The Alveolar–arterial gradient (A-aO2, or A–a gradient), is a measure of the difference between the alveolar concentration (A) of oxygen and the arterial (a) concentration of oxygen. It is used in diagnosing the source of hypoxemia.
The A–a gradient helps to assess the integrity of the alveolar capillary unit. For example, in high altitude, the arterial oxygen PaO2 is low but only because the alveolar oxygen (PAO2) is also low. However, in states of ventilation perfusion mismatch, such as pulmonary embolism or right-to-left shunt, oxygen is not effectively transferred from the alveoli to the blood which results in an elevated A-a gradient.
Even though the partial pressure of oxygen is about equilibrated between the pulmonary capillaries and the alveolar gas, this equilibrium is not maintained as blood travels further through pulmonary circulation. As a rule, PAO2 is always higher than PaO2 by at least 5–10 mmHg, even in a healthy person with normal ventilation and perfusion. This gradient exists due to both physiological right-to-left shunting and a physiological V/Q mismatch caused by gravity-dependent differences in perfusion to various zones of the lungs. The bronchial vessels deliver nutrients and oxygen to certain lung tissues, and some of this spent, deoxygenated venous blood drains into the highly oxygenated pulmonary veins, causing a right-to-left shunt. Further, the effects of gravity alter the flow of both blood and air through various heights of the lung. In the upright lung, both perfusion and ventilation are greatest at the base, but the gradient of perfusion is steeper than that of ventilation so V/Q is higher at the apex than at the base. This means that blood flowing through capillaries at the base of the lung is not fully oxygenated.
The equation for calculating the A–a gradient is:
- PAO2 = alveolar PO2 (calculated from the alveolar gas equation)
- PaO2 = arterial PO2 (measured in arterial blood)
In its expanded form, the A–a gradient can be calculated by:
On room air ( FiO2 = 0.21, or 21% ), at sea level ( Patm = 760 mmHg ) assuming 100% humidity in the alveoli (PH2O = 47 mmHg), a simplified version of the equation is:
Values and meaning
The A–a gradient is useful in determining the source of hypoxemia. The measurement helps isolate the location of the problem as either intrapulmonary (within the lungs) or extrapulmonary (elsewhere in the body).
A normal A–a gradient for a young adult non-smoker breathing air, is between 5–10 mmHg. Normally, the A–a gradient increases with age. For every decade a person has lived, their A–a gradient is expected to increase by 1 mmHg. A conservative estimate of normal A–a gradient is less than [age in years/4] + 4. Thus, a 40-year-old should have an A–a gradient less than 14.
Because A–a gradient is approximated as: (150 − 5/4(PCO2)) – PaO2 at sea level and on room air (0.21x(760-47) = 149.7 mmHg for the alveolar oxygen partial pressure, after accounting for the water vapor), the direct mathematical cause of a large value is that the blood has a low PaO2, a low PaCO2, or both. CO2 is very easily exchanged in the lungs and low PaCO2 directly correlates with high minute ventilation; therefore a low arterial PaCO2 indicates that extra respiratory effort is being used to oxygenate the blood. A low PaO2 indicates that the patient's current minute ventilation (whether high or normal) is not enough to allow adequate oxygen diffusion into the blood. Therefore, the A–a gradient essentially demonstrates a high respiratory effort (low arterial PaCO2) relative to the achieved level of oxygenation (arterial PaO2). A high A–a gradient could indicate a patient breathing hard to achieve normal oxygenation, a patient breathing normally and attaining low oxygenation, or a patient breathing hard and still failing to achieve normal oxygenation.
If lack of oxygenation is proportional to low respiratory effort, then the A–a gradient is not increased; a healthy person who hypoventilates would have hypoxia, but a normal A–a gradient. At an extreme, high CO2 levels from hypoventilation can mask an existing high A–a gradient. This mathematical artifact makes A–a gradient more clinically useful in the setting of hyperventilation.
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