Alveolar Gas Exchange

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  • O2 and CO2 cross the blood-gas barrier by passive diffusion.
  • The distance from alveolar lumen to erythrocyte cytoplasm is about 0.3 μm.


  • O2 diffuses rapidly across this barrier, equilibrating with blood in about 0.25 s. At rest, erythrocyte transit time in alveolar capillaries is about 0.75 s, however in exercise it falls to as little as 0.25 s.
  • The time taken for diffusion can be greatly increased by lung disease which results in thickening of the blood-gas barrier and consequent diffusion-limitation of oxygen transport.
  • A reduction in the pressure gradient driving diffusion will also slow diffusion.
  • This is seen at high altitude, where PAO2 is reduced by a greater amount than the fall in venous PO2.

Carbon Dioxide

  • CO2 has a much higher water solubility than O2 and penetrates an aqueous membrane 20x as rapidly as O2
  • The pressure gradient driving its diffusion is only 5 mmHg. In healthy lungs the time taken for alveolar gas to equilibrate with pulmonary capillary blood is about the same as with O2: 0.25 s.
  • Hypercapnia is never caused by decreased diffusing capacity (except when carbonic anhydrase is inhibited by acetazolamide which slows conversion of bicarb to carbonic acid to CO2)