The most common cause of arterial hypoxemia in individuals with respiratory disorders is a mismatch between ventilation and perfusion. In this situation, the distribution of alveolar ventilation is uneven between the two gas-exchange units. As a result, the unit with decreased ventilation has a V̇ /Q̇ ratio of less than 1, while the unit with increased ventilation has a V̇ /Q̇ ratio greater than 1. This leads to variations in the alveolar and end-capillary gas compositions. The blood from the unit with decreased ventilation has abnormal arterial O2 content and CO2 content. On the other hand, the unit with increased ventilation has a lower CO2 content and a higher O2 content due to overventilation. The actual values of PaO2 and PaCO2 depend on the contribution of each unit to arterial blood. The alveolar-arterial O2 gradient (AaDO2) is increased because the relative overventilation of one unit does not fully compensate for the underventilation of the other unit.

The effects of ventilation/perfusion mismatching on gas exchange can be seen in Figure 23.11. A decrease in ventilation to one lung unit can be caused by various factors such as mucus obstruction, airway edema, bronchospasm, a foreign body, or a tumor. This results in a decrease in PACO2 and an increase in PAO2 in the affected unit. The PiCO2 and PiO2 values are not given. In the pulmonary artery, PvCO2 is 46 and PvO2 is 40. The pulmonary vein has a PvCO2 of 40.5 and a PvO2 of 89. The values for PlCO2 and PlO2 are not provided.

Compensation for underventilation of one unit can be achieved by adding extra O2 or removing extra CO2. However, the failure to fully compensate is greater for O2 than for CO2. This can be observed by comparing the flatness of the upper part of the oxyhemoglobin dissociation curve to the slope of the CO2 dissociation curve. Increased ventilation leads to an increase in PAO2, but it does not significantly increase the O2 content in the blood due to near saturation of hemoglobin in the overventilated areas. In contrast, increased ventilation results in the removal of more CO2 due to the steeper slope of the CO2 curve. As long as a gradient is maintained, CO2 diffusion will occur because CO2 moves by diffusion.

PAO2 is influenced by the rate of O2 uptake and the rate of O2 replenishment by ventilation. Oxygen uptake depends on lung blood flow and the metabolic demands of tissues. A decrease in ventilation leads to a decrease in PAO2, which subsequently decreases PaO2. VA and PACO2 have a direct but inverse relationship. When ventilation is halved, PACO2 doubles, resulting in an increase in PaCO2 according to Eq. 23.16. Insufficient ventilation to maintain normal CO2 levels is referred to as hypoventilation. Hypoventilation always leads to a decrease in PaO2 and an increase in PaCO2.
Mismatching between ventilation and perfusion is the most frequent cause of arterial hypoxemia in individuals with respiratory disorders. In the most common example, the composition of mixed venous blood, total blood flow (cardiac output), and the distribution of blood flow are normal. However, when alveolar ventilation is distributed unevenly between the two gas-exchange units (
Fig. 23.11 ) and blood flow is equally distributed, the unit with decreased ventilation has a V̇ /Q̇ ratio of less than 1, whereas the unit with the increased ventilation has a V̇ /Q̇ of greater than 1. This causes the alveolar and end-capillary gas compositions to vary. Both the arterial O2 content and CO2 content are abnormal in the blood that has come from the unit with the decreased ventilation (V̇ /Q̇ , <1). The unit with the increased ventilation (V̇ /Q̇ , >1) has a lower CO2 content and a higher O2 content because it is being overventilated. The actual PaO2 and PaCO2 vary, depending on the relative contribution of each of these units to arterial blood. The alveolar-arterial O2 gradient (AaDO2) is increased because the relative overventilation of one unit does not fully
PlO2 = 150 PlCO2 = 0 PAO2 = 77 PACO2 = 45 PCO2= 45PO2= 77 PAO2 = 105 PACO2 = 36 PpvO2 = 89 PpvCO2 = 40.5 Pulmonary vein Pulmonary artery PvO2 = 40 PvCO2 = 46 – – Anatomic dead space • Fig. 23.11 Effects of Ventilation/Perfusion Mismatching on Gas Exchange. The decrease in ventilation to the one lung unit could be due to mucus obstruction, airway edema, bronchospasm, a foreign body, or a tumor. PACO2, partial pressure of alveolar carbon dioxide; PAO2, partial pressure of alveolar oxygen; PiCO2, partial pressure of inspired carbon dioxide; PiO2, partial pressure of inspired oxygen; PpvCO2, partial pressure of carbon dioxide in portal venous blood; PpvO2, partial pressure of oxygen in portal venous blood; PvCO2, partial pressure of carbon dioxide in mixed venous blood; PvO2, partial pressure of oxygen in mixed venous blood.
compensate (either by the addition of extra O2 or by the removal of extra CO2) for underventilation of the other unit. The failure to compensate is greater for O2 than for CO2, as indicated by the flatness of the upper part of the oxyhemoglobin dissociation curve, in contrast to the slope of the CO2 dissociation curve (see
Chapter 24).
In other words, increased ventilation increases PAO2, but it adds little extra O2 content to the blood because hemoglobin is close to being 100% saturated in the overventilated areas. This is not the case for CO2, for which the steeper slope of the CO2 curve indicates removal of more CO2 when ventilation increases. Thus inasmuch as CO2 moves by diffusion, then as long as a CO2 gradient is maintained, CO2 diffusion will occur.
The PAO2 is determined by a balance between the rate of O2 uptake and the rate of O2 replenishment by ventilation. Oxygen uptake depends on blood flow through the lung and the metabolic demands of the tissues. If ventilation decreases, PAO2 decreases, and PaO2 subsequently decreases. In addition, VA and PACO2 are directly but inversely related. When ventilation is halved, the PACO2 doubles and thus so does the PaCO2 (see
Eq. 23.16 ). Ventilation insufficient to maintain normal levels of CO2 is called hypoventilation. Hypoventilation always decreases PaO2 and increases PaCO2.