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 [age in years + 10]/ 4. Thus, a 40-year-old should have an A–a gradient around 12.5 mmHg. The value calculated for a patient's A-a gradient can assess if their hypoxia is due to the dysfunction of the alveolar-capillary unit, for which it will elevate, or due to another reason, in which the A-a gradient will be at or lower than the calculated value using the above equation. An abnormally increased A–a gradient suggests a defect in diffusion, V/Q mismatch, or right-to-left shunt. The A-a gradient has clinical utility in patients with hypoxemia of undetermined etiology. The A-a gradient can be broken down categorically as either elevated or normal. Causes of hypoxemia will fall into either category. To better understand which etiologies of hypoxemia falls in either category, we can use a simple analogy. Think of the oxygen's journey through the body like a river. The respiratory system will serve as the first part of the river. Then imagine a waterfall from that point leading to the second part of the river. The waterfall represents the alveolar and capillary walls, and the second part of the river represents the arterial system. The river empties into a lake, which can represent end-organ perfusion. The A-a gradient helps to determine where there is flow obstruction. For example, consider hypoventilation. Patients can exhibit hypoventilation for a variety of reasons; some include CNS depression, neuromuscular diseases such as myasthenia gravis, poor chest elasticity as seen in kyphoscoliosis or patients with vertebral fractures, and many others. Patients with poor ventilation lack oxygen tension throughout their arterial system in addition to the respiratory system. Thus, the river will have decreased flow throughout both parts. Since both the "A" and the "a" decrease in concert, the gradient between the two will remain in normal limits (even though both values will decrease). Thus patients with hypoxemia due to hypoventilation will have an A-a gradient within normal limits. Now let us consider pneumonia. Patients