Iron may be considered a trace element comparable with zinc if the two-thirds present as haemoglobin is discounted. The recommended daily intake is between 10 and 15 mg per day. Of this, 1-2 mg is absorbed, closely regulated by mechanisms which are still not fully understood. The main transport protein is transferrin, synthesised in the liver at a rate inversely proportional to body stores. Transferrin can bind two molecules of iron and is normally about one third saturated. Ferritin is an iron-storage protein found in most cells of the body, particularly the liver, and which provides a readily available reserve. Haemosiderin is an insoluble aggregate of ferritin deposited in many tissues from which iron is less readily available. Iron loss via the usual excretory routes is minute and apart from loss of blood, desquamation of intestinal and other cells is the only means of depletion.
Iron deficiency is one of the most prevalent disorders, even in developed countries. It occurs most commonly as a result of dietary deficiency in children and through chronic blood loss in adults. Once iron stores are depleted, a hypochromic microcytic anaemia is seen on blood films, with other symptoms including intellectual changes such as reduced mental concentration and effects on the immune system.
Poisoning from inorganic iron tablets was the most common cause of childhood poisoning in this country, but is less so since supplementation during pregnancy is no longer routine. In acute poisoning there are four phases; in the first 6 hours there is vomiting, abdominal pain, diarrhoea, convulsions and shock, followed by a brief recovery phase up to 24 h when further severe symptoms can develop, including coma, convulsions and renal, cardiovascular and hepatic failure. Gastrointestinal strictures may develop in a final phase, after about 6 weeks. Chronic iron overload may arise primarily in genetic haemochromatosis in which there there is excessive iron absorption, or secondary to excessive intake from transfusions (transfusional siderosis), or to alcoholic liver cirrhosis. Treatment of acute poisoning is by infusion of desferrioxamine into the intestine to prevent further absorption, and if poisoning is severe, by giving desferrioxamine intramuscularly. Transfusional siderosis is treated by subcutaneous infusion of desferrioxamine. Some new oral chelating agents are being tried, but appear to chelate other elements e.g. zinc. The treatment for genetic haemochromatosis consists of repeated venesection until iron stores as reflected by the serum ferritin are not excessive. Neonatal haemochromatosis is a rare, but particularly severe iron overload, with an obscure aetiology unrelated to that in adults and which is often fatal. Vigorous therapy with desferrioxamine and antioxidants has achieved limited success.
A low serum ferritin is probably the best biochemical indicator of iron deficiency.
Serum iron and transferrin concentrations alter in many physiological conditions and are difficult to interpret. Measurement of transferrin receptors in serum, which rise in response to deficiency looks promising and is available in specialised centres. The zinc protoporphyrin concentration in blood is also a sensitive indication of iron deficiency anaemia. In acute iron poisoning, a serum iron concentration above 90 µmol/L (5 mg/L), 2-6 hours post ingestion, indicates severe poisoning. After this time, much iron will be intracellular and measurement is of less value. Once desferrioxamine has been given serum measurement is not useful because both chelated and unchelated species are measured and urine is used for monitoring treatment. In addition there are interferences with some of the colorimetric assay procedures and alternative techniques, eg atomic absorption, should be employed for any measurement which have to be made. In iron overload, saturation of transferrin increases; this can be assessed from the total iron binding capacity and serum iron, as percent saturation; values above 60% suggest haemochromatosis. The transferrin index is a newer approach to the same parameter, in which serum is related to directly measured transferrin; values above 1 correspond with increased saturation.
Demonstration of iron histologically or total iron measurement in a liver biopsy are more reliable if the diagnosis of genetic haemochromatosis is uncertain. As iron accumulates in the liver with age, re-calculation of the concentration to give the ‘hepatic iron index’ (liver Fe in µmol g-1/ age in years) is a useful approach. Values greater than 2 are found in genetic haemochromatosis. Identification of the major mutation is possible in some centres.
Measurements of iron in urine during chelation therapy are helpful in haemochromatosis to optimise the dose and evaluate losses of other elements. Diagnosis of neonatal haemochromatosis is more difficult, as transferrin may be low, saturation increased and ferritin raised during the first month of life, and rests on demonstration of extrahepatic and hepatic iron deposition.
Liver Biopsies (or other tissues) for Iron Determination.
Protocol for collection and transport is given in the COPPER – yellow pages.
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Summers KM, Halliday JW, Powell LW. Identification of homozygous hemochromatosis subjects by measurement of hepatic iron index. Hepatology 1990; 12: 20-5
Punnonen K, Irjala K, Rajamaki A. Iron-deficiency anemia is associated with high concentrations of transferrin receptor in serum. Clin Chem 1994; 40: 774-6