The Composition of a Gas Mixture Can Be Described by the Fractional Composition or Partial Pressure

Understanding gas exchange requires an understanding of the measurement of gas composition and the forces causing gas movement within the lungs, blood, and tissues. For convenience, physiologists use many abbreviations when describing gas exchange (Table 47-1). Air contains 21% oxygen (the fraction of oxygen in inspired air, FiO₂, is 0.21). High in the Andes Mountains, the air still contains 21% oxygen, but visitors to those altitudes notice the lack of oxygen. Clearly, therefore, it is not only the fraction of oxygen that is important for gas exchange; the hypoxia at high altitude is a result of the low oxygen partial pressure that is a consequence of the low barometric pressure. At this lower barometric pressure, the oxygen molecules are less densely packed, and therefore the partial pressure of oxygen (PO₂) in the air is decreased. It is this partial pressure (also called tension) that is important in gas transfer.

TABLE 47-1

Common Abbreviations Used in Gas Exchange

Abbreviation	Definition
AaDO2	Alveolar-to-arterial oxygen tension difference
FiO2	Fraction of oxygen in inspired air
FO2	Fraction of oxygen in the gas mixture
PaCO2	Arterial carbon dioxide tension
PACO2	Alveolar carbon dioxide tension
PaO2	Arterial oxygen tension
PAO2	Alveolar oxygen tension
PB	Barometric pressure
PcapCO2	Capillary carbon dioxide tension
PcapO2	Capillary oxygen tension
PCO2	Carbon dioxide tension
PH2O	Partial pressure of water vapor
PiO2	Inspired oxygen tension
PO2	Oxygen tension
PvCO2	Carbon dioxide tension of venous blood
PvO2	Oxygen tension of venous blood
	Mixed venous blood
	Perfusion
R	Respiratory exchange ratio
	Ventilation
	Amount of alveolar ventilation
	Rate of carbon dioxide production
	Rate of oxygen movement between alveolus and blood
	Ratio of alveolar ventilation to blood flow

The partial pressure of oxygen (PO₂) in a dry gas mixture is determined by barometric pressure (PB) and the fraction of oxygen (FO₂) in the gas mixture, as follows:

In the atmosphere, FiO₂ is 0.21, so PO₂ in dry air at sea level when PB = 760 mm Hg is approximately 160 mm Hg:

PO₂ decreases at higher altitudes because barometric pressure decreases.

During inhalation, air is warmed to body temperature and humidified in the larger air passages. The concentration of oxygen and other gases is reduced by the presence of water vapor molecules; therefore, PO₂ is less in humidified than dry air. The PO₂ of humidified gas is calculated as follows:

where PH₂O is the partial pressure of water vapor at body temperature. The PH₂O is determined by the temperature and percentage saturation of the air with water. In a mammal with a body temperature of 38.2° C, PH₂O in saturated air equals 50 mm Hg; therefore, at sea level (PB = 760 mm Hg), the PO₂ of warmed, completely humidified gas in the conducting airways is approximately 149 mm Hg:

Alveolar Gas Composition Is Determined by Alveolar Ventilation and the Exchange of Oxygen and Carbon Dioxide

Because there is only a negligible amount in the inspired air, the main source of carbon dioxide comes to the lungs in the blood returning from the tissues. For this reason, the PACO₂ (alveolar partial pressure of carbon dioxide) is determined by the rate of carbon dioxide production () in relation to the amount of alveolar ventilation ():

where K = PB − PH₂O.

It is obvious from this equation that if increases, as occurs during exercise, must also increase if PACO₂ is to remain constant. If does not increase sufficiently, PACO₂ rises. Similarly, if remains constant and halves, PACO₂ doubles.

Alveolar oxygen tension (PAO₂) is lower than that in inspired air because oxygen and carbon dioxide exchange occurs continuously. During breathing, PAO₂ fluctuates around an average value, increasing during inhalation and decreasing during exhalation. The average oxygen tension in the alveoli of the lung can be calculated from the alveolar gas equation, a simplified version of which follows:

where R, the respiratory exchange ratio, is the ratio of the rate of carbon dioxide production to that of oxygen consumption. The respiratory exchange ratio is determined by the substrates being metabolized by the animal. This equation demonstrates that alveolar oxygen tension is determined by the inspired oxygen tension and the exchange of oxygen for carbon dioxide. Assuming an average R of 0.8 and a PACO₂ of 40 mm Hg, PAO₂ averages approximately 100 mm Hg at sea level, where PB is 760 mm Hg. The alveolar gas equation also shows that whenever PACO₂ increases, PAO₂ decreases, and vice versa.

Alveolar hypoventilation, a decrease in alveolar ventilation in relation to carbon dioxide production, elevates PACO₂ and decreases PAO₂. Figure 47-1 shows the causes of alveolar hypoventilation. It occurs when (1) the central nervous system is depressed by drugs or injury, (2) there is injury to the phrenic nerve that supplies the diaphragm, (3) there is damage to the thorax and respiratory muscles, (4) there is severe airway obstruction (e.g., in exercising horses with laryngeal hemiplegia), or (5) there is lung disease that severely decreases lung compliance.

The converse of alveolar hypoventilation, alveolar hyperventilation, causes a decrease in PACO₂ because ventilation is increased in relation to carbon dioxide production. Therefore, according to the alveolar gas equation, as PACO₂ decreases, PAO₂ increases. Hyperventilation occurs when the need to ventilate is increased by stimuli such as hypoxia, acidosis, or an increase in body temperature.

A modified form of the alveolar gas equation can be used to determine PAO₂ for clinical purposes, as follows:

In this equation, arterial carbon dioxide tension (PaCO₂) is substituted for alveolar carbon dioxide tension (PACO₂).

Exchange of Oxygen and Carbon Dioxide Between the Alveolus and Pulmonary Capillary Blood Occurs by Diffusion

Diffusion is the passive movement of gases down a concentration (partial pressure) gradient. The rate of gas movement between the alveolus and the blood () is determined by the physical properties of the gas (D), the surface area available for diffusion (A), the thickness of the air-blood barrier (x), and the driving pressure gradient of the gas between the alveolus and capillary blood (PAO₂ – PcapO₂), as follows:

D is determined by several factors, including the molecular weight and solubility of the gas. The alveolar surface area (A) available for diffusion is that occupied by perfused pulmonary capillaries. During exercise, more capillaries become perfused by blood, and thus the surface area available for diffusion increases.

In the lung the barrier separating air and blood (x) is less than 1 µm thick (Figure 47-2). However, although thin, this barrier includes a layer of liquid and surfactant lining the alveolar surface; an epithelial layer, usually formed by type I epithelial cells; a basement membrane; variable-thickness interstitium; and a layer of endothelium. In addition to moving gases through this air-blood barrier, diffusion also moves gases within the plasma, allowing oxygen to gain access to erythrocytes and hemoglobin.

Blood entering the alveolar capillary from the small pulmonary arteries is known as mixed venous blood because it has returned to the right side of the heart in veins from all parts of the systemic circulation. The driving pressure for gas diffusion is the difference in oxygen tension between the alveolus (PAO₂) and the capillary blood. PAO₂ averages 100 mm Hg; in a resting animal, blood entering the alveolar capillary—that is, mixed venous blood—has an oxygen tension () of approximately 40 mm Hg. The driving pressure gradient of 60 mm Hg (100−40) causes rapid diffusion of oxygen into the capillary, where it combines with hemoglobin. Hemoglobin takes up oxygen from the plasma and helps maintain the gradient for oxygen diffusion.

Normally, in the resting animal, equilibration between alveolar and capillary oxygen tensions occurs within 0.25 second, approximately one third of the time the blood is in the capillary (Figure 47-3). During strenuous exercise, muscles extract a large amount of oxygen from the blood, so the mixed venous blood returning to the lung contains little oxygen. In addition, during exercise the cardiac output is high, and the velocity of blood flow through the capillaries is rapid. More oxygen must therefore be transferred in less time than in the resting animal. Under these strenuous conditions, diffusion equilibrium may not occur, and the oxygen tension of blood leaving the lung and entering the systemic arteries (PaO₂) may decrease during intense exercise. This exercise-associated hypoxemia is observed in racing Thoroughbred horses.