Every day, the human body produces a staggering 200 billion red blood cells (RBCs), necessitating the utilization of more than 2 × 10^15 iron atoms per second to sustain adequate erythropoiesis. These figures equate to the generation of 20 mL of blood daily, comprising 6 g of hemoglobin and 20 mg of iron. Such remarkable quantities underscore the centrality of RBC production and breakdown in iron physiology, offering an ideal backdrop to explore recent advancements in comprehending the systemic and cellular mechanisms governing iron homeostasis and related disorders.
Iron deficiency, the predominant cause of anemia globally, poses a significant health challenge. Iron-deficiency anemia is characterized by diminished numbers of small (microcytic) and hypoferremic erythrocytes. Beyond its role in erythropoiesis, iron plays a crucial role in mitochondrial function, DNA synthesis and repair, and various enzymatic reactions crucial for cellular survival. Iron deficiency has been linked to cognitive developmental impairments in children, diminished physical performance, and adverse pregnancy outcomes.
Conversely, iron overload is a prevalent and equally deleterious condition, impacting vital organs such as the liver, heart, and pancreas. In Western populations, genetic factors, notably hereditary hemochromatosis resulting from mutations in genes involved in systemic iron sensing, contribute significantly to iron overload. Additionally, disorders causing ineffective erythropoiesis and secondary iron loading, such as thalassemias, also play a role. There is a growing recognition that acquired metabolic disorders can induce iron overload, further complicating pathogenesis.
While the field of iron therapeutics is advancing, substantial strides have been made in understanding iron biology, encompassing both molecular physiology and disease mechanisms. Red blood cells, as the primary consumers and the largest physiological reservoir of iron, serve as a pertinent model to elucidate key facets of cellular and systemic iron homeostasis. However, the overarching principles applicable to the erythron extend to other cell and organ systems. The brain, heart, kidneys, and vasculature, among others, are under intense scrutiny. Furthermore, multifaceted pathologies, including cell and tissue degeneration, inflammatory disorders, and cancer, involve aberrant iron management.
With the foundational tenets of systemic and cellular iron regulation now well-established, delving into the nuances specific to various cell types and exploring the role of iron in intricate pathologies promises a bountiful yield for future research.
Dr. Amel Hamdi
Assistant Professor of Hematology and molecular Biology
College of Health Sciences
Abu Dhabi University