Untitled Quiz

Erythropoiesis

• Approximately 10^12 new erythrocytes are produced daily
• Pronormoblast is the earliest erythrocyte precursor in the bone marrow
• Pronormoblast gives rise to a series of smaller normoblasts through cell divisions, eventually producing 16 mature red cells
• Nucleated red blood cells (NRBCs) are not typically present in peripheral blood, but their presence can indicate extramedullary erythropoiesis or marrow diseases

Haemoglobin

• Haemoglobin (Hb) is a specialized protein that carries oxygen to tissues and returns carbon dioxide to the lungs
• Each red cell contains approximately 640 million Hb molecules
• Each HbA molecule consists of 4 polypeptide chains (α2β2) with a haem group
• Molecular weight of HbA is 68,000
• Two other haemoglobins present in normal adult blood are HbF and HbA2

Hb Function

• Haemoglobin molecules move and change shape as they load and unload oxygen
• 2,3-diphosphoglycerate (2,3-DPG) enters the Hb molecule when oxygen is unloaded, reducing the molecule's affinity for oxygen
• The P50 of normal blood is 26.6 mmHg, and shifts in the curve are influenced by 2,3-DPG, H+ ions, CO2, and Hb structure
• High concentrations of 2,3-DPG, H+ ions, or CO2, or the presence of certain haemoglobins (e.g., HbS), shift the curve to the right, making oxygen release easier

Red Cell Metabolism

• Embden-Meyerhof pathway: glucose is metabolized to lactate, generating 2 ATP molecules
• ATP is used to maintain red cell volume, shape, and flexibility, and to power the membrane ATPase sodium pump
• NADH is generated and used by methaemoglobin reductase to reduce functionally dead methaemoglobin
• The Luebering-Rapoport shunt generates 1,2-DPG, which forms a complex with Hb, regulating oxygen affinity

Hexose Monophosphate Pathway

• 10% of glycolysis occurs through this pathway, generating NADPH
• NADPH is used to maintain sulphydryl (SH) groups in the red cell membrane
• NADPH is also used by methaemoglobin reductase to maintain haemoglobin iron in the functionally active Fe2+ state

The Red Cell

• Must be able to pass through the microcirculation (minimum diameter of 3.5 μm) and maintain osmotic equilibrium
• Maintains haemoglobin in a reduced (ferrous) state
• Travels approximately 480 km (300 miles) throughout its 120-day lifespan
• Generates energy as ATP via the anaerobic glycolytic pathway and reducing power as NADH and NADPH

Anaemia

• Defined as a reduction in the haemoglobin concentration of the blood below normal for age and sex
• Normal values vary between different laboratories, but typical values are provided