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CE Article: Understanding the Gas Exchange Process

This article is available on our LMS for CE credit.


Students will be able to describe the make up of atmospheric air and how it relates to patient care;

Students will be able to describe the passive and active processes of inhalation and exhalation;

Students will be able to apply their knowledge of the gas exchange process to a sick patient.

Trillions of cellular metabolic processes happen in the human body. Most of these cellular functions require oxygen to effectively and efficiently complete these processes. In most cases, this oxygen consumption results in the creation of carbon dioxide, a potentially dangerous byproduct of cellular metabolism. This large-scale use of oxygen, and the resulting creation of carbon dioxide, requires a highly efficient absorption/elimination and transport system.

The body has two routes for the elimination of carbon dioxide: the lungs and the kidneys (the lungs being the primary and most efficient route).1 However, the lungs are only one route available for the absorption of oxygen, and the blood (or cardiovascular system) is the only method available for its transportation. Because of this, the lungs must maintain normal function. To do so, they need to work in conjunction with the cardiovascular system and interact with the environment in a highly effective manner. This will allow them to proficiently facilitate the exchange of these vital and dangerous gases.

Gas exchange is the process of absorbing inhaled atmospheric oxygen molecules into the bloodstream and offloading carbon dioxide from the bloodstream into the atmosphere.2 This process is completed in the lungs through the diffusion of gases from areas of high concentration to areas of low concentration. The process also requires that oxygen move from its gaseous environment into a liquid environment and carbon dioxide move from a liquid environment into a gaseous environment. This article explores the gas-exchange process by taking a closer look at the molecular content of atmospheric air, how lungs interact with their environment, the gas carrying capacity of red blood cells and conditions that can hamper the exchange process.

Gases and Pressures

Atmospheric air generally contains 78% nitrogen, 21% oxygen and a 1% of a mixture of the following gases:

  • Argon,
  • Carbon dioxide,
  • Neon,
  • Helium,
  • Methane,
  • Krypton,
  • Hydrogen,
  • Nitrous oxide,
  • Xenon,
  • Ozone,
  • Sulfur dioxide, and
  • Nitrogen dioxide.3

Although this ratio mixture remains constant regardless of altitude, this does not mean that the same number of molecules is present in a cubed meter of air at different altitudes. Every molecule of air in the earth’s atmospheric has its own individual weight. The cumulative weight of all of these molecules pressing downward, due to the earth’s gravity, creates what is known as atmospheric pressure.3

Atmospheric air pressures change as altitude changes because of the relative combined molecular weight. At sea level, atmospheric pressure is 14.7 PSI (760 mmHg/Torr or 1 ATM). At 10,000 feet above sea level, atmospheric pressure is 10 PSI (517 mmHg/Torr or 0.68 ATM).4 The difference is due to the fact that there are fewer molecules at 10,000 feet pushing down than there are at sea level. This decreases their combined weight and reduces the pressure that forces the molecules together. As the atmospheric pressure decreases, air molecules spread out and the air becomes thinner (e.g., lower molecule content per cubed meter). This is the basis of Boyle’s Law, which states that volume and pressure are inversely related.5

Every molecule of a given mixture of gas is responsible for the mixture’s overall pressure. Additionally, according to Dalton’s law of partial pressures, each type of gas is partially responsible for the mixture’s overall pressure.3 This means that the percentages of nitrogen (78%), oxygen (21%), and the mix of gases (1%) all partially contribute to the 14.7 PSI (760 mmHg/Torr or 1 ATM) of air pressure at sea level, the 10 PSI (517 mmHg/Torr or 0.68 ATM) at 10,000 feet above sea level and so on. If the percentage concentration of any gas is increased, its partial pressure will increase and vice versa.

Differences in gas pressures, partial or otherwise, create diffusion gradients that facilitate the movement of gas molecules from areas of high concentration to areas of low concentration. This is true even if the concentration gradient involves a gas and a liquid, such as blood. Henry’s law states that the amount of gas that dissolves into a liquid is directly proportional to the partial pressure of that gas.3 It also states that when a liquid is exposed to a gas mixture that does not contain the same gas concentration, a pressure gradient is created by the difference in partial pressures. The partial pressure difference will cause molecules in the air to diffuse into the liquid and unbound gas molecules in the liquid to diffuse into the air. Henry’s law helps explain how oxygen from atmospheric air enters the blood and carbon dioxide leaves the blood into the air.

Just because a gas can dissolve into a liquid solution, this does not mean that it will bond and become part of the liquid matrix. Oxygen does not readily dissolve in blood. Therefore, the body relies on an alternate transport system that uses hemoglobin to transport oxygen. Carbon dioxide, on the other hand, will most often bond with a water molecule to form carbonic acid, which can, depending on the body’s needs, then be converted into bicarbonate, freeing a hydrogen atom. The presence or absence of carbon dioxide can affect the amount of free hydrogen molecules in the body. Because of this, a balance between carbonic acid and bicarbonate must be maintained to sustain normal blood and tissue pH levels. The efficient removal of carbon dioxide by the lungs is essential to the maintenance of this balance.

Anatomy of the Lungs

Air enters the lungs and travels through progressively narrowing passages to the alveolus, where gas exchange between the body and the atmosphere takes place. With an average thickness of 0.5 micrometers (0.1 micrometers in some areas) the alveolar wall separates the air in the lungs from the pulmonary capillaries by only a few layers of cells, allowing for the rapid movement of oxygen and carbon dioxide molecules in and out of the bloodstream.6

Alveoli are hollow spherical shaped structures that are clustered in bundles resembling grapes on the vine. Their shape provides a greater surface area for atmospheric air to come into contact with pulmonary capillaries and facilitate gas exchange. The size of an individual alveolus is somewhat consistent, therefore how many alveolus a lung contains depends on the lung’s overall size.7 One cubic millimeter of alveolar tissue contains about 170 individual alveoli, and an average pair of lungs contain about 480 million alveoli.5 This large number of alveoli creates a massive surface area for gas exchange that is around 35 times larger than the surface area of the skin.6

The amount of air that enters and leaves the lungs in one breath is referred to as tidal volume (Vt), which includes air that is unusable by alveoli (air in the dead space) because it remains in the areas of the lung that do not contain alveoli (dead space) and is therefore not useable for gas exchange. A healthy adult has a tidal volume of anywhere from 5 to 7 mL/kg (average of about 500 mL), which includes around 150 mL of air in the dead space (VD).8

Over the course of one minute, the volume of air entering and leaving the lungs is referred to minute volume (Mv), and the volume of air that reaches the alveoli is referred to as alveolar ventilation (VA). Alveolar ventilation can be calculated by subtracting the are in the dead space from the tidal volume and multiplying the result by the number of breaths per minute (R), (Vt – VD) x R = VA. A person breathing 12 times per minute with an average tidal volume of 500 mL and 150 mL of air in the dead space would have 4,200 mL of air reaching the alveolar membranes every minute (500 mL – 150 mL = 350 mL tidal volume, 350 mL x 12 = 4,200 mL minute volume).

Any medical condition, disease or injury of the lungs, brain, chest, abdomen, cardiovascular system, or blood cells can dramatically affect the body’s ability to absorb a sufficient supply of oxygen and eliminate harmful carbon dioxide.

Physiology of Breathing

The physiology of breathing happens in two phases: 1) mechanical (ventilations), and 2) cellular (respirations). The process of mechanical ventilation is regulated by the brain to physically move air in and out of the lungs so that oxygen and carbon dioxide can be exchanged with atmospheric air.9 The movement of air is the result of positive and negative pressure differences created within the thoracic cavity. During inhalation, the diaphragm contracts in a downward motion and the intercostal muscles contract pulling the ribs outward which causes the cavity containing the lungs to expand and enlarge.10 This movement creates a negative pressure environment within the thoracic cavity that draws air into the lungs. The inhalation process is considered an active process because it requires muscle contraction to move the diaphragm and ribs to create negative thoracic pressures.

Exhalation, on the other hand, is generally a passive process. In healthy persons when active contraction of the diaphragm and intercostal muscles ceases, the diaphragm and ribs move back to their relaxed positions.10 This passive process creates positive pressure inside the thoracic cavity by reducing the internal thoracic volume. The positive pressure that is created pushes air out of the lungs. This process is typically passive but can be active by recruiting accessory respiratory muscles when necessary, for instance when coughing, blowing out candles, or blowing up a balloon.

At the cellular level, respirations occur as a part of a process or a cycle referred to as the citric acid cycle, which is also known as the Kreb’s cycle. During the citric acid cycle, a series of reactions consume glucose, oxygen, and several other metabolic components to create 30 adenosine triphosphate (ATP) molecules.10 These ATP molecules are then used within the cell as a source of energy for various cellular activities. Only cells containing mitochondria are capable of creating ATP because the citric acid cycle occurs exclusively within cellular mitochondria.10 Mitochondria-containing cells are capable of running thousands of citric acid cycles simultaneously, resulting in the production of tens of thousands of ATP molecules.

Although the citric acid cycle produces essential ATP, it also produces carbon dioxide, a potentially harmful byproduct. The process of converting one glucose molecule into 30 ATP molecules also produces six carbon dioxide molecules.11 Excess carbon dioxide in the presence of water will form carbonic acid, a weak acid capable of adversely affecting tissue pH levels.8 Cellular respiration requires both delivery of large quantities of oxygen and the removal of large quantities of carbon dioxide.

Red Blood Cells

Red blood cells are durable unbound cells designed to carry oxygen and, to a lesser degree, carbon dioxide to and from body tissues while withstanding the forces of bouncing off the walls of the vascular system, collisions with other cells and the high pressure forces of the capillary networks. Externally, their round shape combined with a relatively thick edge and a thinner center increases their surface area while still allowing for them to move freely through the vascular network. Internally, they are predominantly comprised of antioxidant enzymes and structural proteins that protect and support the cell. However, they lack a nucleus and contain only a few organelles, which prevents them from dividing or repairing themselves.13 The remaining third of the cell contains hemoglobin, an iron, and amino acid-containing protein capable of binding with oxygen and carbon dioxide.6,12 The majority of oxygen, which is transported in the blood, is bound to the iron portion of the hemoglobin, while only about 20% of carbon dioxide is transported in this way.12 The remaining carbon dioxide is transported bound in easily reversible molecules of bicarbonate or carbonic acid.14

The average adult has about 25 trillion circulating red blood cells. Each red blood cell contains about 280 million hemoglobin molecules and each hemoglobin molecule can carry up to four oxygen molecules.6 With room for more than 1 billion oxygen molecules per cell, the total circulating oxygen-carrying capacity of the average adult is roughly 2.8 septillion (2.8 x 1024) molecules. This massive oxygen-carrying ability of red blood cells helps maintain some reserve oxygen capacity for the body. As the red blood cells pass through the capillaries at the tissue level, they off-load 25–35% of the oxygen they carry, leaving 65–75% of the oxygen in reserve.15 The brain further uses this reserve capacity by regulating the cerebral vessels to create a cerebral blood/oxygen reserve.16 In other places, myoglobin, a cellular protein similar to hemoglobin, is the primary source of oxygen reserves, myoglobin is predominantly found in cardiac and skeletal muscles.17 These reserves provide the body the necessary oxygen needed to rapidly respond to stressful events.

Cardiovascular System

The cardiovascular system is specially designed to move blood throughout the body. This system consists of two primary components, the heart (pump) and the vessels (arteries, veins and capillaries). The heart, which weighs 250–300 grams, is a relatively small organ with a large and unending job.8 This four-chambered hollow organ is the sole means of moving blood throughout the entire body. The amount of blood pumped out of the heart in one beat is called stroke volume (SV), which is on average 60–100 mL. The amount of blood pumped by the heart in one minute is called cardiac output (CO). Cardiac output can be calculated with the following formula: CO = SV x HR).8 Over the course of an average day, the heart will circulate between 7,000–9,000 L of blood.8

The transport system for blood throughout the body is the vascular system, which is divided into two circuits: the pulmonary and systemic circuits.8 The pulmonary circuit circulates blood to and from the lungs via the right side of the heart. The systemic circuit circulates blood to the entire body via the left side of the heart. The right side of the heart (right atrium and right ventricle) receives oxygen-depleted, carbon-dioxide rich blood from the body via the superior and inferior venae cavae. From there, blood passes through the right atrium into the right ventricle, where it is then pumped into the pulmonary circuit via the pulmonary artery. Once the blood is in the pulmonary arteries, it is pushed through the capillaries surrounding the alveoli of the lungs and collected in the pulmonary veins. The pulmonary veins return the oxygen-rich blood, which has been depleted of carbon dioxide, to the left side of the heart.

The left side of the heart (left atrium and left ventricle) receives the freshly oxygenated blood from the pulmonary circuit. The blood passes through the left atrium into the left ventricle, where it is pumped to the body via the ascending and descending aorta. Blood is pushed through the arterial network and into the capillaries at the tissue level and collected in the veins. The venous system collects the oxygen-depleted, carbon-dioxide rich blood from the body via the superior and inferior venae cavae, and the cycle repeats.

Under normal conditions, blood pressure in the pulmonary circuit is much lower than the blood pressure in the systemic circuit.21 This difference results from the lower vascular resistance attributed to the much smaller size of the pulmonary circuit.21 The dramatic difference in vascular resistance also helps explain the significant differences in the muscle thicknesses of the left and right sides of the heart.

The cardiovascular system and the lungs play equally vital roles in the gas-exchange process. An inefficiency of one system will compromise both. The coloration between the amount of air reaching the alveoli and the amount of blood reaching the capillaries surrounding the alveoli can be measured using what is known as the ventilation-perfusion or V/Q ratio (V/Q = Mv / CO).22 This number is important in determining the combined efficiency of the cardiovascular system and the lungs. A ventilation-perfusion ratio of 0.8 (4 L minute volume /5 L cardiac output) would typically yield normal blood gas levels.19 A decrease in V/Q ratio, whether caused by a decrease Mv or increased CO, will result in a buildup of carbon dioxide levels.

Gas-Exchange Process

The purpose of mechanical ventilation is to bring oxygen molecules into contact with alveolar capillaries of the lungs. The functionality of the lungs completely depends on the number of oxygen molecules that not only reach the alveolus but are able to pass through the alveolar membrane and reach the hemoglobin of the red blood cells. At sea level, a cubic meter of atmospheric air (21% oxygen concentration) contains approximately 5.2 septillion oxygen molecules (5.2 x 1024), roughly two times the oxygen-carrying capacity of all the body’s hemoglobin.4

Atmospheric air contains 21% oxygen, which means that the pressure that oxygen alone exerts at sea level is slightly more than three PSI (155 mmHg) [14.7 PSI x 21%]. Conversely, atmospheric air contains only 0.04% carbon dioxide, which exerts a paltry 0.006 PSI (0.31 mmHg/Torr or 0.0004 ATM) [14.7 PSI x 0.04%].3,6 According to Henry’s law, as long as there is a pressure difference, gases will diffuse through air or liquid in an effort to balance out the partial pressures of each medium. Because the body is 70% water, even at the relatively low concentration of 21%, the alveolus and surrounding tissues will become saturated with oxygen when they come in contact with atmospheric air. However, carbon dioxide will readily leave the tissues because the atmospheric concentrations are so low. At sea level (21% oxygen concentration), approximately 2.6 sextillion (2.6 x 1021) oxygen molecules are inhaled with each breath and 1.9 sextillion (1.9 x 1021) are exhaled (15.3% oxygen concentration).6 The lung tissues and blood vessels absorb roughly 7 quintillion (7 x 1020) oxygen molecules (5.7% of the oxygen inhaled) or 0.025% of the total oxygen-carrying capacity of the blood with each breath. Of course, this absorption/elimination rate depends greatly on bodily metabolic demands, and such activities as exercise or sleeping will have a significant effect on the exchange rates.

Changing the atmospheric concentrations of either oxygen or carbon dioxide will affect their partial pressures and thus their absorption and elimination ratios. If oxygen levels are low, the partial pressure of oxygen will be low and less oxygen will diffuse into the lung tissues. If carbon dioxide levels are high, the partial pressure of carbon dioxide will be high, causing less carbon dioxide to diffuse out of the lung tissues.

Even at normal concentrations (21%), oxygen will saturate deep into the lung tissues through the alveolar and capillary membranes, and connective tissue and into the plasma of the blood. As the blood plasma becomes saturated with oxygen the hemoglobin of the red blood cells will begin to bind with the excess oxygen molecules. Hemoglobin’s affinity for oxygen will increase as more and more oxygen molecules become bound until a saturation point is reached.23 The partial pressure of oxygen needs to be at or above 1.16 PSI or 60 mmHg to maintain this saturation. Once the partial pressure of oxygen drops below this level, oxygen molecules will begin to offload from the hemoglobin. This is what is known as the oxyhemoglobin dissociation curve. So when the red blood cells reach the capillaries of the body tissues, which contain a lower partial pressure of oxygen and higher partial pressure of carbon dioxide, the oxygen will leave the plasma and enter the tissues through the capillary walls. This decreases the oxygen plasma concentrations and the partial pressure of oxygen, causing oxygen to unbind from the hemoglobin of the red blood cells and enter the plasma. As carbon dioxide is released by the cells metabolizing oxygen, much of it is quickly bound to either a water molecule as carbonic acid or a hydrogen molecule and an oxygen molecule as bicarbonate. Some carbon dioxide molecules, however, stay unbound. This creates a higher partial pressure of carbon dioxide in the tissues, which diffuses into the blood plasma and then binds to the hemoglobin of red blood cells.

When the red blood cells return to the capillaries of the lungs, the partial pressure of carbon dioxide in the blood plasma is higher than that of the capillaries and surrounding tissues. This pressure gradient causes carbon dioxide to diffuse out of the plasma, off the hemoglobin, through the capillary and alveolar walls and into the air space of the lungs to be exhaled. Additionally, some of the carbonic acid and bicarbonate will disassociate, freeing carbon dioxide molecules into the plasma and then the tissues of the lungs to be exhaled as well. At the same time, the high partial pressure of oxygen in the alveolar tissues causes oxygen to diffuse back on to the hemoglobin of the red blood cells, and the cycle repeats.

At sea level, higher percentages of oxygen (above 21%) create higher partial pressures, which improves hemoglobin oxygen loading by creating a much steeper concentration gradient and a higher diffusion rate. However, attempting to increase the pressure of oxygen by forcing a higher volume of air into the lungs will not necessarily increase the net movement of oxygen if the concentration of the forced air stays the same. Pressure changes because of altitude can dramatically affect oxygen diffusion rates. At sea level, the partial pressure of oxygen is a little more than 3 PSI (155 mmHg) [14.7 PSI x 0.21%]. However, at 10,000 feet elevation, partial oxygen pressure drops to 2.1 PSI (108 mmHg).4 The percentage of atmospheric oxygen remains the same at 21%, but the partial pressure exerted by oxygen will continue to drop as altitude increases. This drop in pressure will reduce the oxygen molecule content of the air and reduce the oxygen diffusion rate. At 13,435 feet, the molecular oxygen content of a cubed meter of atmospheric air is nearly half that of the air at sea level (even though the percentage of oxygen is still 21%). At 18,044 feet, the molecular oxygen content is so low that humans cannot survive without supplemental oxygen.24

Conversely, scuba diving increases atmospheric pressure by adding the weight of water to the equation. Because water weighs considerably more than air, 33 feet of water depth is the equivalent of one atmosphere, or 14.7 PSI (760 mmHg).25 Therefore, Boyle’s law tells us that a volume of air in the lungs will decrease in size by half at a water depth of 33 feet. However, its pressure will double to 29.4 PSI. The increases in partial the pressures of oxygen and carbon dioxide rarely cause issues because they are metabolized in the body.5 However, partial oxygen pressures at or above 20.58 PSI (1478 mmHg) [6.86 times higher than the partial oxygen pressure at sea level or a water depth of 193 feet are capable of producing acute neurotoxicity.5 Nitrogen, on the other hand, accounts for most of the dissolved gas in the body at water depth. This is because it not only accounts for a larger percentage of the partial pressure, typically 78%, but also because it is not used by any of the body’s processes. Nitrogen partial pressures can build up within the tissues of the body while diving because more nitrogen molecules are absorbed as its partial pressure increases.25


The human body depends completely on the effective absorption and elimination of vital and potentially dangerous respiratory gasses. Many medical and environmental factors can affect the lungs’ ability to facilitate the movement of oxygen from a gaseous state into a liquid state and carbon dioxide from a liquid state to a gaseous state. These conditions typically result in cellular oxygen demand exceeding oxygen supply. When this happens, the body’s natural oxygen reserves are quickly used up. This can decrease, or worse, completely stop, cellular function.

The high metabolic demands of the body require a constant supply of oxygen and the efficient removal of carbon dioxide. Even though the gas-exchange process is a passive diffusion process in which gases diffuse down a concentration gradient, adequate partial pressures must still be present within the lungs for this process to happen. Additionally, the mechanical movement of air in and out of the lungs and the circulation of blood through the pulmonary and systemic circuits must provide sufficient quantities of oxygen while still facilitating effective removal of carbon dioxide.


Dezube, R. "Exchanging Oxygen and Carbon Dioxide." Merck Manuals. June 2019.  Retrieved from

Rusty Gilpin, BT, NRP, is the EMS education program director for Gordon Cooper Technology Center in Shawnee, OK, and oversees all its adult allied health program offerings. In 2013 he received an Innovation Award from the Oklahoma Department of Career and Technology Education for his work in scenario-based education and was named Gordon Cooper Technology Center's Adult Program Person of the Year.

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