Alveolar - Arterial Oxygen
Gradient
INTRODUCTION:
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 Ranges are below the Calculation
section.
Calculation:
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:
Rearranging the equation:
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)
CLINICAL USE:
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)
Hypoxaemia with a normal A-a gradient requires
augmentation of ventilation, and oxygen therapy may be contra-indicated
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.
Hypoxaemia with an increased A-a gradient
usually requires oxygen therapy.
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.
REFERENCE INTERVAL:
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
- divide by 7.5 to convert to kPa
(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)