Medical Physiology, 3rd Edition

Matching Ventilation and Perfusion

The greater the ventilation-perfusion ratio, the higher the image and the lower the image in the alveolar air

In Figure 31-4 we saw that, all other factors being equal, alveolar ventilation determines alveolar image and image. The greater the ventilation, the more closely image and image approach their respective values in inspired air. However, in Figure 31-4 we were really focusing on total alveolar ventilation and how this influences the average, or idealized, alveolar image and image. In fact, we have already learned that both ventilation and perfusion vary among alveoli. In any group of alveoli, the greater the local ventilation, the more closely the composition of local alveolar air approaches that of the inspired air. Similarly, because blood flow removes O2 from the alveolar air and adds CO2, the greater the perfusion, the more closely the composition of local alveolar air approaches that of mixed-venous blood. Thus, the local ventilation-perfusion ratio (image) determines the local image and image.

You might view the alveoli as a sports venue where ventilation and perfusion are engaged in a continuous struggle over control of the composition of alveolar air. To the extent that ventilation gains the upper hand, image rises and image falls. To the extent that perfusion holds sway, these parameters change in the opposite direction.

As a physical analog of this struggle over control of alveolar image, consider water flowing (analogous to image) from a faucet into a sink (alveoli); the water exits (image) through a drain with an adjustable opening. If the drain opening is in midposition and we begin flowing water moderately fast, then the water level (image) will gradually increase and reach a steady state. Increasing the inflow of water (image) will cause the water level (image) to rise until the product of pressure head and drain conductance is high enough to drive water down the drain as fast as the water flows in. If we increase the drain opening and thus the outflow of water (image), then the water level (image) will fall until the decrease in the pressure head matches the increase in drain conductance, so that once again water inflow and outflow are balanced. Just as a high faucet-drain ratio will raise the water level, a high image ratio will increase alveolar image.

Because of the action of gravity, the regional image ratio in an upright subject is greater at the apex of the lung than at the base

We have already seen that when a subject is upright in a gravitational field, ventilation falls from the base to the apex of the lung (see Fig. 31-5B) and that perfusion also falls, but more steeply (see Fig. 31-9B). Thus, it is not surprising that the ratio image itself varies with height in the lung (Fig. 31-10A). image is lowest near the base, where image exceeds image. The ratio gradually increases to 1 at about the level of the third rib and further increases toward the apex, where image falls more precipitously than image.

image

FIGURE 31-10 Regional differences in image ratio and alveolar gas composition. (Data from West JB: Ventilation/Blood Flow and Gas Exchange. Oxford, UK, Blackwell, 1985.)

Table 31-3 shows how differences in image at the apex and base of the lungs influence the regional composition of alveolar air. At the apex (the most rostral 7% of lung volume in this example), where image is highest, alveolar image and image most closely approach their values in inspired air. Because both O2 transport and CO2 transport across the blood-gas barrier are perfusion limited (see pp. 671–673), O2 and CO2have completely equilibrated between the alveolar air and the blood by the end of the pulmonary capillaries. Thus, blood leaving the apex has the same high image and low image as the alveolar air. Of course, the relatively low image produces a respiratory alkalosis (see p. 634) in the blood leaving the apex.

TABLE 31-3

Effect of Regional Differences in image on the Composition of Alveolar Air and Pulmonary-Capillary Blood

LOCATION

FRACTION OF TOTAL LUNG VOLUME

image

image (mm Hg)

image (mm Hg)

pH

image (L/min)

Apex

7%

3.3

132

28

7.55

0.07

Base

13%

0.6

89

42

7.38

1.3

Overall

100%

0.84*

100

40

7.40

5.0

*Because the transport of both O2 and CO2 is perfusion limited, we assume that end-capillary values of image and image are the same as their respective alveolar values. If the overall alveolar ventilation for the two lungs is 4.2 L/min, and if the cardiac output (i.e., perfusion) is 5 L/min, then the overall image ratio for the two lungs is (4.2 L/min)/(5 L/min) = 0.84.

Modified from West JB: Ventilation/Blood Flow and Gas Exchange. Oxford, UK, Blackwell, 1989.

The situation is just the opposite near the base of the lung (the most caudal 13% of lung volume in this example). Because image here is lowest, alveolar image and image tend more toward their values in mixed-venous blood. What impact do these different regions of the lung, each with its own image ratio, have on the composition of systemic arterial blood? Each region makes a contribution that is proportional to its blood flow (see the rightmost column in Table 31-3). Because the apex is poorly perfused, it makes only a small contribution to the overall composition of arterial blood. On the other hand, pulmonary tissue at the base of the lungs, which receives ~26% of total cardiac output, makes a major contribution. As a result, the average composition of blood exiting the lung more closely reflects the composition of the blood that had equilibrated with the air in the base of the lung.

The O2-CO2 diagram introduced as Figure 29-11 is a helpful tool for depicting how different image ratios throughout the lung produce different blood-gas compositions. The curve in Figure 31-10B represents all possible combinations of image and image in the alveolar air or end-pulmonary-capillary blood. The H2O-saturated inspired air (image = 149, image = ~0 mm Hg) represents the rightmost extreme of the diagram. By definition, the image ratio of inspired air is ∞, because it does not come into contact with pulmonary-capillary blood. The mixed-venous blood (image = 40, image = 46 mm Hg) represents the other extreme. By definition, the image ratio of mixed-venous blood is zero, because it has not yet come into contact with alveolar air. With the end points of the diagram established, we can now predict—with the help of the alveolar gas equation (see Equation 31-17), the Bohr effect (see p. 652), and the Haldane effect (see p. 657)—all possible combinations of image and image throughout the lung. As shown in Figure 31-10B, the base, midportion, and apex of the lungs correspond to points along the O2-CO2 diagram between mixed-venous blood at one extreme and inspired air at the other.

The ventilation of unperfused alveoli (local image = ∞) triggers compensatory bronchoconstriction and a fall in surfactant production

The effects of gravity on ventilation and perfusion cause regional image to vary widely, even in idealized lungs (see Fig. 31-10A). However, microscopic or local physiological and pathological variations in ventilation and perfusion can cause even greater mismatches of image, the extremes of which are alveolar dead-space ventilation (this section) and shunt (next section).

Alveolar Dead-Space Ventilation

At one end of the spectrum of image mismatches is the elimination of blood flow to a group of alveoli. For example, if we ligated the pulmonary artery feeding one lung, the affected alveoli would receive no perfusion even though ventilation would initially continue normally (Fig. 31-11A). Above, we saw that such alveolar dead space together with the anatomical dead space constitute the physiological dead space (see Equation 31-8). The ventilation of the unperfused alveoli is called alveolar dead-space ventilation because it does not contribute to gas exchange. Thus, these alveoli behave like conducting airways. imageN31-12

image

FIGURE 31-11 Extreme image mismatch and compensatory response—alveolar dead-space ventilation.

N31-12

Notes on the Differences Between Anatomical and Physiological Dead Space

Contributed by Emile Boulpaep, Walter Boron

There is a fundamental difference between the anatomical and alveolar dead space. The conducting airways are in series with and upstream from (proximal to) the alveoli. The conducting airways have the composition of inspired air only after an inspiration; after an expiration, they have the composition of alveolar air. On the other hand, unperfused alveoli are in parallel with normal alveoli and have the composition of inspired air, regardless of the position in the respiratory cycle.

A natural cause of alveolar dead-space ventilation is a pulmonary embolism, which obstructs blood flow to a group of alveoli. Because one task of the lung is to filter small emboli from the blood (see p. 600), the lung must deal with small regions of alveolar dead-space ventilation on a recurring basis. At the instant the blood flow ceases, the alveoli supplied by the affected vessel(s) contain normal alveolar air. However, each cycle of inspiration and expiration replaces some stale alveolar air with fresh, inspired air. Because no exchange of O2 and CO2 occurs between these unperfused alveoli and pulmonary-capillary blood, the alveolar gas gradually achieves the composition of moist inspired air, with alveolar image rising to ~149 mm Hg and image falling to ~0 mm Hg (see Fig. 31-11A, step 2). By definition, alveolar dead space has a image ratio of ∞, as described by the “Inspired air” point on the x-axis of an O2-CO2 diagram (see Fig. 31-10B).

Redirection of Blood Flow

Blocking blood flow to one group of alveoli diverts blood to other “normal” alveoli, which then become somewhat hyperperfused. Thus, the blockage not only increases image in alveoli downstream from the blockage, but also decreases image in other regions. Redirection of blood flow thus accentuates the nonuniformity of ventilation.

Regulation of Local Ventilation

Because alveolar dead-space ventilation causes alveolar image to fall to ~0 mm Hg in downstream alveoli, it leads to a respiratory alkalosis (see p. 634) in the surrounding interstitial fluid. These local changes trigger a compensatory bronchiolar constriction in the adjacent tissues (see Fig. 31-11B), so that over a period of seconds to minutes, airflow partially diverts away from the unperfused alveoli and toward normal alveoli, to which blood flow is also being diverted. This compensation makes teleological sense, because it tends to correct the image shift in both the unperfused and normal alveoli. The precise mechanism of bronchiolar constriction is unknown, although bronchiolar smooth muscle may contract—at least in part—in response to a high extracellular pH. imageN31-13

N31-13

Bronchiolar Constriction during Alveolar Dead-Space Ventilation

Contributed by Emile Boulpaep, Walter Boron

The precise mechanism of bronchiolar constriction in response to alveolar dead-space ventilation is unknown. However, it is intriguing to speculate that, at least in part, the mechanism may parallel that for the autoregulation of blood flow in the brain. The vascular smooth-muscle cells (VSMCs) of the penetrating cerebral arterioles constrict in response to respiratory alkalosis—which is why one feels dizzy after hyperventilating. This constriction of the VSMCs occurs when one imposes an alkalosis in the complete absence of image. Furthermore, the alkalosis-induced vasoconstriction is due entirely to a pH decrease on the outside of the VSMC. In other words, these cells have some sort of an extracellular pH sensor. A pH increase on the inside of the cell actually has the opposite effect: vasodilation. During extracellular acidosis, the vessels dilate.

In addition to a local respiratory alkalosis, the elimination of perfusion has a second consequence. Downstream from the blockage, alveolar type II pneumocytes become starved for various nutrients, including the lipids they need to make surfactant. (These cells never become starved for O2!) As a result of the decreased blood flow, surfactant production falls over a period of hours to days. The result is a local decrease in compliance, further reducing local ventilation.

These compensatory responses—bronchiolar constriction (i.e., increased resistance, a property of conducting airways) and reduced surfactant production (i.e., decreased compliance, a property of alveoli)—work well only if the alveolar dead space is relatively small, so that an ample volume of healthy tissue remains into which the airflow can divert.

The perfusion of unventilated alveoli (local image = 0) triggers a compensatory hypoxic vasoconstriction

Shunt

Alveolar dead-space ventilation is at one end of the spectrum of image mismatches. At the opposite end is shunt—the flow of blood past unventilated alveoli. For example, if we ligate a mainstem bronchus, then inspired air cannot refresh alveoli distal to the obstruction (see Fig. 31-12A). As a result, mixed-venous blood perfusing the unventilated alveoli “shunts” from the right side to the left side of the heart, without benefit of ventilation. When the low-O2 shunted blood mixes with high-O2 unshunted blood (which is ventilated), the result is that the mixture has a lower-than-normal image, causing hypoxia in the systemic arteries. It is possible to calculate the extent of the shunt from the degree of hypoxia. imageN31-14

image

FIGURE 31-12 Extreme image mismatch and compensatory response—shunt.

N31-14

The Shunt Equation

Contributed by Emile Boulpaep, Walter Boron

shunt is one extreme of a image mismatch and arises when blood perfuses unventilated alveoli. Alveoli may be unventilated because they are downstream from an obstructed conducting airway. Regardless of the mechanism that prevents airflow to these alveoli, the resulting right-to-left shunt causes mixed-venous blood to remain relatively unoxygenated and to go directly to the left side of the heart, where it mixes with oxygenated “arterial” blood. This process is known as venous admixture.

Imagine that 80% of the blood flow to the lungs goes to alveoli that are appropriately ventilated but that 20% goes to alveoli that are downstream from completely obstructed conducting airways. The total perfusion of the lungs is image. The shunt perfusion of the unventilated alveoli is image, 20% in this example, and the shunted blood has an O2 content (units: mL O2/dL) identical to that of mixed-venous blood (image). The difference (image − image) is the perfusion to the normally ventilated alveoli, 80% in our example, and this unshunted blood has an O2 content appropriate for the end of a pulmonary capillary (Cc′).

The blood emerging from the lungs is a mixture of shunted and unshunted blood so that the O2 emerging from the lung is partially O2 carried by the shunted blood and partially O2 carried by the unshunted blood:

image

(NE 31-35)

How much O2 per minute emerges from the lungs in the systemic arterial blood? This amount is the product of the O2 content of this arterial blood (Ca) and the total blood flow out the lungs (image):

image

(NE 31-36)

Similarly, the O2 contributed by the shunted blood is the product of the O2 content and the flow of shunted blood:

image

(NE 31-37)

Finally, the amount of O2 contributed per minute by the unshunted blood is

image

(NE 31-38)

Inserting the expressions for each of the terms in Equations NE 31-36 through NE 31-38 into Equation NE 31-35, we have

image

(NE 31-39)

Rearranging this equation and solving for the fraction of total blood flow that is represented by the shunt (image), we have

image

(NE 31-40)

This expression is known as the shunt equation.

What does Equation NE 31-40 predict for image in our example? We will assume that the O2 content of mixed-venous blood is 15 mL O2/dL blood, whereas that for blood at the end of the pulmonary capillaries is 20 mL O2/dL blood. These values are similar to those given in Table 29-3. If our hypothetical subject—who is affected by a 20% shunt—has systemic arterial blood with an O2 content of 19 mL O2/dL blood, then the shunt equation predicts

image

(NE 31-41)

Thus, the shunt equation predicts that the shunt is 20% of the total blood flow, which is reasonable, inasmuch as we started the example by assuming that 80% of the blood flowed through properly ventilated alveoli.

Natural causes of airway obstruction include aspiration of a foreign body or the presence of a tumor in the lumen of a conducting airway. The collapse of alveoli (atelectasis) also produces a right-to-left shunt, a pathological example of which is pneumothorax (see p. 608). Atelectasis also occurs naturally in dependent regions of the lungs, where PIP is not so negative (see Fig. 31-5C) and surfactant levels gradually decline. Sighing or yawning stimulates surfactant release (see p. 615) and can reverse physiological atelectasis.

Imagine that an infant aspirates a peanut. Initially, the air trapped distal to the obstruction has the composition of normal alveolar air. However, pulmonary-capillary blood gradually extracts O2 from the trapped air and adds CO2. Eventually, the image and image of the trapped air drift to their values in mixed-venous blood. If the shunt is small, so that it does not materially affect the image or image of the systemic arterial blood, then the alveoli will have a image of 40 mm Hg and a image of 46 mm Hg. By definition, shunted alveoli have a image of zero and are represented by the “Mixed-venous blood” point on an O2-CO2diagram (see Fig. 31-10B).

Redirection of Airflow

Blocking airflow to one group of alveoli simultaneously diverts air to normal parts of the lung, which then become somewhat hyperventilated. Thus, shunt not only decreases image in unventilated alveoli, but also increases image in other regions. The net effect is a widening of the nonuniformity of image ratios.

Asthma

Although less dramatic than complete airway obstruction, an incomplete occlusion also decreases image. An example is asthma, in which hyperreactivity of airway smooth muscle increases local airway resistance and decreases ventilation of alveoli distal to the pathology.

Normal Anatomical Shunts

The thebesian veins drain some of the venous blood from the heart muscle, particularly the left ventricle, directly into the corresponding cardiac chamber. Thus, delivery of deoxygenated blood from thebesian veins into the left ventricle (<1% of cardiac output) represents a right-to-left shunt. The bronchial arteries, branches of the aorta that carry ~2% of the cardiac output, supply the conducting airways (see p. 597). After passing through capillaries, about half of the bronchial blood drains into a systemic vein—the azygos vein—and then to the right side of the heart. The other half (~1% of cardiac output) anastomoses with oxygenated blood in pulmonary venules and thus represents part of the anatomical right-to-left shunt (see p. 412).

Pathological Shunts

In Chapter 57, we discuss examples of right-to-left shunts. imageN31-15 Respiratory distress syndrome in the newborn (Box 57-2) can cause airway collapse. Generalized hypoxemia in the newborn can constrict the pulmonary vasculature, as we will see in the next paragraph, leading to pulmonary hypertension and the shunting of blood via the foramen ovale (see p. 1158) or a patent ductus arteriosus (see p. 1158).

N31-15

Right-to-Left Shunts

Contributed by Emile Boulpaep, Walter Boron

Two congenital anomalies of the great vessels in which there may be sizeable right-to-left shunts are tetralogy of Fallot and transposition of the great vessels. Both conditions can cause severe hypoxemia.

Regulation of Local Perfusion

The alveoli that derive from a single terminal bronchiole surround the pulmonary arteriole that supplies these alveoli. Thus, the vascular smooth-muscle cells of this pulmonary arteriole are bathed in an interstitial fluid whose composition reflects that of the local alveolar gas. In the case of shunt, the vascular smooth-muscle cells sense a decrease in image, an increase in image, and a fall in pH. The decrease in local alveolar image triggers a compensatory hypoxic pulmonary vasoconstriction (see p. 687), which the accompanying respiratory acidosis augments (see Fig. 31-12B). Note that this response is just the opposite of that of systemic arterioles, which dilate in response to hypoxia (see pp. 477–478). Hypoxic pulmonary vasoconstriction makes teleological sense because it diverts blood flow away from unventilated alveoli toward normal alveoli, to which airflow is also being diverted. This compensation tends to correct the image shift in both the unventilated and normal alveoli.

If the amount of pulmonary tissue involved is sufficiently small (<20%), then hypoxic vasoconstriction has a minimal effect on overall pulmonary vascular resistance. The vasoconstriction causes a slight increase in pulmonary arterial pressure, which recruits and distends pulmonary vessels outside of the shunt zone. In contrast, global alveolar hypoxia—caused by, for example, ascending to high altitude—produces a generalized hypoxic vasoconstriction that may cause the resistance of the pulmonary vasculature to more than double. In susceptible individuals, the result can be acute mountain sickness (see p. 1232).

Even if whole-lung image and image are normal, exaggerated local image mismatches produce hypoxia and respiratory acidosis

As we saw in Table 31-3, even a normal person has lung regions with image values ranging from ~0.6 to 3.3. In addition, even a normal person has local variations in image due to alveolar dead-space ventilation as well as physiological and anatomical shunts. These physiological image mismatches produces an arterial image (i.e., ~40 mm Hg) that we regard as “normal” and an arterial image (i.e., ~100 mm Hg) that we also regard as “normal.” If pathological processes exaggerate this image mismatch, the result is respiratory acidosis and hypoxia. The sophisticated compensatory responses to alveolar dead-space ventilation and shunt—discussed above—help to minimizes these mismatches. Thus, uncompensated image abnormalities lead to respiratory acidosis and hypoxia. To illustrate how image mismatches produce these consequences, here we examine CO2 and O2 handling first in normal lungs and then in two extreme, idealized cases: alveolar dead-space ventilation and shunt—each in the absence of any local or system-wide compensation.

Normal Lungs

Figure 31-13 shows how an individual with a normal image distribution in each lung handles CO2 and O2. We assume that total image (4.2 L/min) and image (5 L/min) are normal and divided equally between the two lungs. Each lung eliminates half of the 200 mL/min of CO2 produced by metabolism (see Fig. 31-13A), and each takes up half of the 250 mL/min of O2 consumed by metabolism (see Fig. 31-13B). The physiological image distribution, as discussed in the previous paragraph, yields a mean alveolar image of ~40 mm Hg in each lung and a mean alveolar image of ~100 mm Hg. Because the fluxes of CO2 and O2 across the alveolar blood-gas barrier are each perfusion limited (see pp. 671–673), the CO2 and O2 partial pressures in the systemic arterial blood are the same as in the alveoli, and arterial pH is normal.

image

FIGURE 31-13 Normal distribution of image and image. imageN31-18 This is an idealized example. In the upper panels of A and B, the light beige boxes give the alveolar ventilation to each lung as well as the total alveolar ventilation (image). The pink boxes give the blood flow to each lung as well as the total cardiac output (image). The white boxes give the rates of CO2 or O2 transport (in mL/min) at either the pulmonary or systemic capillaries. The blue boxes give the CO2 and O2 partial pressures (in mm Hg) in alveolar air. The lavender boxes give the CO2 partial pressure (in mm Hg) and CO2 content (in mL/dL) in the mixed-venous blood, in the blood leaving each of the lungs, and in the mixed-arterial blood. The dark beige boxes give the same information for O2. The lower panel of A shows hypothetical plots of how total CO2 content varies with image at the Hb-O2 saturations typical of arterial blood (red line) and mixed-venous blood (violet line). The vertical arrow indicates the decrease in total CO2 content between the mixed-venous and arterial blood (4 mL/dL). The lower panel of B shows comparable plots for how total O2 content varies with image at the pH and image values typical of mixed-venous blood (violet curve) and arterial blood (red curve). The vertical arrow indicates the increase in total O2 content between the mixed-venous and arterial blood (5 mL/dL).

N31-18

Analysis of image Patterns in Figure 31-13

Contributed by Emile Boulpaep, Walter Boron

The following is a discussion of Figure 31-13 that is more complete than the material presented in the subsection “Normal Lungs” (see p. 693).

Figure 31-13 is a highly simplified example illustrating the principles underlying how an individual with a normal image in each lung handles CO2 (Fig. 31-13A) and O2 (Fig. 31-13B) as blood flows through the lungs, the systemic circulation, and then back to the lungs. We make the following assumptions:

• Total image (4.2 L/min) and image (5 L/min) are normal.

• image and image are evenly divided between the two lungs. Thus, the overall image ratio is (4.2 L/min)/(5 L/min) or 0.84. Of course, the image in each of the two lungs is also 0.84.

• image and image are uniformly distributed within each lung. In other words, we are ignoring the usual apex-to-base inequalities of both image and image (see Fig. 31-10). In addition, we assume that the lungs are free of pathological causes of either alveolar dead-space ventilation or shunt.

• The system has no physiological right-to-left shunts.

• The image in each lung will be 40 mm Hg; and the image, 100 mm Hg.

• Total-body image will be 200 mL/min and total-body image will be 250 mL/min.

• The entire system is in a steady state.

Predicting precisely how image abnormalities affect the CO2 and O2 partial pressures in the three key compartments (alveoli, arterial blood, and mixed-venous blood) is extremely complicated, in part because changes in image and pH affect O2 carriage (the Bohr effect; see p. 652) and changes in image affect CO2 carriage (the Haldane effect; see p. 657). Moreover, in reality, imageimage, and the image ratio are not uniform throughout each lung. However, although the examples in the text are greatly simplified, they illustrate the principles of how image mismatches lead to abnormalities in the arterial blood gases. We begin here with a discussion of the normal condition. We will consider alveolar dead-space ventilation in imageN31-19 and shunt in imageN31-20.

We will now follow the blood during one circuit through the circulation to see the relationship among the composition of the arterial blood, the CO2 and O2 transport rates in the lung, and the composition of the mixed-venous blood.

CO2 Handling

First consider the fate of CO2 in the following six steps (see Fig. 31-13A):

Step 1: Each lung must first receive and then exhale half of the total 200 mL/min of CO2 that body metabolism produces. In other words, 100 mL of CO2 enters each lung each minute, and because they are in a steady state, each lung exhales precisely this same amount each minute.

Step 2: In each lung, a image of 2.1 L/min dilutes 100 mL of exhaled CO2 (i.e., the exhaled 100 mL of CO2 is contained within the 2100 mL of exhaled air). This combination of image and image corresponds to a image of ~40 mm Hg.

Step 3: Because CO2 transport is perfusion limited (see pp. 671–673), the blood that emerges from each lung has the same image as the alveolar air, 40 mm Hg. According to the CO2 dissociation curve, we see that this image of 40 mm Hg corresponds to an arterial CO2 content of 48 mL/dL (see lower panel of Fig. 31-13A, point a).

Step 4: As the blood flows through the systemic capillaries, it picks up the 200 mL/min of CO2 produced by metabolism. Given a cardiac output of 5 L/min, we can use the Fick principle (see p. 423) to compute how much the CO2 content must rise in the capillaries for each 100 mL of blood:

image

(NE 31-42)


Thus, the mixed-venous CO2 content must be 48 + 4 = 52 mL/dL.

Step 5: According to the CO2 dissociation curve, when the CO2 content of the blood is 52 mL/dL, the mixed-venous image must be 46 mm Hg (lower panel of Fig. 31-13A, point image).

Step 6: As the blood completes the cycle and passes through the pulmonary capillaries, the image falls from 46 mm Hg to its original value of 40 mm Hg as 100 mL of CO2 diffuses from the pulmonary capillaries to the alveoli each minute in each lung. Simultaneously, the CO2 content falls from 52 to 48 mL/dL as CO2 evolves into the alveolar air at the rate of 100 mL/min in each lung (200 mL/min, total).

O2 Handling

Now consider the fate of O2, illustrated in six steps in Figure 31-13B. The situation for O2 is comparable to that for CO2, although the fluxes are all in a direction opposite to those for CO2.

Step 1: Each lung must take up half of the 250 mL/min O2 required by body metabolism, that is, 125 mL/min for each lung.

Step 2: For a image of 40 mm Hg and an RQ (see Equation 31-14) of 0.8, the alveolar gas equation (see Equation 31-17) predicts a image of ~100 mm Hg for each lung.

Step 3: The transport of O2, like that of CO2, is perfusion limited (see pp. 671–673), so that the blood emerging from each lung has a image of ~100 mm Hg. According to the O2 dissociation curve, a image of 100 mm Hg corresponds to an arterial O2 content of 20 mL/dL (see lower panel of Fig. 31-13B, point a).

Step 4: As the blood flows through the systemic capillaries, it must give up 250 mL/min of O2, which will be consumed by metabolism. According to the Fick principle, the decrease in O2 content that occurs as the blood passes through the systemic capillaries is

image

(NE 31-43)


Thus, the mixed-venous O2 content must be 20 − 5 = 15 mL/dL.

Step 5: From the O2 dissociation curve, we see that a mixed-venous O2 content of 15 mL/dL corresponds to a mixed-venous O2 of 40 mm Hg (see lower panel of Fig. 31-13B, point image).

Step 6: As the blood completes the cycle and passes through the lungs, it must pick up 125 mL/min of O2 in each lung. This influx of O2 causes the O2 content to increase from 15 to 20 mL/dL, as the blood image increases from 40 to 100 mm Hg.

Alveolar Dead-Space Ventilation Affecting One Lung

To simulate alveolar dead-space ventilation (Fig. 31-14) in the laboratory, we can surgically ligate the left pulmonary artery, thereby eliminating all perfusion to the left lung. Total image remains at its normal 5 L/min, but all blood goes to the right lung. image remains at its normal 4.2 L/min and is evenly distributed between the two lungs. Thus, the image to the left lung is 2.1/0 or ∞, whereas the image to the right lung is 2.1/5 or 0.42. The overall image is normal, 0.84. The key question is whether a combination of a high image in the abnormal lung and a low image in the normal lung can yield normal blood-gas levels.

image

FIGURE 31-14 Alveolar dead-space ventilation. imageN31-19 The numbers in this idealized example refer to a time after the individual has achieved a new steady state. In the upper panels of A and B, the light beige boxes give the alveolar ventilation to each lung as well as the total alveolar ventilation (image). The pink boxes give the blood flow to each lung as well as the total cardiac output (image). The white boxes give the rates of CO2 or O2 transport (in mL/min) at either the pulmonary or systemic capillaries. The blue boxes give the CO2 and O2 partial pressures (in mm Hg) in alveolar air. The lavender boxes give the CO2 partial pressure (in mm Hg) and CO2 content (in mL/dL) in the mixed-venous blood, in the blood leaving each of the lungs, and in the mixed-arterial blood. The dark beige boxes give the same information for O2. The lower panel of A shows plots of how total CO2 content in this example varies with image at the Hb-O2 saturations of arterial blood (red line) and mixed-venous blood (violet line). Despite the severe respiratory acidosis, the decrease in total CO2 content between the mixed-venous and arterial blood is normal (4 mL/dL). The lower panel of B shows comparable plots for how total O2 content varies with image at the pH and image values of mixed-venous blood (violet curve) and arterial blood (red curve). Despite the severe hypoxia, the increase in total O2 content between the mixed-venous and arterial blood is normal (5 mL/dL).

N31-19

Analysis of image Patterns in Figure 31-14

Contributed by Emile Boulpaep, Walter Boron

The following is a discussion of Figure 31-14 that is more complete than the material presented in the subsection “Alveolar Dead-Space Ventilation Affecting One Lung” (see pp. 693–696).

Figure 31-14 is a highly simplified example that illustrates the principles underlying how alveolar dead-space ventilation affects the handling of CO2 and O2. Except as noted below in this paragraph, all assumptions and parameter values for this example are the same as for the normal case in Figure 31-13. imageN31-18 The key difference in the example in Figure 31-14 is that the left lung receives no perfusionalveolar dead-space ventilation. The total image remains at 5 L/min, but all of this perfusion goes to the right lung. Notice that the image of 4.2 L/min is evenly distributed between the two lungs. Thus, the image of the left lung is 2.1/0 or ∞, whereas the image of the right lung is 2.1/5 or 0.42. The overall image remains 0.84. Can the low image of the normal lung make up for the high image of the abnormal lung?

CO2 Handling

First consider the fate of CO2 in the following seven steps (see Fig. 31-14):

Step 1: In the steady state, the normal right lung must eliminate the entire complement of metabolically produced CO2 production, which is 200 mL/min. This rate of CO2 delivery to the right lung is twice its normal level.

Step 2: In the right lung, the normal image of 2.1 L/min must now dilute twice the normal amount of CO2. Thus, alveolar image in this right lung must be twice normal (i.e., ~80 mm Hg).

Step 3: Because no blood is flowing to the left lung, its alveolar image is the same as the image of inspired air (i.e., ~0 mm Hg). Half of the alveolar air that the subject expires comes from the right lung, and half comes from the left lung. Thus, the mean image is (80 + 0)/2 = 40 mm Hg, which is normal! As we will see below, this mean alveolar image is important for computing the alveolar-arterial (A-a) difference (see Box 31-1).

Step 4: Because the transport of CO2 across the blood-gas barrier is perfusion limited (see pp. 671–673), the blood leaving the right lung has a image that is the same as the alveolar image of the right lung, 80 mm Hg. Because no blood exits from the left lung, the systemic arterial blood also has a image of 80 mm Hg. According to the CO2 dissociation curve, a image of 80 mm Hg (which represents a substantial degree of respiratory acidosis) corresponds to a CO2 content of ~67 mL/dL (see lower panel of Fig. 31-14A, point a).

Step 5: In the systemic capillaries, metabolically produced CO2 enters the blood at the rate of 200 mL/min. As we already know from our analysis of the normal condition in Figure 31-13A, adding 200 mL CO2 to 5 liters of blood increases the CO2 content by 4 mL/dL:

image

(NE 31-44)


Thus, the CO2 content of the blood at the end of the systemic capillaries will be 67 + 4 = 71 mL/dL.

Step 6: According to the CO2 dissociation curve, when the CO2 content of the blood is 71 mL/dL, the mixed-venous image must be 87 mm Hg (see lower panel of Fig. 31-14A, point image).

Step 7: As the blood completes the cycle and passes through the pulmonary capillaries of the right lung, the image falls from 87 mm Hg back to its original value of 80 mm Hg. Simultaneously, the CO2 content falls from 71 mL/dL to its original value of 67 mL/dL as CO2 evolves into the alveolar air at the rate of 200 mL/min.
Thus, even with a severe image abnormality, the lung is able to expel the usual 200 mL/min of CO2, but at a tremendous price: a very high arterial image and thus respiratory acidosis (see p. 633).

O2 Handling

Now consider the fate of O2 (see Fig. 31-14B):

Step 1: The normal right lung must deliver all the O2 required by the body, 250 mL/min. This rate of O2 abstraction from the right lung is twice normal.

Step 2: Because the image ratio of the normal right lung is so low (i.e., half normal), the alveolar image in the right lung must be far lower than the usual value of ~100 mm Hg. Because the image in this lung is 80 mm Hg and RQ is 0.8, we use the alveolar gas equation (see Equation 31-17) to compute a image of 51 mm Hg.

Step 3: Because no blood flow goes to the left lung, its image is ∞, and thus its alveolar image is the same as the image of inspired air (i.e., 149 mm Hg). The mean image of air expired from the two lungs is (51 + 149)/2 = 100 mm Hg and thus is normal—just as the mean image was normal.

Step 4: Because the transport of O2 across the blood-gas barrier is perfusion limited (see pp. 671–673), the image of the blood leaving the right lung is the same as the alveolar image of the right lung, 51 mm Hg. Because no blood exits from the left lung, the systemic arterial blood has the same image as the blood leaving the right lung, namely 51 mm Hg. From the O2 dissociation curve, we see that a image of 51 mm Hg dictates an O2 content of only 14 mL/dL (see lower panel of Fig. 31-14B, point a).

Step 5: In the systemic capillaries, O2 leaves the blood at the rate of 250 mL/min. As we already know from our analysis of Figure 31-13B, removing 250 mL of O2 from 5 L of blood decreases the O2 content by 5 mL/dL:

image

(NE 31-45)


Thus, the O2 content of the blood at the end of the systemic capillaries will be 14 − 5 = 9 mL/dL.

Step 6: According to the O2 dissociation curve, when the O2 content is 9 mL/dL, the mixed-venous image must be 37 mm Hg (see lower panel of Fig. 31-14B, point image).

Step 7: As the blood completes the cycle and passes through the pulmonary capillaries of the right lung, the image rises from 37 to 51 mm Hg, and the O2 content rise from 9 to 14 mL/dL as O2 enters from the alveolar air at the rate of 250 mL/min.

Thus, even with a severe image abnormality, the lung is able to import the usual 250 mL/min of O2, but at a tremendous price: a very low arterial image (hypoxia).

Beware that this analysis, as complicated as it may seem, is highly oversimplified. For example, in step 4 and step 6 of the CO2 analysis, we used a standard CO2 dissociation curve. However, we know that hypoxia will increase the CO2-carrying capacity of blood (Haldane effect; see p. 657). Similarly, in step 4 and step 6 of the O2 analysis, we used a standard O2 dissociation curve. However, we know that respiratory acidosis will decrease the O2-carrying capacity of blood (the Bohr effect; see p. 652). Nevertheless, the take-home message is clear. Even if overall image and image are normal, an uneven distribution of perfusion leads to respiratory acidosis and hypoxia. Thus, the hyperperfused “good” lung cannot make up for the deficit incurred by the hypoperfused “bad” lung. In our example, the fundamental problem is that ventilating unperfused alveoli in the left lung reduces the effective alveolar ventilation by half.

The normal right lung must now eliminate all of the CO2 that the body produces—that is, the right lung must eliminate CO2 at twice the rate that it normally does. However, the right lung has its usual image of 2.1 L/min. Because a normal amount of alveolar air must carry away twice as much CO2 in the new steady state, the right lung's alveolar image doubles to ~80 mm Hg (see Fig. 31-14A). Because the entire cardiac output perfuses the normal right lung, arterial image is also ~80 mm Hg. Thus, even with the severe image abnormality produced by alveolar dead-space ventilation, the lung is able to expel the usual 200mL/min of CO2, but at a tremendous price: a very high arterial image and thus respiratory acidosis.

The normal right lung must also supply all of the body's O2—delivering O2 to the blood at twice its normal rate. However, because the right lung still has its normal image of 2.1 L/min, its alveolar image falls to ~51 mm Hg in the new steady state. The blood leaving the right lung, which is identical to systemic arterial blood, also has a image of ~51 mm Hg. Thus, even with a severe image abnormality, the lung is able to import the usual 250mL/min of O2, but at a tremendous price: a very low arterial image (hypoxia).

We can now answer the question that we posed above. The hyperperfused “good” lung cannot make up for the deficit incurred by the hypoperfused “bad” lung. In our example, the fundamental problem was that the ventilation of unperfused alveoli in the left lung effectively reduced the alveolar ventilation by half. In real life, the body would have compensated both locally and systemically. Locally, bronchiolar constriction and decreased surfactant production in the abnormal left lung (see Fig. 31-11B) would diminish alveolar dead-space ventilation and increase the effective alveolar ventilation to the normal right lung. Systemically, as we discuss in the next chapter, the respiratory acidosis and hypoxia would stimulate chemoreceptors to increase ventilation. If the body could double image to the right lung—and if this right lung has a normal diffusing capacity—then it would be matching the doubled perfusion of the right lung with a doubled ventilation, and all resting blood-gas parameters would return to normal. imageN31-16

N31-16

Surgical Removal of One Lung

Contributed by Walter Boron

As we saw in Figure 30-10, O2 reaches diffusion equilibrium about one third of the way down the pulmonary capillary of a healthy young adult at rest. If one of the two lungs were removed surgically, the remaining lung would receive twice its normal complement of blood flow. However, provided that alveolar ventilation, image, PB, and DL were normal, diffusion equilibrium for O2 would still occur before the end of the pulmonary capillary. If the ventilation-perfusion relationship were also normal for this subject, then arterial image would be normal—at least at rest. However, during exercise, O2 transport could well become diffusion limited. Moreover, if DL were substantially below normal, or if image relationships were problematic, then the subject could exhibit arterial hypoxemia even at rest. Therefore, in patients considered for total pneumonectomy, it is critical to evaluate pulmonary function preoperatively to confirm that the patient would be able to survive postoperatively with the remaining lung.

A massive pulmonary embolism that obstructs the left pulmonary artery is superficially similar to the example that we have just discussed. However, other associated problems (e.g., right heart failure secondary to an increase in pulmonary vascular resistance, release of vasoactive agents) make the pulmonary embolism potentially fatal.

Shunt Affecting One Lung

Imagine that an object occludes the left mainstem bronchus, eliminating all ventilation to the left lung. Total image remains at 4.2 L/min, but all ventilation goes to the right lung. Thus, the image to the left lung is 0/2.5 or 0, whereas the image to the right lung is 4.2/2.5 or 1.68. The overall image is normal, 0.84. Again, the key question is whether a combination of a low image in the abnormal lung and a high image in the normal lung can yield normal blood-gas levels.

The normal right lung must now eliminate CO2 at twice its normal rate. However, the right lung also has twice its normal image. Because twice the normal amount of alveolar air carries away twice the normal amount of CO2, the right lung's new steady-state alveolar image is normal, ~40 mm Hg (Fig. 31-15A). The blood leaving the normal lung also has a image of ~40 mm Hg. However, the unventilated lung has the image of mixed-venous blood, ~51 mm Hg in this example. After the two streams of blood mix—known as venous admixture, because venous blood combines with blood from ventilated alveoli—arterial blood in the left ventricle has a CO2 content that is midway between the CO2 contents of the two streams of blood, corresponding to an arterial image of ~46 mm Hg. Thus, even with the severe image abnormality produced by shunt, the lung is once again able to expel the usual 200mL/min of CO2, but once again at a price: a high arterial image (respiratory acidosis).

image

FIGURE 31-15 Shunt. imageN31-20 The numbers in this idealized example refer to a time after the individual has achieved a new steady state. In the upper panels of A and B, the light beige boxes give the alveolar ventilation to each lung as well as the total alveolar ventilation (image). The pink boxes give the blood flow to each lung as well as the total cardiac output (image). The white boxes give the rates of CO2 or O2 transport (in mL/min) at either the pulmonary or systemic capillaries. The blue boxes give the CO2 and O2 partial pressures (in mm Hg) in alveolar air. The lavender boxes give the CO2 partial pressure (in mm Hg) and CO2 content (in mL/dL) in the mixed-venous blood, in the blood leaving each of the lungs, and in the mixed-arterial blood. The dark beige boxes give the same information for O2. The lower panel of A shows plots of how total CO2 content in this example varies with image at the Hb-O2 saturations for unshunted blood at the end of the pulmonary capillary (red line), for shunted/mixed-venous blood (violet line), and for mixed-arterial blood (green line). Because of the 50% shunt, the decrease in total CO2 content between mixed-venous blood (point image) and unshunted blood (point c) must be twice normal (8 mL/dL) to produce a normal decrease (4 mL/dL) between mixed-venous blood (point image) and mixed-arterial blood (point a). The lower panel of B shows comparable plots for how total O2 content varies with image at the pH and image values of mixed-venous blood (violet curve), arterial blood (red curve), and for mixed-arterial blood (green curve). Because of the 50% shunt, the increase in total O2 content between mixed-venous blood (point image) and unshunted blood (point c) must be twice normal (10 mL/dL) to produce a normal increase (5 mL/dL) between mixed-venous blood (point image) and mixed-arterial blood (point a).

N31-20

Analysis of image Patterns in Figure 31-15

Contributed by Emile Boulpaep, Walter Boron

The following is a discussion of Figure 31-15 that is more complete than the material presented in the subsection “Shunt Affecting One Lung” (see pp. 696–698).

Figure 31-15 is a highly simplified example that illustrates the principles underlying how a shunt affects the handling of CO2 and O2. Except as noted below in this paragraph, all assumptions and parameter values for this example are the same as for the normal case in Figure 31-13. imageN31-18 The key difference in the example in Figure 31-15 is that the left lung receives no ventilation—shunt. The total image remains 4.2 L/min, but all of this ventilation goes to the right lung. Notice that the image of 5 L/min is evenly distributed between the two lungs. Thus, the image of the left lung is 0/2.5 or 0, whereas the image of the right lung is 4.2/2.5 or 1.68. Can the high image of the hyperventilated right lung make up for the low image of the unventilated left lung?

CO2 Handling

First, we will consider the fate of CO2 in the following nine steps (see Fig. 31-15A):

Step 1: In the steady state, the normal right lung must eliminate the entire metabolic production of CO2, 200 mL/min. This rate of CO2 delivery to the right lung is twice normal.

Step 2: The twice-normal amount of CO2 is diluted into a twice-normal image of 4.2 L/min, so that the alveolar image in this right lung must be normal (i.e., 40 mm Hg).

Step 3: Because no air flow goes to the left lung, the air distal to the obstruction in the left lung will have the same image and the same image as mixed-venous blood. However, because this air is not in direct communication with atmosphere, it does not contribute to the mean alveolar image of the expired air. Thus, the mean image is simply the image of the alveolar air in the right lung, 40 mm Hg, which is normal!

Step 4: Because the transport of CO2 across the blood-gas barrier is perfusion limited (see pp. 671–673), the blood leaving the right lung has a image that is the same as the alveolar image on the right, 40 mm Hg. According to the CO2 dissociation curve, when the blood has a image of 40 mm Hg, it must have a CO2 content of 48 mL/dL (see lower panel of Fig. 31-15A, point c). This is the CO2 content after the right lung has extracted CO2 at the rate of 200 mL/min.

Step 5: What was the CO2 content of the blood before the CO2 was extracted? That is, what was the mixed-venous image? According to the Fick principle, the change in CO2 content as the blood passes through the right lung is simply the rate of CO2 extraction divided by the blood flow:

image

(NE 31-46)


Normally (see Fig. 31-13A), the CO2 content of the pulmonary-capillary blood would fall by only 4 mL/dL as it equilibrated with the alveolar air. However, because the rate of CO2 extraction is twice normal, the decrease in CO2 content is also twice normal. Thus, the mixed-venous CO2 content must be 48 + 8 = 56 mL/dL. From the CO2 dissociation curve, we see that this CO2 content corresponds to a mixed-venous image of 51 mm Hg (see lower panel of Fig. 31-15A, point image). Notice that the alveolar air in the obstructed left lung has a image of 51 mm Hg, the same as that of the mixed-venous blood.

Step 6: What happens when the blood from the hyperventilated right lung mixes with the shunted blood from the unventilated left lung? Although one might be tempted to average the two image values (i.e., 40 and 51 mm Hg), this is a mistaken instinct. Instead, one must average the two CO2 contents. As we noted above, the CO2 content of blood emerging from the right lung is 48 mL/dL. The CO2 content of blood emerging from the left lung is the same as for the mixed-venous blood we examined in the previous step, 56 mL/dL. Thus, the mixed arterial CO2 content is (48 + 56)/2 = 52 mL/dL (see lower panel of Fig. 31-15A, point a).

Step 7: According to the CO2 dissociation curve, a CO2 content of 52 mL/dL corresponds to an arterial image of 46 mm Hg (see lower panel of Fig. 31-15A, point a).

Step 8: In the systemic capillaries, adding 200 mL/min of CO2 to 5 L of blood increases the CO2 content by 4 mL/dL, raising the CO2 content from 52 mL/dL (lower panel of Fig. 31-15A, point a) to 56 mL/dL (see lower panel of Fig. 31-15A, point image). Notice that 56 mL/dL is the mixed-venous value we arrived at above in step 5.

Step 9: According to the CO2 dissociation curve, a CO2 content of 56 mL/dL corresponds to a mixed-venous image of 51 mm Hg (see lower panel of Fig. 31-15A, point image). This is the same value that we arrived at above in step 5.

Thus, even with the severe image abnormality represented by shunt, the lung is once again able to expel the usual 200 mL/min of CO2, but once again at a price: a high arterial image (respiratory acidosis). Because there is a image mismatch in this example, we expect there to be an alveolar-arterial (A-a) difference for image.imageN31-17 Because the mean alveolar image is 40 mm Hg, and the arterial image is 46 mm Hg in our example, the A-a difference is 40 − 46 or −6 mm Hg.

O2 Handling

The changes in O2 handling are more extreme (see Fig. 31-15B).

Step 1: The normal right lung must deliver all the O2 required by the body, 250 mL/min. This rate of O2 abstraction from the right lung is twice normal.

Step 2: Because the image ratio of the normal right lung is twice normal, and the O2 extraction rate is twice normal, we would expect the alveolar image in the right lung to be the normal value of ~100 mm Hg. Put differently, because the inspired image (i.e., 149 mm Hg), the alveolar image of the right lung (i.e., 40 mm Hg), and the RQ (i.e., 0.8) are all normal, the alveolar gas equation (see Equation 31-17) yields a normal image for the right lung, ~100 mm Hg.

Step 3: Of course, the image in the unventilated left lung (image = 0) is the same as the image of mixed-venous blood. However, because this air is not in direct communication with atmosphere, it does not contribute to the mean alveolar image of the expired air. Thus, the mean image is simply the image of the alveolar air in the right lung, ~100 mm Hg, which is normal!

Step 4: Because the transport of O2 across the blood-gas barrier is perfusion limited (see pp. 671–673), the image of the blood leaving the right lung is the same as the image in the right lung, ~100 mm Hg. Thus, according to the O2 dissociation curve, the O2 content of this blood must be 20mL/dL (see lower panel of Fig. 31-15B, point c). This value is the O2 content after the right lung has added O2 at the rate of 250 mL/min.

Step 5: What was the O2 content of the mixed-venous blood? According to the Fick principle, the increase in O2 content as the blood passes through the right lung is simply the rate of O2 extraction divided by the blood flow. Normally (see Fig. 31-15B), the O2 content would rise by only 5 mL/dL as the blood equilibrated with the alveolar air. However, because the rate of O2 extraction from the lung is twice normal, the increase in O2 content is also twice normal:

image

(NE 31-47)


Thus, the mixed-venous O2 content must be 10 mL/dL less than the O2 content of the end-capillary blood (i.e., 20 mL/dL). The mixed-venous O2 content is thus 20 − 10 = 10 mL/dL. From the O2 dissociation curve, we see that this O2 content corresponds to a mixed-venous image of 29 mm Hg (see lower panel of Fig. 31-15B, point image). The alveolar air in the obstructed left lung has a image of 29 mm Hg, the same as that of the mixed-venous blood.

Step 6: What happens when the blood from the hyperventilated right lung mixes with the shunted blood from the unventilated left lung? One must average the O2 contents of the blood emerging from the right and left lungs. As we noted above, the O2 content of blood emerging from the right lung is 20 mL/dL. The O2 content of blood emerging from the left lung is the same as for the mixed-venous blood we examined in the previous step, 10 mL/dL. Thus, the mixed arterial O2 content is (20 + 10)/2 = 15 mL/dL (see lower panel of Fig. 31-15B, point a).

Step 7: From the O2 dissociation curve, we see that a mixed-arterial O2 content of 15 mL/dL corresponds to a image of ~40 mm Hg (see lower panel of Fig. 31-15B, point a).

Step 8: In the systemic capillaries, the tissues extract 250 mL/min of O2. Removing 250 mL of O2 from 5 L of blood decreases the O2 content by 5 mL/dL. Thus, the O2 content of the blood at the end of the systemic capillaries will be 15 − 5 = 10 mL/dL. This is the same value we arrived at in step 5 (see lower panel of Fig. 31-15B, point image).

Step 9: According to the O2 dissociation curve, an O2 content of 10 mL/dL corresponds to a mixed-venous image of 29 mm Hg (see lower panel of Fig. 31-15B, point image). This is the same figure we arrived at in step 5.

Thus, even with the severe image abnormality represented by shunt, the lung is able to import the usual 250 mL/min of O2, but at a price: an extremely low arterial image (hypoxia).

The A-a difference for image in this example is 100 − 40 = 60 mm Hg, which indicates a image mismatch of considerable magnitude. In this extreme example, we entirely eliminated airflow to one lung. Less extreme instances of uneven distribution of airflow will lead to less severe degrees of respiratory acidosis and hypoxia.

Again, beware that this example, like the ones in Figure 31-13 and Figure 31-14, is highly oversimplified. Nevertheless, it is clear that even if overall image is normal, and even if the distribution of perfusion is normal, an uneven distribution of ventilation leads to respiratory acidosis and hypoxia. Thus, the overventilated “good” lung cannot make up for the deficit incurred by the underventilated “bad” lung. One fundamental problem is that blood with a normal gas composition from the hyperventilated good lung mixes with shunted blood with a high image and low image. The consequences are perhaps easiest to grasp for O2 transport. The blood leaving the normal right lung has a normal O2 content. The shunted blood leaving the unventilated left lung has a very low O2 content, which is the same as that of mixed-venous blood. Thus, the mixed-arterial blood must have a low O2 content and must be hypoxic.

A second fundamental problem is that—because of the shape of the Hb-O2 dissociation curve—hyperventilating a good lung cannot proportionally increase the O2 content of the blood leaving that lung. What would happen if the subject were to hyperventilate? Not much. It is true that increasing alveolar ventilation might increase the right alveolar image above its starting value of 100 mm Hg. However, because the Hb is already 97.5% saturated with O2 at a image of 100 mm Hg, the added ventilation would do little good. The subject would remain hypoxic.

The normal right lung must also deliver O2 to the blood at twice the normal rate. However, because the right lung's image is also twice its usual value, its new steady-state alveolar image is normal, ~100 mm Hg. The blood leaving the right lung also has a image of ~100 mm Hg, a hemoglobin (Hb) saturation (image) of ~97.5%, and an O2 content of ~20 mL/dL. However, the unventilated lung has a image of mixed-venous blood, ~29 mm Hg in this example. Thus, the blood leaving the shunted lung has an image of ~49% and an O2 content of ~10 mL/dL. After venous admixture, arterial O2 content is (20 + 10)/2 or 15 mL/dL, which corresponds to an arterial image (image) of 73 and a image of ~40 mm Hg. Thus, even with the severe image abnormality caused by shunt, the lung is able to import the usual 250mL/min of O2, but at the price of an extremely low arterial image (hypoxia).

Why did the image mismatch caused by shunt lead to only a mild respiratory acidosis but a severe hypoxia? The fundamental problem is that the Hb-O2 dissociation curve (see Fig. 29-3) is nearly saturated at the normal arterial image. If O2 content were proportional to image, then mixing unshunted blood (image = 100 mm Hg) with shunted blood (image = 29 mm Hg) would have yielded arterial blood with a image of (100 + 29)/2 = ~65 mm Hg, which is far higher than the arterial image of ~40 mm Hg in our example.

In our example, shunt would trigger compensation at two levels. Locally, hypoxic vasoconstriction would divert blood to well-ventilated alveoli. Systemically, an increase in image would lower image and raise image in the normal right lung. In fact, even a modest increase in image would be sufficient to lower arterial image to 40 mm Hg. However, even if image approached infinity (raising the right lung's alveolar image to the inspired image of ~149 mm Hg), arterial image would still be well under 100 mm Hg. In fact, even if the inspired air were 100% O2, the arterial image would still fail to reach 100 mm Hg; because of the shape of the Hb-O2dissociation curve, an increased alveolar image can increase the O2 content of arterial blood only marginally (Box 31-1).

Box 31-1

Clinical Approaches for Diagnosing a image Mismatch

Rather simple diagnostic methods are available for detecting the presence of a image mismatch, assessing its severity, and identifying a shunt.

Diagnosis of Exclusion

The physician can often diagnose a pathological nonuniformity of image by excluding other possibilities. In general, low arterial image—under basal metabolic conditions—could be due to a reduced inspired image (e.g., high altitude), reduced alveolar ventilation, decreased diffusing capacity (DL), or image mismatch. Let us assume that arterial image is appropriate for the altitude (see p. 681) and that results of simple spirometric tests indicate that respiratory mechanics are normal. Because DL is normally about 3-fold greater than necessary for achieving diffusion equilibrium for O2 and CO2 (see pp. 671–672), a problem with DL is unlikely in the absence of a positive history. By default, the most likely cause is a image defect.

Alveolar-Arterial Gradient for O2

The difference between the mean alveolar image and the systemic arterial image is known as the alveolar-arterial (A-a) gradient for image. In our “normal” example in Figure 31-13B, both mean alveolar image and arterial image were 100 mm Hg. In real life, however, physiological image mismatches cause arterial image to be 5 to 15 mm Hg below the mean alveolar value.

A defining characteristic of image mismatches is that they widen the A-a image gradient. In our example of alveolar dead space in Figure 31-14B, the mean alveolar image was (51 + 149)/2 = 100 mm Hg, whereas the systemic arterial image was 51 mm Hg, for an A-a gradient of 49 mm Hg. In our example of shunt in Figure 31-15B, the mean alveolar image was 100 mm Hg, whereas the arterial image was only 40 mm Hg—an A-a gradient of 60 mm Hg.

Because the A-a gradient for image is an index of the severity of the image mismatch, physicians routinely estimate the A-a gradient in the intensive care unit. The approach is to (1) obtain the arterial blood-gas levels, which include image and image; (2) assume that the mean image is the same as the measured image; (3) use the alveolar gas equation (see Equation 31-17) to compute the mean image from mean image; and (4) compute the difference image − image. However, the assumption in point 2 is not entirely true because image mismatches cause an A-a gradient for CO2 just as they do for O2. imageN31-17

N31-17

Alveolar-Arterial Differences for CO2 (Robin Test)

Contributed by Emile Boulpaep, Walter Boron

image mismatches lead not only to an alveolar-arterial (A-a) difference in image, but also to an A-a difference in the CO2 partial pressure (Robin test). In our example of alveolar dead space (see Fig. 31-14A), the A-a difference for CO2 was 40 − 80 or −40 mm Hg, and in our example of shunt (see Fig. 31-15A), it was 40 − 46 or −6 mm Hg. A-a differences for CO2 are smaller than those for O2 both because alveolar image values are lower and because the CO2 dissociation curve is more linear. Clinicians generally do not use the image A-a difference as an index of a image mismatch. In fact, they generally assume that the mean alveolar image is identical to the arterial image, and they use this value in the alveolar gas equation (see Equation 31-17) for computing the mean alveolar image needed to determine the A-a difference for image.

Effect of Breathing 100% O2

Once a image mismatch has been identified, it is important to distinguish between a shunt, which might be corrected surgically, and other causes. Imagine two patients with similar degrees of hypoxia. In the first patient, one lung is relatively hypoventilated (low image) and the other lung is relatively hyperventilated (high image). However, no alveoli are shunted. In the second patient, a complete shunting of blood makes one lung totally unventilated (a image of zero, as in Figure 31-15). The normal lung has a high image. We can distinguish between the two cases by having both subjects inspire 100% O2.

When the patient without predominant shunt breathes 100% O2, the image of the blood leaving both lungs will be far higher than normal (Fig. 31-16A). Blood leaving the hypoventilated lung has a image somewhat lower than that of the blood leaving the hyperventilated lung. However, because the image is on the flat part of the Hb-O2 dissociation curve in both cases, the image values are virtually identical. The miniscule difference in O2 contents between the two streams of blood is due to a difference in dissolved O2. Thus, the mixed systemic arterial blood will have a slightly elevated O2 content, an image of ~100%, and a markedly elevated image.

image

FIGURE 31-16 Analyzing image mismatch by administering 100% O2. Sat, saturation. The image values are in mm Hg, and the image values are in mL/dL.

The situation is very different in the patient with a severe shunt (see Fig. 31-16B). Because blood leaving the shunted lung does not equilibrate with the alveoli ventilated with 100% O2, it has the low imageimage, and O2 content characteristic of mixed-venous blood. Although blood leaving the normal lung will have an extremely high image, both the image and O2 content will be only slightly above normal—like the hyperventilated lung in Figure 31-16A. Thus, when one stream of blood with a slightly increased O2 content (“normal” lung) mixes with another stream with a markedly decreased O2 content (“shunted” lung), the mixed-systemic arterial blood has a lower-than-normal O2 content. This low O2 content translates to a low image and thus to a low systemic arterial image. Thus, unlike subjects with other kinds of image mismatches that do not include substantial shunt (e.g., alveolar dead-space ventilation in Fig. 31-14), those with substantial shunt have low arterial image values, even while breathing 100% O2. Because breathing 100% O2 greatly increases mean alveolar image without substantially increasing arterial image, this maneuver greatly exaggerates the A-a difference for image.

Mixed image Mismatches

Pathological image mismatches cause the range of image ratios to broaden beyond the physiological range. Some alveoli may be true alveolar dead space (i.e., perfusion absent, image = ∞), but others may be more modestly underperfused. Some alveoli may be totally shunted (i.e., ventilation absent, image = 0), but others may be more modestly underventilated. Thus, the left ventricle receives a mixture of blood from alveoli with image ratios from ∞ to zero, corresponding to all of the points along the O2-CO2 diagram in Figure 31-10B. What is the composition of this mixed blood? The principles that we developed in our simplified examples of alveolar dead-space ventilation and shunt still hold. Even if total image and total image remain normal, pathologically high image ratios in some alveoli cannot make up for pathologically low ratios in others, and vice versa. The result of uncompensated pathological image mismatching is always respiratory acidosis and hypoxia.