﻿ GAS EXCHANGE - Respiratory Physiology - Physiology 5th Ed.

## Physiology 5th Ed.

### GAS EXCHANGE

Gas exchange in the respiratory system refers to diffusion of O2 and CO2 in the lungs and in the peripheral tissues. O2 is transferred from alveolar gas into pulmonary capillary blood and, ultimately, delivered to the tissues, where it diffuses from systemic capillary blood into the cells. CO2 is delivered from the tissues to venous blood, to pulmonary capillary blood, and is transferred to alveolar gas to be expired.

Gas Laws

The mechanisms of gas exchange are based on the fundamental properties of gases and include their behavior in solution. This section reviews those principles.

General Gas Law

The general gas law (familiar from chemistry courses) states that the product of pressure times volume of a gas is equal to the number of moles of the gas multiplied by the gas constant multiplied by the temperature. Thus,

where

 P = Pressure (mm Hg) V = Volume (L) n = Moles (mol) R = Gas constant T = Temperature (K)

The only “trick” in applying the general gas law to respiratory physiology is to know that in the gas phase BTPS is used, but in the liquid phase, STPD is used. BTPS means body temperature (37°C, or 310 K), ambient pressure, and gas saturated with water vapor. For gases dissolved in blood, STPD is used, meaning standard temperature (0°C, or 273 K), standard pressure (760 mm Hg), and dry gas. Gas volume at BTPS can be converted to volume at STPD by multiplying the volume (at BTPS) by 273/310 × PB- 47/760 (where PB is barometric pressure and 47 mm Hg is water vapor pressure at 37°C).

Boyle’s Law

Boyle’s law is a special case of the general gas law. It states that, at a given temperature, the product of pressure times volume for a gas is constant. Thus,

The application of Boyle’s law to the respiratory system has been discussed in a previous example. Recall the events occurring during inspiration when the diaphragm contracts to increase lung volume: To keep the product of pressure times volume constant, gas pressure in the lungs must decrease as lung volume increases. (It is this decrease in gas pressure that is the driving force for airflow into the lungs.)

Dalton’s Law of Partial Pressures

Dalton’s law of partial pressures is applied frequently in respiratory physiology. It states that the partial pressure of a gas in a mixture of gases is the pressure that gas would exert if it occupied the total volume of the mixture. Thus, partial pressure is the total pressure multiplied by the fractional concentration of dry gas, or

The relationship for humidified gas is determined by correcting the barometric pressure for the water vapor pressure. Thus,

where

 PX = Partial pressure of gas (mm Hg) PB = Barometric pressure (mm Hg) PH2O = Water vapor pressure at 37°C (47 mm Hg) F = Fractional concentration of gas (no units)

It follows, then, from Dalton’s law of partial pressures, that the sum of partial pressures of all gases in a mixture equals the total pressure of the mixture. Thus, the barometric pressure (PB) is the sum of the partial pressures of O2, CO2, N2, and H2O. The percentages of gases in dry air at a barometric pressure of 760 mm Hg (with the corresponding values for F in parentheses) are as follows: O2, 21% (0.21); N2, 79% (0.79); and CO2, 0% (0). Because air is humidified in the airways, water vapor pressure is obligatory and equal to 47 mm Hg at 37°C.

SAMPLE PROBLEM. Calculate the partial pressure of O2 (PO2) in dry inspired air, and compare that value to the PO2 in humidified tracheal air at 37°C. The fractional concentration of O2 in inspired air is 0.21.

SOLUTION. The PO2 of dry inspired air is calculated by multiplying the pressure of the mixture of gases (i.e., the barometric pressure) by the fractional concentration of O2, which is 0.21. Thus, in dry inspired air,

The PO2 of humidified tracheal air is lower than the PO2 of dry inspired air because the total pressure must be corrected for water vapor pressure (or 47 mm Hg at 37°C). Thus, in humidified tracheal air,

Henry’s Law for Concentrations of Dissolved Gases

Henry’s law deals with gases dissolved in solution (e.g., in blood). Both O2 and CO2 are dissolved in blood (a solution) en route to and from the lungs. To calculate a gas concentration in the liquid phase, the partial pressure in the gas phase first is converted to the partial pressure in the liquid phase; next, the partial pressure in liquid is converted to the concentration in liquid.

An important, but not necessarily self-evident, point is that at equilibrium, the partial pressure of a gas in the liquid phase equals the partial pressure in the gas phase. Thus, if alveolar air has a PO2 of 100 mm Hg, then the capillary blood that equilibrates with alveolar air also will have a PO2 of 100 mm Hg. Henry’s law is used to convert the partial pressure of gas in the liquid phase to the concentration of gas in the liquid phase (e.g., in blood). The concentration of a gas in solution is expressed as volume percent (%), or volume of gas per 100 mL of blood (mL gas/100 mL blood).

Thus, for blood,

where

 CX = Concentration of dissolved gas (mL gas/100 mL blood) PX = Partial pressure of gas (mm Hg) Solubility = Solubility of gas in blood (mL gas/100 mL blood/mm Hg)

Finally, it is important to understand that the concentration of a gas in solution applies only to dissolved gas that is free in solution (calculated with Henry’s law), and it does not include any gas that is present in bound form (e.g., gas bound to hemoglobin or to plasma proteins).

SAMPLE PROBLEM. If the PO2 of arterial blood is 100 mm Hg, what is the concentration of dissolved O2 in blood, given that the solubility of O2 is 0.003 mL O2/100 mL blood/mm Hg?

SOLUTION. To calculate the concentration of dissolved O2 in arterial blood, simply multiply the PO2 by the solubility as follows:

Diffusion of Gases—Fick’s Law

Transfer of gases across cell membranes or capillary walls occurs by simple diffusion, which is discussed in Chapter 1. For gases, the rate of transfer by diffusion () is directly proportional to the driving force, a diffusion coefficient, and the surface area available for diffusion; it is inversely proportional to the thickness of membrane barrier. Thus,

where

 = Volume of gas transferred per unit time D = Diffusion coefficient of the gas A = Surface area ΔP = Partial pressure difference of the gas Δx = Thickness of the membrane

There are two special points regarding diffusion of gases. (1) The driving force for diffusion of a gas is the partial pressure difference of the gas (ΔP) across the membrane, not the concentration difference. Thus, if the PO2 of alveolar air is 100 mm Hg and the PO2 of mixed venous blood that enters the pulmonary capillary is 40 mm Hg, then the partial pressure difference, or driving force, for O2 across the alveolar/pulmonary capillary barrier is 60 mm Hg (100 mm Hg − 40 mm Hg). (2) The diffusion coefficient of a gas (D) is a combination of the usual diffusion coefficient, which depends on molecular weight (see Chapter 1), and the solubility of the gas. The diffusion coefficient of the gas has enormous implications for its diffusion rate, as illustrated by differences in the diffusion rates of CO2 and O2. The diffusion coefficient for CO2 is approximately 20 times higher than the diffusion coefficient for O2; as a result, for a given partial pressure difference, CO2 diffuses approximately 20 times faster than O2.

Several of the terms in the previous equation for diffusion can be combined into a single term called the lung diffusing capacity (DL). DL combines the diffusion coefficient of the gas, the surface area of the membrane (A), and the thickness of the membrane (Δx). DL also takes into account the time required for the gas to combine with proteins in pulmonary capillary blood (e.g., binding of O2 to hemoglobin in red cells). DL can be measured with carbon monoxide (CO) because CO transfer across the alveolar/pulmonary capillary barrier is limited exclusively by the diffusion process. DLCO is measured using the single breath method where the subject breathes a gas mixture containing a low concentration of CO; the rate of disappearance of CO from the gas mixture is proportional to DL. In various diseases, DLchanges in a predictable way. In emphysema, for example, DL decreases because destruction of alveoli results in a decreased surface area for gas exchange. In fibrosis or pulmonary edema, DL decreases because the diffusion distance (membrane thickness or interstitial volume) increases. In anemia, DL decreases because the amount of hemoglobin in red blood cells is reduced (recall that DL includes the protein-binding component of O2 exchange). During exercise, DL increases because additional capillaries are perfused with blood, which increases the surface area for gas exchange.

Forms of Gases in Solution

In alveolar air, there is one form of gas, which is expressed as a partial pressure. However, in solutions such as blood, gases are carried in additional forms. In solution, gas may be dissolved, it may be bound to proteins, or it may be chemically modified. It is important to understand that the total gas concentration in solution is the sum of dissolved gas plus bound gas plus chemically modified gas.

Dissolved gas. All gases in solution are carried, to some extent, in the dissolved form. Henry’s law gives the relationship between the partial pressure of a gas and its concentration in solution: For a given partial pressure, the higher the solubility of the gas, the higher the concentration of gas in solution. In solution, only dissolved gas molecules contribute to the partial pressure. In other words, bound gas and chemically modified gas do not contribute to the partial pressure.

Of the gases found in inspired air, nitrogen (N2) is the only one that is carried only in dissolved form and it is never bound or chemically modified. Because of this simplifying characteristic, N2 is used for certain measurements in respiratory physiology.

Bound gas. O2, CO2, and carbon monoxide (CO) are bound to proteins in blood. O2 and CO bind to hemoglobin inside red blood cells and are carried in this form. CO2 binds to hemoglobin in red blood cells and to plasma proteins.

Chemically modified gas. The most significant example of a chemically modified gas is the conversion of CO2 to bicarbonate (HCO3) in red blood cells by the action of carbonic anhydrase. In fact, most CO2 is carried in blood as HCO3, rather than as dissolved CO2 or as bound CO2.

Overview—Gas Transport in the Lungs

An alveolus and a nearby pulmonary capillary are shown in Figure 5-16. The diagram shows that the pulmonary capillaries are perfused with blood from the right heart (the equivalent of mixed venous blood). Gas exchange then occurs between alveolar gas and the pulmonary capillary: O2 diffuses from alveolar gas into pulmonary capillary blood, and CO2 diffuses from pulmonary capillary blood into alveolar gas. The blood leaving the pulmonary capillary is delivered to the left heart and becomes systemic arterial blood.

Figure 5–16 Schematic diagram of an alveolus and a nearby pulmonary capillary. Mixed venous blood enters the pulmonary capillary; O2 is added to pulmonary capillary blood, and CO2 is removed from it by transfer across the alveolar/capillary barrier. Systemic arterial blood leaves the pulmonary capillary.

Figure 5-17 further elaborates on this scheme in which the values for PO2 and PCO2 have been included at various sites: dry inspired air, humidified tracheal air, alveolar air, mixed venous blood entering the pulmonary capillary, and systemic arterial blood leaving the pulmonary capillary.

Figure 5–17 Values for PO2 and PCO2 in dry inspired air, humidified tracheal air, alveolar air, and pulmonary capillary blood. The numbers are partial pressures in mm Hg.  actually is slightly less than 100 mm Hg because of the physiologic shunt.

In dry inspired air, the PO2 is approximately 160 mm Hg, which is computed by multiplying the barometric pressure times the fractional concentration of O2, 21% (760 mm Hg × 0.21 = 160 mm Hg). For practical purposes, there is no CO2 in dry inspired air and PCO2 is zero.

In humidified tracheal air, it is assumed that the air becomes fully saturated with water vapor. At 37°C, PH2O is 47 mm Hg. Thus, in comparison to dry inspired air, PO2 is reduced because the O2 is “diluted” by water vapor. Again, recall that partial pressures in humidified air are calculated by correcting the barometric pressure for water vapor pressure, then multiplying by the fractional concentration of the gas. Thus, the PO2 of humidified tracheal air is 150 mm Hg ([760 mm Hg − 47 mm Hg] × 0.21 = 150 mm Hg). Because there is no CO2 in inspired air, the PCO2 of humidified tracheal air also is zero. The humidified air enters the alveoli, where gas exchange occurs.

In alveolar air, the values for PO2 and PCO2 are changed substantially when compared with inspired air. (The notations for partial pressures in alveolar air use the modifier “A”; see Table 5-1.)  is 100 mm Hg, which is less than in inspired air, and  is 40 mm Hg, which is greater than in inspired air. These changes occur because O2 leaves alveolar air and is added to pulmonary capillary blood, and CO2 leaves pulmonary capillary blood and enters alveolar air. Normally, the amounts of O2 and CO2 transferred between the alveoli and pulmonary capillary blood correspond to the needs of the body. Thus, on a daily basis, O2 transfer from alveolar air equals O2consumption by the body, and CO2 transfer to alveolar air equals CO2 production.

Blood entering the pulmonary capillaries is mixed venous blood. This blood has been returned from the tissues, via the veins, to the right heart. It is then pumped from the right ventricle into the pulmonary artery, which delivers it to the pulmonary capillaries. The composition of this mixed venous blood reflects metabolic activity of the tissues: The PO2 is relatively low, at 40 mm Hg, because the tissues have taken up and consumed O2; the PCO2 is relatively high, at 46 mm Hg, because the tissues have produced CO2 and added it to venous blood.

The blood that leaves the pulmonary capillaries has been arterialized (oxygenated) and will become systemic arterial blood. (The notations for systemic arterial blood use the modifier “a”; see Table 5-1.) The arterialization is effected by the exchange of O2 and CO2 between alveolar air and pulmonary capillary blood. Because diffusion of gases across the alveolar/capillary barrier is rapid, blood leaving the pulmonary capillaries normally has the same PO2 and PCO2 as alveolar air (i.e., there is complete equilibration). Hence,  is 100 mm Hg and  is 40 mm Hg, just as  is 100 mm Hg and  is 40 mm Hg. This arterialized blood will now be returned to the left heart, pumped out of the left ventricle into the aorta, and begin the cycle again.

There is a small discrepancy between alveolar air and systemic arterial blood: Systemic arterial blood has a slightly lower PO2 than alveolar air. This discrepancy is the result of a physiologic shunt, which describes the small fraction of pulmonary blood flow that bypasses the alveoli and, therefore, is not arterialized.

The physiologic shunt has two sources: bronchial blood flow and a small portion of coronary venous blood that drains directly into the left ventricle rather than going to the lungs to be oxygenated. The physiologic shunt is increased in several pathologic conditions (called a ventilation/perfusion defect). When the size of the shunt increases, equilibration between alveolar gas and pulmonary capillary blood cannot adequately occur and pulmonary capillary blood is not fully arterialized. The A − a difference, which is discussed later in this chapter, expresses the difference in PO2 between alveolar gas (“A”) and systemic arterial blood (“a”). If the shunt is small (i.e., physiologic), then the A − a difference is small or negligible; if the shunt is larger than normal, then the A − a difference increases to the extent that equilibration fails to occur.

The diagram in Figure 5-17 emphasizes the changes in PO2 and PCO2 that occur in the lungs. Not shown on the figure, but implied from the differences between systemic arterial blood and mixed venous blood, are the exchange processes that occur in the systemic tissues. Systemic arterial blood is delivered to the tissues, where O2 diffuses from systemic capillaries into the tissues and is consumed, producing CO2, which diffuses from the tissues into capillaries. This gas exchange in the tissues converts systemic arterial blood to mixed venous blood, which then leaves the capillaries, returns to the right heart, and is delivered to the lungs.

Diffusion-Limited and Perfusion-Limited Gas Exchange

Gas exchange across the alveolar/pulmonary capillary barrier is described as either diffusion-limited or perfusion-limited.

Diffusion-limited gas exchange means that the total amount of gas transported across the alveolar-capillary barrier is limited by the diffusion process. In these cases, as long as the partial pressure gradient for the gas is maintained, diffusion will continue along the length of the capillary.

Perfusion-limited gas exchange means that the total amount of gas transported across the alveolar/capillary barrier is limited by blood flow (i.e., perfusion) through the pulmonary capillaries. In perfusion-limited exchange, the partial pressure gradient is not maintained, and in this case, the only way to increase the amount of gas transported is by increasing blood flow.

Examples of gases transferred by diffusion-limited and perfusion-limited exchange are used to characterize these processes (Fig. 5-18). In the figure, the solid red line shows the partial pressure of a gas in pulmonary capillary blood (Pa) as a function of length along the capillary. The dashed green line across the top of each panel gives the partial pressure of the gas in alveolar air (PA), which is constant. Theshaded pink area gives the partial pressure gradient between alveolar gas and pulmonary capillary blood along the length of the capillary. Because the partial pressure gradient is the driving force for diffusion of the gas, the larger the shaded area, the larger the gradient, and the greater the net transfer of gas.

Figure 5–18 Diffusion-limited (A) and perfusion-limited (B) gas exchange between alveolar air and pulmonary capillary blood. The partial pressure of the gas in pulmonary capillary blood is shown as a function of capillary length by the solid red line. The dashed green lineat the top of the figure shows the partial pressure of the gas in alveolar air (PA). The shaded pink area gives the size of the partial pressure difference between alveolar air and pulmonary capillary blood, which is the driving force for diffusion of the gas. CO, Carbon monoxide; N2O, nitrous oxide.

Two examples are shown: CO is a diffusion-limited gas (see Fig. 5-18A), and nitrous oxide (N2O) is a perfusion-limited gas (see Fig. 5-18B). CO or N2O diffuse out of alveolar gas into the pulmonary capillary, and as a result, Pa for the gas increases along the length of the capillary and approaches or reaches the value for PA. If the value for Pa reaches the value of PA, then complete equilibration has occurred. Once equilibration occurs, there is no longer a driving force for diffusion (i.e., there is no longer a partial pressure gradient), and unless blood flow increases (i.e., more blood enters the pulmonary capillary), gas exchange will cease.

Diffusion-Limited Gas Exchange

Diffusion-limited gas exchange is illustrated by the transport of CO across the alveolar/pulmonary capillary barrier (see Fig. 5-18A). It is also illustrated by the transport of O2 during strenuous exercise and in pathologic conditions such as emphysema and fibrosis.

The partial pressure of CO in alveolar air (PACO), shown as the dashed line, is constant along the length of the capillary. At the beginning of the pulmonary capillary, there is no CO in the blood because none has been transferred from alveolar air and the partial pressure of CO in capillary blood (PaCO) is zero. Thus, at the beginning of the capillary, there is the largest partial pressure gradient for CO and the largest driving force for diffusion of CO from alveolar air into the blood. Moving along the length of the pulmonary capillary, as CO diffuses into pulmonary capillary blood, PaCO begins to rise. As a result, the partial pressure gradient for diffusion decreases. PaCO rises only slightly along the capillary length, however, because in capillary blood, CO is avidly bound to hemoglobin inside the red blood cells. When CO is bound to hemoglobin, it is not free in solution, and therefore, it is not producing a partial pressure. (Recall that only free, dissolved gas causes a partial pressure.) Thus, the binding of CO to hemoglobin keeps the free CO concentration and the partial pressure low, thereby maintaining the gradient for diffusion along the entire length of the capillary.

In summary, net diffusion of CO into the pulmonary capillary depends on, or is “limited” by, the magnitude of the partial pressure gradient, which is maintained because CO is bound to hemoglobin in capillary blood. Thus, CO does not equilibrate by the end of the capillary. In fact, if the capillary were longer, net diffusion would continue indefinitely, or until equilibration occurred.

Perfusion-Limited Gas Exchange

Perfusion-limited gas exchange is illustrated by N2O (see Fig. 5-18B), but also by O2 (under normal conditions) and CO2. N2O is used as the classic example of perfusion-limited exchange because it is not bound in blood at all but is entirely free in solution. As in the CO example, PAN2O is constant, and PaN2O is assumed to be zero at the beginning of the pulmonary capillary. Thus, initially, there is a large partial pressure gradient for N2O between alveolar gas and capillary blood, and N2O rapidly diffuses into the pulmonary capillary. Because all of the N2O remains free in blood, all of it creates a partial pressure. Thus, the partial pressure of N2O in pulmonary capillary blood increases rapidly and is fully equilibrated with alveolar gas in the first one fifth of the capillary. Once equilibration occurs, there is no more partial pressure gradient and, therefore, no more driving force for diffusion. Net diffusion of N2O then ceases, although four fifths of the capillary remains.

Compare the shaded area for N2O (see Fig. 5-18B) with that for CO (see Fig. 5-18A). The much smaller shaded area for N2O illustrates the differences between the two gases. Because equilibration of N2O occurs, the only means for increasing net diffusion of N2O is by increasing blood flow. If more “new” blood is supplied to the pulmonary capillary, then more total N2O can be added to it. Thus, blood flow or perfusion determines, or “limits,” the net transfer of N2O, which is described as perfusion-limited.

O2 Transport—Perfusion-Limited and Diffusion-Limited

Under normal conditions, O2 transport into pulmonary capillaries is perfusion-limited, but under other conditions (e.g., fibrosis or strenuous exercise), it is diffusion-limited. Figure 5-19 illustrates both conditions.

Figure 5–19 O2 diffusion along the length of the pulmonary capillary in normal persons and persons with fibrosis. A, At sea level; B, at high altitude.

Perfusion-limited O2 transport. In the lungs of a normal person at rest, O2 transfer from alveolar air into pulmonary capillary blood is perfusion-limited (although not to the extreme that N2O is perfusion-limited) (see Fig. 5-19A).  is constant at 100 mm Hg. At the beginning of the capillary,  is 40 mm Hg, reflecting the composition of mixed venous blood. There is large partial pressure gradient for O2 between alveolar air and capillary blood, which drives O2 diffusion into the capillary. As O2 is added to pulmonary capillary blood,  increases. The gradient for diffusion is maintained initially because O2 binds to hemoglobin, which keeps the free O2concentration and the partial pressure low. Equilibration of O2 occurs about one third of the distance along the capillary, at which point  becomes equal to , and unless blood flow increases, there can be no more net diffusion of O2. Thus, under normal conditions, O2 transport is perfusion-limited. Another way of describing perfusion-limited O2 exchange is to say that pulmonary blood flow determines net O2 transfer. Thus, increases in pulmonary blood flow (e.g., during exercise) will increase the total amount of O2 transported, and decreases in pulmonary blood flow will decrease the total amount transported.

Diffusion-limited O2 transport. In certain pathologic conditions (e.g., fibrosis) and during strenuous exercise, O2 transfer becomes diffusion limited. For example, in fibrosis the alveolar wall thickens, increasing the diffusion distance for gases and decreasing DL (see Fig. 5-19A). This increased diffusion distance slows the rate of diffusion of O2 and prevents equilibration of O2 between alveolar air and pulmonary capillary blood. In these cases, the partial pressure gradient for O2 is maintained along the entire length of the capillary, converting it to a diffusion-limited process (although not as extreme as in the example of CO; see Fig. 5-18A). Because a partial pressure gradient is maintained along the entire length of the capillary, it may seem that the total amount of O2 transferred would be greater in a person with fibrosis than in a person with normal lungs. Although it is true that the O2 partial pressure gradient is maintained for a longer length of the capillary (because DL is markedly decreased in fibrosis), the total transfer of O2 still is greatly decreased. At the end of the pulmonary capillary, equilibration has not occurred between alveolar air and pulmonary capillary blood ( < ), which will be reflected in a decreased  in systemic arterial blood and decreased  in mixed venous blood.

O2 transport at high altitude. Ascent to high altitude alters some aspects of the O2 equilibration process. At high altitude, barometric pressure is reduced, and with the same fraction of O2 in inspired air, the partial pressure of O2in alveolar gas also will be reduced. In the example shown in Figure 5-19B,  is reduced to 50 mm Hg, compared with the normal value of 100 mm Hg. Mixed venous PO2 is 25 mm Hg (as opposed to the normal value of 40 mm Hg). Therefore, at high altitude, the partial pressure gradient for O2 is greatly reduced compared with sea level (see Fig. 5-19A). Even at the beginning of the pulmonary capillary, the gradient is only 25 mm Hg (50 mm Hg − 25 mm Hg), instead of the normal gradient at sea level of 60 mm Hg (100 mm Hg − 40 mm Hg). This reduction of the partial pressure gradient means that diffusion of O2 will be reduced, equilibration will occur more slowly along the capillary, and complete equilibration will be achieved at a later point along the capillary (two thirds of the capillary length at high altitude, compared with one third of the length at sea level). The final equilibrated value for  is only 50 mm Hg because  is only 50 mm Hg (it is impossible for the equilibrated value to be higher than 50 mm Hg). The slower equilibration of O2 at high altitude is exaggerated in a person with fibrosis. Pulmonary capillary blood does not equilibrate by the end of the capillary, resulting in values for  as low as 30 mm Hg, which will seriously impair O2 delivery to the tissues.

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