How it's calculated
PAO2 (alveolar) is found with the alveolar gas equation: PAO2 = FiO2 × (760 − 47) − (PaCO2 / 0.8), assuming sea-level atmospheric pressure and a respiratory quotient of 0.8. The A-a gradient is then PAO2 − PaO2 (measured from an arterial blood gas), compared against an age-adjusted expected normal of approximately (age / 4) + 4.
Interpretation
| A-a gradient | Likely cause pattern |
|---|---|
| Normal, with hypoxaemia | Hypoventilation or a low inspired O2 fraction (e.g. high altitude) |
| Elevated | V/Q mismatch, diffusion defect, or right-to-left shunt |
Clinical use
- Distinguishes hypoxaemia due to hypoventilation (normal A-a gradient) from hypoxaemia due to V/Q mismatch, diffusion impairment, or shunt (elevated gradient).
- Used in the initial work-up of unexplained hypoxaemia or dyspnoea, alongside the rest of the arterial blood gas and clinical picture.
- A gradient that fails to correct significantly with supplemental oxygen points more toward shunt physiology than V/Q mismatch.
Frequently asked questions
What is a normal A-a gradient?
Roughly (age / 4) + 4 mmHg — the gradient normally widens somewhat with age due to progressive V/Q mismatch.
Why does the formula need FiO2 and not just room air?
The alveolar gas equation calculates alveolar oxygen tension from whatever inspired oxygen fraction is being delivered, so the gradient can still be estimated (with caution) on supplemental oxygen, though it is most reliable and standardised on room air.
What does a normal A-a gradient with hypoxaemia suggest?
That the lungs are gas-exchanging normally — the hypoxaemia is more likely from hypoventilation (e.g. opioid overdose, neuromuscular weakness) or breathing air with a low oxygen fraction, rather than intrinsic lung disease.
References
- West JB. Respiratory Physiology: The Essentials. Lippincott Williams & Wilkins.
- Mellemgaard K. The alveolar-arterial oxygen difference: its size and components in normal man. Acta Physiol Scand. 1966.