Anaemia megaloblastic

Pernicious anaemia, due to B12 deficiency, is one example of the class of anaemias known as megaloblastic anaemias, resulting from an abnormality in erythroblast maturation. 

Bellou A, Aimone-Gastin I, De Korwin JD, Bronowicki JP, Moneret-Vautrin A, Nicolas JP, et al Cobalamin deficiency with megaloblastic anaemia in one patient under long-term omeprazole therapy. J Intern Med 1996 240 161-164. 

C7. Cintron-Rivera, A. A., Folinic acid excretion in tropical sprue. Proc. Conf. Megaloblastic Anaemias and Intestinal Absorption, Puerto Rico, 1960. 

There are many causes of the clinical condition referred to as anaemia. One particular type, whose cause can be traced to a genuine metabolic defect is megaloblastic anaemia and is due to a deficiency of the vitamins B12 (cobalamin) and/or folate. These vitamins are required for normal cell division in all tissues, but the rapid production of red cells makes them more susceptible to deficiency. In megaloblastic anaemia the blood haemoglobin concentration falls the synthesis of haem is not impaired. Examination of the blood reveals the appearance of larger then normal cells called macrocytes and megaloblasts are found in the bone marrow. 

It is the role of jV5-methyl THF which is key to understanding the involvement of cobalamin in megaloblastic anaemia. The metabolic requirement for N-methyl THF is to maintain a supply of the amino acid methionine, the precursor of S-adenosyl methionine (SAM), which is required for a number of methylation reactions. The transfer of the methyl group from jV5-methyl THF to homocysteine is cobalamin-dependent, so in B12 deficiency states, the production of SAM is reduced. Furthermore, the reaction which brings about the formation of Ns-methyl THF from N5,N10-methylene THF is irreversible and controlled by feedback inhibition by SAM. Thus, if B12 is unavailable, SAM concentration falls and Ah -methyl THF accumulates and THF cannot be re-formed. The accumulation of AT-methyl THF is sometimes referred to as the methyl trap because a functional deficiency of folate is created. 

Deficiency of vitamin B12 interferes with production of red blood cells so that anaemia (megaloblastic anaemia) develops (Chapter 15). 

Vitamin Bn deficiency Deficiency, although rare, results in two serious problems megaloblastic anaemia (which is identical to that caused by folate deficiency) and a specific neuropathy called Bi2-associated neuropathy or cobalamin-deficiency-associated neuropathy (previously called, subacute combined degeneration of the cord). A normal healthy adult can survive more than a decade without dietary vitamin B12 without any signs of deficiency since it is synthesised by microorganisms in the colon and then absorbed. However, pernicious anaemia develops fairly rapidly in patients who have a defective vitamin B12 absorption system due to a lack of intrinsic factor. It results in death in 3 days. Minot and Murphy discovered that giving patients liver, which contains the intrinsic factor, and which is lightly cooked to avoid denaturation, cured the anaemia. For this discovery they were awarded the Nobel Prize in Medicine in 1934. 

The serious toxic effect is hyperkalemia. Triamterene produces relatively few other side effects which includes nausea, vomiting, dizziness etc. Megaloblastic anaemia has been reported in patients with alcoholic cirrhosis, which is probably due to inhibition of dihydrofolate reductase in patients with reduced folic acid intake. 

Pyrimethamine is a safe drug and cause only nausea, vomiting, skin reaction e.g. skin rash, pruritus and higher dose can cause megaloblastic anaemia and granulocytopenia. 

Megaloblastic anaemia (pernicious anaemia), demyelinating neurological lesions in the spinal cord infertility. 

Megaloblastic anaemia and gastrointestinal disturbances such as diarrhoea, distension and flatulence. Severe folate deficiency causes infertility or even sterility. 

Deficiency symptoms are glossitis, GIT disturbances, megaloblastic anaemia, subacute combined degeneration of spinal cord, peripheral neuritis, poor memory, mood changes and hallucinations. 

Deficiency symptoms The characteristic feature of folic acid deficiency is megaloblastic anaemia. Deficiency also leads to glossitis, enteritis, diarrhoea, general debility, weight loss and sterility. 

It is indicated in folic acid deficiency states e.g. megaloblastic anaemia, tropical... 

Folacin deficiency produces a megaloblastic anaemia not unlike that produced by vitamin B12 deficiency (120,122,126-130). This is a result of the interdependence of folacin and vitamin B,2 in at least two biochemical pathways in vivo. Folacin deficiency also appears to affect neurological function. 

Filioussi K, Bonovas S, Katsaros T. Should we screen diabetic patients using biguanides for megaloblastic anaemia Aust Fam Physician 2003 32 383 1. 

The well-known dose-related side effects include gingival hyperplasia (due to altered collagen metabolism), cerebellar-vestibular effects (nystagmus, vertigo, ataxia), behavioural changes (confusion, drowsiness, hallucinations), increased seizure frequency, gastrointestinal disturbances (nausea, anorexia), osteomalacia (due to reduced calcium absorption and increased vitamin D metabolism) and megaloblastic anaemia (due to reduced folate absorption). 

H18. Heaton, D., Another case of megaloblastic anaemia of infancy due to maternal pernicious anaemia. N. Engl. J. Med. 300, 202-203 (1979). 

Macrocytic anaemia is defined as one in which the red blood cells are larger than normal. Megaloblastic anaemia is the most common cause of macrocytic anaemia, caused by a deficiency of either vitamin B12 or fohc acid (or both). Deficiency in folate and/or vitamin B12 may result from either inadequate intake or malabsorption. Pernicious anaemia is caused by a lack of intrinsic factor, which is required to absorb vitamin B12 from food (see below). 

Macrocytic anaemia can be further divided into megaloblastic anaemia and non-megaloblastic macrocytic anaemia . Megaloblastic anaemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which results in restricted cell division of the progenitor cells. Non-megaloblastic macrocytic anaemias have different aetiologies (i.e. an unimpaired DNA globin synthesis). 

Adverse effects reported include anorexia, abdominal cramps, vomiting, ataxia, tremor, seizures and megaloblastic anaemia. 

Trichomoniases immunologicaNy normal patient. Pyrimethamine with sulfadiazine for chorioretinitis.and active toxoplasmosis in imimmodeficicnt patients foilnic add is used to counteract the inevitable megaloblastic anaemia. Alternatives include pyrimethamine with clindamycin or clarithromycin or azithromycin Spiramycin for primary toxoplasmosis in pregnant women. Expert advice is essential. Metronidazole or tinidazole is effective... 

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