22nd May 2023

Pathophysiology of iron metabolism

Iron is an essential component of the normal production and regulation of red blood cells, particularly due to its role in haemoglobin formation.

The average human has 3-6g of iron in their body, 80% of which is functional iron contained within haemoglobin and myoglobin. 20% is stored as ferritin and haemosiderin, mainly in the liver but also in the spleen and bone marrow. Only about 4mg of iron circulates in the plasma and is bound to a glycoprotein called transferrin. Free iron can be toxic to cells; in the presence of hydrogen peroxidase, free ferrous iron (Fe²⁺) is oxidised to ferric iron (Fe³⁺) creating reactive oxygen species which can cause DNA damage and cell death.

Dietary iron absorption occurs mostly in the duodenum and jejunum of the small bowel. Dietary iron can come from meat or plants. Iron from meat is termed ‘heme iron’ and 20% is absorbable. Iron from plants is ‘non-heme iron’ and only 2% is absorbable, with absorption rates worsened by co-ingestion with polyphenols (e.g. tea) or calcium, and increased with vitamin C.

Hepcidin is a peptide hormone synthesised in the liver. Hepcidin decreases intestinal iron absorption and recycling of iron from the reticuloendothelial cells. Therefore in the event of iron deficiency, hepcidin expression is decreased, resulting in increased intestinal iron absorption and recycling of iron from the reticuloendothelial cells.

Whilst the body can increase iron absorption in the event of iron deficiency, there is no regulatory pathway for iron excretion. Approximately 1mg of iron is excreted per day in men and post-menopausal women, and this increases to 2mg per day in menstruating women.