Oxygen and Carbon Dioxide Transport





Objectives




  • 1.

    Explain diffusion limitation and perfusion limitation and their importance in gas exchange


  • 2.

    Apply Fick’s law to the alveolar–capillary surface.


  • 3.

    Describe the diffusion of oxygen and carbon dioxide across the alveolar–capillary membrane.


  • 4.

    Describe the structure and function of hemoglobin in gas exchange.


  • 5.

    Explain the oxyhemoglobin dissociation curve, factors that shift the curve, and the effect of these shifts on oxygen uptake and oxygen delivery.


  • 6.

    Understand the differences between oxygen content, oxygen saturation, and Pao 2 .


  • 7.

    Outline the effect of carbon monoxide on oxygen content, oxygen saturation, Pao 2 , and stimulation of peripheral chemoreceptors.


  • 8.

    Describe oxygen consumption.


  • 9.

    Describe the four types of tissue hypoxia.


  • 10.

    Explain carbon dioxide production, metabolism, diffusion, and the carbon dioxide dissociation curve.



The maintenance of cell integrity and normal organ function is dependent on energy expenditure. The major source of energy in cells and organs is provided by the intracellular metabolism of oxygen (O 2 ) ( oxidative metabolism ). During oxidative metabolism, molecular oxygen is consumed within the mitochondrial electron transport system, and adenosine triphosphate (ATP) is generated. Energy is subsequently produced by the hydrolysis of ATP to adenosine diphosphate (ADP) and inorganic phosphate.


O 2 is carried in the blood from the lungs to the tissues in two forms: physically dissolved in the blood and chemically combined to hemoglobin. As O 2 is transported into the tissue, carbon dioxide (CO 2 ), the by-product of cellular metabolism, is transported from the tissues to the blood and then to the lungs by the pulmonary circulation. CO 2 is carried in three forms: physically dissolved in blood, as bicarbonate, and chemically combined to blood proteins as carbamino compounds. O 2 loading and unloading and CO 2 loading and unloading not only occur simultaneously but also facilitate each other both in the lung and in the tissues. Specifically, the uptake of O 2 into the tissues enhances the elimination of CO 2 from the tissues into the blood ( Fig. 8.1 ). Similarly, the uptake of O 2 into the blood through the pulmonary capillaries is facilitated by the simultaneous unloading of CO 2 by the blood. To understand the mechanisms involved in the transport of these gases, three processes must be considered: gas diffusion, O 2 and CO 2 transport processes, and O 2 and CO 2 delivery processes.




Fig. 8.1


Oxygen and carbon dioxide transport occur in both arterial and venous blood. However, the extracted or utilized oxygen is present in arterial blood, where it is transferred from arterial capillaries to the tissue. Only approximately 25% of transported oxygen is actually taken up by the tissue. The source of exhaled carbon dioxide is venous blood; it is expired via the pulmonary capillaries. The flow rates for oxygen ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
V ˙
o 2 ) and carbon dioxide ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-2-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
V ˙
co 2 ) shown are for 1 L of blood. The ratio of CO 2 production to O 2 consumption is the respiratory quotient, R, which at rest is about 0.80.

From Koeppen BM, Stanton BM, eds. Berne and Levy’s Physiology , 7th ed. Philadelphia: Elsevier; 2018.




Gas Diffusion


Diffusion is the passive thermodynamic flow of molecules between regions with different partial pressures. Diffusion of a gas is defined as the net movement of gas molecules from an area in which the particular gas exerts a higher partial pressure to an area in which the gas exerts a lower partial pressure. Diffusion is different from “bulk flow,” which occurs in the conducting airways. In bulk flow, gas movement occurs when there are differences in total pressure with molecules of different gases moving together along the pressure gradients. In diffusion, different gases move according to their individual pressure gradients. In diffusion, gas transport is random, occurs in all directions, and is temperature dependent. Net movement, however, is dependent on the difference in the individual gas’s partial pressure. Diffusion continues until there is no longer a pressure gradient. In the lung and the tissues, diffusion is the major mechanism of gas movement. It is important both for gas movement within the alveoli (air → air) as well as for gas movement across the alveoli into the blood (air → liquid) and for gas movement from the blood into the tissue (liquid → tissue).


O 2 is delivered to the alveoli by bulk flow in the conducting airways. The inspired gas velocity decreases as the alveoli are approached because of the dramatic increase in cross-sectional area of the airways due to the multiple bifurcations (Bernoulli principle, see Fig. 3.9 ). Once in the alveolus, gas movement occurs by diffusion. The process of gas diffusion is passive, non–energy-dependent, and similar whether in a gas or liquid state. O 2 moves through the gas phase in the alveoli according to its own pressure gradient, crosses the approximate 1-μm alveolar–capillary interface, and enters the blood. In moving from a gas phase in the alveolus to a liquid phase in the blood, O 2 obeys Henry’s law (Appendix C), where the amount of gas absorbed by a liquid is determined by the gas pressure and solubility. Both O 2 and CO 2 maintain their molecular characteristics in blood, and both establish a partial pressure in the blood, according to Henry’s law. It is this partial pressure that is measured in an arterial blood gas sample. O 2 and CO 2 in the blood are then carried out of the lung by bulk flow and distributed to the tissues in the body. In the tissues, O 2 diffuses out of the blood, across the interstitium, and into the tissue cell and its mitochondrial membrane.


The rate of diffusion of O 2 and CO 2 through the alveolar–capillary barrier and through the capillary–tissue barrier is governed by Fick’s law of diffusion (Appendix C), which states that the diffusion of a gas ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-3-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
V ˙
gas ) across a sheet of tissue is directly related to the surface area, the diffusion constant of the gas (which is related to the solubility of the gas and inversely to the square root of the molecular weight of the gas and the gas gradient across the tissue and indirectly related to the thickness of the tissue [ Fig. 8.2 ]). A number of interesting and important concepts arise from these two equations. Normally, the thickness of the alveolar–capillary diffusion barrier is only 0.2 to 0.5 μm. The thickness of the barrier, however, is increased in diseases such as interstitial fibrosis and interstitial edema, and the increased thickness of the alveolar–capillary barrier interferes with diffusion. Increased partial pressure of oxygen in the alveoli increases O 2 transport by increasing the pressure gradient, and this is why supplemental O 2 therapy is used to treat many lung diseases. At the blood capillary–tissue barrier (liquid → tissue), Fick’s equation demonstrates that the major rate-limiting step for diffusion from the air to the tissue is at the liquid–tissue interface. This is because at this step, the tissue thickness from the capillaries to the mitochondria is far greater than in the alveolus.




Fig. 8.2


Fick’s law states that the diffusion of a gas ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-4-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
V ˙
gas ) across a sheet of tissue is directly related to the surface area of the tissue (A), the diffusion constant of the specific gas (D), and the partial pressure difference of the gas on each side of the tissue (P 1 − P 2 ) and is inversely related to tissue thickness (T).

From Koeppen BM, Stanton BM, eds. Berne and Levy’s Physiology , 7th ed. Philadelphia: Elsevier; 2018.


The diffusion constants for CO 2 and O 2 favor CO 2 diffusion. This is because the solubility of CO 2 in blood is about 24 times the solubility of O 2 . CO 2 , however, has a higher molecular weight. When both the solubility and the molecular weight are considered together, CO 2 diffuses about 20 times more rapidly through the alveolar–capillary membrane than O 2 . Clinically, this is demonstrated in patients with lung diseases resulting in changes in diffusion in which decreases in blood O 2 occur much earlier than CO 2 increases in blood.




Perfusion Limitation


On average, a red blood cell spends between 0.75 and 1.2 seconds in the pulmonary capillaries. Some red blood cells spend more time than this, and others spend less. Depending on the initial concentration of a gas in inspired air and how rapidly it is removed by the pulmonary capillaries, different gases will have different alveolar partial pressures. This is illustrated in Fig. 8.3 for nitrous oxide (N 2 O), O 2 , and carbon monoxide (CO). The major factors responsible for the difference in the shapes of these relationships are the solubility of the gases in the alveolar–capillary membrane and the solubility of the gases in the blood and their ability to chemically bind to hemoglobin.




Fig. 8.3


Uptake of nitrous oxide (N 2 O), carbon monoxide (CO), and oxygen (O 2 ) in blood relative to their partial pressures and the transit time of the red blood cell in the capillary. For gases that are perfusion-limited (N 2 O and O 2 ), their partial pressures have equilibrated with alveolar pressure before exiting the capillary. In contrast, for CO, a gas that is diffusion-limited, its partial pressure does not reach equilibrium with alveolar pressure. Oxygen uptake in various disease conditions can become diffusion-limited.

From Koeppen BM, Stanton BM, eds. Berne and Levy’s Physiology , 7th ed. Philadelphia: Elsevier; 2018.


Different gases have different solubility factors, which result in different diffusion coefficients. Gases such as N 2 O, nitrogen, and helium have low solubility, whereas ether has high solubility ( Fig. 8.4 ). In general, when the solubility of a gas in the membrane is large, gas will diffuse at a faster rate through the membrane. This is because the highly soluble gas will become dissolved in the barrier more readily than the insoluble gas. N 2 O, ether, and helium move through the alveolar–capillary barrier easily, are insoluble in blood, and do not combine chemically with blood. As a result, the partial pressure gradient across the alveolar–capillary barrier is rapidly abolished (see Fig. 8.3 ). From that point on, no further gas transfer occurs and there is no net diffusion. For these gases, equilibration between alveolar gas and blood occurs rapidly (significantly less than the 0.75 second that the red blood cell spends in the capillary bed) and is driven by the difference in partial pressure. This type of gas exchange is perfusion-limited because blood leaving the capillary has reached equilibrium with alveolar gas. As illustrated in Fig. 8.3 , the partial pressure of N 2 O peaks quickly and is maximal by 0.1 second, at which point no further N 2 O is transferred.




Fig. 8.4


Relationship between the content of dissolved gas and its partial pressure in blood. The solubility of the gas in the liquid is the slope of the line. A linear relationship (i.e., constant solubility at a given temperature) is seen for gases that do not combine chemically with the liquid. Note the high solubility of ether and the very low solubility of oxygen.

Redrawn from Leff A, Schumacker P. Respiratory Physiology: Basics and Applications . Philadelphia: W.B. Saunders; 1993.




Diffusion Limitation


In contrast, the partial pressure of CO in the pulmonary capillary blood rises very slowly compared with N 2 O and O 2 (see Fig. 8.3 ). This is because carbon monoxide has a low solubility in the alveolar–capillary membrane but a high solubility in blood. As a result, equilibration between alveolar gas and blood occurs slowly (significantly greater than the 0.75-second transit time of the red blood cell in the capillary). However, CO solubility varies with CO partial pressure. At partial pressures below 1 to 2 torr, CO solubility is high, whereas at partial pressures greater than 2 torr, CO solubility is small because CO content increases only by adding dissolved CO. For CO, equilibration is not reached during the transit time, resulting in only a minimal increase in the partial pressure. Even though there is only a small increase in partial pressure, if you measured the CO content in the blood (milliliters of CO/milliliters blood) it would be rising rapidly. The reason for this rapid rise is that CO binds chemically with hemoglobin with an affinity that is about 10 times that of oxygen for hemoglobin. The CO that is combined with the hemoglobin does not contribute to the partial pressure of CO because it is no longer physically dissolved in the blood. As a result, the partial pressure gradient for CO is maintained throughout the capillary bed, and exchange of CO is still occurring as the red blood cell leaves the end of the capillary because its rate of equilibration is slow relative to the time spent in the capillary. This type of gas transfer is diffusion-limited . For CO, this occurs because its solubility in the membrane is low, whereas its solubility in blood is high. In the absence of red blood cells, CO uptake would be perfusion-limited because now both the “blood” and the membrane have a similar low solubility to CO.




Diffusion Of O 2 And CO 2


O 2 (and CO 2 and CO) combines chemically with blood. As a result, the relationship between gas content in the blood and partial pressure is nonlinear ( Fig. 8.5 ). The slope of the relationship for any gas is its effective solubility . The effective solubility of oxygen varies with partial pressure and is greatest at lower partial pressures. O 2 has a relatively low solubility in the membrane of the blood–gas barrier but a high effective solubility in blood because of its combining with hemoglobin. O 2 does not combine with hemoglobin as quickly as CO binds, and so the partial pressure of O 2 in the blood rises more rapidly than does the partial pressure of CO (see Fig. 8.3 ). Once bound to hemoglobin, O 2 no longer exerts a partial pressure, and so the partial pressure gradient across the alveolar-capillary membrane is maintained, and O 2 transfer continues. Hemoglobin, however, quickly becomes saturated with O 2 . When this happens, the partial pressure of O 2 in the blood rises rapidly and is equal to the alveolar partial pressure. At this point, no further O 2 transfer from the alveolus to the equilibrated blood can occur. Thus under normal conditions, O 2 transfer from the alveolus to the pulmonary capillary is perfusion-limited. That is, the rate of equilibration is sufficiently rapid (usually within 0.25 second) for complete equilibration to occur during the transit time of the red blood cell within the capillary.




Fig. 8.5


Oxygen and carbon monoxide content as a function of their partial pressure in blood. The effective solubility of each gas in blood is equivalent to the slope of the line at any point. Thus oxygen is highly soluble at partial pressures of 20 to 60 torr but relatively insoluble above 100 torr (where most of the hemoglobin sites are occupied). In contrast, carbon monoxide solubility is extremely large at a partial pressure of less than 1 torr. At partial pressures greater than 1 torr, carbon monoxide content increases by adding dissolved carbon monoxide only and its solubility is small.

Redrawn from Leff A, Schumacker P. Respiratory Physiology: Basics and Applications . Philadelphia: W.B. Saunders; 1993.




Diffusion of CO 2


The time course of CO 2 equilibration in the pulmonary capillary is shown in Fig. 8.6 . In a normal individual, equilibrium is reached in about 0.25 second, the same time period for O 2 . The effective solubility of CO 2 is higher than that of O 2 because CO 2 is more soluble in blood than O 2 , and its solubility is less variable ( Fig. 8.7 ). If the diffusivity of CO 2 is 20 times higher than that of O 2 and the solubility is higher, why is the time to equilibrium the same? It is the same because the partial pressure gradient for CO 2 is much less than the gradient for O 2 , and CO 2 has a lower membrane–blood solubility ratio. As a consequence, O 2 and CO 2 take approximately the same amount of time to reach equilibration, and CO 2 transfer, like that of O 2 , is usually perfusion-limited.




Fig. 8.6


Partial pressure of carbon dioxide as a function of the duration of time that the red blood cell spends in the capillary. Under normal conditions, the Pco 2 of blood entering the capillary is 46 torr and decreases to 40 torr by the time the blood leaves the capillary. When the diffusion through the alveolar-capillary barrier is reduced to one-fourth and one-eighth of normal, the Pco 2 approaches but is not normal by the time the blood leaves the capillary. With exercise, the time spent in the capillary is reduced to 0.25 second. This is sufficient in the normal lung but can result in an abnormal Paco 2 in the lung with abnormal diffusion.

Redrawn from Wagner PD, West JB. Effects of diffusion impairment on O 2 and CO 2 time courses in pulmonary capillaries. J Appl Physiol . 1972;33:62.



Fig. 8.7


Carbon dioxide content as a function of its partial pressure in blood. Carbon dioxide is much more soluble in blood than is oxygen (compare with Fig. 8.5 and note the steeper slope). Unlike oxygen, its solubility is relatively constant as a function of partial pressure (the solubility is the slope of the line).

Redrawn from Leff A, Schumacker P. Respiratory Physiology: Basics and Applications . Philadelphia: W.B. Saunders; 1993.


Diffusion limitation for both O 2 and CO 2 could occur if the red blood cell spent less than 0.25 second in the capillary bed. Occasionally, this can be seen in very fit athletes during vigorous exercise and in healthy subjects who exercise at high altitude. It may also be present during exercise in individuals with an abnormally thickened barrier due to fibrosis or interstitial edema and at rest in individuals with severe lung disease.




Oxygen Transport


Oxygen is carried in the blood in both the dissolved gaseous state in plasma and bound to hemoglobin (Hgb) as oxyhemoglobin (HgbO 2 ) within red blood cells. O 2 transport occurs primarily through HgbO 2 , with a minimal contribution of dissolved O 2 . For example, at a Pa o 2 of 100 mm Hg, only 3 mL of O 2 is dissolved in 1 L of plasma. The contribution of hemoglobin within the red blood cell enhances the O 2 -carrying capacity of blood by about 65-fold. Non–O 2 -bound hemoglobin is referred to as deoxyhemoglobin, or reduced hemoglobin.




Hemoglobin Structure


Hemoglobin has a molecular weight of 66,500 kDa and consists of four nonprotein O 2 -binding heme groups and four polypeptide chains, which make up the globin protein portion of the Hgb molecule ( Fig. 8.8 ). The four polypeptide chains of adult Hgb (hemoglobin type A, or HgbA) are composed of two alpha chains and two beta chains. Iron is present in each heme group in the reduced ferrous (Fe +2 ) form and is the site of O 2 -binding. Each of the polypeptide chains can bind one molecule of oxygen to the iron-binding site on its own heme group. Both the globin component and the heme group with its iron atom in the reduced or ferrous state must be in a proper spatial orientation for the chemical reaction with oxygen to occur.




Fig. 8.8


Schematic illustration of a hemoglobin molecule showing the globin (protein) component with two alpha and two beta chains and the four iron-containing heme groups (oxygen-binding) positioned in the center of each globin portion. Each hemoglobin molecule can bind four oxygen molecules.

From Koeppen BM, Stanton BM, eds. Berne and Levy’s Physiology , 7th ed. Philadelphia: Elsevier; 2018.


Variations in the amino acid sequence of the globin subunits have significant physiologic consequences. For example, fetal Hgb (HgbF) is produced by the fetus to meet the oxygen demands of its specialized environment. HgbF is composed of two alpha chains and two gamma chains. This change in structure in HgbF increases its affinity for O 2 and aids in the transport of O 2 across the placenta. In addition, as discussed later in this chapter, HgbF is not affected or inhibited by the glycolysis product 2,3-diphosphoglycerate (2,3-DPG) in red blood cells, thus further enhancing O 2 uptake. During the first year of life, HgbF is replaced by HgbA.


Genetic substitutions of various amino acids result in a number of abnormal hemoglobins. These changes usually occur in the alpha and beta chains. More than 125 abnormal hemoglobins have been reported.



Clinical Box


The most important and most common of the genetic Hgb amino acid substitutions is sickle cell hemoglobin (HgbS), which results in the disease called sickle cell anemia. Sickle cell anemia is an inherited, homozygous, recessive condition in which individuals have an amino acid substitution (valine for glutamic acid) on the beta chain of the hemoglobin molecule. This creates HgbS, which when unbound (deoxyhemoglobin) forms a gel that distorts the normal biconcave shape of the red blood cell to create a crescent or “sickle” form. This change in shape increases the tendency of the red blood cell to form thrombi or clots that obstruct small vessels and results in a clinical condition known as a sickle cell crisis . The symptoms of this condition vary, depending on the site of the obstruction. If it occurs in the central nervous system, patients suffer a stroke. If it occurs in the lung, patients can suffer a pulmonary infarction with death of the lung tissue. Although in its homozygous form sickle cell anemia is a life-shortening clinical condition, individuals with the heterozygous form (sickle cell trait) are resistant to malaria. Thus there is a survival advantage in regions in the world where malaria is prevalent.






Clinical Box


The most important and most common of the genetic Hgb amino acid substitutions is sickle cell hemoglobin (HgbS), which results in the disease called sickle cell anemia. Sickle cell anemia is an inherited, homozygous, recessive condition in which individuals have an amino acid substitution (valine for glutamic acid) on the beta chain of the hemoglobin molecule. This creates HgbS, which when unbound (deoxyhemoglobin) forms a gel that distorts the normal biconcave shape of the red blood cell to create a crescent or “sickle” form. This change in shape increases the tendency of the red blood cell to form thrombi or clots that obstruct small vessels and results in a clinical condition known as a sickle cell crisis . The symptoms of this condition vary, depending on the site of the obstruction. If it occurs in the central nervous system, patients suffer a stroke. If it occurs in the lung, patients can suffer a pulmonary infarction with death of the lung tissue. Although in its homozygous form sickle cell anemia is a life-shortening clinical condition, individuals with the heterozygous form (sickle cell trait) are resistant to malaria. Thus there is a survival advantage in regions in the world where malaria is prevalent.




Oxygen Binding to Hemoglobin


The binding of O 2 to hemoglobin alters the light absorption characteristics of hemoglobin; this is responsible for the difference in color between oxygenated arterial blood (HgbO 2 ) and deoxygenated venous blood (Hgb). The binding of O 2 to hemoglobin is readily reversible, and this ready reversibility is a critical component that facilitates the delivery of O 2 to the tissue from the blood. The binding and dissociation of O 2 with Hgb occurs in milliseconds, which is well suited for the average capillary transit time of 0.75 second for the red blood cell.


There are ∼280 million Hgb molecules per red blood cell, which provides a unique and efficient mechanism to transport O 2 . Because the amount of hemoglobin present in each red blood cell is relatively equal, the amount of hemoglobin in blood is directly proportional to the percentage of blood volume occupied by red blood cells ( hematocrit ). It should be noted that myoglobin , the O 2 -carrying and storage protein of muscle tissue, is similar to hemoglobin in structure and function except that it has only one subunit of the hemoglobin molecule; thus its molecular weight is about one-fourth that of hemoglobin. Myoglobin aids in the transfer of O 2 from blood to muscle cells and in the storage of O 2 , which is especially critical in O 2 -deprived conditions.


When oxygen combines with hemoglobin, the iron usually remains in the ferrous state. In a condition known as methemoglobinemia , compounds such as nitrites and various cyanides (released in the environment during the burning of plastics or in the workplace from photo supplies, electroplating, and mining) can oxidize the iron molecule in the heme group changing it from the reduced ferrous state to the ferric state (Fe +3 ). Hemoglobin with iron in the ferric state is brown instead of red. Methemoglobin blocks the release of O 2 from hemoglobin, which inhibits delivery of O 2 to the tissues, a critical aspect of reversible O 2 transport. Under normal conditions, ∼1% to 2% of hemoglobin-binding sites are in the ferric state. Intracellular enzymes such as glutathione reductase can reduce the methemoglobin back to the functioning ferrous state. Patients with methemoglobinemia have an absence of glutathione reductase.




Dissolved Oxygen


Oxygen diffuses passively from the alveolus to the plasma, where it dissolves. In its dissolved form, O 2 maintains its molecular structure and gaseous state. It is this form that is measured clinically in an arterial blood gas sample as the Pa o 2 . The dissolved O 2 in blood is the product of the oxygen solubility (0.00304 mL O 2 /dL ⋅ torr) times the oxygen tension (torr). In a healthy normal adult, approximately 0.3 mL of O 2 is dissolved in 100 mL blood. This is commonly expressed as 0.3 volumes percent (vol%), where the vol% is equal to the mL O 2 /100 mL blood. It can be seen that the O 2 dissolved in plasma is insufficient to meet the body’s O 2 demands. In particular, the resting oxygen consumption of an adult is 200 to 300 mL O 2 /min. For dissolved oxygen to meet this resting O 2 consumption, a cardiac output of almost 67 L/min would be required; that is,


<SPAN role=presentation tabIndex=0 id=MathJax-Element-5-Frame class=MathJax style="POSITION: relative" data-mathml='200mLO2/min0.3mLO2/100mLblood=66,666mLbloodmin66.7L/min’>200mLO2/min0.3mLO2/100mLblood=66,666mLbloodmin66.7L/min200mLO2/min0.3mLO2/100mLblood=66,666mLbloodmin66.7L/min
200 mL O 2 / min 0.3 mL O 2 / 100 mL blood = 66 , 666 mL blood min 66.7 L / min


During exercise, this cardiac output would need to further increase 10–15-fold. Normal individuals can achieve a cardiac output with vigorous exercise in the range of 25 L/min. Clearly, dissolved oxygen in the blood cannot meet the metabolic needs of the body even at rest, much less during exercise. Thus the contribution of dissolved oxygen to total O 2 transport is small. In fact, when calculating the O 2 content in blood, the dissolved O 2 is frequently ignored. This small amount of additional dissolved O 2 becomes significant, however, in individuals with severe hypoxemia being treated with high levels of inspired oxygen.




Oxygen Saturation


Each hemoglobin molecule can bind up to four O 2 atoms, and each gram of hemoglobin can bind up to 1.34 mL (range of 1.34 to 1.39 mL depending on methemoglobin levels) of O 2 . The term oxygen saturation (S o 2 ) refers to the amount of O 2 bound to hemoglobin relative to the maximal amount of O 2 (100% O 2 capacity) that can bind hemoglobin. It is equal to the O 2 content in the blood (minus the physically dissolved O 2 ) divided by the O 2 -carrying capacity of hemoglobin in the blood times 100%.


<SPAN role=presentation tabIndex=0 id=MathJax-Element-6-Frame class=MathJax style="POSITION: relative" data-mathml='%Hgbsaturation=O2boundtoHgbO2−carryingcapcityofHgb×100%’>%Hgbsaturation=O2boundtoHgbO2carryingcapcityofHgb×100%%Hgbsaturation=O2boundtoHgbO2−carryingcapcityofHgb×100%
% Hgb saturation = O 2 bound to Hgb O 2 − carrying capcity of Hgb × 100 %


Both O 2 content and O 2 -carrying capacity are dependent on the amount of hemoglobin in blood and both are expressed as milliliters O 2 /100 milliliters blood. In contrast, hemoglobin saturation is only a percentage. Thus HgbO 2 saturation is not interchangeable with the O 2 content. Individuals with different Hgb levels will have different O 2 contents but can have the same hemoglobin saturation.


At 100% saturation (100% S o 2 ), the heme group is fully saturated with oxygen. Correspondingly, at 75% S o 2 , three of the four heme groups are occupied by O 2 . The binding of O 2 to each heme group increases the affinity of the hemoglobin molecule to bind additional O 2 . Thus, when three of the heme groups are O 2 -bound, the affinity of the fourth heme group to bind O 2 is increased. Because there are about 14 g Hgb/100 mL blood, the normal O 2 capacity is 18.76 mL (1 g Hgb binds 1.34 mL O 2 × 14 g Hgb) of O 2 /100 mL blood. A mildly anemic individual with an Hgb concentration of 10 g/100 mL blood and normal lungs would only have an O 2 capacity of 13.40 mL O 2 /100 mL blood; a severely anemic individual with an Hgb concentration of 5 g would have an O 2 capacity of 6.70 mL O 2 /100 mL blood—one-third of normal.




Oxygen Content (Concentration) of Blood


The O 2 content in blood is the volume of O 2 contained per unit volume of blood. The total O 2 content is the sum of the O 2 bound to hemoglobin and the dissolved O 2 . The hemoglobin-bound O 2 content is determined by the concentration of hemoglobin (in g/dL), the O 2 -binding capacity of the hemoglobin (1.34 mL O 2 /g Hgb), and the percent saturation of the hemoglobin. The dissolved O 2 content is the product of the O 2 solubility (0.00304 mL O 2 /dL ⋅ torr) times the O 2 tension (torr). Oxygen content decreases with increased CO 2 and CO and in individuals with anemia ( Fig. 8.9 ).




Fig. 8.9


Comparison of oxygen content curves under three conditions shows why HgbCO is so toxic to the oxygen transport system. Fifty percent [Hgb] represents a reduction in circulating hemoglobin by half; 50% HgbCO represents binding of half the circulating hemoglobin with CO. The 50% [Hgb] and 50% HgbCO curves show the same decreased oxygen content in arterial blood. However, CO has a profound effect in lowering venous Po 2 . The arterial (a) and mixed venous ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-7-Frame class=MathJax style="POSITION: relative" data-mathml='v¯’>v
v ¯
) points of constant cardiac output are indicated.

From Koeppen BM, Stanton BM, eds. Berne and Levy’s Physiology , 7th ed. Philadelphia: Elsevier; 2018.


As an example, consider an arterial blood gas with a Pa o 2 of 60 torr and an arterial Sa o 2 of 90%. The patient’s hemoglobin is 14 g/dL. What would the total (Hgb-bound and dissolved) O 2 content be?


<SPAN role=presentation tabIndex=0 id=MathJax-Element-8-Frame class=MathJax style="POSITION: relative" data-mathml='Hgb−boundO2content=1.34mLgHgb×14gHgbdLblood×90%Saturation100=16.88mL/dLblood’>HgbboundO2content=1.34mL𝑔Hgb×14gHgbdLblood×90%Saturation100=16.88mL/dLbloodHgb−boundO2content=1.34mLgHgb×14gHgbdLblood×90%Saturation100=16.88mL/dLblood
Hgb − bound O 2 content = 1.34 mL g Hgb × 14 g Hgb dL blood × 90 % Saturation 100 = 16.88 mL / dL blood

<SPAN role=presentation tabIndex=0 id=MathJax-Element-9-Frame class=MathJax style="POSITION: relative" data-mathml='DissolvedO2content=PaO2×O2solubility=60torr×0.0034mLO2/dL.torr=0.18mLO2/dL’>DissolvedO2content=PaO2×O2solubility=60torr×0.0034mLO2/dL.torr=0.18mLO2/dLDissolvedO2content=PaO2×O2solubility=60torr×0.0034mLO2/dL.torr=0.18mLO2/dL
Dissolved O 2 content = PaO 2 × O 2 solubility = 60 torr × 0.0034 mL O 2 / dL.torr = 0.18 mL O 2 / dL

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