Structural and Functional Basis of Ventilation, Perfusion, and Gas Exchange

The lung exists for gas exchange, that is, the transfer of oxygen from the air to the blood and carbon dioxide from the blood to the air. Its basic structural unit is the alveolus—a roughly polygonal gas-filled tissue “bubble” whose walls are filled with capillaries. The human lung contains some 300 million alveoli, and their diameters average about 300 m. The strategy of dividing the lung up into a massive number of very small units keeps the total gas volume low enough for the lungs to fit inside the chest while at the same time creating an enormous interfacial surface area for exchange of oxygen and carbon dioxide between gas and blood. To enable gas exchange, alveoli are supplied with both inspired gas via the airways and venous blood from the right side of the heart. The gas and blood must be kept in very close proximity to one another for gas exchange to occur, but they must still remain physically completely separated. Separation is accomplished via the blood–gas barrier—a thin (about 0.3 m) layer of cells and supporting matrix. Oxygen and carbon dioxide exchange occurs by diffusion through the blood–gas barrier along partial pressure gradients between alveolar gas and capillary blood. As a gas exchanger, the lung is the servant of the body tissues. Under steady-state conditions, the lungs absorb from the air exactly that amount of oxygen per minute needed to support tissue metabolism—no more and no less. This is true also for the elimination of carbon dioxide produced by metabolism. The first step in this process is ventilation, a process of sequential inhalation and exhalation of gas. During each inspiration, oxygen is inhaled from the air, at a concentration of about 21% (or partial pressure, PO2, of about 150 mm Hg). Inhalation is accomplished by the fall in alveolar gas pressure to below atmospheric pressure following contraction of the diaphragm and chest wall muscles, which expand the thoracic cavity, thus reducing intrathoracic pressure. When intrathoracic pressure falls, so too does alveolar pressure. As alveolar pressure falls below atmospheric pressure, air flows from the environment along the airways to reach the alveoli, where it mixes with alveolar gas remaining from prior breaths. Because oxygen molecules move continually across the blood–gas barrier into the pulmonary capillary blood, the alveolar oxygen level from prior breaths is considerably lower than inspired. The freshly inhaled oxygen thus “tops up” the alveolar oxygen store, replacing the molecules that have moved into the blood. This process serves to stabilize the alveolar oxygen concentration over time at about 14%, or about 100 mm Hg. An analogy would be adding 1 gallon of gasoline every 20 miles to the tank of a car that does 20 miles per gallon: the amount of gasoline in the tank will oscillate around 0.5 gallons about a constant level as long as topping up is continued. Each gallon added is the equivalent of each breath raising alveolar oxygen levels; continued driving depletes the fuel level at a steady rate, much as oxygen molecules constantly move into the blood to supply the cells of the body. If the fuel tank is large relative to the 1-gallon “tidal volume” of gasoline, the fuel level oscillations are relatively small, allowing a simple view of the tank as having an essentially constant amount of gasoline over time. Since tidal volume is normally only about 500 mL, whereas functional residual capacity (FRC) is some 4,000 mL, the oscillations of oxygen about the mean are indeed very small. Thus, if average alveolar PO2 is about 100 mm Hg, each inspiration raises this to about 102 mm Hg. During each expiration, it is obvious that no oxygen can move from the air to the alveoli, but oxygen still moves from the alveolar gas into the blood, reducing the alveolar PO2 to about 98 mm Hg by the end of the exhalation. For most purposes, it is entirely satisfactory to consider the alveolar PO2 to be constant over time, despite the tidal nature of breathing and the 2 mm Hg PO2 oscillation.1 Once oxygen has moved across the blood–gas barrier into the pulmonary capillary blood, a process of passive diffusion,2 almost all of it ( 98%) binds to hemoglobin in the red blood cells. The remainder is physically dissolved in the water of the plasma and red cells. These cells spend only about 0.75 seconds3 in the pulmonary microcirculation taking on oxygen molecules. This period of time reflects the high rate of bloodflow through the pulmonary vascular bed (about 6 L/min) and the small capillary blood volume at any instant (about 75 mL). The ratio of capillary volume to CHAPTER 17