Haematinics I: Patho-Physiological and Clinical Aspects

Summary

Iron plays an important role in certain basic physiological processes, particularly the synthesis of haemoglobin and myoglobin. Dietary sources rich in iron are meat, eggs and leafy vegetables. The average human has approximately 4 g of iron, and absorbs about 10 % of the food iron ingested. Increased absorption occurs when iron stores are diminished, and when erythropoiesis is active. For adult males, 1 mg of iron absorbed each day is probably sufficient, but for adult females, 2 mg per day are required, and for pregnant females, 3 to 3.5 mg per day are necessary to meet the increased demands.

Iron deficiency is a common disease in modern society, and is likely to remain so. It is not a definitive diagnosis, but a symptom complex, and in every instance where iron deficiency is demonstrated, a cause must be sought and identified with confidence before treatment is commenced. An adequate history and physical examination are important in reaching this diagnosis; aided by a full blood picture, and, in most instances, a determination of the serum iron level and latent iron binding capacity. A careful menstrual history in iron-deficient women is essential.

Vitamin B₁₂ is synthesised in higher animals indirectly from bacterial sources, and for man to have an adequate vitamin B₁₂ intake, some form of dietary meat and animal products is essential. Hydroxocobalamin is a more efficient therapeutic agent than cyanocobalamin, and should be given by injection. The daily requirement for vitamin B₁₂ for the healthy adult is between 2 and 5 μg, representing up to 70 % of the dietary vitamin. Smaller doses will produce a therapeutic response in deficient states, but will not sustain health. The metabolism of vitamin B₁₂ within the body is complex, and is not as clearly understood as the body’s handling of iron.

In the investigation of a patient with megaloblastic anaemia, the nature, extent and cause of the underlying disorder must be assessed — megaloblastic anaemia is but a symptom, and a definitive diagnosis is required before intelligent treatment is possible. Again, history and physical examination are essential elements in reaching the diagnosis. Peripheral blood cell counts and examination of cell morphology in the peripheral blood and bone marrow will assist the diagnosis. Vitamin B₁₂ deficiency may be diagnosed when low vitamin B₁₂ serum levels have been demonstrated, when methylmalonic acid excretion in the urine is low, and when an optimum response to a standard dose of vitamin B₁₂ is achieved. When vitamin B₁₂ deficiency has been diagnosed, gastric causes should be sought in the first instance, usually by gastroscopy, testing for histamine-fast achlorhydria, and by demonstrating the failure to absorb a radioactive tracer dose of vitamin B₁₂, which is absorbed when the defect is corrected by the addition of intrinsic factor. If a gastric cause cannot be implicated, an intestinal cause of failure of absorption is likely. Dietary inadequacy leading to vitamin B₁₂ deficiency is unusual, except in persons who are entirely vegetarian.

The body’s folates are obtained from plant and animal foodstuffs, particularly liver and yeast, and they exist as polyglutamates of tetrahydrofolate. The dietary requirement (free folate) is between 150 and 200 μg per day.

When a megaloblastic anaemia is demonstrated in the presence of pregnancy, during anticonvulsant therapy for epilepsy, or in the chronic alcoholic, folate deficiency is commonly the underlying cause. However, folate deficiency may be due to inadequate dietary intake, intestinal malabsorption, or an increased requirement due to cellular turnover, and in a number of cases, more than one of these factors may be involved. The diagnosis of folate deficiency requires the exclusion of vitamin B₁₂ deficiency, demonstration of low serum folate, and possibly, a low red cell folate. Here again, the haematological response to a therapeutic dose of folate (200 μg daily, preferably by injection) is an important diagnostic feature.