The Gas Exchanger: Matching Ventilation and Perfusion

Carbon Dioxide Elimination Revisited: Joining Ventilation and Perfusion

Earlier in this chapter we described the relationship between alveolar ventilation and P_aCO₂. To appreciate fully the factors that affect this relationship, we must examine more closely the ways in which carbon dioxide is transported to and eliminated from the lungs.

Carbon Dioxide and Hemoglobin ↑

Carbon dioxide is carried in the blood in three forms. First, CO₂ is bound to hemoglobin. Second, it is dissolved in the plasma component of blood. Finally, the dissolved CO₂ is in equilibrium with carbonic acid. Carbon dioxide and water combine to form carbonic acid, which dissociates to a proton and a molecule of bicarbonate.

(In Chapters 6 and 7, we discuss this reaction and the importance of this relationship for the control of ventilation and the acid–base status of the body.) The dissolved carbon dioxide can be expressed as a partial pressure. The term carbon dioxide content in the blood, however, is reserved for the amount bound to hemoglobin plus the amount dissolved in the blood.

As blood travels from the lungs to the tissues, relatively little carbon dioxide is bound to hemoglobin. The PCO₂ of arterial blood in a normal individual ranges between 36 and 44 mm Hg. When the blood reaches the capillaries that perfuse metabolically active tissue, oxygen, which is in high concentration in the blood relative to the tissue, diffuses from the blood to support aerobic metabolism. Carbon dioxide, in high concentration in the tissues relative to the blood, diffuses from the tissues into the blood.

The relationship between carbon dioxide content in the blood and PCO₂ in the blood is relatively linear over the range found in the blood in humans (Fig 5-6). (It is common to see the term content used interchangeably with the more accurate term concentration when referring to the value for mL gas per 100 mL blood. You will see this for oxygen as well.)

The linear nature of this relationship makes it possible for the body to maintain a normal P_aCO₂, even in the presence of some poorly ventilated alveoli. If an alveolus is receiving little ventilation, the PCO₂ in the alveolus rapidly increases (carbon dioxide is diffusing from blood to the alveolus, but the gas in the alveolus is not being replaced with fresh gas from the atmosphere, which contains virtually no carbon dioxide). The result is that the diffusion gradient for carbon dioxide from the blood to the alveolus diminishes. Ultimately, the blood exiting the alveolus in the pulmonary vein has almost the same carbon dioxide content as the blood entering the alveolus. The P_aCO₂ increases and, as discussed in Chapter 6, stimulates the respiratory controller, which leads to an increase in ventilation as the body tries to compensate to restore P_aCO₂ to normal levels.

In the presence of some poorly ventilated alveoli, an increase in total ventilation restores P_aCO₂ to normal only if the carbon dioxide content of the blood leaving the normal alveoli can be lowered to a degree sufficient to compensate for the higher carbon dioxide content of the blood exiting the diseased alveoli. The linear relationship of the carbon dioxide curve makes this possible. Maximal ventilation of a normal alveolus can result in an alveolar PCO₂, and P_aCO₂, of 10 to 12 mm Hg. This process greatly reduces the carbon dioxide content of the blood perfusing this alveolus. When this blood mixes with blood from poorly ventilated alveoli, the final P_aCO₂ of the combined blood may be normal.

Use Animated Figure 5-6 to adjust the ventilation of the alveoli and observe what happens when you decrease ventilation for one alveolus and increase ventilation in another. Note that the well-ventilated alveolus can compensate for the poorly ventilated alveolus in terms of the CO₂ content of the outgoing mixed blood. As mentioned, this ability to compensate results from the linear relationship of the carbon dioxide dissociation curve, as seen in the diagram. Later in the chapter, we will see how the nonlinear shape of the oxygen dissociation curve creates a different situation for oxygen content when we mix blood from well-ventilated and poorly ventilated alveoli.

Hemoglobin contains four heme sites that bind oxygen and a protein chain onto which carbon dioxide binds. In the presence of high levels of carbon dioxide in the tissues, the increased binding of the protein chain alters the configuration of oxygen binding sites leading to release to oxygen to the tissue. When blood returns from metabolically active tissue to the right side of the heart, it has a high carbon dioxide content and low oxygen content. In the pulmonary capillary, the blood is exposed to a high PO₂ in the alveolus. The oxygen in the alveolus diffuses into the capillary blood, and carbon dioxide is released from hemoglobin; the hemoglobin binds oxygen in preference to carbon dioxide. The preferential binding of hemoglobin for oxygen and the resulting shift of carbon dioxide from being bound to hemoglobin to being dissolved in plasma is manifest as a shift to the right in the carbon dioxide-hemoglobin dissociation curve.

This shift in the curve is termed the Haldane effect (Fig. 5-7). Note that for any given level of carbon dioxide content, the P_aCO₂ is higher in the presence of a high concentration of oxygen. If, because of a problem with the respiratory controller or the ventilatory pump, the lungs are not able to increase alveolar ventilation to eliminate the increased amount of dissolved carbon dioxide, the P_aCO₂ will increase. This is one of the reasons, for example, that a patient with emphysema may have an increase in P_aCO₂ with administration of supplemental oxygen.

Physiological Causes of Hypercapnia ↑

There are four basic physiological causes of hypercapnia (i.e., elevated P_aCO₂), and they can all be derived from a basic relationship discussed earlier in this chapter:

If alveolar ventilation () is reduced and carbon dioxide production () remains constant, the P_aCO₂ must increase. Three physiologic changes may result in a decrease in alveolar ventilation: (1) a decrease in total or minute ventilation (); (2) an increase in dead space ventilation attributable to a rapid, shallow breathing pattern; and (3) an increase in dead space caused by mismatch in the context of a constant . The fourth physiological cause of hypercapnia is an increase in carbon dioxide production in the context of a patient who is unable to compensate by increasing ventilation, either because of a controller problem (e.g., a drug overdose that suppresses the respiratory controller) or an abnormality of the ventilatory pump, as is seen with severe emphysema.

Ventilation/perfusion mismatch, the result of diseases of the gas exchanger that lead to a disproportionate amount of blood going to relatively poorly ventilated alveoli, is a common finding, but the mismatch causes hypercapnia relatively infrequently. As the P_aCO₂ begins to increase, the body's usual response is to increase ventilation (more on this in Chapter 6). As the well-ventilated alveoli receive an increase in the amount of gas entering and exiting each minute, the PCO₂ in those lung units may decrease well below normal levels. Based on the carbon dioxide–hemoglobin dissociation curve described previously, the blood perfusing those units leaves the alveoli with a very low carbon dioxide content and compensates for the high carbon dioxide level in the blood coming from the poorly ventilated alveoli (see Animated Figure 5-6).