The exchange of gas between the body and the outside environment is referred to as “external respiration.” The process of external respiration takes place between the lungs and the atmospheric air we breathe. This takes place in the tiny spherical sacs of the lungs called “alveoli” and the blood supply carried in by very tiny blood vessels in the lungs called the “pulmonary capillaries.” Collectively, we refer to the conjoining of these two systems as the “alveolar-capillary membrane” (ACM). The process of gas exchange at this level is one of physics and pure diffusion, the movement of gas from an area of high concentration to an area of low concentration, until the two areas are equilibrated or equal. As we take air in or inhale air (inhalation), we are bringing in a gas (air) that comprises primarily nitrogen (N₂) and 20.9% oxygen (O₂). The amount of oxygen in the inspired air, or the fraction of inspired oxygen (FiO₂), is greater inside the alveoli than the amount of oxygen contained in the pulmonary capillaries. Utilizing the gradient of diffusion and movement of gas from a high to a low concentration, oxygen leaves the alveoli, crosses the ACM, and enters the red blood cell (RBC). As oxygen moves in, carbon dioxide (CO₂) is simultaneously moving out. Again, under the laws of diffusion, the amount of CO₂
inside the RBC is significantly higher than the amount of CO₂ inside the alveoli, and CO₂ diffuses from the RBC into the alveoli to be excreted or expired during exhalation. Under normal conditions, this takes place very quickly at the level of the ACM, usually in about 0.25 seconds. The amount of contact time that the average RBC has with the ACM is about 0.75 seconds.

After the exchange of gas in the lungs, oxygenated blood returns to the heart to be distributed throughout the body through the left ventricle, arteries, and the body’s systemic circulation. The blood travels the arterial circulation to be distributed throughout the body and to its many organ systems. As the RBCs make their way through the smaller blood vessels, they eventually reach the arterial capillaries of the body. These capillaries are the end point of a network of blood vessels that feed the entire body with nutrients, electrolytes, and oxygen. At the capillary level, much as in the capillaries of the lungs, the RBC comes into contact with the capillary wall and the adjoining tissues.

Under normal circumstances, internal or cellular respiration utilizes oxygen to create energy, with the waste product primarily being CO₂ through the aerobic pathway of the Krebs cycle. At the tissue level, the amount of oxygen inside the RBC is greater than the amount outside the RBC in the tissues, and O₂ moves out of the RBC and into the tissues. Again, simultaneous exchange of CO₂ is taking place as CO₂ leaves the tissues and moves into the plasma and RBC for return to the lungs and elimination; then the process starts all over again. The concentration of CO₂ is greater in the tissues compared with the RBC, so CO₂ leaves the tissues and diffuses out into the plasma and RBC. The transport of both CO₂ and O₂ within the body is a bit more complex than described here, but it sets the foundation for further discussion.