Figure 1. Effective and Ineffective Erythropoiesis.

(A) Baseline erythropoiesis generates red blood cells to replace old and damaged cells. Physiological levels of ERFE and hepcidin at baseline provide sufficient iron for steady state production of erythrocytes. (B) When the kidneys sense cellular hypoxia, they secrete EPO which stimulates erythropoiesis and the production of ERFE. As ERFE suppresses hepcidin, iron is mobilized from stores for use by the expanded population of maturing red blood cells. (C) In β-thalassemia, most erythroblasts do not generate mature erythrocytes, causing anemia and tissue hypoxia. This results in high levels of EPO and ERFE, chronically low hepcidin, and iron overload. (D) In chronic kidney disease, low EPO production, low clearance of hepcidin by the kidney, and inflammation can lead to low iron availability in the erythroid system.