Hematology · USMLE Step 1 and Step 2

Anemia of Chronic Disease song

Anemia of Chronic Disease - Iron Studies, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Anemia of Chronic Disease

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Key points in this song10

Anemia of chronic disease (ACD) is caused by hepcidin upregulation in response to chronic inflammation, which blocks ferroportin and traps iron in macrophages and hepatocytes, reducing iron availability for erythropoiesis.
Classic lab pattern: low serum iron, low TIBC (transferrin), high ferritin, and low transferrin saturation — distinguishing it from iron deficiency anemia, which shows low ferritin and high TIBC.
The anemia is typically normocytic normochromic but can become microcytic hypochromic in longstanding cases, making it overlap with iron deficiency anemia on peripheral smear.
Underlying conditions include chronic infections (TB, osteomyelitis), autoimmune diseases (rheumatoid arthritis, SLE), malignancies, and chronic kidney disease — any condition driving sustained IL-6, IL-1, and TNF-α release.
IL-6 is the primary cytokine stimulating hepatic hepcidin synthesis; hepcidin is the master iron regulatory hormone and is the central mediator of ACD pathophysiology.
Erythropoietin (EPO) levels are inappropriately low relative to the degree of anemia in ACD, and erythroid progenitor cells show blunted response to EPO due to inflammatory cytokine suppression.
Bone marrow biopsy in ACD shows adequate or increased iron stores in macrophages (stainable iron) but decreased sideroblasts, confirming iron is present but inaccessible.
Treatment targets the underlying disease; recombinant EPO (epoetin alfa) is used in ACD associated with chronic kidney disease or chemotherapy-related anemia when hemoglobin falls below 10 g/dL.
Soluble transferrin receptor (sTfR) levels are normal or mildly elevated in ACD but markedly elevated in iron deficiency anemia, making sTfR-to-log-ferritin ratio a useful distinguishing tool.
In combined iron deficiency and ACD (common in IBD or malignancy), ferritin may appear falsely normal due to its role as an acute-phase reactant, requiring careful interpretation alongside other iron indices.