Physiology 5th Ed.


Hypoxemia is defined as a decrease in arterial PO2. Hypoxia is defined as a decrease in O2 delivery to, or utilization by, the tissues. Hypoxemia is one cause of tissue hypoxia, although it is not the only cause.


Hypoxemia, a decrease in arterial PO2, has multiple causes, which are summarized in Table 5-5.

Table 5–5 Causes of Hypoxemia


One useful tool for comparing the various causes of hypoxemia is the A − a gradient, or A − a difference. The A − a gradient is the difference between the PO2 of alveolar gas (image) and the PO2 of systemic arterial blood (image). As explained earlier in this chapter, in this context, “A” stands for alveolar PO2 and “a” stands for systemic arterial PO2.


image is calculated with the alveolar gas equation and substituted as follows:


Briefly, the A − a gradient describes whether there has been equilibration of O2 between alveolar gas and pulmonary capillary blood (which becomes systemic arterial blood). Normally, O2 equilibrates across the alveolar-pulmonary capillary barrier and the A − a gradient is close to zero. In some but not all causes of hypoxemia, the A − a gradient is increased, or widened, signifying a defect in O2 equilibration.

image High altitude causes hypoxemia because barometric pressure (PB) is decreased, which decreases the PO2 of inspired air (image) and of alveolar air (image). Equilibration of O2 across the alveolar/pulmonary capillary barrier is normal, and systemic arterial blood achieves the same (lower) PO2 as alveolar air. Because image and image are nearly equal, the A − a gradient is normal. At high altitude, breathing supplemental O2 raises arterial PO2 by raising inspired and alveolar PO2.

image Hypoventilation causes hypoxemia by decreasing alveolar PO2 (less fresh inspired air is brought into alveoli). Equilibration of O2 is normal, and systemic arterial blood achieves the same (lower) PO2 as alveolar air. image and image are nearly equal, and the A − a gradient is normal. In hypoventilation, breathing supplemental O2 raises arterial PO2 by raising the alveolar PO2.

image Diffusion defects (e.g., fibrosis, pulmonary edema) cause hypoxemia by increasing diffusion distance or decreasing surface area for diffusion. Equilibration of O2 is impaired, image is less than image, and the A − a gradient is increased, or widened. With diffusion defects, breathing supplemental O2 raises arterial PO2 by raising alveolar PO2 and increasing the driving force for O2 diffusion.

image imagedefects always cause hypoxemia and increased A − a gradient. Recall that image defects usually present as a constellation of abnormalities that may include regions of dead space, high image, low image and shunt. Recall also that high image regions have a high PO2 and low image regions have a low PO2. The question may then arise: Inimagedefects, why don’t regions of high imagecompensate for regions of low imageso that the PO2 of blood leaving the lungs is normal? The answer is that while high image regions have blood with a high PO2, blood flow to those regions is low (i.e., high image ratio) and contributes little to total blood flow. Low image regions, where PO2 is low, have the highest blood flow and the greatest overall effect on PO2 of blood leaving the lungs. In image defects, supplemental O2 can be helpful, primarily because it raises the PO2 of low image regions where blood flow is highest.

image Right-to-left shunts (right-to-left cardiac shunts, intrapulmonary shunts) always cause hypoxemia and increased A − a gradient. Shunted blood completely bypasses ventilated alveoli and cannot be oxygenated (see Fig. 5-27). Because shunted blood mixes with, and dilutes, normally oxygenated blood (nonshunted blood), the PO2 of blood leaving the lungs must be lower than normal. Supplemental O2has a limited effect in raising the PO2 of systemic arterial blood because it can only raise the PO2 of normal nonshunted blood; the shunted blood continues to have a dilutional effect. Therefore, the ability of supplemental O2 to raise the image of systemic arterial blood will depend on the size of the shunt: The larger the shunt, the less effective is supplemental O2.

  Another feature of treating right-to-left shunts with supplemental O2 is that it never corrects the increased A − a gradient; in fact, as supplemental O2 is administered, the A − a increases or widens because image increases faster than image increases.


Hypoxia is decreased O2 delivery to the tissues. Because O2 delivery is the product of cardiac output and O2 content of blood, hypoxia is caused by decreased cardiac output (blood flow) or decreased O2content of blood. Recall that O2 content of blood is determined primarily by the amount of O2-hemoglobin. Causes of hypoxia are summarized in Table 5-6.

Table 5–6 Causes of Hypoxia




↓ Cardiac output

↓ Blood flow


↓ image


↓ O2 saturation of hemoglobin


↓ O2 content of blood



↓ Hemoglobin concentration


↓ O2 content of blood



monoxide poisoning

↓ O2 content of blood Left shift of O2-hemoglobin curve

Cyanide poisoning

↓ O2 utilization by tissues

decrease in cardiac output and a decrease in regional (local) blood flow are self-evident causes of hypoxia. Hypoxemia (due to any cause; see Table 5-5) is a major cause of hypoxia. The reason that hypoxemia causes hypoxia is that a decreased image reduces the percent saturation of hemoglobin (see Fig. 5-20). O2-hemoglobin is the major form of O2 in blood; thus, a decrease in the amount of O2-hemoglobin means a decrease in total O2 content. Anemia,or decreased hemoglobin concentration, also decreases the amount of O2-hemoglobin in blood. Carbon monoxide (COpoisoning causes hypoxia because CO occupies binding sites on hemoglobin that normally are occupied by O2; thus, CO decreases the O2 content of blood. Cyanide poisoning interferes with O2 utilization of tissue; it is one cause of hypoxia that does not involve decreased blood flow or decreased O2 content of blood.