Anaemia of chronic disease: hepcidin and functional iron deficiency
In anaemia of chronic disease, also called anaemia of inflammation, hepcidin (the hormone that controls iron release) makes iron present but unavailable to the bone marrow.
Remember
Cytokines (chemical messengers from immune cells) raise hepcidin, so iron is unavailable even though the body's stores are normal: the deficiency is functional.
Memory aid
hepcidin locks the iron in the warehouse while the factory runs out of stock
The warehouse stands for the iron stores, which are normal, and the factory for the marrow, which runs short of iron.
Anaemia of chronic disease is also called anaemia of inflammation, and it is the commonest anaemia in hospital patients. It complicates chronic inflammatory conditions (rheumatoid arthritis is an example), chronic infections such as tuberculosis, and cancer.
During inflammation, immune cells release cytokines, which are chemical messengers (interleukin-6 is one), and these tell the liver to make more hepcidin, the hormone that controls iron release.
Hepcidin has two effects. In the gut it removes ferroportin (the channel that lets iron out of cells), which reduces absorption of iron. In macrophages (the scavenger cells that store iron and recycle it from old red cells) it traps the iron they hold.
This is a functional iron deficiency. Iron stores are normal or even high, but the iron is locked away and out of reach of the marrow, so developing red cells run short of it. An absolute iron deficiency, as from a poor diet, is different, because the stores are empty.
There are other contributors too. Cytokines also reduce erythropoietin (EPO), which is made by the kidney and stimulates the bone marrow, and they make the marrow less responsive to what is left, so erythropoiesis (the making of red blood cells) is inhibited. Inflammation also raises macrophage activity, which shortens red cell life. These factors together cause the anaemia.
Early on the red cells are normocytic (normal-sized), and they may become microcytic (small) later. Treatment is to control the underlying disease.
In chronic kidney disease, where the kidneys are failing, persistent inflammation raises hepcidin and the failing kidneys also clear less of it, so its level rises further. Iron taken by mouth is then poorly absorbed, and iron often has to be given intravenously. A raised ferritin (the form in which iron is stored) does not exclude a coexisting absolute iron deficiency.
Key facts
- Trigger
- Cytokines such as interleukin-6 tell the liver to make more hepcidin.
- Iron stores
- Stores are normal or high, and ferritin is normal or raised, yet the iron is locked away from the bone marrow.
- Other contributors
- Cytokines reduce erythropoietin and blunt the marrow's response to it, and inflammation shortens red cell life.
- Red cell size
- The cells are normocytic early on and may become microcytic later.
- Chronic kidney disease
- Inflammation raises hepcidin and failing kidneys also clear less of it, so iron by mouth is poorly absorbed and iron often has to be given intravenously.
- Erythropoietin in kidney disease
- Erythropoietin deficiency is the main cause of the anaemia in chronic kidney disease, and it is treated with EPO supplements, whereas hepcidin explains why iron by mouth is poorly absorbed.
- Treatment of anaemia of inflammation
- Control of the underlying disease is the treatment.
Exam traps
- Poor dietary iron does not explain this anaemia, because a poor diet causes an absolute iron deficiency with empty stores, whereas here the stores are normal but inaccessible.
- Reduced erythropoietin contributes to the anaemia, yet it does not create the functional iron deficiency, because hepcidin holding iron back does that.
- Chronic gastrointestinal bleeding causes true loss of iron and an absolute deficiency with low ferritin, whereas here the iron is still in the body but locked away.
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