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Although carbon dioxide is more soluble in blood than oxygen, both gasses rely on a specialized transport system to facilitate the movement of most gas molecules between the lungs and various tissues in the body.
Oxygen Transport in the Blood
About 98% of oxygen is transported from the lungs to the body's tissues by erythrocytes using hemoglobin. A small fraction of oxygen (~2 percent) can directly dissolve into the plasma from the alveoli. Hemoglobin, a metalloprotein found in red blood cells, plays a crucial role in binding oxygen molecules. Comprising four subunits, hemoglobin has a quaternary structure where each subunit encases an iron atom within the heme (See Chapter 8, Figure 5). As oxygen binds to the first site in the heme, it triggers a conformational shift in hemoglobin, enhancing the affinity for subsequent oxygen molecules. With each binding, the affinity for more oxygen increases until all four heme sites are occupied. At this stage, hemoglobin is referred to as fully saturated with oxygen. Partial saturation occurs when one to three heme sites are occupied. The percentage of available heme units bound to oxygen at a given time defines hemoglobin saturation. Hemoglobin saturation of 100% means every heme unit in all erythrocytes is bound to oxygen. In a healthy individual with normal hemoglobin levels, hemoglobin saturation typically falls between 95% and 99%.53
Oxygen Dissociation from Hemoglobin
The reversible chemical reaction depicting the production of oxyhemoglobin (Hb–O2) occurs when oxygen binds to hemoglobin and is articulated as follows:
\[\mathrm{Hb}+\ce{O2} \rightleftharpoons \mathrm{Hb}-\ce{O2} \nonumber \]
Partial pressure plays a vital role in the binding and release of oxygen from heme. The oxygen–hemoglobin dissociation curve describes the relationship between partial pressure and the binding and subsequent dissociation of oxygen from heme. The graph in Figures 30 and 31 shows the oxygen-hemoglobin dissociation curve, which plots oxygen saturation of hemoglobin (%) on the y-axis against the partial pressure of oxygen (mmHg) on the x-axis. The curve demonstrates how hemoglobin binds to oxygen at different partial pressures. At high oxygen partial pressures (found in the lungs), hemoglobin saturation approaches 100%, indicating maximum oxygen binding. At lower oxygen partial pressures (found in tissues), hemoglobin releases oxygen to meet tissue demand. The volume of oxygen unloaded to tissues is shown as the vertical difference between the saturation at the lung and tissue levels.
Figure 30 | Oxygen-Hemoglobin Dissociation and Effects of pH, 2,3-bisphosphoglycerate (BPG), and Temperature |10 This graph illustrates the oxygen-hemoglobin dissociation curve and the influence of several factors. The curve shows the relationship between oxygen partial pressure and hemoglobin saturation. Factors such as \(\ce{CO2}\), pH (Bohr effect), DPG, and temperature can shift the curve, altering hemoglobin's oxygen affinity.
Figure 30 also illustrates the effect of pH (Bohr effect) on hemoglobin's affinity for oxygen. The Bohr effect refers to the influence of pH on hemoglobin's affinity for oxygen. It describes how changes in pH, typically caused by changes in carbon dioxide concentration, affect the binding of oxygen to hemoglobin. When carbon dioxide levels increase (resulting in a decrease in pH), the hemoglobin's affinity for oxygen decreases, allowing for more efficient unloading of oxygen to the tissues that need it. Higher pH (alkalinity) increases hemoglobin's affinity for oxygen, shifting the curve leftward, resulting in higher saturation at a given partial pressure. Conversely, a lower pH (increased acidity) decreases hemoglobin’s affinity for oxygen, shifting the curve rightward, facilitating oxygen release to tissues. This mechanism helps tissues receive more oxygen when they are metabolically active and produce more carbon dioxide, which lowers pH.
The oxygen – hemoglobin saturation/dissociation curve can be influenced by factors beyond partial pressure. Certain hormones (e.g., androgens, epinephrine, thyroid hormones, and growth hormone) stimulate erythrocytes to produce 2,3-bisphosphoglycerate (BPG), a byproduct of glycolysis. BPG facilitates oxygen dissociation from hemoglobin. Higher concentrations of BPG expedite oxygen release from hemoglobin, despite its partial pressure (Figure 30).
Temperature variation can impact the rate of dissociation; higher temperatures accelerate dissociation, aiding in oxygen release, while lower temperatures inhibit dissociation (Figure 30). The human body, though, tightly regulates temperature, except in highly active tissues that generate more heat due to increased energy expenditure, consequently promoting oxygen release from hemoglobin and aiding oxygen delivery.
Oxygen Dissociation from Hemoglobin of the Fetus
In the fetal stage, despite having its own circulation and erythrocytes, the fetus relies on the mother for oxygen supply. Blood is delivered to the fetus through the umbilical cord, connected to the placenta, separated from the maternal blood by the chorion. Gas exchange at the chorion is akin to the respiratory membrane. The partial pressure of oxygen in maternal blood at the placenta (35 to 50 mm Hg) is lower than in maternal arterial blood due to the unique structural and metabolic environment of the intervillous space. This drop in pressure begins as oxygenated maternal blood from the spiral arteries enters the intervillous space, where it immediately mixes with deoxygenated blood. This mixing effectively dilutes the oxygen concentration within the pool. There is still a difference in oxygen partial pressures between maternal and fetal blood, around 20 mm Hg in fetal blood (Figure 31). Consequently, there is diffusion of oxygen into the fetal bloodstream.The fetus’s hemoglobin has a higher affinity for oxygen than maternal hemoglobin, aiding in oxygen transfer to the fetal circulation.
Figure 31 | Oxygen-Hemoglobin Dissociation Curves in Fetus and Adult |54 Fetal hemoglobin has a greater affinity for oxygen than adult hemoglobin.
The p50 value of hemoglobin occurs when hemoglobin is 50% saturated with oxygen. The typical p50 value is around 27 mmHg. A rightward shift increases p50, leading to reduced hemoglobin affinity for oxygen and, subsequently, the release of oxygen from hemoglobin. This curve governs automatic control mechanisms that regulate oxygen delivery to various tissues based on their metabolic demands. Highly active tissues like muscles have lower tissue oxygen partial pressures, about 20 mm Hg, due to rapid oxygen utilization for ATP production. The disparity between the capillary and tissue oxygen pressures allows a substantial release of oxygen from hemoglobin into these tissues. Conversely, tissues with lower metabolic rates, such as adipose tissue, maintain relatively higher oxygen partial pressures, leading to a limited release of oxygen from hemoglobin.
Effects of Carbon Monoxide (\(\ce{CO}\)) on Hemoglobin and Oxygen Transport
\(\ce{CO}\) binds to hemoglobin with an affinity that is 250 times that of oxygen to form carboxyhemoglobin. When the partial pressure of \(\ce{CO}\) is only 1/250 that of oxygen, equal amounts of \(\ce{CO}\) and oxygen will bind to hemoglobin. Because oxygen cannot bind to heme groups that are bound to \(\ce{CO}\), the presence of \(\ce{CO}\) decreases the number of oxygen-binding sites available on hemoglobin. Hemoglobin bound to oxygen is reduced to 50%, which means that one half the binding sites would be bound to \(\ce{CO}\) and one half the binding sites would be available for oxygen. The implications for oxygen transport are obvious: This effect alone would reduce oxygen content of blood and oxygen delivery to tissues by 50 percent. \(\ce{CO}\) causes a left shift of the oxygen-hemoglobin dissociation curve. Those heme groups not bound to \(\ce{CO}\) have an increased affinity for oxygen. Thus, P50 is decreased, making it more difficult for oxygen to be unloaded in the tissues. Together, these two effects of \(\ce{CO}\) on oxygen binding to hemoglobin are catastrophic for oxygen delivery to tissues. Not only is there reduced oxygen-binding capacity of hemoglobin, but the remaining heme sites bind oxygen more tightly.55
Carbon Dioxide Transport in the Blood
Carbon dioxide is transported via three primary mechanisms. Initially, some carbon dioxide molecules dissolve in the blood plasma. Secondly, it is transported in the form of bicarbonate, which also dissolves within the plasma. Lastly, carbon dioxide is transported in a manner similar to the transportation of oxygen by erythrocytes (Figure 32).
Figure 32 | Carbon Dioxide Transport |56
This diagram illustrates the three pathways by which carbon dioxide (CO2) produced by tissue cells enters the blood for transport to the lungs. a. Formation of Carbaminohemoglobin: CO2 diffuses into the red blood cell (RBC) and binds directly to hemoglobin (Hb), forming carbaminohemoglobin (HbCO2). b. Bicarbonate Buffer System: The majority of CO2 enters the RBC and undergoes a chemical transformation: CO2 reacts with water (H2O) to form carbonic acid (H2CO3), a process catalyzed by the enzyme carbonic anhydrase. Carbonic acid quickly dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3−). The H+ ions bind to hemoglobin (Hb) to maintain pH, while the bicarbonate (HCO3−) diffuses out of the RBC into the plasma. c. Dissolved in Plasma: A small portion of the CO2 diffuses from the tissue cells into the capillary and remains physically dissolved in the blood plasma.
The transportation of carbon dioxide within the blood primarily occurs through three significant mechanisms. Approximately seven percent of carbon dioxide molecules that diffuse into the blood from tissues dissolve in plasma. This dissolved carbon dioxide travels in the bloodstream and, upon reaching the pulmonary capillaries, diffuses into the alveoli and is exhaled during respiration.
The largest portion, roughly 70 percent, of carbon dioxide entering the blood from tissues is transported as bicarbonate. Most bicarbonate is formed in red blood cells following the diffusion of carbon dioxide into capillaries. An enzyme within red blood cells, carbonic anhydrase, catalyzes the reaction of carbon dioxide and water to form carbonic acid. This compound dissociates into two ions: bicarbonate and hydrogen ions. There is a higher concentration of bicarbonate within red blood cells compared to the surrounding blood plasma, leading to its movement into the plasma in exchange for chloride ions, a process termed the chloride shift. This exchange occurs via a protein called bicarbonate chloride exchanger which maintains the electrical charge of the cells and plasma.57
Figure 33 | Gas Exchange Between the Alveolus and Blood |58 This figure illustrates the complex process of gas exchange in the lungs, including the diffusion of gases across the alveolar-capillary membrane, the role of hemoglobin in oxygen transport, and the bicarbonate buffer system in regulating blood pH. \(\ce{H2CO3}\) - carbonic acid; \(\ce{HCO3-}\) - bicarbonate.
Upon reaching the pulmonary capillaries, oxygen enters the red blood cell and binds to hemoglobin. Hydrogen ions are released by oxyhemoglobin. Much of the bicarbonate reenters the erythrocytes, exchanging with chloride ions (reverse chloride shift). The hydrogen ions and bicarbonate then form carbonic acid, which, with the help of carbonic anhydrase, converts back into carbon dioxide and water (Figure 33). This carbon dioxide diffuses from the red blood cells into the plasma and further moves across the respiratory membrane into the alveoli for exhalation during respiration.
Around 20 percent of the total carbon dioxide binds to hemoglobin and is transported to the lungs. This binding occurs not with the iron as in the case of oxygen but with amino acid moieties on the globin portions of hemoglobin. The resulting compound, carbaminohemoglobin, gives deoxygenated blood its characteristic dark red color.
The binding and release of carbon dioxide by hemoglobin are dependent on the partial pressure of carbon dioxide. When blood reaches the tissues, the lower partial pressure of carbon dioxide causes carbon dioxide to leave the tissues and enter the blood. Subsequently, it moves into red blood cells and binds to hemoglobin. Conversely, at the pulmonary capillaries, the high partial pressure of carbon dioxide in the blood causes carbon dioxide to readily dissociate from hemoglobin and pass into the alveoli for exhalation.
Ventilatory Response to Carbon Dioxide
In a healthy individual with adequate oxygen levels, minute ventilation shows an increase of 2 to 5 liters per minute (averaging at 2.5 liters per minute) for every one-millimeter increase in alveolar P\(\ce{CO2}\). This response holds true within the P\(\ce{CO2}\) range of 40 to 70 mm Hg. However, higher concentrations of carbon dioxide beyond this range would cause direct respiratory depression, resulting in symptoms such as dyspnea, intense headaches due to cerebral vasodilation, restlessness, faintness, and, at P\(\ce{CO2}\) levels above 100 mm Hg, loss of consciousness. Narcotic and anesthetic agents can reduce the response to carbon dioxide, leading to a dose-related increase in end-tidal carbon dioxide. Additionally, surgical stimulation counteracts respiratory depression and lowers arterial P\(\ce{CO2}\). Furthermore, anesthetic agents significantly depress the function of peripheral chemoreceptors, in addition to reducing the response to carbon dioxide in ventilation. At lower doses, narcotics depress the respiratory rate without altering the tidal volume. However, increased narcotic doses result in reductions of both the tidal volume and the respiratory rate by diminishing the sensitivity of the central respiratory centers to carbon dioxide stimulation. This reduced sensitivity is observed through a decrease in the slope of the arterial P\(\ce{CO2}\) alveolar ventilation response curve and shifts to the right. Narcotics also suppress the hypoxic drive. The impact of narcotics is more pronounced in patients who are sleeping compared to those who are awake.59
The Haldane effect outlines the relationship between the oxygenation state of hemoglobin and its capacity to carry carbon dioxide (Figure 34). It describes how oxygenation and deoxygenation of hemoglobin affect its ability to carry carbon dioxide. Deoxygenated hemoglobin has a higher capacity to carry carbon dioxide compared to oxygenated hemoglobin. As hemoglobin releases oxygen in tissues, it has a higher affinity for carbon dioxide.
Figure 34 | The Haldane Effect |10 This graph describes the relationship between the partial pressure of oxygen (P\(\ce{O2}\)) and the carbon dioxide (\(\ce{CO2}\)) content in the blood. The x-axis represents the partial pressure of \(\ce{CO2}\) (P\(\ce{CO2}\)) in mmHg, and the y-axis represents the \(\ce{CO2}\) content in the blood as volumes percent. Two curves are shown: one representing blood with a P\(\ce{O2}\) of 40 mmHg (dashed line) and the other representing blood with a P\(\ce{O2}\) of 100 mmHg (solid line). The curve with P\(\ce{O2}\) of 100 mmHg is higher than the curve with P\(\ce{O2}\) of 40 mmHg, indicating that at any given P\(\ce{CO2}\), blood with a higher P\(\ce{O2}\) carries less \(\ce{CO2}\). The arrow from point B to point A represents the change in \(\ce{CO2}\) content as blood transitions from a lower P\(\ce{O2}\) (40 mmHg) to a higher P\(\ce{O2}\) (100 mmHg). This demonstrates that as P\(\ce{O2}\) increases, the \(\ce{CO2}\) content in the blood decreases, illustrating the Haldane effect. This effect is crucial for enhancing \(\ce{CO2}\) release in the lungs where P\(\ce{O2}\) is high.
12.7: Transport of Gases is shared under a CC BY-NC-SA license and was authored, remixed, and/or curated by LibreTexts.
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