Anemia of Chronic Disease

Anemia of chronic disease (ACD), also called anemia of inflammation, is the second most common anemia worldwide after iron deficiency. The central mechanism involves hepcidin, a hepatic peptide hormone that is upregulated by inflammatory cytokines (IL-6, TNF-alpha, IL-1). Chronic inflammatory states — including infections, autoimmune disorders, CKD, malignancy, and heart failure — stimulate macrophages to produce IL-6, which activates the JAK-STAT3 signaling pathway in hepatocytes, driving hepcidin transcription. Elevated hepcidin binds to ferroportin on enterocytes and macrophages, causing its internalization and degradation. This traps iron within macrophages of the reticuloendothelial system and blocks intestinal iron absorption, creating functional iron deficiency despite adequate total body iron stores. Additionally, inflammatory cytokines directly suppress erythropoietin (EPO) production in the kidney, blunt bone marrow responsiveness to EPO, and shorten red blood cell lifespan from the normal 120 days to approximately 80 days through macrophage-mediated erythrophagocytosis. The result is a normocytic, normochromic anemia (may become microcytic if prolonged) with characteristically LOW serum iron, LOW TIBC, and NORMAL-to-ELEVATED ferritin — the key laboratory pattern distinguishing ACD from iron deficiency anemia where ferritin is low and TIBC...