For efficient gas exchange there must be a match between ventilation of the alveoli ([Vdot]A) and their perfusion ([Qdot]). There is a wide variation in the [Vdot]A/[Qdot] ratio throughout both normal and diseased lung. In the normal lung the extreme relationships between alveolar ventilation and perfusion are:

• ventilation with reduced perfusion (physiological deadspace)
• perfusion with reduced ventilation (physiological shunting).

In normal lungs there is a tendency for ventilation to exceed perfusion towards the apices, with the reverse occurring at the bases.

An increased physiological shunt results in arterial hypoxaemia. The effects of an increased physiological deadspace can usually be overcome by a compensatory increase in the ventilation of normally perfused alveoli. In advanced disease this compensation cannot occur, leading to increased alveolar and arterial Pco2, together with hypoxaemia which cannot be compensated by increasing ventilation.

Hypoxaemia occurs more readily than hypercapnia because of the different ways in which oxygen and carbon dioxide are carried in the blood. Carbon dioxide can be considered to be in simple solution in the plasma, the volume carried being proportional to the partial pressure. Oxygen is carried in chemical combination with haemoglobin in the red blood cells, and the relationship between the volume carried and the partial pressure is not linear. Alveolar hyperventilation reduces the alveolar Pco2 and diffusion leads to a proportional fall in the carbon dioxide content of the blood. However, as the haemoglobin is already saturated with oxygen, there is no significant increase in the blood oxygen content as a result of increasing the alveolar Po2 through hyperventilation. The hypoxaemia of even a small amount of physiological shunting cannot therefore be compensated for by hyperventilation.

In individuals who have mild disease of the lung causing slight [Vdot]A/[Qdot] mismatch, the Pao2 and Paco2 may still be normal. Increasing the requirements for gas exchange by exercise will widen the [Vdot]A/[Qdot] mismatch and the Pao2 will fall. [Vdot]A/[Qdot] mismatch is by far the most common cause of arterial hypoxaemia.

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