23.7 Respiration_ Gas Transport.pdf

23.7 Respiration: Gas Transport The fourth process of respiration is gas transport. Gas transport is the movement of respiratory gases (O2 and CO2) within the blood between the lungs and systemic cells in body tissues. 23.7a Oxygen Transport LEARNING OBJECTIVE 44. Explain why hemoglobin is essential...

23.7 Respiration: Gas Transport The fourth process of respiration is gas transport. Gas transport is the movement of respiratory gases (O2 and CO2) within the blood between the lungs and systemic cells in body tissues. 23.7a Oxygen Transport LEARNING OBJECTIVE 44. Explain why hemoglobin is essential to oxygen transport. Oxygen is transported within blood from the alveoli through pulmonary veins of the pulmonary circulation to the left side of the heart. Then blood is pumped into the aorta and through arteries of the systemic circulation to enter systemic capillaries (see figure 19.3). Oxygen then diffuses from the blood within systemic capillaries into systemic cells. The ability of blood to transport oxygen is dependent upon two factors: the solubility coefficient of oxygen in blood plasma and the presence of hemoglobin (Hb). Our discussion of gas solubility and Henry’s law (see section 23.6a) pointed out that the solubility coefficient of oxygen is very low (0.024). This means that only small amounts of oxygen (less than 2%) are dissolved in the plasma. Consequently, about 98% of the oxygen in the blood must be transported within erythrocytes, where it attaches to the iron within hemoglobin molecules (see figure 23.27c). Oxygen bound to hemoglobin is referred to as oxyhemoglobin (abbreviated HbO2). Hemoglobin without bound oxygen is called deoxyhemoglobin (abbreviated as HHb): What is the oxygen carrying capacity of erythrocytes? Recall from section 18.3b that an erythrocyte is a biconcave, flexible cell with no nucleus or mitochondria and few organelles. It retains its plasma membrane, and its primary substance is hemoglobin. Thus, an erythrocyte can be described as simply a “bag of hemoglobin.” Erythrocytes are the most numerous cells within the human body (estimated to be over 20 trillion), with each erythrocyte containing about 280 million hemoglobin molecules. Thus, erythrocytes have a very high oxygen carrying capacity. WHAT DID YOU LEARN? 33 Why is such a small percentage (about 2%) of oxygen dissolved in plasma and most transported on hemoglobin? 23.7b Carbon Dioxide Transport LEARNING OBJECTIVE 45. Describe the three ways carbon dioxide is transported in the blood. Cells typically produce about 200 mL/min of carbon dioxide as a waste product during cellular respiration. Carbon dioxide is transported from systemic cells within deoxygenated blood through veins of the systemic circulation to the right side of the heart, then pumped into the pulmonary trunk and pulmonary arteries to enter pulmonary capillaries (see figure 19.3). Carbon dioxide then diffuses from the blood within pulmonary capillaries into the alveoli. Whereas hemoglobin is the major means of transporting oxygen, carbon dioxide has three means of being transported in the blood from the systemic cells to the alveoli: (a) CO2 dissolved within plasma, (b) CO2 attached to the globin portion of hemoglobin, and (c) as bicarbonate ( ) dissolved within plasma. We previously noted that the solubility coefficient of carbon dioxide is 0.57 (see section 23.6a). Due to both this value and the small partial pressure gradient for CO2 (i.e., 45 mm Hg → 40 mm Hg), approximately 7% of carbon dioxide is transported to the alveoli as a dissolved gas within the plasma of blood. Page 934 INTEGRATE CLINICAL VIEW 23.17 Measuring Blood Oxygen Levels with a Pulse Oximeter M. Constantini/PhotoAlto One way to measure blood oxygen levels is with a blood sample. A noninvasive and indirect way to measure blood oxygen levels is to use a pulse oximeter. This device is applied to a translucent area of the body, usually a finger or an earlobe. Two wavelengths of light, both red (660 nm) and infrared (940 nm), are emitted from light-emitting diodes (LEDs) and directed through the finger or earlobe. The device contains a photodiode on the other side that can measure the hemoglobin saturation by determining the ratio of absorption by oxyhemoglobin (which absorbs more infrared light) to the absorption by deoxyhemoglobin (which absorbs more red light). Normal readings include hemoglobin saturation that is greater than 95%. Hemoglobin is capable of transporting about 23% of the CO2 as a carbaminohemoglobin compound. The CO2 is attached to amine groups (—NH2) in the globin protein: The remaining 70% of the CO2 diffuses from the plasma into erythrocytes and combines with water to form bicarbonate ( carbonic anhydrase): ) and H+ (a chemical reaction catalyzed by then diffuses from erythrocytes into the plasma. (The H+ binds to hemoglobin within erythrocytes, which buffers the H+, helping to prevent pH changes; see section 25.5d.) Thus, the largest percentage of CO2 is carried from the systemic cells to the lungs in plasma as dissolved. Carbon dioxide is regenerated (and H+ is released from hemoglobin) when blood moves through pulmonary capillaries and this process is reversed. Figure 23.31 provides a summary of the details of this conversion and its reversal within erythrocytes, which is referred to collectively as the chloride shift. Figure 23.31 Conversion of Carbon Dioxide to Bicarbonate. (a) In systemic capillaries, CO2 enters erythrocytes, where it combines with H2O as carbonic anhydrase converts it to carbonic acid (H2CO3). This compound then splits into bicarbonate ion (HCO3−) and hydrogen ion (H+). HCO3− leaves the erythrocyte and is replaced by Cl− during the chloride shift to equalize the charges (to prevent development of a negative charge on the outside of the erythrocyte). HCO3− is transported in plasma. H+ produced during the chloride shift binds with and is buffered by hemoglobin, thus helping to prevent a decrease in pH. (b) The process is reversed in pulmonary capillaries. Cl− leaves the erythrocyte and HCO3− enters during the chloride shift. HCO3− recombines with H+ to reform H2CO3, which carbonic anhydrase converts to CO2 and H2O. CO2 exits the erythrocyte. It then diffuses into the alveoli and is expired. Concept Overview Physiology Interactives How important is carbonic anhydrase located within erythrocytes in the transport of CO2? Consider the role of carbonic anhydrase as you read this section. At Systemic Cells Recall from section 23.6c that the Pco2 is lower within the blood of systemic capillaries than in systemic cells. This is why CO2 diffuses from systemic cells into the blood of systemic capillaries during tissue gas exchange. In addition, as described in this section, CO2 then diffuses from the plasma into erythrocytes and is converted to by carbonic anhydrase. It is this conversion of CO2 to that keeps the Pco2 within erythrocytes relatively low compared to that in the plasma, allowing CO2 to continue to diffuse from the plasma into erythrocytes. It is also what keeps the blood Pco2 relatively low in comparison to that in systemic cells, allowing CO2 to continue to diffuse from systemic cells into the blood. Thus, carbonic anhydrase allows for the continuous net movement of CO2 from systemic cells into erythrocytes (where the CO2 is converted to ). then moves from erythrocytes into the blood plasma, and it is in this form that it is transported from systemic cells to the lungs. Within the Lungs Recall from section 23.6b that the Pco2 is greater within the blood of pulmonary capillaries than in alveoli. This is why CO2 diffuses from the blood of pulmonary capillaries into alveoli during pulmonary gas exchange. In addition, as described in this section, in the plasma reenters erythrocytes and is converted back to CO2 by carbonic anhydrase. It is this conversion of to CO2 that keeps the Pco2 within erythrocytes relatively high compared to that in the plasma, allowing CO2 to diffuse from erythrocytes into the plasma. It is also what keeps the blood Pco2 relatively high compared to that in alveoli, allowing CO2 to continue to diffuse from the blood into alveoli. Thus, carbonic anhydrase allows for the continuous net movement of CO2 from erythrocytes into alveoli. Air within alveoli containing CO2 is then expired into the atmosphere during pulmonary ventilation. Carbonic anhydrase was first described in section 3.3a as an enzyme that produces H2CO3 molecules, which are split into and H+ at a rate of up to 2.16 billion per hour! Thus, without carbonic anhydrase (which functions in the transport of approximately 70% of the movement of CO2 from systemic cells to alveoli), CO2 transport would be limited to the much smaller amounts that are transported dissolved within blood plasma (about 7%) and attached to hemoglobin (about 23%). WHAT DID YOU LEARN? 34 How is the majority of carbon dioxide transported within the blood? 23.7c Hemoglobin as a Transport Molecule LEARNING OBJECTIVES 46. Explain oxygen binding to hemoglobin and the oxygen-hemoglobin saturation curve. 47. Describe hemoglobin as a transport molecule and what occurs during pulmonary and tissue gas exchange. Hemoglobin (see figure 23.27c) transports three substances relative to respiration activities: (a) oxygen attached to iron, (b) carbon dioxide bound to the globin, and (c) hydrogen ions bound to the globin, as described. A critical aspect of this transport is that the binding or release of one substance causes a conformational change that temporarily alters the shape of the hemoglobin molecule. This change influences the ability of hemoglobin to bind or release the other two substances. The primary focus of this section is on the variables that influence hemoglobin’s binding and release of oxygen. Hemoglobin and Binding of Oxygen Because one hemoglobin molecule has four iron atoms, each hemoglobin molecule may bind a maximum of four O2 molecules. The amount of oxygen bound to hemoglobin is expressed as the percent O2 saturation of hemoglobin. For example, when oxygen is bound to onequarter of the available iron binding sites, the hemoglobin is said to be 25% saturated, and if all iron sites are occupied by oxygen, hemoglobin is 100% saturated. Hemoglobin saturation is determined by several variables. The most important variable is the Po2. Predictably, as the Po2 increases, hemoglobin saturation increases. The binding of each O2 molecule causes a conformational change in hemoglobin that makes it progressively easier for each additional O2 molecule to bind to an available iron. This increase in the ease of oxygen binding is termed the cooperative binding effect of O2 loading. Page 935 Oxygen-Hemoglobin Saturation Curve The graph shown in figure 23.32 relates the Po2 and percent O2 saturation of hemoglobin called the oxygen-hemoglobin saturation curve (or oxyhemoglobin dissociation curve). Notice that the relationship between Po2 and hemoglobin saturation is not linear (a straight line). The plotted points on the graph produce an S-shaped, or sigmoidal, curve. Figure 23.32 Oxygen-Hemoglobin Saturation Curve. The percent O2 saturation of hemoglobin increases as Po2 increases. Relatively large changes in percent O2 saturation of hemoglobin occur as Po2 changes from 0 to 60 mm Hg. At Po2 greater than 60 mm Hg, changes in percent O2 saturation of hemoglobin are much smaller. (The letter labels are discussed in the text.) Concept Overview Physiology Interactives Relatively large changes occur in the hemoglobin saturation as the Po2 increases initially. For example, a change in Po2 from 20 to 40 mm Hg, a difference of 20 mm Hg, results in the hemoglobin saturation increasing from about 35% to 75% saturated (a change of 40%) as a result of the cooperative binding effect. The curve is very steep in this part of the graph. A Po2 of at least 60 mm Hg causes hemoglobin to become over 90% saturated. When Po2 values are higher than 60 mm Hg, only relatively small changes in hemoglobin saturation occur. A change in Po2 from 80 to 100 mm Hg, a difference of 20 mm Hg, results in the hemoglobin saturation changing from 95% to 98% saturated—a very small difference of only 3%. Figure 23.32 has application to the physiologic processes of oxygen loading that occurs during both pulmonary gas exchange in the lungs and oxygen unloading that occurs during tissue gas exchange at the systemic cells as described next. The Oxygen-Hemoglobin Saturation Curve and Pulmonary Gas Exchange Hemoglobin loads with oxygen as blood moves through the pulmonary capillaries in the lungs. The alveolar Po2 is 104 mm Hg at sea level. What would hemoglobin saturation be after the blood is transported through the pulmonary capillaries? The graph in figure 23.32 (label e) helps us determine that hemoglobin would be approximately 98% saturated. If we ascend a high mountain, the air thins and environmental Po2 decreases; this is accompanied by a decrease in alveolar Po2. How does this influence the hemoglobin saturation that occurs during pulmonary gas exchange? Figure 23.32 can be used to determine approximate oxygen percent saturation values by selecting several altitudes that are correlated with specific alveolar Po2 values. For example, at an elevation of about 5000 feet, the Po2 is 81 mm Hg. The hemoglobin saturation would be approximately 95% ( figure 23.32, label d). If we continue to ascend and reach an altitude of about 9000 feet, the Po2 value is 65 mm Hg. The hemoglobin saturation would be about 91% ( figure 23.32, label c). In comparison, at an altitude of around 17,000 feet, the alveolar Po2 is 40 mm Hg. The hemoglobin saturation would be only 75% ( figure 23.32, label b). Page 936 Increases in altitude from sea level (with accompanying decreases in alveolar Po2) initially result in only small changes in hemoglobin saturation; thus, changes in oxygen delivery are minimal. However, ascending to a very high altitude, with its accompanying large decrease in alveolar Po2, results in large decreases in hemoglobin saturation. The adverse physiologic effects from a decrease in alveolar Po2, referred to as altitude sickness, can occur in some individuals at altitudes as low as 6600 feet but occur for most individuals at altitudes greater than 8200 feet. Milder symptoms of altitude sickness include headache, nausea, and difficulty sleeping; more severe symptoms include pulmonary edema (see Clinical View 19.1: “Congestive Heart Failure”) and cerebral edema (see Clinical View 20.5: “Cerebral Edema”). The Oxygen-Hemoglobin Saturation Curve and Tissue Gas Exchange The oxygen-hemoglobin curve can also help us to understand how PO2 influences the percent saturation of hemoglobin during tissue gas exchange. Oxygen is released from hemoglobin during its transport through systemic capillaries. The partial pressure of oxygen in systemic cells (e.g., muscle tissue) during resting conditions is approximately 40 mm Hg, and hemoglobin saturation is therefore 75% ( figure 23.32, label b). Hemoglobin in the blood is 98% saturated with oxygen as it leaves the lungs (when at sea level), and then after it flows through the systemic capillaries during resting conditions it is still relatively saturated with oxygen at approximately 75%. Therefore, under resting conditions only a small percentage of the oxygen (approximately 20–25%) transported by the hemoglobin is released as it passes through systemic capillaries. The amount of oxygen that remains bound to the hemoglobin after passing through the systemic capillaries is referred to as the oxygen reserve. The oxygen reserve provides a means for additional oxygen to be delivered to systemic cells under increased metabolic demands, as occurs during exercise. If systemic cell Po2 decreases to 20 mm Hg (e.g., active muscle tissue), as occurs during vigorous exercise, then what is the hemoglobin saturation? Vigorous exercise produces a large decrease in the hemoglobin saturation, meaning that more oxygen is unloaded. The hemoglobin saturation in the blood leaving systemic capillaries would be only 35% ( figure 23.32, label a). INTEGRATE CONCEPT CONNECTION Hemoglobin is a protein, and like all proteins, its three-dimensional structure is maintained by weak intramolecular interactions between the amino acid monomers that compose it, as described in section 2.8b. These interactions include hydrogen bonding, electrostatic attractions between oppositely charged groups, and association of nonpolar groups. Increases in temperature, changes in pH, and the binding of some ions weaken or break these bonds, ultimately resulting in conformational changes in the shape of a protein. WHAT DO YOU THINK? 7 Is more or less oxygen delivered to the systemic cells under the conditions of the lower cellular Po2 (such as during exercise)? Is the oxygen reserve higher or lower? Other Variables That Influence Hemoglobin’s Binding and Release of Oxygen Blood Po2 is the most significant factor in hemoglobin’s ability to bind and release oxygen during gas exchange, as just described. However, other variables can influence the amount of oxygen binding to hemoglobin during pulmonary gas exchange and the amount of oxygen released from hemoglobin during tissue gas exchange. We first discuss how these variables influence the binding of oxygen during pulmonary gas exchange ( figure 23.33a). We know that during pulmonary gas exchange, oxygen is diffusing into the blood and binding with hemoglobin as carbon dioxide is being released from hemoglobin (with the accompanying release of H+ from hemoglobin). The release of both CO2 and H+ from the globin of hemoglobin causes a conformational change in the hemoglobin. This change in the shape of hemoglobin facilitates the binding of oxygen to the iron. Thus, the “jumping off” of CO2 and H+ makes it easier for O2 to “jump on.” Figure 23.33 Hemoglobin as a Transport Molecule. Hemoglobin as a transport molecule during (a) pulmonary gas exchange and (b) tissue gas exchange. Page 937 In comparison, we know that during tissue gas exchange, oxygen is being released from hemoglobin as both CO2 and H+ are binding to hemoglobin ( figure 23.33b). The binding of CO2 and H+ to hemoglobin causes a conformational change in hemoglobin that decreases the affinity of hemoglobin for oxygen. The conformational change in hemoglobin facilitates the release of oxygen (which is called the Bohr effect). Thus, the “jumping on” of CO2 and H+ makes it easier for O2 to “jump off.” There are several other variables that alter the affinity of hemoglobin for oxygen and the amount of oxygen released during tissue gas exchange. These include: Temperature. Metabolic activities increase body temperature. This elevated temperature has the same effect on hemoglobin that an increase in temperature has on all proteins—it makes hemoglobin more flexible. This interferes with hemoglobin’s ability to bind and hold oxygen, so additional oxygen is released from hemoglobin during tissue gas exchange. Presence of 2,3-BPG. 2,3-BPG (2,3-biphosphoglycerate) is produced within erythrocytes in an alternative (glycolytic) metabolic pathway ( figure 23.33b). The enzymatic process for 2,3-BPG production is stimulated by certain hormones that bind to erythrocyte receptors, including thyroid hormone, epinephrine, growth hormone, and testosterone. Other changes, including chronically low oxygen and change in altitude, also induce formation of 2,3-BPG. Consider that when you exercise, these changes—increased CO2, increased H+, increased temperature, and increased 2,3-BPG—are occurring in skeletal muscle tissue, interfering with hemoglobin’s ability to bind oxygen. Consequently, all of these facilitate the release of additional oxygen from hemoglobin to the systemic cells (e.g., skeletal muscle tissue during tissue gas exchange). Influence on the Oxygen-Hemoglobin Saturation Curve We can observe the effect of two of these variables (temperature and pH) on oxygen release as shown on the oxygen-hemoglobin saturation curve ( figure 23.34). When temperature increases from 37°C to 43°C, at any given Po2, hemoglobin saturation is lower than when the temperature is 37°C ( figure 23.34a). If temperature decreases, hemoglobin saturation increases. Similar changes in hemoglobin saturation are observed with changes in pH, which is inversely related to H+ concentration ( figure 23.34b). Figure 23.34 Variables that Influence the Percent Saturation of Hemoglobin. Both a change in (a) Temperature and (b) blood pH cause a shift in the saturation curve. Factors that bring about a decrease in oxygen affinity to hemoglobin (e.g., increase in temperature, increase in H+, increase in CO2, increase in 2,3-BPG) and the additional release of oxygen are said to cause a shift right in the saturation curve. In contrast, the variables that bring about an increase in oxygen affinity to hemoglobin (e.g., decrease in temperature, decrease in H+, decrease in CO2, decrease in 2,3-BPG) result in release of less oxygen and are said to cause a shift left. Thus, oxygen release from hemoglobin to our systemic cells during tissue gas exchange is influenced by the PO2 at the cells, as well as changes in other variables. These other variables (temperature, PCO2, H+, and 2,3-BPG) can cause either more oxygen to be released (which is observed as shift right on the oxygenhemoglobin saturation curve) or less oxygen to be released (which is observed as a shift left on the oxygen-hemoglobin saturation curve). Page 938 Summary of Respiration Figure 23.35 is a visual 2-page overview of the four events of respiration. It depicts the seemingly effortless task of moving oxygen and carbon dioxide between the environment and our systemic cells. Remember that all of the processes are occurring simultaneously and continuously. If any of the systems involved in respiration—respiratory, skeletal, muscular, nervous, or cardiovascular—are unable to function normally, a homeostatic imbalance in respiratory gas exchange occurs. imbalances. Table 23.2 summarizes many of the causes of these homeostatic Table 23.2 Causes of Respiratory Homeostatic Imbalances System Physiologic Consequences Clinical Example(s) RESPIRATORY SYSTEM Airway obstruction Decreased airflow into alveoli Asthma, bronchitis Thickened respiratory Decreased pulmonary gas Pulmonary edema, pneumonia membrane exchange Loss of respiratory Decreased pulmonary gas membrane surface exchange Emphysema, lung cancer SKELETAL SYSTEM Arthritis or deformities of Impaired ability to cause Rheumatoid arthritis, congenital thoracic cage or vertebral dimensional volume changes in deformities column thoracic cavity MUSCULAR SYSTEM Paralysis of respiratory Impaired ability to cause Polio, muscular dystrophy, myasthenia muscles dimensional volume changes in gravis thoracic cavity NERVOUS SYSTEM Brainstem injury Decreased ability to stimulate Oversedation of muscles of breathing Trauma Drug use respiratory center Spinal cord injuries Decreased ability to stimulate Trauma (e.g., diving or motorcycle muscles of breathing accident) CARDIOVASCULAR SYSTEM Pulmonary embolism Anemia Blockage in pulmonary artery, Slowed blood flow from immobilization and blood does not reach lung (e.g., prolonged bedrest, long plane flight, capillaries for gas exchange confinement to wheelchair) Decreased erythrocytes or Low iron, pernicious anemia (inability to hemoglobin concentration with absorb B12) decreased gas transport System Physiologic Consequences Clinical Example(s) Decreased blood flow Decreased gas transport and gas Atherosclerosis, congestive heart failure, exchange hemorrhage WHAT DID YOU LEARN? 35 How does oxygen movement occur during pulmonary gas exchange, gas transport, and tissue gas exchange? 36 How does carbon dioxide movement occur during tissue gas exchange, gas transport, and pulmonary gas exchange? 37 Does hemoglobin saturation increase or decrease during pulmonary gas exchange? 38 How is oxygen release from hemoglobin during tissue gas exchange altered by Po2, Co2, H+ concentration, temperature, and 2,3-BPG?