Functional Iron Deficiency
A functional iron deficiency exists when the total body iron stores are normal or decreased, but the iron supply to the bone marrow and other tissues is inadequate. The ultimate consequence of this functional disturbance of iron homeostasis is anemia. Absolute and functional deficiencies can coexist.9
Functional iron deficiency can be present in many acute and chronic inflammatory states. In these conditions, ferritin can apparently be normal or even increased, because inflammatory states are known to increase serum ferritin levels. Thus, the predictive value of ferritin is limited in inflammation as it is an acute phase protein.9
It is now known that hepcidin plays a key role in pathogenesis by controlling iron availability to tissues: in cases of acute or chronic inflammatory states or infection, hepcidin production and release is induced by circulating pro-inflammatory cytokines, especially interleukin-6. This results in increased internalization and degradation of ferroportin and subsequent cellular iron retention, which in turn blocks iron transportation into the circulation.5, 10
Characteristics of functional iron deficiency 5, 21
- Normal to elevated serum ferritin (in case of inflammation)
- Transferrin saturation <20%
- Increased fraction of hypochromic erythrocytes and reticulocytes
- Reduced mean erythrocyte volume (MCV) and reduced mean cellular hemoglobin (MCH)
- Often less good response to oral iron therapy
- Insufficient response of hemoglobin to erythropoiesis-stimulating substances (ESA).
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- Hunt JR. High-, but not low-bioavailability diets enable substantial control of women’'s iron absorption in relation to body iron stores, with minimal adaptation within several weeks, The American Journal of Clinical Nutrition, Volume 78, Issue 6, 1 December 2003, Pages 1168–1177
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- Douglas B. Kell and Etheresia Pretorius. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics, 2014,6, 748.
- T. N. Tran, S. K. Eubanks, K. J. Schaffer, C. Y. J. Zhou and M. C. Linder, Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron, Blood, 1997, 90, 4979–4986.
- L. A. Cohen, L. Gutierrez, A. Weiss, Y. Leichtmann- Bardoogo, D. L. Zhang, D. R. Crooks, R. Sougrat, A. Morgenstern, B. Galy, M. W. Hentze, F. J. Lazaro, T. A. Rouault and E. G. Meyron-Holtz, Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 2010 116:1574-1584; doi: https://doi.org/10.1182/blood-2009-11-253815
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