Respiratory & Critical CareEvidence-Based Golden Standard
Alveolar-Arterial Oxygen Gradient (A-a Gradient)
Measures the integrity of alveolar-capillary gas exchange to differentiate extrapulmonary hypoventilation from intrinsic pulmonary parenchymal or vascular disease.
P_A O₂ = (P_atm - 47) × FiO₂ - (PaCO₂ / 0.8)
A-a Gradient = P_A O₂ - PaO₂
Expected Normal = (Age / 4) + 4
Published Clinical Benchmark Cases
Clinical Parameters & Inputs
Room air is 0.21 (21%). Supplemental oxygen increases FiO2.
Unit: mmHg
mmHg
Unit: mmHg
mmHg
Unit: mmHg
mmHg
Sea level standard is 760 mmHg. High altitude lowers Patm.
Computed OutputNormal A-a Gradient (Extrapulmonary / Hypoventilation)
4.7mmHg
Diagnostic Interpretation
A-a Gradient is normal (4.7 mmHg, expected ≤ 14 mmHg). If hypoxemia is present, it is caused by extrapulmonary hypoventilation (opioid overdose, neuromuscular weakness, severe obesity hypoventilation, CNS depression) or low ambient oxygen tension (high altitude). Pulmonary parenchyma is structurally intact.
Calculation Breakdown
Calculated Alveolar PO₂ (P_A O₂)
(760 - 47) × 0.21 - (40 / 0.8) =99.7 mmHg
A-a Gradient (P_A O₂ - PaO₂)
99.7 - 95 =4.7 mmHg
Age-Adjusted Expected Normal
(40 / 4) + 4 =~14 mmHg
Clinical Decision Pearls
- A normal A-a gradient with hypoxemia and hypercapnia is the hallmark of pure hypoventilation (e.g. opioid overdose), reversible with naloxone/ventilation.
- An elevated A-a gradient with acute hypoxemia mandates evaluation for pulmonary embolism, pneumonia, or pulmonary edema.
Limitations & Confounders
- Accurate primarily on room air (FiO2 0.21). High inspired oxygen concentrations (FiO2 > 0.5) significantly widen the physiological gradient.
Evidence & Citations
- Kanber GJ, et al. The alveolar-arterial oxygen gradient in normal subjects. Dis Chest. 1968;53(3):269-276.
- Mellemgaard K. The alveolar-arterial oxygen difference: its size and components in normal man. Acta Physiol Scand. 1966;67(1):10-20.