Blood Gas Transport

• What are the two main ways oxygen (O₂) is transported in the blood?

  1. Bound to haemoglobin (Hb) – ~98.5% of O₂ binds to haemoglobin in red blood cells.
  2. Dissolved in plasma – ~1.5% of O₂ is transported as a dissolved gas in blood plasma.
• What is the structure of haemoglobin and how does it facilitate oxygen transport?

  • Haemoglobin is a tetrameric protein with four polypeptide chains (2 alpha, 2 beta).
  • Each chain contains a heme group with an iron (Fe²⁺) ion that binds one O₂ molecule.
  • Each haemoglobin molecule can carry up to four O₂ molecules.
• What is cooperative binding in haemoglobin?

  • Cooperative binding means that when one O₂ molecule binds, hemoglobin undergoes a conformational change, increasing its affinity for more O₂.
  • This is described by the oxygen dissociation curve, which is sigmoidal (S-shaped).
• What factors influence oxygen binding and release from haemoglobin?

  • pO₂ (partial pressure of O₂) – Higher pO₂ promotes binding; lower pO₂ promotes release.
  • pH (Bohr effect) – Lower pH (acidic) decreases affinity, releasing O₂.
  • CO₂ levels – Increased CO₂ promotes O₂ release by forming carbonic acid.
  • Temperature – Higher temperature decreases affinity, promoting O₂ release.
  • 2,3-BPG (2,3-bisphosphoglycerate) – Increases O₂ release in tissues by stabilising the deoxygenated form of Hb.
• What is the Bohr effect?

  • The Bohr effect describes how increased CO₂ and decreased pH reduce hemoglobin’s affinity for O₂, promoting O₂ release in tissues.
  • In the lungs, where CO₂ is lower and pH is higher, haemoglobin’s affinity for O₂ increases.
• What are the three main ways carbon dioxide (CO₂) is transported in the blood?

  1. As bicarbonate ions (HCO₃⁻) (~70%) – CO₂ reacts with water in RBCs (catalysed by carbonic anhydrase) to form HCO₃⁻, which diffuses into plasma.
  2. Bound to hemoglobin (~20-23%) – CO₂ binds to the globin (not heme) part of hemoglobin, forming carbaminohemoglobin (HbCO₂).
  3. Dissolved in plasma (~7-10%) – CO₂ is more soluble in blood than O₂ and travels in plasma.
• What is the Haldane effect?

  • The Haldane effect describes how oxygenation of haemoglobin reduces its ability to bind CO₂ and H⁺, promoting CO₂ release in the lungs.
  • Conversely, deoxygenated haemoglobin binds more CO₂ and H⁺, enhancing CO₂ transport in tissues.
• How does the bicarbonate system regulate blood pH?

  • The carbonic acid-bicarbonate buffer system maintains pH:

  CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

  • In tissues: CO₂ increases → more H⁺ and HCO₃⁻ → lowers pH (more acidic).
  • In lungs: CO₂ is exhaled → reaction shifts left → H⁺ decreases → raises pH (less acidic).
• What is the chloride shift?

  • In tissues, HCO₃⁻ diffuses out of RBCs into plasma, and Cl⁻ enters RBCs to maintain electrical neutrality (Hamburger phenomenon).
  • In lungs, the process is reversed as HCO₃⁻ re-enters RBCs to form CO₂ for exhalation.
• How does foetal haemoglobin (HbF) differ from adult haemoglobin (HbA) in oxygen transport?

  • HbF has a higher O₂ affinity than HbA, allowing efficient O₂ transfer from maternal to foetal blood.
  • HbF binds less 2,3-BPG, preventing O₂ release until it reaches foetal tissues.
• What is oxygen-haemoglobin affinity?

  Oxygen-haemoglobin affinity refers to the strength of the bond between oxygen (O₂) and haemoglobin (Hb), influencing how easily oxygen binds in the lungs and is released to tissues.
•  What is the oxygen dissociation curve?

  A sigmoidal (S-shaped) graph that represents the relationship between the partial pressure of oxygen (pO₂) and haemoglobin saturation. It reflects haemoglobin’s affinity for oxygen.
• How does an increase in CO₂ affect oxygen-haemoglobin affinity?

   Increased CO₂ lowers pH (due to carbonic acid formation), reducing haemoglobin’s oxygen affinity (right shift in the dissociation curve), enhancing oxygen delivery to tissues.
• How does pH influence oxygen-haemoglobin affinity?

  • Lower pH (acidosis) decreases affinity (right shift), promoting O₂ release.
  • Higher pH (alkalosis) increases affinity (left shift), making oxygen binding stronger but reducing tissue delivery.
• How does temperature affect oxygen-haemoglobin affinity?

  • Increased temperature reduces haemoglobin’s oxygen affinity (right shift), facilitating oxygen unloading in active tissues.
  • Decreased temperature increases affinity (left shift), reducing O₂ release.
• What is 2,3-Bisphosphoglycerate (2,3-BPG) and how does it affect oxygen affinity?

  2,3-BPG is a molecule that binds to haemoglobin, reducing its oxygen affinity (right shift), enhancing oxygen release to tissues. It increases in conditions like hypoxia, anemia, and chronic lung disease.
• What happens to oxygen-haemoglobin affinity during exercise?

  Exercise increases CO₂, decreases pH, raises temperature, and increases 2,3-BPG, all reducing haemoglobin’s oxygen affinity (right shift), enhancing oxygen unloading to active muscles.
• What is the significance of a right shift in the oxygen dissociation curve?

  A right shift means decreased haemoglobin affinity for oxygen, promoting O₂ unloading in tissues. Causes: ↑ CO₂, ↓ pH, ↑ temperature, ↑ 2,3-BPG.
• What is the significance of a left shift in the oxygen dissociation curve?

  A left shift indicates increased haemoglobin affinity for oxygen, making O₂ less available to tissues. Causes: ↓ CO₂, ↑ pH, ↓ temperature, ↓ 2,3-BPG.
• What is anaemia, and how does it impact blood oxygen transport?

  • Anaemia is a condition characterised by a decreased red blood cell (RBC) count or haemoglobin (Hb) concentration, reducing the blood’s oxygen-carrying capacity.
  • Despite normal oxygen saturation and partial pressure (PaO₂), total oxygen content (CaO₂) is reduced.
  • This leads to tissue hypoxia, resulting in fatigue, pallor, shortness of breath, and tachycardia.
• Why does oxygen saturation (SaO₂) remain normal in anaemia?

  • In anaemia, the fractional saturation of haemoglobin with oxygen (SaO₂) remains normal because the available haemoglobin molecules are still fully saturated.
  • However, the total oxygen content (CaO₂) is reduced due to fewer haemoglobin molecules available to carry oxygen.
• What are common causes of anaemia?

  • Iron deficiency anaemia (most common) – due to chronic blood loss or inadequate dietary intake.
  • Vitamin B12/folate deficiency – impairs RBC production.
  • Haemolytic anaemia – increased RBC destruction (e.g., sickle cell disease, G6PD deficiency).
  • Aplastic anaemia – failure of bone marrow to produce RBCs.
  • Chronic disease anaemia – due to inflammation, kidney disease, or malignancy.
• How does anaemia affect the oxygen dissociation curve?

  • Anaemia does not significantly shift the oxygen dissociation curve but results in lower oxygen content at all levels of PaO₂.
  • In chronic anaemia, the body compensates by increasing 2,3-BPG production, shifting the curve rightward, enhancing oxygen unloading to tissues.
•  What is carbon monoxide (CO) poisoning, and how does it affect oxygen transport?

  • CO poisoning occurs when carbon monoxide binds to haemoglobin with 200-250 times greater affinity than oxygen, forming carboxyhaemoglobin (COHb).
  • COHb prevents oxygen from binding, reducing oxygen transport.
  • Additionally, CO causes a leftward shift of the oxygen dissociation curve, meaning that the oxygen bound to haemoglobin is less readily released to tissues, worsening hypoxia.
• Why does carbon monoxide poisoning cause severe hypoxia despite normal PaO₂?

  • PaO₂ (partial pressure of oxygen in blood) remains normal because dissolved oxygen is unaffected.
  • However, oxygen content (CaO₂) is significantly reduced due to the displacement of oxygen by CO on haemoglobin.
  • Additionally, the leftward shift of the oxygen dissociation curve impairs oxygen unloading, exacerbating tissue hypoxia.
•  What are the clinical signs and symptoms of carbon monoxide poisoning?

  • Mild exposure: Headache, dizziness, nausea, confusion.
  • Moderate exposure: Cherry-red skin (due to COHb), dyspnoea, tachycardia, muscle weakness.
  • Severe exposure: Seizures, arrhythmias, coma, death.
• What is the treatment for carbon monoxide poisoning?

  • Immediate removal from CO exposure.
  • 100% oxygen therapy via non-rebreather mask – reduces COHb half-life (from ~5-6 hours in room air to ~90 minutes).
  • Hyperbaric oxygen therapy (HBOT) in severe cases – further reduces COHb half-life and enhances oxygen delivery.
• How is carbon monoxide poisoning diagnosed?

  • Pulse oximetry is unreliable as it cannot differentiate between oxyhaemoglobin (O₂Hb) and carboxyhaemoglobin (COHb).
  • Co-oximetry is required to measure COHb levels.
  • Arterial blood gas (ABG) may show metabolic acidosis (lactic acidosis from tissue hypoxia).
• Why is the Bohr effect important for oxygen delivery?

  The Bohr effect enhances oxygen unloading in metabolically active tissues.

  • Tissues with high CO₂ production (e.g., muscles during exercise) cause a local drop in pH.
  • Hemoglobin releases more O₂ where it is needed most.
• How does the Haldane effect work mechanistically?

  1. In the lungs, O₂ binds to hemoglobin, causing a conformational change that releases CO₂ and H⁺.
  2. Released H⁺ shifts the equilibrium, converting HCO₃⁻ back into CO₂, which is exhaled.
  3. In tissues, deoxygenated Hb binds more CO₂ and H⁺, enhancing CO₂ transport.
• Why is the Haldane effect important for CO₂ transport?

  • In tissues, deoxygenated Hb binds more CO₂ and H⁺, helping remove CO₂ from active tissues.
  • In the lungs, oxygenation of Hb frees CO₂ for exhalation, ensuring efficient CO₂ clearance
• How do the Bohr and Haldane effects interact?

  • The Bohr effect helps offload O₂ in tissues where CO₂ is high.
  • The Haldane effect helps load CO₂ in tissues and unload it in the lungs.
  • Together, they optimise O₂ delivery and CO₂ removal, maintaining blood gas balance.