The (A-a)PO2 difference is elevated in patients with hypoxemia due to shunt, diffusion limitation, or V/Q mismatch. It is normal in patients with pure hypoventilation resulting in lower alveolar and lower arterial PO2 but no change in (A-a)PO2. However, the (A-a)PO2 difference is difficult to interpret in patients with elevated PCO2 and V/Q mismatch; e.g., COPD.
Why is this so?
Basically, this is due to the shape of the O2 dissociation curve.
The figure below is from the article: http://ajrccm.atsjournals.org/content/143/1/4.full.pdf+html