Disorders of iron metabolism. Part II: iron deficiency and iron overload

Abstract

Main disorders of iron metabolismIncreased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron deficiency anaemia. In chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, resulting in hypoferraemia and iron restricted erythropoiesis, despite normal iron stores (functional iron deficiency), and finally anaemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD+ID). In contrast, low hepcidin expression may lead to hereditary haemochromatosis (HH type I, mutations of the HFE gene) and type II (mutations of the hemojuvelin and hepcidin genes). Mutations of transferrin receptor 2 lead to HH type III, whereas those of the ferroportin gene lead to HH type IV. All these syndromes are characterised by iron overload. As transferrin becomes saturated in iron overload states, non-transferrin bound iron appears. Part of this iron is highly reactive (labile plasma iron), inducing free radical formation. Free radicals are responsible for the parenchymal cell injury associated with iron overload syndromes.Role of laboratory testing in diagnosisIn iron deficiency status, laboratory tests may provide evidence of iron depletion in the body or reflect iron deficient red cell production. Increased transferrin saturation and/or ferritin levels are the main cues for further investigation of iron overload. The appropriate combination of different laboratory tests with an integrated algorithm will help to establish a correct diagnosis of iron overload, iron deficiency and anaemia.Review of treatment optionsIndications, advantages and side effects of the different options for treating iron overload (phlebotomy and iron chelators) and iron deficiency (oral or intravenous iron formulations) will be discussed.

Iron status in obese women

“…There exist some expectation that inflammatory response also significantly affects iron the status towards causing decrease in iron stores. It is also well known that inflammation interferes with iron metabolism, and erythropoiesis causing anaemia of chronic disease (ACD), also known as anaemia of inflammation, confirmed in the presence of chronic inflammation (increased CRP level in the absence of other inflammatory cause), diminished haemoglobin level and a low TSAT [10][11][12][13][14][15][16][17][18][19][20][21].…”

Quantitative data on the magnitude of the systemic inflammatory response and its relationship with serum measures of iron status

“…Where there is a chronic inflammatory state, iron status can be determined using indices that directly describe the erythrocyte population, such as hemoglobin concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), or peripheral blood film microscopy. 21 It is well understood that erythropoiesis is affected by both chronic and acute inflammation however the above indices are less subject to rapid change than acute phase proteins and are less likely to be useful in acute systemic inflammation. 9 Platelets are also routinely measured as part of a full blood count (FBC).…”

Metabolic response to subacute and subchronic iron overload in a rat model

“…The drop in UIBC and TIBC attended by the rise in % transferrin saturation and liver and serum iron is coincident with the onset of lipid peroxidation and oxidative stress shown in an integral part of this experiment [1]. This could indicate that the ability of transferrin to safely bind serum iron is impaired, not only because the iron stores are elevated and there is limited capacity for transferrin molecules to accept additional iron, but also because, as an acute-phase reactant, transferrin activity could be altered in the presence of chemical stress [23].…”