What is the primary mechanism leading to anemia in chronic disease?

The primary mechanism leading to anemia in chronic disease is the sequestration of iron. In chronic conditions such as infections, malignancies, or inflammatory diseases, the body alters its iron metabolism as a defensive response. The liver produces hepcidin, a hormone that regulates iron homeostasis by reducing iron absorption from the gut and inhibiting the release of iron from macrophages and hepatocytes.

This sequestration effectively limits the availability of iron for hemoglobin synthesis despite the body's potentially normal iron stores, contributing to a functional iron deficiency. In this way, even though there might be sufficient iron in the body, it is not accessible for red blood cell production, leading to anemia.

Underproduction of erythropoietin, increased red blood cell destruction, and bone marrow infiltration are not the primary mechanisms in anemia of chronic disease; while they may contribute to anemia in other contexts or conditions, they do not encapsulate the main process occurring in chronic disease states.