Iron Metabolism

Three questions orient the iron studies: Is iron absent, present but unavailable, or accumulating? Hepcidin answers much of this by controlling ferroportin, the cellular route through which iron leaves enterocytes, macrophages, and hepatocytes. When hepcidin is high, iron becomes trapped in storage or recycling compartments and less reaches the circulation. When hepcidin is low—or ferroportin cannot respond—intestinal absorption and release from stores continue despite adequate body iron. That distinction explains a common diagnostic trap. Low serum iron or transferrin saturation can reflect true depletion or inflammation-driven iron restriction, while an elevated ferritin can reflect iron stores, inflammation, liver disease, or more than one process. Ferritin thresholds also depend on the clinical purpose: WHO uses less than 12 µg/L in apparently healthy children under five years and less than 15 µg/L from age five onward to identify depleted stores, whereas the AGA uses less than 45 ng/mL in the gastrointestinal evaluation of iron-deficiency anemia. In inflammatory disease or CKD, ferritin must be interpreted with markers such as CRP, transferrin saturation, or soluble transferrin receptor.