Schematic representation of the regulation of iron metabolism in absolute ID. Iron depletion occurs commonly and is related to associations among blood loss, low dietary iron intake, and malabsorption. Low iron decreases hepcidin (H) production, allowing for ferroportin (F) activity in duodenal enterocytes, to transfer iron (Fe) absorbed from the diet to transferrin (T), and mobilize iron stored in hepatocytes and macrophages. With progressive iron depletion, the intracellular store of ferritin (iron-rich) is depleted, and serum ferritin (iron-poor) release by macrophages decreases proportionately, along with a progressive decrease in circulating transferrin-bound iron. Low iron also upregulates hepatic production of transferrin, resulting in high TIBC, contributing to low TSAT. Lack of iron available to the BM eventually manifests as hypochromic, microcytic anemia.