Absolute and functional ID. ID can be absolute, when total body iron is decreased, or functional, when total body iron is normal or increased but sufficient iron is not available to target tissues because of iron sequestration in the storage pool (iron maldistribution). Both storage and functional pools are smaller in absolute ID, whereas only the functional pool is reduced in functional ID. Either condition can occur independently or coexist in an individual patient. Absolute ID in HF can occur due to reduced intake because of anorexia, cardiac cachexia, impaired iron absorption because of intestinal edema, and hepcidin-induced downregulation of iron transporters such as ferroportin. Other causes include gastrointestinal blood losses related to use of aspirin, antiplatelet agents, or anticoagulants, or important coexisting conditions, such as malignancies of the gastrointestinal or genitourinary tract.^24,42,63-65  Functional ID in HF results from mechanisms similar to those responsible for the anemia of chronic disease or inflammation.^16,66  HF is associated with increased levels of inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-18, and tumor necrosis factor-α (TNF-α). These cytokines, particularly IL-6, upregulate hepatic hepcidin production via JAK/Stat3, which binds, internalizes, and degrades ferroportin. This results in impairment of iron absorption into the blood from enterocytes and entrapment of iron in the storage pool (liver and reticuloendothelial cells [RES]). Together, these effects result in relative iron depletion in erythroid cells as well as nonerythroid tissues (functional pool). Inflammatory cytokines also blunt renal erythropoietin production and erythroblast responsiveness to erythropoietin. Erythroblast proliferation is also directly inhibited by elevated levels of hepcidin, further impairing Hb synthesis. Tf, transferrin. Reprinted from Anand and Gupta¹  with permission.