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The alveolar-arterial oxygen difference (also called A-a gradient or A-a O₂ difference)
The alveolar-arterial oxygen difference (also called A-a gradient or A-a O₂ difference) is the difference between alveolar oxygen partial pressure (PAO₂) and arterial oxygen partial pressure (PaO₂), measured in mmHg. It reflects how efficiently oxygen transfers from the alveoli to the blood.
Normal Values (on room air, FiO₂ = 0.21)
The normal A-a gradient varies primarily with age due to increasing ventilation-perfusion mismatch and minor physiological shunting as people get older. It is not significantly affected by minor changes in PaCO₂ in healthy people, but the main factors are age and FiO₂.
Commonly accepted normal ranges (on room air):
Young healthy adults (e.g., 20–30 years): 5–10 mmHg (often cited as <10 mmHg)
Overall healthy non-smokers: <15–20 mmHg (varies by source)
Increases with age — a practical rule of thumb for the upper limit of normal is:
Expected upper limit of normal A-a gradient ≈ (age in years / 4) + 4
Examples using this formula:
Age 20: (20/4) + 4 = 9 mmHg
Age 40: (40/4) + 4 = 14 mmHg
Age 60: (60/4) + 4 = 19 mmHg
Age 80: (80/4) + 4 = 24 mmHg
Some sources use slight variations, like (age + 10)/4 or simply note it rises by ~1 mmHg per decade of life.
Key Points:
A normal A-a gradient in a hypoxic patient suggests the cause is not lung parenchymal issue (e.g., hypoventilation, low inspired O₂, or extrapulmonary shunts).
An elevated A-a gradient points to intrapulmonary problems like V/Q mismatch, shunt, or diffusion limitation (e.g., pneumonia, pulmonary edema, ARDS, PE).
On higher FiO₂ (supplemental oxygen), the A-a gradient normally increases (roughly 5–7 mmHg per 10% rise in FiO₂), and can reach >100 mmHg even in healthy lungs on 100% O₂ due to absorption atelectasis and other effects.