Oxygen and Carbon Dioxide Transport in the Blood

Dr Ziyad Sahe

Learning Objectives

• Describe the structure of haemoglobin and its suitability for oxygen carriage.
• Understand mutations in haemoglobin genes and their structural consequences.
• Comment on the role of methaemoglobin in erythrocytes.
• Draw and label the oxygen-haemoglobin dissociation curve.
• Explain the influence of temperature and pH on the curve.
• Define haematocrit and its regulation.
• Discuss the transport mechanisms of carbon dioxide in blood.

Carriage of Oxygen

• Oxygen is a powerful oxidizing agent. High concentrations can damage organic molecules.
• Red blood cells (erythrocytes) are specially designed for oxygen transport.

Oxidation and Reduction

• Oxidation: loss of electrons; releases energy, often as heat.
• Reduction: gain of electrons; forms complex molecules from simpler ones and requires energy.
• Example: Fe^{2+} \rightarrow Fe^{3+} + e^-
• Reactions can be reversible if they involve small energy transfers.
• Example reaction: NAD oxidation/reduction is crucial in bodily electron transfer processes.

Erythrocytes

• Contain haemoglobin, enabling reversible oxygen binding without oxidation.
• Structure: Biconcave disks, approx. 7 μm in diameter and 2 μm thick.
• Mature red cells lack nuclei and mitochondria, possibly due to oxygen damage.

Immature Erythrocytes: Reticulocytes

• Comprise 1-2% of circulating red blood cells.
• Characterized by a visible reticular network of ribosomal RNA when stained.
• Cannot divide or repair themselves due to the absence of organelles.

Glucose Transporters in Erythrocytes: GLUT1

• Mature red blood cells produce ATP via glycolysis (less efficient than aerobic metabolism).
• High levels of lactate result in low pH in red cells.
• GLUT1 facilitates unregulated glucose uptake, independent of insulin.

Erythrocytes and Oxidative Damage

• Contain antioxidants like Vitamin C to mitigate oxidative damage from oxygen.
• Over time, haemoglobin converts to methaemoglobin; aging RBCs are recognized and phagocytized by immune cells.

Haemoglobin Structure

• Comprised of four subunits, each with a heme prosthetic group.
• Stability arises from salt bridges, hydrogen bonds, and hydrophobic interactions among polypeptide chains.
• Oxygen temporarily binds to the ferrous iron in the heme group but cannot fully oxidize due to steric hindrance.

Methemoglobinemia

• In normal individuals, 1-2% of haemoglobin is methaemoglobin.
• Levels above 2% indicate methaemoglobinemia, potentially genetic or due to chemicals.
• Elevated methaemoglobin levels signal the removal of aging RBCs.

Congenital Hemoglobinemia

• Caused by methaemoglobin reductase deficiency (rare).
• Common in populations like Alaskan Inuit, where affected individuals develop polycythemia to compensate for increased methaemoglobin levels.

Sickle Cell Anemia

• The most common hemoglobin disorder caused by hemoglobin S formation due to a valine substitution for glutamic acid.
• Results in misshapen, inflexible RBCs that can obstruct blood vessels, impairing organ blood flow.

Variants of Haemoglobin

• Variability in subunits affects oxygen affinity (e.g., adult hemoglobin A: (2\alpha, 2\beta) , fetal hemoglobin F: (2\alpha, 2\gamma) ).
• Fetal hemoglobin possesses a higher oxygen affinity for optimal placental oxygen uptake.

Oxygen Binding and Unloading

• 2,3-DPG binds to deoxygenated β subunits of hemoglobin, enhancing oxygen release in hypoxic conditions.

Haemoglobin Saturation

• Measured as the ratio of oxyhaemoglobin to total hemoglobin (SO2).
• Typically assessed with a pulse oximeter (SpO2) or arterial oxygen saturation (SaO2).

Cooperative Binding of Haemoglobin

• Oxygen dissociation curves illustrate the relationship between partial pressure of oxygen (pO2) and hemoglobin saturation.
• Saturation is affected by each successive binding of O2, making the relationship non-linear.

The Oxygen-Haemoglobin Dissociation Curve

• Characteristic 'S' shape; flat in high pO2 range, steep in medium/low pO2 range (20-40 mm Hg).
• High pO2 in lungs maintains over 90% saturation.

Effects of Temperature and pH on the Curve

• Temperature: Elevated temperatures shift the curve right, facilitating oxygen unloading.
• pH: Increased CO2 in metabolically active tissues generates acidity, shifting the curve right (Bohr effect), enhancing oxygen release.

Myoglobin in Muscle

• Myoglobin (Mb) is a single subunit hemoglobin variant with higher oxygen affinity than hemoglobin, storing oxygen in muscle tissues.
• Rhabdomyolysis occurs when myoglobin is released from damaged muscle, potentially causing acute renal failure due to toxicity to renal epithelium.

Haematocrit

• Percentage of blood volume occupied by red blood cells; typically about 45%.

Erythropoietin (EPO)

• EPO is a hormone released by kidney interstitial cells during hypoxia.
• Synthetic EPO can treat anemia from chronic kidney disease and cancer-related chemotherapy.

Carbon Dioxide Transport by Blood

• RBCs carry CO2 back to the lungs, primarily converting it to bicarbonate (HCO3-) via carbonic anhydrase (CA).
• CO2 transport: 70% as bicarbonate, 20% bound to hemoglobin (carbaminohemoglobin), 10% dissolved in plasma.