anemia is a classical symptom of vitamin B12 deficiency. However, recent studies have demonstrated that subjects with vitamin B12 deficiency often lack anemia and macrocytosis, and that there is a dissociation between the neurological and hematological manifestations. 

Gastrointestinal signs and symptoms of vitamin B12 deficiency occur in 26% of cases. These include sore tongue, stomatitis, mucosal ulceration, appetite loss, flatulence, and constipation or diarrhea. Appetite loss, excess gas, and diarrhea are probably related to the underlying gastric disorder (i.e., gastric atrophy) in pernicious anemia. Gastrointestinal symptoms may occur in the absence of symptomatic anemia or macrocytosis. 

Hematological indices are the simplest way to diagnose megaloblastic anemia, a typical symptom of vitamin B12 deficiency. 

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