In this episode of Hospital Medicine Unplugged, we unpack iron deficiency anemia (IDA) and anemia of chronic disease/inflammation (ACD/AI)—absolute iron depletion versus hepcidin-driven iron lock-down, and why that distinction matters on the wards.

We sprint through the core physiology: IDA runs on empty iron stores—low ferritin, low TSAT, low hepcidin, microcytosis. ACD/AI keeps iron trapped inside macrophages—normal/high ferritin, low TSAT, low transferrin, high hepcidin—producing a functional deficiency despite adequate stores.

Diagnosis starts with the do-first labs: CBC with indices, smear, ferritin, serum iron, TIBC, TSAT, CRP, ± soluble transferrin receptor (sTfR) and reticulocyte Hb. Ferritin <30 ng/mL screams IDA, but in inflammation we need a higher cutoff (<100). sTfR high = IDA; normal = ACD/AI. Hepcidin stays low in IDA, high in ACD.

Symptom patterns help but aren’t definitive: IDA brings classic iron-depletion clues (pica, restless legs, glossitis), while ACD/AI blends into the underlying chronic disease. Overlap syndromes blur the picture—ferritin “normal,” TSAT low, inflammation high—the most common and the most misdiagnosed group in the hospital.

Management stays principle-driven:
• Treat the cause first—stop the bleed, fix malabsorption, control inflammation.
• Replete iron: oral every-other-day for pure IDA; IV iron for inflammation, malabsorption, or rapid repletion needs.
• ACD/AI leans on underlying disease control; ESA therapy only in selected CKD/cancer patients.
• Overlap syndromes? Think IV iron early; oral will fail against hepcidin.

Risk matters: anemia on admission predicts longer stay, higher readmission, and higher mortality. The sickest group—older adults with multiple comorbidities—often has mixed pathology and needs aggressive evaluation and structured follow-up every 3–6 months with CBC and iron studies.

We close with future directions: hepcidin antagonists, HIF-PH inhibitors, and precision biomarkers (hepcidin, sTfR) that may finally crack the code of inflammation-mediated iron restriction. For now, stick to the fundamentals: identify absolute vs functional deficiency, interpret ferritin through the lens of inflammation, choose the right route for iron, and never overlook an “inappropriately normal” ferritin.