التمثيل الغذائي لخلايا الدم الحمراء

RBC Metabolism and Iron Disorders

• Objectives: To understand the structural and functional features of red blood cells (RBCs), the metabolic pathways in RBCs related to their functions, the role of G6PD in protecting cells from oxidative damage, essential iron compounds, iron metabolism, biochemical function of iron, laboratory assessment of iron status, and disorders of iron metabolism.

Introduction to Red Blood Cells (RBCs)

• RBCs are not true cells; they lack a nucleus and nucleic acids, and thus cannot reproduce.
• They lack cellular organelles like mitochondria, Golgi, endoplasmic reticulum (ER), and lysosomes.
• They lack synthetic activities like protein, lipid, and carbohydrate synthesis.
• RBCs must be easily deformable to squeeze through tight spots in microcirculation.
• RBCs contain 35% solids, primarily hemoglobin (the chief protein).
• Other proteins are present with lipids and oligosaccharides, forming the stroma and cell membrane.
• Potassium, magnesium, and zinc concentrations are higher in RBCs than in plasma.

Functions of RBCs

• RBCs have relatively simple functions compared to other human cells.
• Their main roles are to deliver oxygen to tissues and remove carbon dioxide and protons produced by tissue metabolism.
• These functions are performed by hemoglobin.

Metabolism of RBCs

• RBCs lack mitochondria, so they cannot use the respiratory chain, citric acid cycle, or fatty acid oxidation.
• Energy production relies on anaerobic glycolysis, breaking down glucose to produce lactate and ATP for maintaining cell shape and ion transport.

Metabolic Pathways in RBCs

• Glucose Transport: Glucose enters RBCs via facilitated diffusion using glucose transporters (GLUT-1), independent of insulin.
• Glycolysis: Glucose is metabolized through anaerobic glycolysis, producing 2 ATP molecules and lactate.
• 2,3-BPG Production: Some glycolysis pathways lead to the production of 2,3-bisphosphoglycerate (2,3-BPG) which modifies hemoglobin affinity for oxygen and assists in oxygen unloading in tissues.
• Pentose Phosphate Pathway (PPP): RBCs have an active PPP that produces NADPH, important for maintaining reduced glutathione, crucial for preventing RBC membrane oxidation.

Role of G6PD

• Glucose-6-phosphate dehydrogenase (G6PD) is the first enzyme in the pentose phosphate pathway (PPP).
• Deficiencies in G6PD lead to reduced NADPH production, causing oxidative damage and ending in acute hemolytic anemia.

Essential Iron Compounds

• Iron is an essential element present mainly in porphyrin complexes (e.g., heme), and iron storage proteins (ferritin, hemosiderin).
• Heme is a critical component of hemoglobin and myoglobin, and is formed by the incorporation of ferrous iron Fe2+ into protoporphyrin.

Iron Metabolism

• About 5-10% of dietary iron is absorbed via active transport in the duodenum.
• Iron is absorbed as ferrous (Fe2+) form more easily than ferric (Fe3+).
• The absorption rate is controlled by body iron stores and erythropoietic rate.
• Ascorbic acid facilitates iron absorption, while substances like phytates inhibit absorption.
• After absorption, iron is either incorporated into ferritin for storage in mucosal cells, or directly transported to plasma combined with transferrin.
• Iron stores are found in the liver, spleen, and bone marrow as ferritin.
• The amount of iron is regulated in tissues such as the liver in different physiological conditions.

Laboratory Assessment of Iron Status

• Serum iron: this value is not a reliable assessment of iron stores level. It fluctuates widely in health.
• Serum ferritin: this is the most valuable assessment for iron stores, as its levels are closely related to iron stores and it is not affected by inflammation.
• Serum transferrin and total iron-binding capacity (TIBC): It is useful to determine iron deficiency, which can be reflected by reduced serum transferrin saturation.

Disorders of Iron Metabolism

• Iron Deficiency: Caused by inadequate intake, impaired absorption, chronic blood loss, and increased demand, mainly in young children, adolescent females, and pregnant women. It leads to microcytic hypochromic anemia and other symptoms, like fatigue.
• Iron Overload: Less common than iron deficiency. Can result from increased iron intake, parenteral iron administration (e.g., multiple blood transfusions), or genetic disorders like hereditary hemochromatosis. Its symptoms include iron deposits in tissues (liver, pancreas, etc.), causing damage.

Iron Poisoning

• Iron poisoning, primarily in children, can be life-threatening.
• Initial symptoms may include epigastric pain, nausea, vomiting, and potential haematemesis.
• Later stages involve acute encephalopathy and circulatory failure, acute liver and renal failure, demanding immediate treatment with chelating agents like desferrioxamine to facilitate iron excretion.