Red Blood Cells and Haemoglobin Overview

Red Blood Cells and Haemoglobin

• Red blood cells (erythrocytes) have a lifespan of 120 days
• Normal erythrocyte concentration in blood is 3.9-6.5 x 10¹²/L
• They lack a nucleus and organelles
• Contain millions of haemoglobin molecules, a red oxygen-carrying pigment
• Have a biconcave disc shape, providing a larger surface area than a sphere of the same volume
• Primary function is carrying oxygen (O₂) and carbon dioxide (CO₂) between lungs and tissues
• Also involved in pH buffering

Erythrocyte Function

• The primary function is O₂ and CO₂ transport between the lungs and tissues
• The large surface area facilitates this function
• pH buffering is also a function

Gas Exchange and Transport

• 1000 ml of O₂ is transported by haemoglobin (Hb) per minute. Most O₂ is transported by Hb, with small amounts dissolved in plasma
• O₂ content of the blood depends on:
  • Hb concentration
  • Hb affinity for O₂
  • O₂ solubility in the blood (minor effect)

CO₂ Transport

• CO₂ is transported in three forms:
  • ~90% as bicarbonate
  • ~5% as carbamino compounds (combining with plasma proteins and haemoglobin)
  • ~5% in physical solution (CO₂ is significantly more soluble in blood than O₂)

Electrolytes Balance

• Chloride, potassium, and hydrogen ions are transported across the red cell membrane
• In stored blood, extracellular potassium levels are high due to disrupted active transport

Erythropoiesis

• Erythropoiesis is the production of red blood cells in bone marrow
• This process starts with a pronormoblast, progressing through early, intermediate, and late normoblasts to reticulocytes, and finally to erythrocytes
• There are progressive changes in cell appearance and increasing amounts of haemoglobin in each stage

Regulation of Erythropoiesis

• Erythropoietin (EPO) is the hormone that regulates erythropoiesis
• It's a heavily glycosylated polypeptide
• 165 amino acids long, weighing 30,400 kDa
• Mainly produced by endothelial cells in the renal cortex (90%) and by Kupffer cells and hepatocytes in the liver (10%)

Control of Erythropoietin Drive

• Hypoxia is the primary stimulus for EPO secretion
• Any factor decreasing oxygen transport to tissues compared to demand can trigger EPO production

Iron Metabolism

• Total iron storage in the body is approximately 4g, mainly as haemoglobin
• Daily iron requirement is about 1 mg
• Iron absorption is controlled by proteins in the gut
• Iron transfer rate from epithelial cells to plasma depends on iron requirements, being highest when iron stores are low or erythropoiesis is high

Haem Metabolism

• Haem is part of a porphyrin family, characterized by a tetrapyrrole ring
• Haem contains an iron ion (Fe²⁺) at the centre of the protoporphyrin IX ring, vital for haemoglobin's oxygen-binding properties

Haem Biosynthesis

• Haem synthesis occurs in the mitochondria of immature red blood cells in the bone marrow
• The process is outlined in the provided figure

Haem Breakdown

• Haem breakdown occurs in macrophages within the spleen, bone marrow, and liver

Haemoglobin

• Haemoglobin (Hb) is composed of four globin chains held together by non-covalent interactions
• Each globin chain has a hydrophobic pocket containing the haem molecule
• Hb can carry four oxygen molecules
• Different types of haemoglobin exist during development, having different chain combinations

Genetics of Haemoglobin

• Genes encoding haemoglobin chains ε, γ, δ, and β are located on chromosome 11, while genes for the α-chains are on chromosome 16
• Each globin gene contains three exons and two introns
• Globin chains are synthesized separately and assemble to form functional haemoglobin

Physiological Properties of Haemoglobin

• One oxygen molecule binding to Hb increases the affinity of remaining haem groups for oxygen, causing a sigmoidal oxygen dissociation curve
• CO₂, H⁺, 2,3-DPG, and temperature affect the oxygen dissociation curve position, but not the shape
• Haemoglobin variants can alter the oxygen dissociation curve position, e.g. sickle cell haemoglobin

Oxygen Dissociation Curve

• A plot of partial oxygen pressure (x-axis) against oxygen saturation (y-axis)
• Shows the relationship between oxygen pressure and haemoglobin's ability to bind oxygen

Metabolism of Red Cells

• Glycolysis (Embden-Meyerhof pathway) is the main glycolytic pathway in red blood cells, metabolizing glucose to lactate
• This pathway produces 2 ATP molecules per glucose molecule, with no net NADH production
• The hexose monophosphate shunt (HMP) is an oxidative pathway in red blood cells and accounts for ~5% of glucose metabolism, producing two NADPH molecules per glucose-6-phosphate entering the shunt

Prevention of Haem Oxidation

• Haemoglobin oxidation (Fe²⁺ to Fe³⁺) forms methaemoglobin, which reduces oxygen-carrying capacity
• Excess methaemoglobin can be caused by toxic substances or abnormal haemoglobin types, or NADH methaemoglobin reductase deficiencies

Full Blood Count and Reticulocyte Count

• Blood samples are treated with EDTA (anticoagulant)
• Automated analysers provide data like haemoglobin concentration, haematocrit, red blood cell count, mean cell volume (MCV), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), white blood cell count (with differential), platelet count, and red cell distribution width (RDW)

Peripheral Blood Film

• Examination of a peripheral blood film shows the morphology of blood cells and any inclusions

Normal Red Blood Cells

• Normal red blood cells typically measure less than 7.2 µm in diameter and have a central pallor reflecting their biconcave shape. Platelets are small, irregular, and densely staining

Red Blood Cell Abnormalities

• Various red blood cell abnormalities on peripheral blood films are described, with diagnostic inferences. (e.g., anisocytosis, poikilocytosis, spherocytes, sickle cells etc.)

Red Blood Cell Cytoskeleton

• The erythrocyte plasma membrane is supported by a cytoskeleton (a dense, fibrillar protein shell)
• Maintaining cell shape, strength, and flexibility is critical for the erythrocyte's role in circulation
• The key structural proteins (integral and peripheral) of the red blood cell cytoskeleton are described. (e.g., Band 3, glycophorins, spectrin, ankyrin, 4.1 protein, actin)

This quiz covers essential information about red blood cells and their primary component, haemoglobin. Topics include the structure, lifespan, and function of erythrocytes, as well as their role in gas exchange and buffering pH levels in the body. Test your understanding of these vital processes in human physiology.