Vitamin B12 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. 

Die neurological disorder associated with severe vitamin B12 deficiency is termed funicular myelitis. Vitamin B12 deficiency leads to disturbed choline-, phospholipid-, and nucleic-acid synthesis, resulting in spinal marrow damages. Disturbed myelin synthesis finally causes irreversible neurological failure. In addition, there are psychiatric disturbances (disturbed memory, apathy). 

When funicular myelitis occurs in advanced stages of vitamin B12 deficiency, patients are given 250 pg vitamin B12/d during the first 2 weeks of treatment to alleviate the symptoms and to replenish the stores. If the deficiency has been caused by disturbed vitamin B12 absoiption, lifelong monthly injections of 100 pg vitamin B12 are indicated [2]. 

Vitamin B12 (cyanocobalamin) is used to treat a vitamin B12 deficiency. A vitamin B12 deficiency may be seen in ... 

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. 

Tests to exclude possible causes of dementia include a depression screen, vitamin B12 deficiency, thyroid function tests [thyroid-stimulating hormone (TSH) and free triiodothyronine and thyroxine], complete blood cell count, and chemistry panel.21... 

Addison s disease, pheochromocytoma, hyperadrenocorticism, hyponatremia, hyperkalemia, vitamin B12 deficiency... 

Vitamin B12 1 80-600 pg/mL (1 33-738 pmol/L) Used to determine vitamin B12 deficiency. 

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. 

When treating folic acid deficiency, an initial daily dose of 1 mg/day by mouth typically is effective. Absorption of folic acid generally is rapid and complete. However, patients with malabsorption syndromes may require larger doses (up to 5 mg/day). Similar to vitamin B12 deficiency, resolution of symptoms and reticulocytosis is prompt, occurring within days of commencing therapy. Hgb will start to rise after 2 weeks of therapy and may take from 2 to 4 months to resolve the deficiency completely. Afterwards, if the underlying deficiency is corrected, folic acid replacement can be discontinued. However, in cases where folic acid is consumed rapidly or absorbed poorly, chronic replacement may be required. 

In patients with vitamin B12 deficiency, methylmalonic acid and homocysteine levels may be high. Monitor for resolution of neurologic symptoms (i.e., confusion and paresthesias), if applicable, and Hgb levels periodically until the levels normalize. 

Bradford GS, Taylor CT Omeprazole and vitamin B12 deficiency. Ann Pharmacother 1999 33 641-643. 

The enzyme mediating remethylation, 5-methyltetrahy-drofolate-betaine methyltransferase (Fig. 40-4 reaction 4), utilizes methylcobalamin as a cofactor. The kinetics of the reaction favor remethylation. Faulty remethylation can occur secondary to (1) dietary factors, e.g. vitamin B12 deficiency (2) a congenital absence of the apoenzyme (3) a congenital inability to convert folate or B12 to the methylated, metabolically active form (see below) or (4) the presence of a metabolic inhibitor, e.g. an antifolate agent that is used in an antineoplastic regimen. 

PPIs are usually well tolerated. Potential adverse effects include headache, dizziness, somnolence, diarrhea, constipation, nausea, and vitamin B12 deficiency. All PPIs can decrease the absorption of drugs such as ketoco-nazole or itraconazole that require an acidic environment for absorption. Other drug interactions vary with each agent. 

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

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). 

H5. Heinrich, H. C., Biochemical principles of diagnosis and therapy of vitamin B12 deficiencies (B12 hypo- and avitaminoses) of man and of domestic animals. III. The vitamin B12 picture in serums of domestic animals. Deut. tierdrztl. Wochschr. 12, 179-181 (1954). 

Persons with a metabolic disturbance in the conversion of cyanide to thiocyanate may be at greater risk. A defect in the rhodanese system and vitamin B12 deficiency have been associated with tobacco amblyopia and Leber s hereditary optic atrophy in persons exposed to cyanide in tobacco smoke (Wilson 1983). 

Clearly this patient has both clinical and haematological symptoms of severe anaemia. The cause is too few red cells low RBC count and PCV but the erythrocytes which are present contain a higher than usual concentration of haemoglobin (MCHC result). Iron deficiency and vitamin B12 deficiency can be ruled out by the high serum ferritin and normal MCV results respectively. The negative HbS screen rules out sickle cell anaemia which is fairly common in Africans. 

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... 

Table 10.4 lists the various medications that can be stopped and medical illnesses that can be treated to reverse dementia. In some cases, such as hypothyroidism or dehydration, the reversal can be complete. More often, the dementia is only partially reversed or its further progression is halted. Examples of these partial improvements include normal pressure hydrocephalus and vitamin B12 deficiency. 

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... 

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