Gas exchange is the physiological process of diffusion where oxygen moves from the lungs to the bloodstream during inhalation, and carbon dioxide (CO2) moves from the blood to the lungs for removal during exhalation.

This is a fundamental topic that must be understood by anyone working in the field of respiratory care. This guide will provide a brief overview of gas exchange and the process of diffusion. It contains helpful practice questions for your benefit as well.

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What is the Function of the Lungs?

The primary goal of the lungs is to take in oxygen and remove carbon dioxide during a normal breathing cycle.

This cycle is what leads to gas exchange.

The lungs help ensure that oxygenated blood is circulated throughout the body. Once carbon dioxide-rich blood is returned back to the lungs, it can be removed from the body via exhalation.

What is Gas Exchange?

Gas exchange is a complex process that occurs both at the cellular level and at the lungs. As we take a breath in, oxygen moves into the lungs and then diffuses into the pulmonary circulation.

Oxygen molecules are picked up by red blood cells and transported through arteries to all of the organs and tissues of the body. The process of metabolism naturally causes carbon dioxide to build up in our body tissues.

This is when CO2 diffuses into capillary blood and is transported through veins to the lungs, where it can be removed during exhalation. Both oxygenation and ventilation occur simultaneously as gases are being exchanged into and out of the body.

This is literally where gas exchange gets its name.

The process of gas exchange occurs normally and naturally in healthy individuals. However, when certain diseases are present, gas exchange becomes impaired, which results in physiologic imbalances that can cause severe medical issues, including death.

What is Pulmonary Diffusion?

To understand how gas exchange works, it is important to understand pulmonary diffusion.

Diffusion is the movement of molecules from an area of high concentration to an area of low concentration. This occurs until there is an equal distribution of these molecules throughout the space they are occupying.

For diffusion to take place, there must be a membrane that is permeable to the molecule in question. The most important membrane in gas exchange is the alveolar-capillary membrane.

This thin, semipermeable barrier separates the alveoli (air sacs) from the tiny capillaries that surround them. This is where oxygen and carbon dioxide diffuse across in order to enter and exit the bloodstream.

alveoli pulmonary diffusion

Alveolar-Capillary Membrane

The alveolar-capillary membrane is made up of several different types of cells, including:

  • Type I alveolar cells
  • Type II alveolar cells
  • Capillary endothelial cells
  • Basement membrane

The alveolar cells are the primary cell type involved in gas exchange. These cells make up the walls of the alveoli and are responsible for secreting surfactant.

Type I alveolar cells are the primary cell type involved in gas exchange. These cells make up the walls of the alveoli and are responsible for secreting surfactant. Type II alveolar cells secrete surfactant as well, but they also have the ability to regenerate Type I cells.

Capillary endothelial cells line the capillaries and have small pores that allow gases to diffuse in and out of the bloodstream. The basement membrane is a thin layer of connective tissue that sits beneath the alveolar cells and serves to support them.

In order for oxygen and carbon dioxide to diffuse across the alveolar-capillary membrane, there must be a difference in partial pressure between the two gases. The partial pressure refers to the amount of that gas in a given space.

Gas Exchange Practice Questions:

1. What are the two forms in which oxygen is transported?
Physically dissolved in plasma and chemically bound to hemoglobin

2. What are the additional costs of increased ventilation?
Increased work of breathing, increased oxygen consumption, and a higher burden of external ventilation

3. What is the alveolar air equation based on Dalton’s law?
PAO2=FiO2 x (PB-47)-(PACO2/0.8)

4. What must exist in order for gas exchange to occur between the alveoli and pulmonary capillaries?
A difference in partial pressures

5. What is an area with ventilation but no blood flow called?
Dead space

6. What is the formula for figuring out how much oxygen is dissolved in the plasma?
Henry’s Law, which states: Dissolved oxygen (mL/dL) = PO2 x 0.003

7. The oxyhemoglobin dissociation curve describes what?
It describes the relationship between PAO2 and SaO2.

8. What is hemoglobin saturation?
Hemoglobin saturation is the percentage of hemoglobin that is carrying oxygen compared to the total hemoglobin.

9. How many oxygen receptors does hemoglobin have?

10. How much oxygen is bound to hemoglobin?
1.34 mL of oxygen per gram of hemoglobin

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11. What is the normal CO2 pressure in veins?
46 mmHg

12. What is the normal oxygen pressure in veins?
40 mmHg

13. What is respiration?
The process of moving oxygen to tissues for aerobic metabolism and removing CO2

14. What is a right-left shunt?
Malfunction in the septum that causes deoxygenated blood to travel from the RIGHT atrium to the LEFT atrium

15. What is the total O2 content of blood equation?
CaO2=(0.003 x PaO2) + (Hb x 1.34 x SaO2)

16. What disorders lead to alveolar deadspace?
Pulmonary emboli, partial obstruction of the pulmonary vasculature, destroyed pulmonary vasculature, and reduced cardiac output

17. What are the causes of a relative shunt?
COPD, restrictive disorders, and any condition resulting in hypoventilation

18. What is carboxyhemoglobin?
The combination of carbon monoxide bound to hemoglobin

19. What is deadspace ventilation?
When there is ventilation in excess of perfusion

20. What is methemoglobin?
Ferric iron that cannot bind with oxygen and alters the HbO2 affinity; it causes a left shift in the HbO2 curve

21. What is needed for the CaO2 to be adequate?
Sufficient hemoglobin

22. What is the P50?
It shows the PO2 when the hemoglobin is 50% saturated with oxygen.

23. What is a reduction in blood flow called?
Shock or ischemia

24. How can we analyze gas exchange between the lungs and the blood?
In arterial blood, we can analyze the oxygen and CO2 levels. In expired air, we can analyze the CO2 levels.

25. What is the best value to assess ventilation?

26. What is the formula for alveolar minute ventilation?
Frequency x (Tidal Volume – Physiological Deadspace)

27. What is the importance of the Bohr effect on oxygen transport?
A low pH shifts the HbO2 curve to the right, and a high pH shifts the curve to the left.

28. How is the majority of the oxygen in the body carried?
Bound to hemoglobin

29. What is the normal methemoglobin percentage reading?
1%-2% on a CO-oximeter

30. What leads to an increased PaCO2?
Decreased VA, increased VCO2, and increased VD

31. What is respiration?
The process of taking oxygen into the body for tissue utilization and removing CO2 into the atmosphere

32. What is the normal range for SaO2?

33. What causes carbon dioxide to build up in the tissues?

34. Carbon dioxide diffuses into what?
It diffuses into capillary blood before being carried to the lungs for removal.

35. Gas movement between the lungs and tissues occurs because of what?
Simple diffusion

36. What ratio represents a perfect V/Q balance?

37. What is the most common approach to analyzing gas exchange between the blood and tissues?
Measure oxygen levels in mixed venous blood

38. What is the difference between the oxygen and carbon dioxide diffusion gradients?
Oxygen has a cascade gradient moving from the atmosphere into the cell. Carbon dioxide moves from the cell into the atmosphere.

39. The carbon dioxide diffusion gradient cascade causes what?
It causes CO2 to move from tissues into venous blood, which is transported to the lungs. Then it is exhaled out into the atmosphere.

40. The alveolar partial pressure of carbon dioxide varies directly with what?
It varies with the body’s production of CO2 and inversely with alveolar ventilation.

41. What is the portion of the cardiac output that returns to the left heart without being oxygenated?
Anatomic shunt

42. Respiratory control mechanisms normally maintain the PaCO2 within a range of what?
35-45 mmHg

43. If carbon dioxide production increases, what happens to ventilation?
Ventilation automatically increases to maintain the PaCO2 within the normal range.

44. What is the most important factor in determining the alveolar partial pressure of oxygen?
The inspired partial pressure of oxygen

45. Oxygen in the lungs is diluted by what?
Water vapor and carbon dioxide

46. What is the alveolar air equation formula?
PAO2= FiO2 x (PB-47)-(PaCO2/0.8)

47. According to Dalton’s law, the partial pressure of alveolar nitrogen must be what?
It must be equal to the pressure it would exert if it alone were present.

48. What are the barriers to gas diffusion?
Alveolar epithelium, interstitial space and structures, capillary endothelium, and RBC membranes

49. When a patient is breathing room air, what is the sum of the alveolar PO2 and alveolar PCO2?
140 mmHg

50. If a patient is breathing room air at sea level, the respiratory therapist should or shouldn’t expect to see a PaO2 any higher than 120 mmHg during hyperventilation?
They should not expect to see a PaO2 higher than 120 mmHg.

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51. A PO2 value that is higher than 120 mmHg indicates what?
The patient is breathing supplemental oxygen

52. What is diffusion?
The process of gas molecules moving from an area of high partial pressure to an area of low partial pressure

53. In order for oxygen to diffuse into and out of the lungs and tissues, oxygen and carbon dioxide must move through what?

54. What three barriers must be penetrated in order for oxygen and CO2 to move between the alveoli and pulmonary capillary blood?
Alveolar epithelium, interstitial space, and capillary endothelium

55. What is Fick’s first law of diffusion?
It states that the greater the surface area, diffusion constant, and pressure gradient, the more diffusion will occur.

56. Diffusion in the lungs mainly depends on what?
Gas pressure gradients

57. What is the pressure gradient for oxygen diffusion into the blood?
60 mmHg

58. Does carbon dioxide diffuse faster or slower across the alveolar-capillary membrane than oxygen?
It diffuses 20 times faster than oxygen because it has higher solubility in the plasma.

59. The diffusion time in the lungs depends on what?
The rate of pulmonary blood flow

60. How long does blood take to flow through the pulmonary capillary?
0.75 seconds

61. Low concentrations of what is used to measure the diffusion capacity of the lungs?
Carbon monoxide

62. The PaO2 of a healthy person breathing at sea level is approximately how much less than the calculated PaO2?
5-10 mmHg

63. What two factors account for a 5-10 mmHg difference in the calculated PaO2?
(1) Right-to-left shunts in pulmonary and cardiac circulation, and (2) Regional differences in pulmonary ventilation and blood flow

64. What does a right-to-left shunt cause poorly oxygenated venous blood to do?
It causes it to move directly into the arterial circulation, lowering the oxygen content of the arterial blood.

65. What is the ideal ventilation and perfusion ratio?

66. What does a high ventilation/perfusion ratio indicate?
It indicates that either ventilation is greater than normal, perfusion is less than normal, or both.

67. A pressure gradient must exist for gas to move between what?
The alveoli and pulmonary capillaries

68. Does perfusion increase or decrease as you move further down into the lung bases?
It increases because the bases of the lungs receive nearly 20 times as much blood flow as the apices.

69. Does ventilation increase or decrease as you move further down into the lung bases?
It increases; there are four times as much ventilation in the bases of the lungs compared to the apices.

70. Blood carries oxygen in what two forms?
(1) Dissolved in plasma and erythrocyte fluid, and (2) Combines with hemoglobin inside red blood cells

71. What is the formula for dissolved oxygen in the blood?
Dissolved oxygen = PO2 x 0.003

72. Deoxygenated hemoglobin serves as a what during transport?
An important blood buffer for hydrogen ions

73. What is oxyhemoglobin?
Oxygen molecules bound to hemoglobin

74. In whole blood, each gram of normal hemoglobin can carry how many mL of oxygen?
1.34 mL

75. Hemoglobin increases the oxygen-carrying capacity of the blood by how much?
70-fold as compared to plasma alone

76. What is the portion of inspired air that is exhaled without being exposed to perfused alveoli?

77. According to Fick’s equation, if the oxygen consumption remains constant, a decrease in cardiac output will do what to the arteriovenous oxygen content difference?
It will increase the C(a-v)O2

78. According to Fick’s equation, if the cardiac output increases and oxygen consumption remains constant, what will happen to the arteriovenous oxygen content difference?
The C(a-v)O2 will decrease

79. What factors other than the HbO2 curve will affect the loading and unloading of oxygen?
Blood pH, body temperature, erythrocyte concentration of certain organic phosphates, variations in the structure of hemoglobin, and chemical combinations of hemoglobin with substances other than oxygen

80. A low pH shifts the oxyhemoglobin curve to the?

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81. A high pH shifts the oxyhemoglobin curve to the?

82. When blood pH drops and shifts the curve to the right, the hemoglobin saturation for a given PO2 will do what?
It will decrease

83. As blood pH increases and the curve shifts to the left, hemoglobin saturation for a given PO2 does what?
It increases

84. As blood inside the tissues picks up CO2, the pH decreases, and the HbO2 curve shifts in which direction?
It shifts to the right, therefore, decreasing the affinity of hemoglobin for oxygen.

85. Which way does the HbO2 shift when there is a drop in body temperature?
It shifts the curve to the left, which increases the hemoglobin affinity for oxygen.

86. As body temperature increases, the oxyhemoglobin curve shifts which way?
It shifts to the right, and the affinity of hemoglobin for oxygen decreases.

87. What happens to CO2 and PaO2 levels if you increase deadspace?
CO2 increases and PaO2 decreases

88. What is the normal level of carbon dioxide production for an adult?
200 mL/minute

89. Hemoglobin’s affinity for carbon monoxide is how much greater than it is for oxygen?
200 times greater

90. The combination of carbon monoxide and hemoglobin shifts the HbO2 curve in which direction?
It shifts it to the left, impeding oxygen delivery to the tissues.

91. What is the treatment for carbon monoxide poisoning?
You should provide the patient with as much oxygen as possible because oxygen reduces the half-life of carboxyhemoglobin.

92. What is a normal P50?
26.6 mmHg

93. Conditions that cause a decrease in hemoglobin affinity for oxygen cause a shift in which direction?
These conditions cause a shift to the right.

94. How much carbon dioxide is carried in the blood?
45-55 mL/dL

95. What are the three ways carbon dioxide is carried in the blood?
(1) Dissolved in a physical solution, (2) Chemically combined with protein, and (3) Ionized as bicarbonate

96. What is hydrolysis?
The chemical process in which a molecule is cleaved into two parts by the addition of a molecule of water

97. What does the hydrolysis of CO2 form?
Carbonic acid

98. What enzyme enhances the hydrolysis reaction?
Carbonic anhydrase

99. What are three causes of hypoxia?
1) Arterial blood oxygen content is decreased, 2) Cardiac output or perfusion is decreased, and 3) Abnormal cellular function prevents the proper uptake of oxygen

100. When does hypoxemia occur?
When the partial pressure of oxygen in arterial blood (PaO2) is decreased

101. What causes a decreased PaO2?
Low ambient PO2, hypoventilation, impaired diffusion, V/Q imbalances, right-to-left anatomical or physiological shunting, aging, and altitude

102. What is the approximate PaO2 at the age of 60?
85 mmHg

103. What is the most common cause of hypoxemia in patients with lung diseases?
Ventilation/perfusion imbalances

104. What happens when ventilation is greater than perfusion?
There is wasted ventilation (i.e., alveolar dead space)

105. What happens when ventilation is less than perfusion?
The ventilation/perfusion ratio is decreased, and blood leaves the lungs with abnormally low oxygen content.

106. What does a ventilation/perfusion ratio of 0 represent?
It means that there is blood flow but no ventilation, which is equivalent to a right-to-left anatomical shunt.

107. How can you differentiate between hypoxemia caused by a V/Q imbalance and hypoxemia caused by shunting?
If the FiO2 is greater than 50% and the PaO2 is less than 50%, significant shunting is present. Otherwise, the hypoxemia would be caused by a V/Q imbalance.

108. For the arterial oxygen content to be adequate, there must also be what?
There must be enough normal hemoglobin in the blood

109. Can hypoxia occur if the hemoglobin is low, even when the PaO2 is normal?
Yes, because there is low oxygen content in arterial blood.

110. What can low hemoglobin content do to the oxygen-carrying capacity of the blood?
It can seriously impair the oxygen-carrying capacity of the blood.

111. What are two types of reduced blood flow?
1) Circulatory failure (shock) and 2) Local reduction in perfusion (ischemia)

112. Any disorder that lowers alveolar ventilation relative to metabolic need impairs what?
Carbon dioxide removal

113. What happens as a result of impaired CO2 removal by the lungs?
Hypercapnia and respiratory acidosis

114. When does a decrease in alveolar ventilation occur?
When the minute ventilation is inadequate, dead space ventilation per minute increases, or a ventilation/perfusion imbalance exists

115. Inadequate minute ventilation is caused by what?
Decreased tidal volume

116. Inadequate minute ventilation occurs in what type of conditions?
Restrictive conditions, such as atelectasis and neuromuscular disorders, and conditions that impede thoracic expansion (e.g., kyphoscoliosis)

117. What causes increased dead space ventilation?
Rapid shallow breathing or increased physiologic dead space

118. What does increased dead space ventilation result in?
The proportion of wasted deadspace increases, which lowers alveolar ventilation and impairs CO2 removal.

119. In theory, a V/Q imbalance should cause an increased PaCO2. However, many patients who are hypoxemic due to a V/Q imbalance have a low or normal PaCO2. What does this suggest?
It suggests that V/Q imbalances have a greater effect on oxygenation than carbon dioxide removal.

120. What must happen to compensate for a high PaCO2 value with V/Q imbalances?
The patient’s minute ventilation must increase.

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121. When a patient is hypercapnic, what must happen for them to maintain a normal PaCO2?
They must sustain a higher than normal minute ventilation.

122. What disorders can lead to alveolar deadspace?
Pulmonary edema, partial obstruction of the pulmonary vasculature, destroyed pulmonary vasculature, and reduced cardiac output

123. How does gas move across the system?
Simple diffusion

124. How long is pulmonary blood exposed to alveolar gas?
0.75 seconds

125. How long is pulmonary blood exposed to alveolar gas during exercise?
0.25 seconds

126. How many times greater is ventilation at the bases?
Four times greater

127. How many times higher is blood flow at the bases?
20 times higher

128. What is ventilation that enters into the alveoli without any perfusion?
Alveolar deadspace

129. What are the normal values for the partial pressure of arterial blood?
O2 = 100 mmHg and CO2 = 40 mmHg

130. What are the normal values for the partial pressure of venous blood?
O2 = 40 mmHg and CO2 = 46 mmHg


What is Pulmonary Ventilation?

Pulmonary ventilation is the process of moving air in and out of the lungs. This occurs through a series of muscular contractions and relaxations that create negative pressure within the thoracic cavity.

As the thoracic cavity expands, air is drawn into the lungs. The opposite occurs during expiration as the thoracic cavity contracts, and air is forced out of the lungs. Pulmonary ventilation is vital for gas exchange to take place.

Where Does Gas Exchange Occur in the Lungs?

Gas exchange occurs in the alveoli. These are small, sack-like structures that are lined with a thin layer of type I alveolar cells. The alveoli are surrounded by a network of capillaries.

These vessels are lined with endothelial cells that have small pores that allow gases to diffuse across them. Oxygen and carbon dioxide diffuse across the alveolar-capillary membrane in order to reach equilibrium.

What Factors Affect Gas Exchange?

There are several factors that can affect how well gas exchange occurs in the lungs. One factor is the surface area of the alveolar-capillary membrane. This is the area over which diffusion can take place.

The surface area of the alveolar-capillary membrane is increased by having a larger number of alveoli and a greater density of capillaries.

Another factor that affects gas exchange is ventilation. This is the rate at which air moves in and out of the lungs. Increasing ventilation will increase the rate of gas exchange. However, too much ventilation can also be detrimental as it can cause a decrease in the partial pressure of oxygen in the alveoli.

Finally, the thickness of the alveolar-capillary membrane can also affect gas exchange. A thicker membrane will decrease the rate of diffusion.

What is the Main Function of Gas Exchange?

The main function of gas exchange is to ensure that the blood is supplied with oxygen while helping get rid of carbon dioxide.

Oxygen is essential for cellular respiration, which is the process that cells use to produce energy. Carbon dioxide is a waste product of cellular respiration and must be removed from the body.

Gas exchange ensures that these important gases are exchanged between the lungs and the blood.

What is Impaired Gas Exchange?

There are several conditions that can lead to impaired gas exchange. One condition is hypoventilation. This is when ventilation is decreased, which can lead to a build-up of carbon dioxide in the blood.

Another condition is atelectasis. This is when the alveoli collapse, which prevents oxygen from diffusing into the blood. A third condition is pneumonia, which is an infection of the lungs that can cause the alveoli to fill with fluid. This makes it difficult for oxygen to diffuse into the blood.

Finally, chronic obstructive pulmonary disease (COPD) is a condition that makes it difficult to breathe and can also lead to impaired gas exchange.

What is the Difference Between External and Internal Respiration?

External respiration is the process of exchanging gases between the lungs and the blood. Internal respiration is the process of exchanging gases between the blood and the cells. Both of these processes are necessary for gas exchange to occur.

External respiration is responsible for exchanging oxygen and carbon dioxide between the lungs and the blood. Internal respiration is responsible for exchanging oxygen and carbon dioxide between the blood and the cells.

Both of these processes are necessary for the body to function properly.

Final Thoughts

Gas exchange is an essential process that is required for human survival. That is why this is such an important topic, especially for respiratory therapists!

I hope that this overview has given you a better understanding of how gas exchange works in the body.

We have a similar guide on ventilation and perfusion that I think you’ll find helpful. Thank you so much for reading and, as always, breathe easy, my friend.

Medical Disclaimer: This content is for educational and informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Please consult with a physician with any questions that you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you read in this article. We strive for 100% accuracy, but errors may occur, and medications, protocols, and treatment methods may change over time.


The following are the sources that were used while doing research for this article:

  • Faarc, Kacmarek Robert PhD Rrt, et al. Egan’s Fundamentals of Respiratory Care. 12th ed., Mosby, 2020. [Link]
  • Jardins, Des Terry. Cardiopulmonary Anatomy & Physiology: Essentials of Respiratory Care. 7th ed., Cengage Learning, 2019. [Link]
  • “Transport of Gases between the Environment and Alveoli – Theoretical Foundations.” National Center for Biotechnology Information, U.S. National Library of Medicine, 2 Apr. 2015,
  • Wagner, Peter. “The Physiological Basis of Pulmonary Gas Exchange: Implications for Clinical Interpretation of Arterial Blood Gases.” European Respiratory Society, 1 Jan. 2015,

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