A-a Gradient — Formula & Interpretation
At sea level: PAO₂ = (FiO₂ × 713) − (PaCO₂ ÷ 0.8)
A-a Gradient = PAO₂ − PaO₂
Age-adjusted normal A-a gradient = (Age ÷ 4) + 4 mmHg
Normal range at rest (room air): 5–15 mmHg (young) up to 25 mmHg (elderly)
Clinical Significance of A-a Gradient
The A-a gradient measures the efficiency of oxygen transfer from alveoli to blood. A normal A-a gradient in a hypoxaemic patient suggests a non-pulmonary cause — such as hypoventilation or low inspired oxygen. An elevated A-a gradient confirms a pulmonary problem — either V/Q mismatch, diffusion impairment, or shunt.
- Hypoventilation (↑PaCO₂)
- Opioid/sedative overdose
- Neuromuscular disease
- High altitude (low FiO₂)
- Central hypoventilation
- V/Q mismatch (PE, COPD, asthma)
- Pulmonary oedema
- Pneumonia / consolidation
- ARDS
- Pulmonary fibrosis
- Intracardiac shunt (ASD, VSD)
- Atelectasis
A-a Gradient in PE Diagnosis
An elevated A-a gradient is present in ~85% of patients with pulmonary embolism. However, a normal A-a gradient does NOT exclude PE — ~15% of PE patients have a normal A-a gradient, particularly young patients with smaller emboli. The A-a gradient is best used in conjunction with clinical pre-test probability (Wells Score) rather than as a standalone rule-out test. A normal A-a gradient combined with low Wells score significantly reduces PE probability.
A-a Gradient on Supplemental Oxygen
On higher FiO₂, the normal A-a gradient increases — the formula assumes this is accounted for. On 100% FiO₂, the normal A-a gradient can be up to 100 mmHg in healthy adults. A useful rule: on 100% O₂, PaO₂ should be >500 mmHg. If PaO₂ <300 mmHg on 100% O₂, there is significant intrapulmonary or intracardiac shunt.