Oxygen-Hemoglobin Dissociation Curve

Overview 

image 2022 09 16T125758.188

  • Oxygen-hemoglobin dissociation curve
    • sigmoidal shape is characteristic of positive cooperativity
      • binding of 1 O2 molecule to 1 subunit of deoxyhemoglobin increases affinity for Oin adjacent subunits
    • P50 is PO2 at which hemoglobin is 50% saturated
      • ↑ P50 → ↓ hemoglobin affinity for O2
        • 50% saturation achieved at higher-than-normal P50
      • ↓ P50 → ↑ hemoglobin affinity for O2
        • 50% saturation achieved at lower-than-normal P50
  • Loading and unloading of oxygen 
    • in lungs
      • PaO2 ≈ 100 mm Hg
      • hemoglobin % saturation ≈ 100%
      • facilitates maximal O2 loading into arterial blood in lungs
    • in peripheral tissues
      • PvO2 ≈ 40 mm Hg
      • hemoglobin % saturation ≈ 75%
      • facilitates O2 unloading into peripheral tissues
  • Shift to right
    • mechanism
      • ↑ P50 → ↓ hemoglobin affinity for O2 → ↑ O2 unloading
    • causes
      • ↑ PCO2, ↓ pH (Bohr Effect)
        • ↑ PCO→ ↑ H+ → ↓ pH
          • CO2 + H2O  → H2CO3 → H+ HCO3
            • ↑ PCO2 → equilibrium reaction shifts right
              • Le Chatelier’s principle
        • ↑ CO2, ↑ H+ bind hemoglobin and stabilize low O2 affinity T (taut) state
          • ↓ hemoglobin affinity for O2 → ↑ O2 unloading
            • e.g., exercise → ↑ PCO2, ↓ pH
              • ↑ O2 unloading ensures O2 delivery meets O2 demand in skeletal muscle
      • ↑ temperature
        • e.g., ↑ tissue metabolism → ↑ temperature
      • ↑ 2,3-bisphosphoglycerate (2,3-BPG)
        • high altitude → hypoxemia → ↑ synthesis of 2,3-BPG
          • Also seen in heart failure, anemia, morbid obesity, etc. 
        • ↑ 2,3-BPG binds hemoglobin and stabilizes low O2 affinity T (taut) state
          • ↓ hemoglobin affinity for O2 → ↑ O2 unloading
  • Shift to left 
    • mechanism
      • ↓ P50→ ↑ hemoglobin affinity for O→ ↓ O2 unloading
    • causes
      • ↓ PCO2, ↑ pH (Bohr Effect)
        • ↓ PCO→ ↓ H+ → ↑ pH
        • ↓ CO2, ↓ H+ → stabilizes high O2 affinity R (relaxed) state
          • ↑ hemoglobin affinity for O2 → ↑ O2 loading
        • conversely, ↑ O2  decreases Hb affinity for CO2/H (Haldane effect)
      • ↓ temperature
        • ↓ tissue metabolism → ↓ temperature
      • ↓ 2,3-bisphosphoglycerate (2,3-BPG)
      • hemoglobin F
        • fetal hemoglobin
        • 2 α subunits and 2 γ subunits (α2γ2)
          • ↑ affinity for O2, ↓ affinity for 2,3-BPG
            • facilitates O2 delivery from mother to fetus