Used to determine cause of hypoxemia
The mechanism of hypoxemia is often multifactorial, meaning that many disease-states will cause hypoxemia via a combination of V/Q mismatch, shunt, and diffusion impairment.
Common causes of V/Q mismatch include obstructive pulmonary disease, interstitial lung disease, and pulmonary vascular disease.
Common causes of shunt include arteriovenous malformations, hepatopulmonary syndrome, and underventilated alveoli (ie. atelectasis or alveoli filled with edema, pus, blood, etc).
Common causes of diffusion impairment include interstitial lung disease and other causes of pulmonary fibrosis / inflammation.
The A-a gradient normally will increase with increasing FiO2, sometimes reaching values over 100 with inhalation of 100% oxygen. Another formula takes into account patient temperature which can have a minor impact on pH2O.
Acta Physiologica Scandinavica 1966, 67 (1): 10-20
Rodriguez-Roisin R, Roca J.
Intensive Care Medicine 2005, 31 (8): 1017-9
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