Pulmonology
A-a Gradient
Alveolar-arterial oxygen gradient (kPa).
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Background
The alveolar-arterial (A-a) gradient is the difference between the calculated alveolar oxygen tension (PAO₂) and the measured arterial oxygen tension (PaO₂). PAO₂ is derived from the alveolar gas equation using the fraction of inspired oxygen, the atmospheric pressure minus water vapour pressure, and the arterial carbon dioxide tension divided by the respiratory quotient. Expressed here in kPa at sea level, the gradient indicates how efficiently oxygen is moving from the alveoli into the blood. It is used to work out the mechanism behind a low arterial oxygen level.
Interpreting the result
A normal A-a gradient with hypoxaemia points to hypoventilation or a low inspired oxygen, because gas exchange across the membrane is intact. A raised gradient indicates a problem with gas exchange itself — such as ventilation/perfusion mismatch, shunt or diffusion impairment — as seen in pneumonia, pulmonary embolism, oedema or fibrosis. The normal gradient rises with age, roughly age divided by 10 plus 0.5 kPa, so this must be allowed for. The gradient is a mechanism tool, not a diagnosis.
Worked example
A 70-year-old breathing room air (FiO₂ 21%) has a PaCO₂ of 5 kPa and PaO₂ of 8 kPa. PAO₂ ≈ (0.21 × 95) − (5 ÷ 0.8) ≈ 19.95 − 6.25 ≈ 13.7 kPa, so the A-a gradient ≈ 13.7 − 8 ≈ 5.7 kPa — clearly above the age-expected value, indicating impaired gas exchange.
Critical actions
This uses kPa at sea level (atmospheric − water vapour ≈ 95 kPa, RQ 0.8). The normal gradient rises with age (roughly age/10 + 0.5 kPa). A raised gradient indicates impaired gas exchange.
Pearls / pitfalls
- The expected normal gradient widens with age and with higher inspired oxygen, so a single fixed cut-off is misleading.
- Make sure the inputs are in consistent units; mixing kPa and mmHg will give a nonsensical gradient.
- A normal gradient with hypoxaemia suggests hypoventilation or low inspired oxygen rather than a lung gas-exchange problem.
- A high inspired oxygen exaggerates the gradient, so interpret values obtained on supplemental oxygen with care.
Evidence & validation
The gradient is derived directly from the alveolar gas equation, a long-established physiological relationship, and is a standard part of arterial blood gas interpretation in respiratory and critical-care practice.
Frequently asked questions
What does a raised A-a gradient indicate?
A raised gradient means oxygen is not transferring efficiently from alveoli to blood, pointing to ventilation/perfusion mismatch, shunt or diffusion impairment — for example in pneumonia, pulmonary embolism, oedema or fibrosis.
What does a normal gradient with low oxygen mean?
If the gradient is normal but the patient is hypoxaemic, the cause is usually hypoventilation or a low inspired oxygen concentration, because the gas-exchange surface itself is working.
How does age affect the normal gradient?
The expected gradient rises with age, approximately age divided by 10 plus 0.5 kPa. An older person therefore has a higher normal value, and this must be allowed for before calling a gradient abnormal.
Why does supplemental oxygen change the gradient?
Breathing a higher fraction of inspired oxygen raises the alveolar oxygen tension and tends to widen the gradient, so values measured on oxygen are harder to interpret and are best assessed against the inspired concentration used.
Does the A-a gradient diagnose pulmonary embolism?
No. A raised gradient is consistent with embolism but is non-specific and can be normal in some cases, so it cannot rule the diagnosis in or out; dedicated investigations are needed.
References
- Curran-Everett D. A classic learning opportunity from Fenn, Rahn, and Otis (1946): the alveolar gas equation. Adv Physiol Educ. 2006.
- West JB. Respiratory Physiology: The Essentials. Lippincott Williams & Wilkins.
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