Carbon Dioxide Transport

Overview

• Transport of CO₂ in blood (peripheral tissues → RBC → lungs)
  • peripheral tissues
    • metabolically active tissues produce CO₂, which diffuses across the cell membrane and eventually into the RBC at the level of the capllaries
  • RBC
    • carbaminohemoglobin
      • ↑ pCO₂ is produced in peripheral tissues
        • this facilitates CO₂ binding to Hb, forming carbaminohemoglobin (CO₂-Hb)
      • in turn, the Taut (T) state of Hb is stabilized
        • Bohr effect
          • enhanced release of O₂ in the presence of low pH or increased pCO₂
            • CO₂-Hb → ↓ Hb affinity for O₂ → ↑ O₂ unloading into tissues
              • right shift in the hemoglobin-oxygen (Hb-O₂) dissociation curve 
            • H⁺ produced by converting CO₂ + H₂O to HCO₃^– + H⁺ via carbonic anhydrase (CA) which contributes in lowering the pH
            • protonated Hb stabilizes the T state, facilitating O₂ release into tissues
              • (oxyhemoglobin) HbO₂ + H⁺ ↔ HbH + O₂ (deoxyhemoglobin)
        • Haldane effect
          • at low pO₂ levels, the carrying capacity of CO₂ increases
            • in other words, there is an increase affinity for CO₂ when there is less O₂ bound to hemoglobin
    • bicarbonate (HCO₃^–)
      • CA reversibly catalyzes the formation of HCO₃^– from the hydration of CO₂
      • this reaction is reversible, thus CA is also involved in the dehydration of H₂CO₃
        • CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃^– 
          • the produced H⁺ remains in the RBC, where it is buffered by deoxyhemoglobin
          • deoxyhemoglobin is a better H⁺ buffer than oxyhemoglobin
      • the produced HCO₃^– is transported into the plasma via a chloride-bicarbonate (Cl-HCO₃) exchanger (AE1 or band three protein)
        • this describes the chloride (or Hamburger) shift
  • lung
    • the reactions mentioned above occur in reverse inside the lung
      •  carbaminohemoglobin
        • Bohr effect 
          • in lungs (low PCO₂), CO₂ dissociates from hemoglobin and stabilizes high O₂ affinity Relaxed (R) state
            • hemoglobin-oxygen dissociation curve left shifts → ↑ hemoglobin affinity for O₂ → ↑ O₂ loading
        • Haldane effect
          • O₂ loading → ↓ hemoglobin affinity for CO₂ → ↑ CO₂ unloading
      • bicarbonate
        • HCO₃^– is exchanged for Cl^– (chloride shift) across RBC membranes
          • HCO₃^– enters RBCs
        • Haldane effect
          • O₂ loading → ↓ hemoglobin affinity for H⁺→ ↑ H⁺ unloading
          • H⁺ + HCO₃^– → H₂CO₃ → CO₂ + H₂O
          • ↑ H⁺ drives equilibrium reactions to right (CO₂ formation).