RBC Metabolism & Iron Disorders

RBC Metabolism & Iron Disorders

• Red blood cells (RBCs) are not true cells; they lack a nucleus and nucleic acids, thus cannot reproduce.

• RBCs lack organelles like mitochondria, Golgi, ER and lysosomes. Therefore, they lack synthetic activities for proteins, lipids and carbohydrates.

• RBCs have a deformable structure allowing them to squeeze through tight spots in the circulatory system.

• RBCs contain 35% solids, chiefly hemoglobin (the main protein).

• Other proteins, lipids, and oligosaccharides form the cell membrane and stroma.

• RBCs have higher potassium, magnesium and zinc concentrations compared to plasma.

• RBCs have simple functions, primarily delivering oxygen and removing carbon dioxide and protons, conducted by hemoglobin.

• RBC metabolism lacks mitochondria, the citric acid cycle, and fatty acid oxidation. Energy is derived from anaerobic glycolysis (glucose breakdown to lactic acid).

• ATP produced in glycolysis is crucial for maintaining the biconcave shape of RBCs and regulating ion and water transport.

• Glucose is transported into RBCs through facilitated diffusion by GLUT-1 transporters, independent of insulin.

• Glucose is metabolized through anaerobic glycolysis, producing 2 molecules of ATP and lactate. Lactate is converted to glucose in the liver.

• 2,3-bisphosphoglycerate (2,3 BPG) is produced in RBCs (by bisphosphoglyceratemutase), impacting hemoglobin's oxygen affinity. This helps in oxygen release to tissues.

• RBCs possess a pentose phosphate pathway (PPP) for glucose, providing NADPH as a critical source. NADPH is essential in maintaining reduced glutathione, which protects RBCs from oxidative damage.

• Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the PPP; its deficiency can lead to oxidative damage and hemolytic anemia.

• Iron is a vital component in hemoglobin, myoglobin, cytochromes, catalase, and peroxidase.

• Iron is necessary for electron transport chain (ETC) and oxidative phosphorylation.

• Iron is essential for various enzymes including peroxidase for phagocytosis and killing of bacteria.

• Iron is needed for non-heme proteins such as succinate dehydrogenase and flavoproteins. Iron also facilitates oxygen transport, storage and utilization, influencing immune competence.

• Iron is mostly absorbed as ferrous iron (Fe2+).

• About 5-10% of dietary iron is absorbed via active transport in the duodenum.

• Iron absorption depends on physiological and dietary factors (e.g., iron stores, rate of erythropoiesis, diet components).

• Substances like phytates inhibit iron absorption.

• Adult human iron levels are approximately 70 mmol (4 g).

• Normal daily intake is 0.2-0.4 mmol (10-20 mg).

• Iron is stored in liver, spleen and bone marrow as ferritin. Ferritin contains approximately 23% iron.

• Serum ferritin is a good marker for iron stores. Elevated levels suggest iron overload; low levels indicate depletion.

• Hemosiderin is an iron storage form if ferritin levels are high.


• Iron is excreted primarily in feces, with minimal amounts in urine.

• Laboratory assessment of iron status includes serum iron, total iron-binding capacity (TIBC) and serum ferritin. Levels fluctuate in response to various factors (e.g., diurnal changes, menses, pregnancy).

• Iron deficiency and iron overload are important disorders of iron metabolism.

• Iron deficiency, caused by inadequate intake, impaired absorption, chronic blood loss or increased demands can lead to microcytic hypochromic anemia and related symptoms.

• Iron overload, potentially due to increased intake or absorption, blood transfusions, or genetic disorders (e.g., hereditary hemochromatosis), leads to tissue damage and related issues.

• Iron poisoning is a significant emergency particularly in children and requires immediate treatment.