Gas Exchange and Transport

Christopher A. Hirsch

Chapter Objectives

After reading this chapter you will be able to:

Describe how oxygen and carbon dioxide move between the atmosphere and tissues.

Identify what determines alveolar oxygen and carbon dioxide pressures.

Calculate the alveolar partial pressure of oxygen at any given barometric pressure and fraction of inspired oxygen.

State the effects that normal regional variations in ventilation and perfusion have on gas exchange.

Describe how to compute total oxygen content for arterial blood.

State the factors that cause the arteriovenous oxygen content difference to change.

Identify the factors that affect oxygen loading and unloading from hemoglobin.

Describe how carbon dioxide is carried in the blood.

Describe how oxygen and carbon dioxide transport are interrelated.

Describe the factors that impair oxygen delivery to the tissues and how to distinguish among them.

State the factors that impair carbon dioxide removal.

carboxyhemoglobin (HbCO)

dead space

dysoxia

fetal hemoglobin (HbF)

Fick equation

Fick’s first law of diffusion

right-to-left anatomic shunts

sickle cell hemoglobin

venous admixture

ventilation/perfusion ratio ()

Respiration is the process of getting oxygen (O₂) into the body for tissue use and removing carbon dioxide (CO₂) into the atmosphere. This complex process involves both gas exchange (at the lungs and at the cellular level) and transport of the gases. O₂ must be moved into the lungs, where it diffuses into the pulmonary circulation and is transported in the blood to the tissues. CO₂ builds up in the tissues because of metabolism and diffuses into the capillary blood before being carried to the lung for exchange with alveolar gases. Normally, these processes are well integrated. However, in disease states, impaired gas exchange or transport can cause physiologic imbalances, which can alter function or threaten survival. At such times, respiratory care intervention may be the only way to maintain or restore a level of function consistent with life. This chapter provides the background knowledge that respiratory therapists (RTs) need to understand and treat patients with diseases that affect gas exchange.

Diffusion

Whole-Body Diffusion Gradients

Gas movement between the lungs and tissues occurs via simple diffusion (see Chapters 6 and 8). Figure 11-1 shows the normal diffusion gradients for O₂ and CO₂. For O₂, there is a stepwise downward “cascade” of partial pressures from the normal atmospheric inspired partial pressure of O₂ (PiO₂) of 159 mm Hg to a low point of 40 mm Hg or less in the capillaries. The intracellular PO₂ (approximately 5 mm Hg) provides the final gradient for O₂ diffusion into the cell.

FIGURE 11-1 Normal diffusion gradients for O₂ and CO₂. There is a downward cascade for O₂ from air to cells, with a reverse gradient for CO₂.

The diffusion gradient for CO₂ is the opposite of the diffusion gradient for O₂. The partial pressure of CO₂ (PCO₂) is highest in the cells (approximately 60 mm Hg) and lowest in room air (1 mm Hg). This reverse cascade causes CO₂ movement from the tissues into the venous blood, which is transported to the lungs and—with the aid of ventilation—out to the atmosphere.

Determinants of Alveolar Gas Tensions

Alveolar Carbon Dioxide

The alveolar partial pressure of CO₂ (P_ACO₂) varies directly with the body’s production of CO₂ () and inversely with alveolar ventilation (). The relationship is expressed by the following formula:

PACO2=V˙CO2×0.863V˙A

Where:

P_ACO₂ = Alveolar CO₂ tension (mm Hg)

= Rate of CO₂ produced (in ml/min standard temperature and pressure, dry [STPD])

= Alveolar ventilation (ml/min body temperature and pressure, saturated [BTPS])

Because is expressed as a flow of dry gas at 0° C and 760 mm Hg, and is reported as saturated gas at body temperature and ambient pressure, the factor 863 is employed to correct the measurement for comparison under the same conditions. It confers the units of pressure to the resulting dimensionless ratio of flow rates.

As an example, given of 200 ml/min and alveolar ventilation of 4315 ml/min, application of this formula yields a P_ACO₂ of approximately 40 mm Hg:

PACO2=(863mm Hg×200ml/min)÷4315ml/min=40mm Hg

P_ACO₂ increases above this level if CO₂ production increases while alveolar ventilation remains constant or if alveolar ventilation decreases while remains constant. An increase in dead space, the portion of inspired air that is exhaled without being exposed to perfused alveoli, can also lead to an increased P_ACO₂:

V˙=(VT−VD)×f

Where:

= Alveolar ventilation

V_T = Tidal volume

V_D = Dead space volume

f = Ventilatory frequency

Likewise, P_ACO₂ decreases if CO₂ production decreases or alveolar ventilation increases. Normally, complex respiratory control mechanisms maintain P_ACO₂ within a range of 35 to 45 mm Hg under various conditions (see Chapter 14). If CO₂ production increases, as with exercise or fever, ventilation automatically increases to maintain P_ACO₂ within normal range.

Alveolar Oxygen Tensions

Many factors determine the alveolar partial pressure of O₂ (P_AO₂). Most important is PiO₂. In addition, when O₂ is in the lungs, it is diluted by both water vapor and CO₂. To account for all these factors, the following alveolar air equation is applied:

PAO2=FiO2×(PB−47)−(PACO2÷0.8)

Where:

FiO₂ = Fraction of inspired O₂ (decimal)

P_B = Barometric pressure (mm Hg)

47 = Water vapor tension (in mm Hg) at 37° C

P_ACO₂ = Alveolar PCO₂

0.8 = Normal respiratory exchange ratio (R)

The equation component FiO₂ × (P_B − 47) is a simple application of Dalton’s law:

Partial pressure=Fractional concentration×Total pressure

However, under BTPS conditions in the lungs, the total pressure available for O₂ is reduced by an amount equal to the saturated water vapor pressure at 37° C, or 47 mm Hg.

The equation component (PaCO₂ ÷ 0.8) accounts for the alveolar CO₂. However, PaCO₂ cannot simply be subtracted, as was done for water vapor. Instead, the equation must be corrected for the difference between O₂ and CO₂ movement into and out of the alveoli, which is done by dividing the P_ACO₂ by R. R is the ratio of CO₂ excretion to O₂ uptake, which normally averages 0.8 throughout the lung. In addition, because PaCO₂ nearly equals P_ACO₂, PaCO₂ can be substituted for P_ACO₂. For example, if FiO₂ is 0.21, P_B is 760 mm Hg, and PaCO₂ is 40 mm Hg, the normal alveolar partial pressure of O₂ can be estimated as follows:

PAO2=0.21×(760mm Hg−47)−(40mm Hg÷0.8)=99.73mm Hg

In clinical practice, if a patient is breathing 60% or more O₂ (FiO₂ ≥ 0.60), the correction for R can be dropped because the magnitude of the correction to PaCO₂ falls below significance relative to the much larger calculated FiO₂ (P_B − 47). This yields the following simplified form of the alveolar air equation:

PAO2=FiO2(PB−47)−PaCO2

The accompanying Mini Clini provides an example of how to use the alveolar air equation.

Mini Clini

Alveolar-Arterial PO₂ Difference and a/A Ratio

Not all of the O₂ from the alveoli gets into the blood. Why this occurs is discussed later in this chapter. This Mini Clini considers how the efficiency of O₂ transfer from the alveoli to the blood can be computed.

Several bedside computations can be used to estimate the efficiency of pulmonary O₂ transfer. The most common computation is the difference between the alveolar and arterial PO₂, called the A-a gradient (P[A−a]O₂). Normally, this difference is small—only 5 to 10 mm Hg when air is breathed and no more than 65 mm Hg when 100% O₂ is breathed.

Another common bedside computation is the ratio of arterial to alveolar PO₂, called the a/A ratio. The a/A ratio should be thought of as the proportion of O₂ getting from the alveoli to the blood. Normally, this proportion is at least 90% (a ratio of 0.9).

Problem

Compute and interpret the P(A−a)O₂ and a/A ratio for a 45-year-old woman breathing 70% O₂ at sea level, with the following blood gas values: PaO₂, 50 mm Hg; PaCO₂, 50 mm Hg.

Discussion

1. Compute P_AO₂ using one form of the alveolar O₂ equation as follows: P_AO₂ = FiO₂ × (P_B − 47) − P_ACO₂ (patient breathing >60% O₂)

P_AO₂ = Alveolar O₂ tension (mm Hg)

FiO₂ = Inspired O₂ fraction (decimal)

P_ACO₂ = Alveolar CO₂ tension (mm Hg, often estimated by arterial CO₂ tension)

P_AO₂ = 0.7 × (760 mm Hg − 47 mm Hg) − 50 mm Hg

P_AO₂ = 449 mm Hg

2. Compute P(A−a)O₂ as follows:

P(A−a)O₂ = P_AO₂ − PaO₂

PaO₂ = Arterial O₂ tension (mm Hg)

P(A−a)O₂ = 449 mm Hg − 50 mm Hg

P(A−a)O₂ = 399 mm Hg

3. Compute a/A ratio as follows:

a/A = PaO₂/P_AO₂

a/A = 50 mm Hg/449 mm Hg

a/A = 0.11

Discusson

Both the P(A−a)O₂ and the a/A ratio are abnormal. Compared with a normal value of 65 mm Hg or less, the P(A−a)O₂ of nearly 400 mm Hg is very high. This P(A−a)O₂ indicates a large difference between the alveolar and arterial PO₂ values (i.e., inefficient O₂ transfer). Likewise, the a/A ratio of 0.11 indicates that only approximately 11% of the O₂ in the alveoli is getting into the blood. Although the patient is receiving a high FiO₂ (0.70), she has a severe problem getting O₂ into her blood and needs immediate evaluation by a critical care physician.

Changes in Alveolar Gas Partial Tensions

In addition to CO₂, O₂, and water vapor, alveoli normally contain nitrogen. Nitrogen is inert and plays no role in gas exchange; however, it occupies space and exerts pressure. According to Dalton’s law, the partial pressure of alveolar nitrogen (P_AN₂) must equal the pressure it would exert if it alone were present. To compute P_AN₂, subtract the pressures exerted by all the other alveolar gases, as follows:

PAN2=PB−(PAO2+PACO2+PH2O)

PAN2=760mm Hg−(100mm Hg+40mm Hg+47mm Hg)

PAN2=760mm Hg−187mm Hg

PAN2=573mm Hg

Because both water vapor tension and P_AN₂ remain constant, the only partial pressures that change in the alveolus are O₂ and CO₂. Based on the alveolar air equation, if FiO₂ remains constant, P_AO₂ must vary inversely with P_ACO₂.2–4

Rule of Thumb

When the patient is breathing room air, the sum of P_AO₂ and P_ACO₂ equals about 140 mm Hg (100 mm Hg and 40 mm Hg). Changes in ventilation that cause P_ACO₂ to vary also vary the resulting P_AO₂ to keep the total at 140 mm Hg. If P_ACO₂ of a patient breathing room air increases from 40 mm Hg to 60 mm Hg (an increase of 20 mm Hg), P_AO₂ should decrease by approximately 20 mm Hg. This equation assumes a constant value for R.

P_ACO₂ itself varies inversely with the level of alveolar ventilation. For a constant CO₂ production, a decrease in simultaneously increases P_ACO₂ and decreases P_AO₂, whereas an increase in has the opposite effect (Figure 11-2). However, ventilation can be increased only so much. Neural control mechanisms and the increased work of breathing prevent decreases in P_ACO₂ much below 15 to 20 mm Hg. Whenever a patient is breathing room air at sea level, the RT should not expect to see a PaO₂ greater than 120 mm Hg during hyperventilation. PaO₂ values greater than 120 mm Hg indicate that the patient is breathing supplemental O₂. The accompanying Mini Clini presents a clinical application of these principles.

FIGURE 11-2 Effect of alveolar ventilation on alveolar gases. (Modified from Pilbeam SP: Mechanical ventilation, ed 4, St Louis, 2006, Mosby.)

Mini Clini

Assessing Arterial Gas Partial Pressures

Problem

The RT is given the following arterial blood gas report for a patient who was just admitted to the emergency department: PaO₂ = 170 mm Hg; PaCO₂ = 23 mm Hg. Without additional data, what conclusions can the RT draw about the FiO₂ in this case?

Discussion

In room air, the total pressure exerted by O₂ and CO₂ in the alveoli (and blood) should be approximately 140 mm Hg. In this case, the total is 170 mm Hg (PaO₂) + 23 mm Hg (PaCO₂), or 193 mm Hg. Whenever total pressure significantly exceeds 140 mm Hg and PaO₂ is greater than 120 mm Hg, the RT can be assured that the patient is breathing supplemental O₂.

Mechanism of Diffusion

As described in Chapter 6, diffusion is the process whereby gas molecules move from an area of high partial pressure to an area of low partial pressure. To diffuse into and out of the lung and tissues, O₂ and CO₂ must move through significant barriers.

Barriers to Diffusion

The barrier to gaseous diffusion in the lung is the alveolar-capillary membrane. For CO₂ or O₂ to move between the alveoli and the pulmonary capillary blood, the following three barriers must be penetrated: (1) alveolar epithelium, (2) interstitial space, and (3) capillary endothelium. In addition, to pass into and out of the red blood cells (RBCs), these gases also must traverse the erythrocyte membrane.5,6

Fick’s First Law of Diffusion

The bulk movement of a gas through a biologic membrane () is described by Fick’s first law of diffusion:

V˙gas=[(A×D)÷T](P1−P2)

In this formula, A is the cross-sectional area available for diffusion, D is the diffusion coefficient of the gas, T is the thickness of the membrane, and (P₁ − P₂) is the partial pressure gradient across the membrane.

According to Fick’s law, the greater the surface area, diffusion constant, and pressure gradient, the more diffusion occurs. Conversely, with greater the distance across the membrane (thickness), less diffusion occurs. Given that the area of and distance across the alveolar-capillary membrane are constant in healthy people, diffusion in the normal lung mainly depends on gas pressure gradients.

Pulmonary Diffusion Gradients

For gas exchange to occur between the alveoli and pulmonary capillaries, a difference in partial pressures (P₁ − P₂) must exist. Figure 11-3 shows the size and direction of these gradients for O₂ and CO₂. In the normal lung, the alveolar PO₂ averages approximately 100 mm Hg, whereas the mean PCO₂ is approximately 40 mm Hg. Venous blood returning to the lungs has a lower PO₂ (40 mm Hg) than alveolar gas. The pressure gradient for O₂ diffusion into the blood is approximately 60 mm Hg (100 mm Hg − 40 mm Hg). As blood flows past the alveolus, it takes up O₂ and moves to the left atrium with a PO₂ close to 100 mm Hg in healthy people.

FIGURE 11-3 Ventilation maintains mean alveolar gas pressures for O₂ and CO₂ at approximately 100 mm Hg and 40 mm Hg. As blood enters the venous end of the capillary, it gives up CO₂ and loads O₂ until these two gases are in equilibrium with alveolar pressures. At this point, the blood is “arterialized.”

Because venous blood has higher PCO₂ than alveolar gas (46 mm Hg vs. 40 mm Hg), the pressure gradient for CO₂ causes it to diffuse in the opposite direction, from the blood into the alveolus. This diffusion continues until capillary PCO₂ equilibrates with the alveolar level, at approximately 40 mm Hg.

Although the pressure gradient for CO₂ is approximately one-tenth of the pressure gradient for O₂, CO₂ has little difficulty diffusing across the alveolar-capillary membrane. CO₂ diffuses approximately 20 times faster across the alveolar-capillary membrane than O₂ because of its much higher solubility in plasma. Disorders that impair the diffusion capacity of the lung (D_L) can affect O₂ movement into the blood, especially when blood flow through the lung is rapid because the time the RBCs are in contact with the alveoli is reduced.

Time Limits to Diffusion

For blood leaving the pulmonary capillary to be adequately oxygenated, it must spend sufficient time in contact with the alveolus to allow equilibration.5,8 If the time available for diffusion is inadequate, blood leaving the lungs may not be fully oxygenated. The diffusion time in the lung depends on the rate of pulmonary blood flow. As depicted in Figure 11-4, blood normally takes approximately 0.75 second to pass through the pulmonary capillary. This time is more than enough to ensure complete diffusion of O₂ across the alveolar-capillary membrane normally.

FIGURE 11-4 Alveolar-capillary PO₂ gradient. Normal transit time for RBC in the pulmonary capillary is approximately 0.75 second. Normally, blood PO₂ equilibrates with the alveolar PO₂ well before it reaches the end of the capillary.

If blood flow increases, such as during heavy exercise, capillary transit time can decrease to 0.25 second. This short time frame is adequate to ensure that equilibration occurs as long as no other factors impair diffusion. However, in the presence of a diffusion limitation, rapid blood flow through the pulmonary circulation can result in inadequate oxygenation. High fever and septic shock, which often cause increased cardiac output, are good examples of conditions that limit diffusion time because of increased blood flow.

In clinical practice, knowledge of D_L can be helpful in evaluating certain diseases. D_L is the bulk flow of gas (ml/min) that diffuses into the blood for each 1-mm Hg difference in the pressure gradient. Although O₂ can be used to measure D_L, low concentrations (0.1% to 0.3%) of carbon monoxide are used more commonly. Chapter 19 provides details on the technique for measuring D_L and its diagnostic use.

Systemic Diffusion Gradients

Partial pressure gradients in the tissues are the opposite of the partial pressure gradients in the lung. As cellular metabolism depletes its O₂, intracellular PO₂ decreases to less than PO₂ of the blood entering the tissue capillary. O₂ diffuses from the tissue capillary blood (PO₂ = 100 mm Hg) to the cells (PO₂ < 40 mm Hg). Simultaneously, CO₂ diffuses from the cells (PCO₂ > 46 mm Hg) into the capillary blood (PCO₂ = 40 mm Hg). After equilibration, blood leaves the tissue capillaries with PO₂ of approximately 40 mm Hg and PCO₂ of approximately 46 mm Hg.

Just as arterial blood reflects pulmonary gas exchange, venous blood reflects events occurring in the tissues. The use of venous blood to assess tissue oxygenation is discussed in Chapter 46.

Normal Variations from Ideal Gas Exchange

This chapter has focused so far almost entirely on gas pressures in a perfect alveolus (i.e., one with ideal ventilation and blood flow). In reality, the normal lung is an imperfect organ of gas exchange. Clinically, this imperfection becomes clear, PaO₂ is measured in the average individual. Rather than equaling P_AO₂ of 100 mm Hg, PaO₂ of healthy individuals breathing air at sea level is approximately 5 to 10 mm Hg less than the calculated PaO₂. Two factors account for this difference: (1) right-to-left shunts in the pulmonary and cardiac circulation and (2) regional differences in pulmonary ventilation and blood flow.

Anatomic Shunts

A shunt is the portion of the cardiac output that returns to the left heart without being oxygenated by exposure to ventilated alveoli. Two right-to-left anatomic shunts exist in normal humans: (1) bronchial venous drainage and (2) thebesian venous drainage (see Chapters 8 and 9). A right-to-left shunt causes poorly oxygenated venous blood to move directly into the arterial circulation (venous admixture), reducing the O₂ content of arterial blood. Together, these normal shunts account for approximately three-fourths of the normal difference between P_AO₂ and PaO₂. The remaining difference is a result of normal inequalities in pulmonary ventilation and perfusion.⁵

Regional Inequalities in Ventilation and Perfusion

The normal respiratory exchange ratio of 0.8 assumes that ventilation and perfusion in the lung are in balance, with every liter of alveolar ventilation () matched by approximately 1 L of pulmonary capillary blood flow (). Any variation from this perfect balance alters gas tensions in the affected alveoli. As previously discussed, changes in affect P_ACO₂, which alters P_AO₂. Changes in blood flow also alter alveolar gas pressures. If blood flow to an area of the lung increases, CO₂ coming from the tissues is delivered faster, causing an increase in P_ACO₂ if minute ventilation remains the same. At the same time, O₂ is taken up by the capillaries faster than restored by ventilation, causing a decrease in alveolar P_AO₂. Decrease in pulmonary capillary blood flow has the opposite effect (i.e., decrease in P_ACO₂ and increase in P_AO₂) assuming minute ventilation remains the same.5,7,8

Ventilation/Perfusion Ratio

Changes in and are expressed as a ratio called the ventilation/perfusion ratio (). An ideal ratio of 1.0 indicates that ventilation and perfusion are in perfect balance. A high indicates that ventilation is greater than normal, perfusion is less than normal, or both. In the presence of a high , PO₂ is greater and PCO₂ is less than normal. Conversely, a low indicates that ventilation is less than normal, perfusion is greater than normal, or both. In areas with a low , P_AO₂ is less than normal and P_ACO₂ is greater than normal.

Effect of Alterations in Ventilation/Perfusion Ratio

Figure 11-5 shows graphs of the effect of changes on the respiratory exchange ratio (R), plotting all possible values of P_AO₂ and P_ACO₂. When ventilation and perfusion are in perfect balance ( = 0.99), R equals 0.8. At this point, P_AO₂ and P_ACO₂ values equal the ideal values of 100 mm Hg and 40 mm Hg.