What is a normal A-a gradient?

A normal A-a gradient is estimated by the formula: (Age/4) + 4. For a young healthy adult, a normal gradient is approximately 5–15 mmHg. An elevated A-a gradient suggests a pulmonary cause of hypoxemia such as V/Q mismatch, shunt, or diffusion impairment.

How do you calculate the A-a gradient?

The A-a gradient is calculated as: A-a gradient = PAO₂ − PaO₂, where PAO₂ (alveolar oxygen) = (FiO₂ × (Patm − PH₂O)) − (PaCO₂ / RQ). At sea level on room air: PAO₂ = (0.21 × 713) − (PaCO₂ / 0.8).

What does an elevated A-a gradient indicate?

An elevated A-a gradient indicates a pulmonary cause of hypoxemia, including V/Q mismatch (e.g., PE, pneumonia), right-to-left shunt, or diffusion impairment (e.g., interstitial lung disease). A normal A-a gradient with hypoxemia suggests hypoventilation or low FiO₂ as the cause.

Does the A-a gradient change with age?

Yes, the A-a gradient normally increases with age due to age-related decreases in PaO₂. The expected normal upper limit can be estimated as (Age/4) + 4 mmHg. This means an A-a gradient of 20 mmHg may be normal for an 80-year-old but elevated for a 20-year-old.

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A-a Gradient Calculator

Alveolar-arterial oxygen gradient — helps differentiate causes of hypoxemia.

Inputs

Age (years)

FiO₂ (%) Room air = 21%

PaO₂ (mmHg)

PaCO₂ (mmHg)

Atmospheric Pressure (mmHg) Standard = 760 mmHg. Adjust for altitude.

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Enter values to calculate A-a gradient.

Normal A-a gradient= (Age/4) + 4 mmHg

Normal (on room air)< 10–15 mmHg in young adults

ElevatedV/Q mismatch, shunt, or diffusion impairment

Normal gradient + hypoxemiaHypoventilation or low FiO₂

Disclaimer: For educational purposes only. Not a substitute for clinical judgment.

When to use

Use the A-a gradient to differentiate causes of hypoxemia: a normal gradient suggests hypoventilation or low inspired O₂, while an elevated gradient suggests V/Q mismatch, shunt, or diffusion impairment.

Clinical pearls

The A-a gradient normally increases with age: expected normal ≈ (Age/4) + 4.
On room air, a gradient >15 mmHg in a young adult is elevated.
The gradient increases with higher FiO₂ — interpret cautiously on supplemental O₂.
COPD, PE, pneumonia, and pulmonary fibrosis all cause elevated A-a gradients.

References

Malley WJ. Clinical Blood Gases: Assessment & Intervention. 2nd ed. Saunders, 2005.
Staub NC. Alveolar-arterial oxygen tension gradient due to diffusion. J Appl Physiol. 1963;18:673-680.

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About This Tool

What Is the A-a Gradient?

The alveolar-arterial (A-a) oxygen gradient is the difference between the partial pressure of oxygen in the alveoli (PAO₂) and in arterial blood (PaO₂). It is a measure of the efficiency of gas exchange across the alveolar-capillary membrane. The A-a gradient helps clinicians differentiate between pulmonary and extrapulmonary causes of hypoxemia, making it a fundamental tool in the evaluation of respiratory failure and hypoxemia.

How It Is Calculated

The A-a gradient is calculated as PAO₂ − PaO₂, where PAO₂ is derived from the alveolar gas equation: PAO₂ = FiO₂ × (Patm − PH₂O) − (PaCO₂ / R). The respiratory quotient (R) is assumed to be 0.8, and water vapor pressure (PH₂O) at body temperature is 47 mmHg. On room air at sea level: PAO₂ = 0.21 × (760 − 47) − (PaCO₂ / 0.8) = 149.7 − (PaCO₂ × 1.25). The resulting gradient is then compared to the age-expected normal: approximately (Age/4) + 4 mmHg.

Clinical Significance

A normal A-a gradient in a hypoxemic patient points to hypoventilation (e.g., opioid overdose, neuromuscular disease) or low inspired oxygen (high altitude) as the cause. An elevated gradient indicates a problem at the pulmonary level: V/Q mismatch (COPD, PE, pneumonia), right-to-left shunt (intracardiac shunt, severe ARDS), or diffusion impairment (pulmonary fibrosis). The A-a gradient is most clinically useful on room air — it increases at higher FiO₂ levels and should be interpreted cautiously in patients on supplemental oxygen.

🔑 Clinical Pearls

Normal A-a gradient on room air rules out significant pulmonary parenchymal disease as the cause of hypoxemia.
In PE, the A-a gradient is almost always elevated, but a normal gradient does not definitively exclude PE.
The PaO₂/FiO₂ (P/F) ratio is often preferred in ICU settings for simplicity; A-a gradient provides more granularity.
At altitude, reduce Patm accordingly — Denver (~1600m) ≈ 630 mmHg, Mexico City (~2200m) ≈ 580 mmHg.

Key References

Malley WJ. Clinical Blood Gases: Assessment & Intervention. 2nd ed. Saunders, 2005.
Harris EA, et al. The normal alveolar-arterial oxygen-tension gradient in man. Clin Sci Mol Med. 1974;46(1):89-104.
Kanber GJ, et al. The alveolar-arterial oxygen gradient in young and elderly subjects breathing room air. J Gerontol. 1968;23:174-177.

Formula last verified: February 2026