Haemochromatosis and Iron Storage Disorders

Abstract

The total body iron in an adult man is between 4 and 5 g. Approximately two-thirds of this is contained in circulating haemoglobin and. to a much lesser extent, the myoglobin and iron containing enzymes, such as mitochondrial cytochromes. The remainder, approximately 1.5 g, is stored in the liver, which is also the site of synthesis of the main protein involved in iron transport, apotransferrin. In physiological quantities, iron is principally in the form of ferritin, a complex molecule composed of a shell of protein with a core containing micellar ionic iron, dispersed through the cytoplasm and not normally visible by light microscopy. As the quantity of iron increases, ferritin molecules aggregate together and become incorporated into lysosomes. These eventually will become visible as golden-brown granules of haemosiderin, often grouped in the pericanalicular portion of the liver cell. The iron is now demonstrable histochemically by Perl’s Prussian blue reaction which stains iron bright blue (care must be exercised with acid fixatives such as Zenker’s, which may render a proportion of the tissue iron unstainable). In contrast to copper-staining in Wilson’s disease, there is a good correlation between the amount of iron as assessed on an arbitrary four-point scale and total hepatic iron as measured chemically^1,2. Most storage iron is found in parenchymal cells, and is derived from transferrin and from free haemoglobin. Kupffer cell iron is largely derived from the breakdown of red cells and is usually rapidly returned to the bone marrow.