Iron Physiology
April 30th, 2020
Overview
Iron is an important mineral that plays a role in multiple physiologic processes including oxygenation, protein synthesis and cellular respiration. The metabolism of iron is outlined below.
Roles of Iron
- Oxygen transport (as haemoglobin)
- Muscle oxygenation (as myoglobin)
- Synthesis of DNA, RNA and proteins
- Cellular respiration (as cytochromes)
- Immune function
- Myelin sheath formation
Absorption
Most iron absorption occurs in the duodenum, from haem and ionic iron sources. All iron is converted to the ferrous (Fe2+) form prior to absorption through DMT1 channels. From the intestinal epithelium, iron is transferred into the circulation via ferroportin 1.
Iron Transport
Once in plasma, iron is oxidised by hephaestin and then bound to transferrin, which transports iron in the blood. Transferrin enters cells (mainly red blood cells, hepatic and immune cells) via receptor-mediated endocytosis through binding to transferrin receptors (TfR).
RBC Lifecycle
Most serum iron is transported into erythroid cells, where it is incorporated into haem molecules that combine with globular proteins to form haemoglobin.
Once red cells are lysed, the iron is salvaged from the haem molecule by macrophages and is reentered into the circulation.
Storage
Iron is mainly stored within macrophages and the liver, though a small amount may also be stored in cardiomyocytes. Iron is mainly stored as ferritin, though a small amount is also stored as haemosiderin.
Regulation
Hepcidin is the major iron regulatory protein. It regulates the intestinal absorption (by ferroportin 1), the recycling (by macrophages) and hepatic storage of iron.
Hepcidin levels are modulated by many factors including serum iron levels, anaemia, hypoxia and inflammation.
Overexpression of hepcidin in the setting of (IL-6 mediated) inflammation is suspected to be the driving process in anaemia of chronic disease.
Excretion
There is no mechanism by which iron is excreted, though 1-2mg of iron is lost daily due to enteric desquamation or minor blood loss.
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