P4.23.6^23.6. Oxygen and Carbon Dioxide Transport in the Blood^845^852^,,^39576^39713%
23.6
Oxygen and Carbon Dioxide Transport in the Blood
    LEARNING OUTCOMES

    After reading this section, you should be able to:

  1. Describe the partial pressure gradients of oxygen and carbon dioxide.
  2. Explain how oxygen and carbon dioxide are transported in the blood.
  3. Discuss the factors that affect oxygen and carbon dioxide transport in the blood.
  4. Explain the carbon dioxide exchange in the lungs and at the tissues.
  5. Contrast fetal hemoglobin with maternal hemoglobin.

Once oxygen diffuses through the respiratory membrane into the blood, most of it combines reversibly with hemoglobin, and a smaller amount dissolves in the plasma. Hemoglobin transports oxygen from the pulmonary capillaries through the blood vessels to the tissue capillaries, where some of the oxygen is released. The oxygen diffuses from the blood to tissue cells, where it is used in aerobic respiration.

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Cells produce carbon dioxide during aerobic respiration. The carbon dioxide diffuses from the cells into the tissue capillaries. Once carbon dioxide enters the blood, it is transported in three ways: dissolved in the plasma, in combination with hemoglobin, or in the form of bicarbonate ions (HCO3).

Oxygen Partial Pressure Gradients

The Po2 within the alveoli averages approximately 104 mm Hg, whereas the Po2 in blood flowing into the pulmonary capillaries is approximately 40 mm Hg (figure 23.16 step 1). Consequently, oxygen diffuses down its partial pressure gradient from the alveoli into the pulmonary capillary blood. By the time blood flows through the first third of the pulmonary capillary beds, an equilibrium has been achieved, and the Po2 in the blood is 104 mm Hg, which is equivalent to the Po2 in the alveoli. Even with the greater velocity of blood flow associated with exercise, by the time blood reaches the venous ends of the pulmonary capillaries, the Po2 in the capillaries has achieved the same value as that in the alveoli (figure 23.16, step 2).

PROCESS FIGURE 23.16
Gas ExchangePartial pressure gradients of oxygen and carbon dioxide between the alveoli and the pulmonary capillaries and between the tissues and the tissue capillaries are responsible for gas exchange. All partial pressures shown are expressed in mm Hg.

Changes in the Partial Pressures of Oxygen and Carbon Dioxide

Gas Exchange During Respiration

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Blood leaving the pulmonary capillaries has a Po2 of 104 mm Hg, but blood leaving the lungs in the pulmonary veins has a Po2 of approximately 95 mm Hg. This decrease in the Po2 occurs because the blood from the pulmonary capillaries mixes with deoxygenated (shunted) blood from the bronchial veins (figure 23.16, step 3).

The blood that enters the arterial end of the tissue capillaries has a Po2 of approximately 95 mm Hg. The Po2 of the interstitial fluid, in contrast, is close to 40 mm Hg and is probably near 20 mm Hg in the individual cells. Oxygen diffuses from the tissue capillaries to the interstitial fluid and from the interstitial fluid into the body's cells, where it is used in aerobic respiration. Because the cells use oxygen continuously, a constant partial pressure gradient exists for oxygen from the tissue capillaries to the cells (figure 23.16, steps 4 and 5).

Carbon Dioxide Partial Pressure Gradients

Carbon dioxide is continually produced as a by-product of cellular respiration, and a partial pressure gradient is established from tissue cells to the blood within the tissue capillaries. The intracellular Pco2 is approximately 46 mm Hg, and the interstitial fluid Pco2 is approximately 45 mm Hg. At the arterial end of the tissue capillaries, the Pco2 is close to 40 mm Hg. As blood flows through the tissue capillaries, carbon dioxide diffuses from a higher Pco2 to a lower Pco2 until an equilibrium in Pco2 is established. At the venous end of the capillaries, blood has a Pco2 of 45 mm Hg (figure 23.16, step 5).

After blood leaves the venous end of the capillaries, it is transported through the cardiovascular system to the lungs. At the arterial end of the pulmonary capillaries, the Pco2 is 45 mm Hg. Because the Pco2 is approximately 40 mm Hg in the alveoli, carbon dioxide diffuses from the pulmonary capillaries into the alveoli. At the venous end of the pulmonary capillaries, the Pco2 has again decreased to 40 mm Hg (figure 23.16, steps 1 and 2).

Hemoglobin and Oxygen Transport

Approximately 98.5% of the oxygen transported in the blood from the lungs to the tissues is transported in combination with hemoglobin in red blood cells, and the remaining 1.5% is dissolved in the water part of the plasma. The combination of oxygen with hemoglobin is reversible. In the pulmonary capillaries, oxygen binds to hemoglobin; in the tissue spaces, oxygen diffuses away from hemoglobin and enters the tissues.

Effect of Po2

The oxygen-hemoglobin dissociation curve describes the percent saturation of hemoglobin in the blood at different blood Po2 values. Hemoglobin is 100% saturated with oxygen when four oxygen molecules are bound to each hemoglobin molecule in the blood. There are four heme groups in a hemoglobin molecule (see chapter 19), and an oxygen molecule is bound to each heme group. Hemoglobin is 50% saturated with oxygen when there is an average of two oxygen molecules bound to each hemoglobin molecule.

The Po2 in the blood leaving the pulmonary capillaries is normally 104 mm Hg. At that partial pressure, hemoglobin is 98% saturated (figure 23.17a). Decreases in the Po2 in the pulmonary capillaries have a relatively small effect on hemoglobin saturation, as shown by the fairly flat shape of the upper part of the oxygen-hemoglobin dissociation curve. Even if the blood Po2 decreases from 104 mm Hg to 60 mm Hg, hemoglobin is still 90% saturated. Hemoglobin is very effective at picking up oxygen in the lungs, even if the Po2 in the pulmonary capillaries decreases significantly.

 
FIGURE 23.17
Oxygen-Hemoglobin Dissociation CurveThe oxygen-hemoglobin dissociation curve shows the percent saturation of hemoglobin as a function on Po2. The ability of hemoglobin to pick up oxygen in the lungs and release it in the tissues is like a glass filling and emptying.

In a resting person, the normal blood Po2 leaving the tissue capillaries is 40 mm Hg, and hemoglobin is 75% saturated. Thus, 23% (98% − 75%) of the oxygen picked up in the lungs is released from hemoglobin and diffuses into the tissues (figure 23.17b). The 75% of oxygen still bound to the hemoglobin is an oxygen reserve, which can be released if blood Po2 decreases further. In the tissues, a relatively small change in blood Po2 results in a relatively large change in hemoglobin saturation, as shown by the steep slope of the oxygen-hemoglobin dissociation curve. For example, during vigorous exercise, the Po2 in skeletal muscle capillaries can decline to levels as low as 15 mm Hg because of the increased use of oxygen during aerobic respiration in skeletal muscle cells (see chapter 9). At a Po2 of 15 mm Hg, hemoglobin is only 25% saturated, resulting in the release of 73% (98% − 25%) of the oxygen picked up in the lungs (figure 23.17c). Thus, as tissues use more oxygen, hemoglobin releases more oxygen to those tissues.

ASSESS YOUR PROGRESS
  1. Describe the partial pressure of oxygen and carbon dioxide in the alveoli, lung capillaries, tissue capillaries, and tissues.

  2. How do these pressures account for the movement of oxygen and carbon dioxide between air and blood, and between blood and tissues?

  3. Name the two ways oxygen is transported in the blood, and state the percentage of total oxygen transport for which each method is responsible.

  4. How does the oxygen-hemoglobin dissociation curve explain the uptake of oxygen in the lungs and the release of oxygen in tissues?

Effect of pH, Pco2, and Temperature

In addition to Po2, three other factors influence the degree to which oxygen binds to hemoglobin: blood pH, Pco2, and temperature (figure 23.18). As the pH of the blood declines, the amount of oxygen bound to hemoglobin at any given Po2 also declines. This occurs because decreased pH results from an increase in H+, and the H+ combine with the protein part of the hemoglobin molecule and change its three-dimensional structure, causing a decrease in the hemoglobin's ability to bind oxygen. Conversely, an increase in blood pH results in an increase in hemoglobin's ability to bind oxygen. The effect of pH on the oxygen-hemoglobin dissociation curve is called the Bohr effect, after its discoverer, Christian Bohr.

 

FUNDAMENTAL Figure

FIGURE 23.18
Effects of Shifting the Oxygen-Hemoglobin Dissociation Curve

An increase in Pco2 also decreases hemoglobin's ability to bind oxygen because of the effect of carbon dioxide on pH. Within red blood cells, an enzyme called carbonic anhydrase catalyzes this reversible reaction:

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As carbon dioxide levels increase, more H+ are produced, and the pH declines. As carbon dioxide levels decline, the reaction proceeds in the opposite direction, resulting in a decrease in H+ concentration and an increase in pH. Thus, changes in carbon dioxide levels indirectly produce a Bohr effect by altering pH. In addition, carbon dioxide can directly affect hemoglobin's ability to bind oxygen, to a small extent. When carbon dioxide binds to the α- and β-globin chains of hemoglobin (see chapter 19), hemoglobin's ability to bind oxygen decreases.

As blood passes through tissue capillaries, carbon dioxide enters the blood from the tissues. As a consequence, blood carbon dioxide levels increase, pH decreases, and hemoglobin has less affinity for oxygen in the tissue capillaries. Therefore, a greater amount of oxygen is released in the tissue capillaries than would be released if carbon dioxide were not present. When blood is returned to the lungs and passes through the pulmonary capillaries, carbon dioxide leaves the capillaries and enters the alveoli. As a result, carbon dioxide levels in the pulmonary capillaries are reduced, pH increases, and hemoglobin's affinity for oxygen increases.

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An increase in temperature also decreases oxygen's tendency to remain bound to hemoglobin. Therefore, elevated temperatures resulting from increased metabolism increase the amount of oxygen released into the tissues by hemoglobin. In less metabolically active tissues in which the temperature is lower, less oxygen is released from hemoglobin.

When hemoglobin's affinity for oxygen decreases, the oxygen-hemoglobin dissociation curve is shifted to the right, and hemoglobin releases more oxygen (figure 23.18a). During exercise, when carbon dioxide and acidic substances, such as lactic acid, accumulate and the temperature increases in the tissue spaces, the oxygen-hemoglobin curve shifts to the right. Under these conditions, as much as 75–85% of the oxygen is released from the hemoglobin. In the lungs, however, the curve shifts to the left because of the lower carbon dioxide levels, lower temperature, and lower lactic acid levels. Therefore, hemoglobin's affinity for oxygen increases, and it becomes easily saturated (figure 23.18b).

During resting conditions, approximately 5 mL of oxygen are transported to the tissues in each 100 mL of blood, and cardiac output is approximately 5000 mL/min. Consequently, 250 mL of oxygen are delivered to the tissues each minute. During exercise, this value can increase up to 15 times. Oxygen transport can be increased threefold because of a greater degree of oxygen release from hemoglobin in the tissue capillaries, and the rate of oxygen transport is increased another five times because of the increase in cardiac output. Consequently, the volume of oxygen delivered to the tissues can be as high as 3750 mL/min (15 × 250 mL/min). Highly trained athletes can increase this volume to as high as 5000 mL/min.

Predict 7

In carbon monoxide (CO) poisoning, CO binds to hemoglobin, thereby decreasing the uptake of oxygen by hemoglobin. In addition, when CO binds to hemoglobin, the oxygen-hemoglobin dissociation curve shifts to the left. How does this shift affect the ability of tissues to get oxygen? Explain.

Predict 7
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Effect of BPG

As red blood cells metabolize glucose for energy, they produce a by-product called 2,3-bisphosphoglycerate (BPG; formerly called diphosphoglycerate). BPG binds to hemoglobin, reducing its affinity for oxygen, which increases its ability to release oxygen. A potent trigger for increased BPG production is low blood oxygen. For example, barometric pressure is lower at high altitudes than at sea level, causing both the partial pressure of oxygen in the alveoli and the percent saturation of blood with oxygen in the pulmonary capillaries to be lower. Consequently, the blood holds less oxygen for delivery to tissues. BPG helps increase oxygen delivery to tissues because higher levels of BPG increase the release of oxygen in tissues (the oxygen-hemoglobin dissociation curve shifts to the right). On the other hand, when blood is removed from the body and stored in a blood bank, the BPG levels in the stored blood decrease. As BPG levels decrease, the blood becomes unsuitable for transfusion after approximately 6 weeks because the hemoglobin releases less oxygen to the tissues. Banked blood is, therefore, discarded after 6 weeks of storage.

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Predict 8

If a person lacks the enzyme necessary for BPG synthesis, does he or she exhibit anemia (a lower than normal number of red blood cells) or erythrocytosis (a higher than normal number of red blood cells)? Explain.

Predict 8
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Fetal Hemoglobin

As fetal blood circulates through the placenta, oxygen is released from the mother's blood into the fetal blood, and carbon dioxide is released from fetal blood into the mother's blood. Fetal blood is very efficient at picking up oxygen for several reasons:

  1. The concentration of fetal hemoglobin is approximately 50% greater than the concentration of maternal hemoglobin.

  2. Fetal hemoglobin is different from maternal hemoglobin. Its oxygen-hemoglobin dissociation curve is to the left of the maternal oxygen-hemoglobin dissociation curve. Thus, for a given Po2, fetal hemoglobin can hold on more tightly to oxygen than maternal hemoglobin can.

  3. BPG has little effect on fetal hemoglobin. That is, BPG does not cause fetal hemoglobin to release oxygen.

ASSESS YOUR PROGRESS
  1. What is the Bohr effect? How is it related to blood carbon dioxide?

  2. Why is it advantageous for the oxygen-hemoglobin dissociation curve to shift to the left in the lungs and to the right in tissues?

  3. How does temperature affect oxygen's tendency to bind to hemoglobin?

  4. How does BPG affect the release of oxygen from hemoglobin?

  5. Why is fetal hemoglobin's affinity for oxygen greater than that of maternal hemoglobin?

Predict 9

How does the movement of CO2 from fetal blood into maternal blood increase the movement of oxygen from maternal blood into fetal blood? (Hint: Consider the shift of the oxygenhemoglobin dissociation curve.)

Predict 9
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Transport of Carbon Dioxide

Carbon dioxide is transported in the blood in three forms: as HCO3 dissolved in the plasma or the red blood cells, as CO2 dissolved in the plasma, or as CO2 bound to hemoglobin.

Carbon Dioxide Exchange in Tissues

Carbon dioxide diffuses from tissues into the plasma of blood (figure 23.19a). Most of the carbon dioxide diffuses from tissues into red blood cells. Inside the red blood cells, the carbon dioxide reacts with water to form carbonic acid, a reaction catalyzed by carbonic anhydrase. Carbonic acid then dissociates to form HCO3. About 70% of blood carbon dioxide is transported in the form of HCO3 dissolved in either the red blood cells or the plasma. Another 7% is transported as CO2 dissolved in the plasma, and approximately 23% is transported bound to hemoglobin.

 

FUNDAMENTAL Figure

FIGURE 23.19
Gas Exchange

Removing HCO3 from inside the red blood cells promotes carbon dioxide transport because, as the HCO3 concentration decreases, more carbon dioxide combines with water to form additional HCO3 and H+ (see “Reversible Reactions,” chapter 2). In a process called chloride shift (figure 23.19a, step 4), antiporters exchange Cl for HCO3. This exchange maintains electrical balance in the red blood cells and plasma as HCO3 diffuse out of, and Cl diffuse into, red blood cells.

Hydrogen ions bind to hemoglobin (figure 23.19a, step 6), resulting in three effects: (1) The transport of carbon dioxide increases because, as H+ concentration decreases, more carbon dioxide combines with water to form additional HCO3 and H+; (2) the pH inside the red blood cells does not decrease because hemoglobin is a buffer, preventing an increase in H+ concentration; and (3) the affinity of hemoglobin for oxygen decreases. Hemoglobin releases oxygen in tissue capillaries because of decreased Po2 (see figure 23.17). Hemoglobin's decreased affinity for oxygen shifts the oxygen-hemoglobin curve to the right (the Bohr effect; see figure 23.18a) and results in an increase in the release of oxygen from hemoglobin.

Approximately 23% of blood carbon dioxide is transported bound to hemoglobin. Many carbon dioxide molecules bind in a reversible fashion to the α- and β-globin chains of hemoglobin molecules (figure 23.19a, step 7). Carbon dioxide's ability to bind to hemoglobin is affected by the amount of oxygen bound to hemoglobin. The smaller the amount of oxygen bound to hemoglobin, the greater the amount of carbon dioxide able to bind to it, and vice versa. This relationship is called the Haldane effect. In tissues, as hemoglobin releases oxygen, the hemoglobin gains an increased ability to pick up carbon dioxide.

Carbon Dioxide Exchange in the Lungs

Carbon dioxide diffuses from red blood cells and plasma into the alveoli (figure 23.19b). As carbon dioxide levels in the red blood cells decrease, carbonic acid is converted to carbon dioxide and water. In response, HCO3 join with H+ to form carbonic acid. As HCO3 and H+ concentrations decrease because of this reaction, HCO3 enter red blood cells in exchange for Cl, and H+ are released from hemoglobin. Hemoglobin picks up oxygen in pulmonary capillaries because of increased Po2 (see figure 23.17). The release of H+ from hemoglobin increases hemoglobin's affinity for oxygen, shifting the oxygen-hemoglobin curve to the left (Bohr effect; see figure 23.18b). Oxygen from the alveoli diffuses into the pulmonary capillaries and into the red blood cells, where it binds with hemoglobin. Carbon dioxide is released from hemoglobin and diffuses out of the red blood cells into the alveoli. As hemoglobin binds to oxygen, it more readily releases carbon dioxide (Haldane effect).

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Carbon Dioxide and Blood pH

Blood pH refers to the pH in plasma, not inside red blood cells. As plasma carbon dioxide levels increase, H+ levels increase, and blood pH decreases. An important function of the respiratory system is to regulate blood pH by changing plasma carbon dioxide levels (see chapter 27). Hyperventilation decreases plasma carbon dioxide, and hypoventilation increases it.

ASSESS YOUR PROGRESS
  1. How does the lowering HCO3 concentrations inside red blood cells affect carbon dioxide transport?

  2. What is the chloride shift, and what does it accomplish?

  3. Name three effects produced by H+ binding to hemoglobin.

  4. What is the Haldane effect?

  5. What effect does blood carbon dioxide level have on blood pH?

Predict 10

Explain the effect of (1) hyperventilation and (2) holding one's breath on blood pH.

Predict 10
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