The Alveolar–arterial gradient (A-, 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 a useful parameter for narrowing the differential diagnosis of hypoxemia. The A–a gradient helps to assess the integrity of the alveolar capillary unit. For example, in high altitude, the arterial oxygen is low but only because the alveolar oxygen () 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. In a perfect system, no A-a gradient would exist: oxygen would diffuse and equalize across the capillary membrane, and the pressures in the arterial system and alveoli would be effectively equal (resulting in an A-a gradient of zero). However 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, is always higher than 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 ratio 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. Equation The equation for calculating the A–a gradient is: Where: = alveolar (calculated from the alveolar gas equation) = arterial (measured in arterial blood) In its expanded form, the A–a gradient can be calculated by: On room air ( = 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 Clinical Significance The A–a gradient