Alveolar-Arterial Gradient and Mechanisms of Hypoxaemia
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Direct answer
The alveolar-arterial gradient is the difference between alveolar and arterial oxygen tension, normally small and rising with age. It separates hypoxaemia from hypoventilation or low inspired oxygen, where the gradient is normal, from V/Q mismatch, shunt and diffusion limitation, where it is raised. Calculating it requires the alveolar gas equation, using the inspired oxygen fraction, barometric pressure and arterial carbon dioxide tension.
What you must remember
- Alveolar gas equation: PAO2 = FiO2 × (barometric pressure minus 47 mmHg) minus PaCO2 divided by the respiratory quotient, usually taken as 0.8.
- Normal gradient: roughly age divided by 4, plus 4 mmHg, so the normal value rises with age.
- Hypoventilation: the gradient is normal while PaCO2 is raised, because alveolar and arterial oxygen fall together.
- Low inspired oxygen: the gradient is normal, as at high altitude where barometric pressure and FiO2 fall.
- V/Q mismatch: a raised gradient that responds well to supplemental oxygen, as in pneumonia, asthma and pulmonary embolism.
- Shunt: a raised gradient that responds poorly to oxygen, because blood bypasses ventilated alveoli.
- Diffusion limitation: a raised gradient that widens on exercise and corrects with supplemental oxygen, seen in conditions such as pulmonary fibrosis.
Using the gradient to find the mechanism
Every arterial blood gas can be sorted into a mechanism once paired values are available. The steps turn a set of numbers into a working diagnosis.
- Calculate the alveolar oxygen: Use the FiO2, barometric pressure minus the water vapour pressure of 47 mmHg, and PaCO2 divided by 0.8 to obtain PAO2.
- Subtract the arterial value: The gradient is PAO2 minus PaO2, and a value above the age-predicted normal indicates a lung cause.
- Check the PaCO2: A raised PaCO2 with a normal gradient points to hypoventilation, where the problem lies in ventilation rather than gas exchange.
- Check the inspired oxygen: A normal gradient with normal PaCO2 and a low FiO2 points to altitude or low inspired oxygen.
- Test the oxygen response: Hypoxaemia that corrects with supplemental oxygen suggests V/Q mismatch or diffusion limitation, while poor correction suggests shunt.
- Consider the clinical context: Pneumonia, pulmonary embolism, fibrosis and cardiac shunts each produce a characteristic pattern that supports the mechanism.
Where the gradient gets misread
Most errors come from applying a fixed normal value or reading oxygen therapy as proof of a mechanism.
- Trap: calling hypercapnia with a normal gradient a V/Q problem Correct: a normal gradient with raised PaCO2 is hypoventilation, because the alveolar and arterial values fall in parallel.
- Trap: using one normal gradient value for every age Correct: the normal gradient rises with age, so an older adult can have a gradient that is normal for age.
- Trap: expecting 100 per cent oxygen to correct a shunt Correct: shunted blood bypasses alveoli, so even high-concentration oxygen corrects PaO2 only partially.
Frequently asked questions
What is the alveolar gas equation used for?
The alveolar gas equation estimates alveolar oxygen tension, which is then compared with arterial oxygen tension to calculate the alveolar-arterial gradient. It uses the inspired oxygen fraction, barometric pressure, water vapour pressure and PaCO2 divided by a respiratory quotient of 0.8.
What is the normal alveolar-arterial gradient?
The normal alveolar-arterial gradient is roughly age divided by four, plus four mmHg, so it increases with age. A young adult breathing room air normally has a small gradient, while an older person may normally have a larger one.
Why is the gradient normal in hypoventilation?
In hypoventilation both alveolar and arterial oxygen tensions fall together, so the difference between them stays normal. The raised PaCO2 is the clue, and the problem lies in ventilation rather than gas exchange.
Which mechanisms of hypoxaemia respond to oxygen therapy?
V/Q mismatch and diffusion limitation respond well to supplemental oxygen, because the affected alveoli can still be ventilated. Shunt responds poorly, because blood bypasses ventilated alveoli, so even high-concentration oxygen corrects PaO2 only partially.