The anemia seen in anemia of chronic disease is characterized by low serum iron levels. What contributes to these low levels?

In anemia of chronic disease, the underlying pathophysiology involves the role of hepcidin, a key regulator of iron metabolism. Hepcidin is a liver-produced hormone that controls iron homeostasis by inhibiting iron absorption from the intestines and the release of iron from macrophages and liver stores. In the context of chronic inflammation or disease, levels of hepcidin increase, leading to reduced serum iron levels and subsequently affecting the ability of erythropoiesis to produce adequate red blood cells.

As inflammation occurs, pro-inflammatory cytokines stimulate hepcidin production, which causes the sequestration of iron in storage sites (such as macrophages) and decreases its availability in the serum. This results in a relative deficiency of iron for hemoglobin synthesis, even though the total body iron stores may be normal or even elevated.

Thus, the increased hepcidin levels associated with chronic disease directly contribute to the low serum iron levels observed in this type of anemia, providing a clear link between chronic inflammation and iron metabolism disruption.