The alveolar-arterial (A-a) oxygen gradient is a measure of the efficiency of the transfer of oxygen from the lungs to the blood. Oxygen normally diffuses rapidly across alveolar membranes, and so the gradient is normally close to zero.
The gradient is best determined if the arterial blood is drawn after the patient has been breathing ambient air for at least 5 minutes
The Clinical Use and Reference Intervals are below the Calculation section.
The gradient is: P(A-a)O2 = PAO2 - PaO2
where PAO2 is the partial pressure of oxygen in alveolar air and PaO2 is the partial pressure of oxygen in arterial blood.
PaO2 is measured in the arterial blood sample by the blood gas analyser.
PAO2 is calculated according to the alveolar air equation, which follows:
PB = PAO2 + PACO2 + PAN2 + PAH2O
where the barometric pressure PB equals the sum of the individual partial pressures all of the component gases in alveolar air:
PAO2 = PB - (PACO2 + PAN2 + PAH2O)
PB is the barometric pressure, which is measured by the blood gas analyser.
PaCO2, the measured arterial carbon dioxide pressure is substituted for PACO2, the alveolar carbon dioxide pressure. This is not strictly valid, but because carbon dioxide is very soluble in water and diffuses at twenty times the rate of oxygen, the error is small in most patients. If there is marked ventilation/perfusion inequality or arterio-venous shunting, the calculated gradient will be lower than the true gradient.
PAN2 is the pressure of nitrogen, and is constant in normal air. If oxygen is being added to inspired air, PAN2 can be calculated by difference.
PAH2O is the pressure of water in alveolar air, and is constant.
The gradient is therefore measured and calculated as:
P(A-a)O2 = [PB - (PaCO2 + k)] - PaO2
(where constant k = PAN2 + PAH2O)
The gradient is used to distinguish two primary causes of hypoxaemia:
1. Hypoxaemia caused by alveolar hypoventilation alone (e.g. neuromuscular disease, drug overdose, chest wall disease), where the gradient is normal (both alveolar and arterial oxygen are reduced)
2. Hypoxaemia due to a ventilation-perfusion mismatch, right to left veno-arterial shunting of blood, or a barrier to oxygen diffusion (e.g. obstructive airways disease, parenchymal lung disease, pulmonary oedema, pulmonary vascular disease, intra-cardiac shunting, and the hepatopulmonary syndrome) where the gradient is increased.
Although the gradient is increased in the majority of patients with a pulmonary embolus, a significant number will have a normal gradient. It should not be used as screening test for this condition, but is useful for confirmation and for monitoring treatment if it is abnormal.
The gradient may also be falsely lowered if there is a high alveolar PCO2.
The gradient is increased in smokers, and it increases with normal aging.
This is age dependent, with the mean P(A - a)O2 gradient for age being:
P(A-a)O2 = 2.5 + 0.21(age in years) mm Hg
(ref.: Mellengaard K The alveolar-arterial oxygen difference: Its size and components in normal man. Acta Physiol Scand. 1966, 67:10-20.)
The maximum (mean + 2SD) A-a gradient for age is:
20 years < 2.5 kPa (19 mm Hg)
40 years < 3.2 kPa (24 mm Hg)
60 years < 3.7 kPa (28 mm Hg)
80 years < 4.0 kPa (30 mm Hg)