Iron Deficiency and Anaemia

Iron Deficiency and Anaemia

• Iron is abundant in the Earth’s crust but its deficiency is the leading cause of anaemia, affecting around 500 million globally.
• High prevalence in low-income regions, notably sub-Saharan Africa and South Asia, where poor dietary quality and parasitic infections exacerbate iron loss.
• Anaemia due to iron deficiency presents as microcytic, hypochromic, characterized by low mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH), resulting in small, pale red blood cells.
• Main differential diagnoses for microcytic, hypochromic anaemia include iron deficiency, anaemia of chronic disease, and thalassaemia.

Iron Transport and Storage

• Iron transport and storage are facilitated by three key proteins: transferrin, transferrin receptor 1 (TfR1), and ferritin.
• Each transferrin molecule can bind up to two iron atoms, delivering iron primarily to erythroblasts in the bone marrow for haemoglobin synthesis.
• After red blood cells age, they are degraded in macrophages, releasing iron back into plasma, which associates with transferrin.
• Dietary iron absorption occurs predominantly in the duodenum and jejunum, constituting a minor portion of plasma transferrin iron.
• Excess iron beyond haemoglobin synthesis is also recycled into transferrin from erythrocytes.
• Ferritin, a water-soluble protein containing 20% iron by weight, acts as a store for iron and is not visible through light microscopy.
• Haemosiderin is an insoluble iron complex, containing around 37% iron, visible after staining; it arises from the partial digestion of ferritin.

Iron Regulation Mechanisms

• Synthesis levels of ferritin, TfR1, δ-aminolaevulinic acid synthase (ALA-S), and divalent metal transporter 1 (DMT-1) closely relate to iron status.
• Iron overload causes ferritin levels to rise while decreasing TfR1 and DMT-1, whereas iron deficiency leads to low ferritin and ALA-S and increased TfR1.
• Iron regulatory proteins (IRPs) bind to iron response elements (IREs) on mRNAs for ferritin, TfR1, ALA-S, and DMT-1, regulating protein synthesis based on iron levels.
• Upstream binding of IRP to IREs decreases protein synthesis, while downstream binding stabilizes mRNA, enhancing translation.
• Elevated plasma iron levels lead to increased iron transfer to organs, causing tissue damage and pathological conditions associated with iron overload.
• Free iron in plasma (non-transferrin bound iron) poses a toxicity risk to various organs.

Learn about the global prevalence of iron deficiency, its impact on anaemia, and the characteristics of microcytic and hypochromic anaemia.