Dynamics: Setting the System in Motion

The Flow-Volume Loop and Flow Limitation

We have now reached the point at which we can integrate all of the isolated physical principles we have been describing with respect to flow through tubes and apply them to the specific circumstance of air movement in the lungs. As we develop the concepts of the flow–volume loop and flow limitation, you may find it useful to refer to the discussion of one or more of the principles outlined earlier in the chapter.

The Volume-Time Plot ↑

To measure the total amount of gas exhaled by a person, you ask her to breathe in until she cannot get any more into her lungs (she is now at total lung capacity [TLC]), and then exhale as hard and fast as possible until she cannot blow out any more (she is now at residual volume [RV]). The volume of the exhaled gas is the vital capacity (VC). To see how to plot the graph of volume versus time, look at Figure 4-11. Notice that the curve is steeper at the beginning (near zero exhaled volume) than near the end when the VC maximum is complete. The slope of the curve at any point along the graph is equal to the flow at that point (flow = ΔVolume/ΔTime).

Consider a new way of plotting this information. Take the flow, as determined from the slope of the volume–time plot at each point of the curve, and plot that flow as a function of the absolute volume at which it occurred (Fig. 4-12).

The patient is asked, at the end of a normal exhalation (functional residual capacity [FRC]), to take a deep breath in to TLC and then breathe out as hard and fast as possible until no more air will come out of the lung (i.e., RV). The resulting plot gives us an instant visualization of the inspiratory and expiratory flow at all lung volumes. Notice that the expiratory flow is greatest at the beginning of the expiratory maneuver and then gradually declines until RV is reached. The VC can be calculated as the distance between TLC and RV on the volume axis.

Two elements of this graph must be emphasized and understood to avoid confusion at a later time. First, each point along the outer line of the graph (i.e., the maximal forced maneuver) represents the maximal flow at a given volume. Second, time is not explicitly represented in this graph. Looking at the graph alone, you cannot determine whether the maneuver took 1 or 10 seconds. It is not possible, for example, to calculate from this graph how much air was exhaled during the first second of the expiratory maneuver (a quantity called the forced expiratory volume in 1 second [FEV1]). Failure to remember these points will lead to errors in interpreting data from flow–volume loops in clinical practice.

Use Animated Figure 4-12A to see the flow–volume plot (upper left) being traced during normal inspiration and expiration. A spirogram is also shown (center), providing an overview of the changes in lung volume translated onto a rotating roll of paper. Observe as the subject performs a forced vital capacity (FVC) maneuver and pay attention to the shape and time course of the resulting plots. Note how much air is exhaled in the first second of the forced maneuver. There is a great deal going on in this diagram, and you may find it helpful to watch the video as it loops and then pause it to use the timeline scrubber to move back and forth.

Animated Figure 4-12B demonstrates that the expiratory volume-time plot and flow-volume plot are simply different viewpoints on a forced expiration. Upon initial viewing of the three-dimensional diagram, the first graph that appears is a flow-volume plot (shown on the left as a shaded surface and on the right as a line graph, analogous to the upper half of Figure 4-12). Note that the maximal flows occur at high lung volumes but also observe that this perspective has no time axis, so we cannot tell what fraction of air was exhaled in the first second. Now drag the 'Horizontal' slider all the way to the left, and you will see the flow-time plot come into view. Again, note how flow is maximal very near the beginning of the forced expiration and then declines slowly over the course of the expiration.

Now drag the 'Vertical' slider all the way to the right, and you will see the volume-time plot come into view (analogous to Figure 4-11). Observe that the steepest slope is near the beginning of expiration, and this corresponds to the time when flow is maximal (the flow is equal to the slope of the volume-versus-time graph).

Maximal Expiratory Flow: The Forces to be Considered ↑

As discussed earlier in this chapter, flow through a tube is determined by the driving pressure (i.e., the difference in pressure between the two ends of the tube) and the resistance of the tube. The difference in pressure along the tube is determined by the equation

When considering the driving pressure during a forced exhalation, we must examine the factors that determine alveolar pressure (one end of the tube). The other end of the tube is the mouth, where the pressure is always equal to atmospheric pressure, or 0 by convention. The alveolar pressure is the result of the elastic recoil of the lung and the pleural pressure.

Elastic recoil of the lung is determined by the intrinsic properties of the lung, and, for a given lung, by the volume of the lung. The greater the lung tissue is stretched, the greater the elastic recoil forces. Surface forces, related partly to the density of surfactant in the surface layer, as discussed in Chapter 3, also contribute to the recoil of the alveoli. The density of surfactant in the surface layer tends to be less at TLC than at lower lung volumes during exhalation. Surface forces, therefore, are greatest at TLC. The pleural pressure during exhalation is determined by the position of the chest wall relative to its relaxation volume and the stiffness or recoil of the chest wall. In addition, you must consider the forces that can be generated by the expiratory muscles. Pleural pressure is greatest (most positive) when a person attempts to do a forced exhalation from TLC. At this volume, the chest wall is farthest above its relaxation volume, and the expiratory muscles are at their greatest length (hence, in the best position to generate tension). Consequently, alveolar pressure, and therefore, driving pressure, is greatest at TLC.

The resistance of the airways varies with their diameter. The cross-sectional area of the airways, particularly the small airways, varies with the size of the lung. The greater the lung volume, the greater is the diameter of the airways. Thus, airway resistance is least when the lung volume is at TLC. Taken together, the factors that determine driving pressure and the resistance of the lung explain why expiratory flow is maximal at TLC.

Expiratory Flow Limitation ↑

As you view Figure 4-12, you notice that the flow diminishes as lung volume decreases. Part of this decrease in flow is because of the fact that the driving pressure decreases as lung volume declines; the elastic recoil of the lungs and chest wall is less at lower lung volumes, and the expiratory muscles are shorter, thereby reducing their potential to generate tension. Furthermore, the airway resistance increases as lung volume declines because the size of the small airways depends on the pull of the surrounding lung tissue. But what if you could strengthen your expiratory muscles? Could you generate a flow at FRC that would equal the flow at TLC? To answer this question, we must take a closer look at what happens to the transmural pressure across the airways during a forced exhalation.

Imagine you are at a lung volume between FRC and TLC. You begin a forced exhalation. The expiratory muscles contract, squeezing the pleural space and raising pleural pressure, thereby generating a maximal pressure in the alveolus. A pressure differential between the alveolus and the mouth now exists, and air exits the alveolus to begin its journey to the mouth. The gas exits the alveolus at a flow determined by the driving pressure and the resistance of the airway; assume that this initial flow is constant until the gas exits the mouth. As the gas moves along the bronchial tree toward the mouth, a loss of pressure occurs because of airway resistance, the increasing velocity (remember the Bernoulli effect and the analogy of the multiple one-lane highways merging into a single two-lane highway), and the transition from laminar flow in the peripheral airways to the turbulent flow of the central airways (see Quick Check 4-3).

As pressure within the airway declines, you may eventually arrive at a point at which the pressure inside the airway is the same as the pressure outside the airway (pressure outside the airway is essentially equal to pleural pressure); at that point, transmural pressure is 0. Any further loss of pressure within the airway leads to a negative transmural pressure and the compression or collapse of the airway. The point at which transmural pressure of the airway is 0 is called the EPP (recall the Starling resistor) because the pressure inside and outside the airway are now the same. If the EPP occurs in the most central airways of the lung, as is the case in normal, healthy lungs, where the walls of the airway are largely supported by cartilage, the effects of a negative transmural pressure are minimized. In contrast, if the EPP occurs in the small, peripheral airways, as may be the case in diseased lungs (e.g., in emphysema), the development of a negative transmural pressure leads to collapse of the airway (Fig. 4-13).

If the EPP occurs in a relatively unsupported airway and collapse occurs, flow essentially stops. As we described in our discussion of the Starling resistor, when flow ceases, static conditions are established in the airway, and the pressure equalizes between the alveolus and the EPP. Transmural pressure is now positive again, and the airway opens. Flow is reestablished, and pressure in the airway decreases, which again leads to the development of the EPP.

As soon as the EPP has occurred, the driving pressure that determines flow is no longer the difference in pressure between the alveolus and the mouth. Rather, the driving pressure is now the difference between alveolar pressure and pleural pressure as the airway cycles between open and closed states. Trying to exhale more forcefully by increasing the force of contraction of the muscles, and thereby the pleural pressure, has no effect. If pleural pressure increases, alveolar pressure, which is the sum of elastic recoil pressure and pleural pressure, must increase by the same amount; the driving pressure remains the same (Fig. 4-14). Under these conditions, one has achieved flow limitation, that is, maneuvers to produce an increase in pleural pressure do not yield an increase in flow. When flow limitation is present, the driving pressure is equal to the elastic recoil of the alveolus.

Whether EPP develops in a peripheral or central airway depends on the difference between the alveolar pressure and the pleural pressure at the beginning of the expiratory maneuver. The difference between alveolar and pleural pressure is the elastic recoil pressure. Thus, elastic recoil pressure is the determining factor for the location of the EPP. To the extent that the exhalation is at a lower lung volume, EPP is more likely to be in the peripheral airways. In disease states such as emphysema, in which the elastic recoil of the lungs is diminished, the likelihood of reaching EPP in the peripheral airways is increased for any lung volume (Fig. 4-15).

Use Animated Figure 4-15 to observe the effect of elastic recoil on the location of the EPP. Before playing the animations, compare emphysema with the normal state by using the selection buttons and the slider and observe the difference in the elastic recoil pressures (magnitude of the arrow shown in alveolus). Use the slider to watch the animations and notice how the lower elastic recoil pressure for emphysema leads to an EPP in more peripheral airways. If you have a keyboard, you can also click the textbox or slider and then use the up and down arrows (press or press and hold) to move through the animation. Remember that the animations are of forced expirations, so pleural pressure starts out negative (for the initial static state, with negative pressure shown as the arrow pointing away from the alveolus) and rapidly becomes positive as the expiratory muscles apply force.

Presence of Flow Limitation on the Flow-Volume Loop ↑

The flow-volume loop is one of the essential elements of the tests of clinical pulmonary function. A firm understanding of the physiology underlying this test is critical for assessing a range of lung diseases.

Developing the Flow-Volume Loop

To begin, take a deep breath in until you have reached TLC and then exhale as hard and as fast as you can until you are at RV. Collect and measure the volume of exhaled gas and plot the volume as a function of time (see Fig. 4-11). The slope of the curve, which represents flow (ΔV/Δt), is most steep at the beginning of the exhalation, when you are exhaling near TLC. In contrast, as you near RV, the slope gradually diminishes.

As we described previously, by plotting the instantaneous slope as a function of absolute volume, you can generate a graph that represents maximal flows for all volumes during the expiratory maneuver. Recall that the amount of gas exhaled during the forced expiratory maneuver (from TLC to RV) is the forced vital capacity (FVC). (Fig. 4-16, also see Animated Figure 4-12A)

Once you have reached RV, if you inspire as hard and fast as you can back to TLC and again plot the flow as a function of lung volume, you have created the inspiratory portion of the curve. If you now relax and breathe normally, you will see a smaller curve within the envelope of the maximal inspiratory and expiratory maneuvers (Fig. 4-17).

Each point on the outer curve represents the maximal flow achievable at a given lung volume. Recall that time is not represented on this graph. You cannot calculate the FEV₁ from this graph. We are visualizing only flow at different lung volumes.

As you examine the normal flow-volume loop, observe the following. First, the maximal expiratory flow is somewhat greater than the maximal inspiratory flow. Second, the maximal inspiratory flow occurs approximately halfway between RV and TLC, but the maximal expiratory flow is very close to TLC. Third, the decline in flow from the point of maximal flow until the end of exhalation is relatively linear. To understand these findings, we need to consider the forces (i.e., muscle contraction, recoil of the lung, and recoil of the chest wall) that generate a pressure differential across the airways and the factors that impede flow (i.e., resistance, size of airways, turbulence). We will use the principles we have outlined in the early sections of this chapter.

Expiratory flow is maximal near TLC when recoil inward of the lungs and chest wall is greatest, when the muscles of exhalation are longest and thus best able to generate tension, and when the airways are at their greatest diameter. Maximal inspiratory flow is achieved at a lung volume that represents a tradeoff between the length of the inspiratory muscles (longest at RV), the recoil of the chest wall outward (greatest at RV) and the lung inward (least at RV), and the diameter of the airways (smallest at RV). The decline in the maximal expiratory flow with decreasing lung volume, known as expiratory flow limitation, reflects the balance of airway and pleural pressures, that is, the transmural pressure across the airways.

Expiratory Flow Limitation: Passive Versus Forced Exhalation

We will now reexamine the concept of flow limitation and use it to understand the shape of the flow-volume loop. Some of this may seem repetitive, but these are important concepts for the interpretation of pulmonary function tests and for a full appreciation of normal physiology as well as the pathophysiology of obstructive lung disease.

First, let us examine a passive exhalation from a lung volume approximately 0.5 L above FRC, that is, at the end of a normal resting inhalation (see part A of Animated Figure 4-13 below). At the start of the expiration, alveolar pressure is 0 because we are under static conditions (no flow) with the airway open. As previously described, during the expiration, alveolar pressure is positive because of the recoil of the lung (secondary to elastic and surface forces), and pleural pressure is slightly negative because of the opposing forces of the lung and chest wall. The difference in pressure between the alveolus and the mouth propels air into the airway. As air moves along the airway from the alveolus to the mouth, the gas has to overcome resistance, leading to a loss of pressure in the airway. In addition, as air proceeds from millions of small peripheral airways to a lesser number of more central airways, the velocity of the gas must increase for flow to be constant. In accord with Bernoulli's principle, this results in a further loss of pressure within the airway. Finally, as you transition from laminar to turbulent flow in the central airways, an even greater pressure differential (in other words, pressure decrease), is necessary to maintain a constant flow. Thus, as air travels from the alveolus to the mouth during the expiratory maneuver, the intra-airway pressure progressively diminishes. The pleural pressure, which surrounds the alveolus and the airways, is negative throughout the entire passive exhalation near FRC because the chest wall is below its resting volume and is recoiling outward. As a result, there is always a positive transmural pressure (pressure inside greater than pressure outside) across the airway despite the loss of pressure within the airways. Flow is unencumbered by collapse of airways. Use part A of Animated Figure 4-13 to view a passive expiration, and pay special attention to the transmural pressure (difference between pressure inside the alveolus or airway and pressure outside, or pleural pressure). Think about the following questions before you continue reading the text: What would be different about pleural pressure during a forced expiration? How might this affect transmural pressure?

Now contrast the passive exhalation with what occurs during a forced expiratory maneuver that begins near TLC (see part B of Animated Figure 4-13). The pleural pressure at the very beginning of the maneuver (static state) is negative, a consequence of the collapsing force on the lung and the net expanding force on the chest wall at this volume (inspiratory muscles pulling out on the chest wall; elastic recoil of the chest wall inward at TLC). Taken together, these forces tend to pull apart the pleural surfaces. The recoil pressure of the lungs is approximately 30 cm H₂O at TLC.

The expiratory muscles are now activated. Assume that the pleural pressure during the forced expiration reaches 60 cm H₂O (note: pleural pressure is now positive because the chest wall is above its resting volume and is recoiling inward and because you are activating expiratory muscles to squeeze the chest wall, pleura, and lungs). This means that the pressure within the alveolus (recall: P_alv = P_el + P_pl) reaches 90 cm H₂O. As before, we assume a constant flow must be maintained from the alveolus to the mouth.

The pressure around the airway, as already noted, is essentially equivalent to the pleural pressure. For the purpose of this analysis, the pleural pressure may be viewed as constant throughout the thorax. The pressure in the alveolus is greater than the pressure in the pleural space (P_alv = P_el + P_pl), but as the pressure in the airway diminishes with the flow of gas from alveolus to mouth, one may now reach a point at which the pressure inside and outside the airway are the same (in our example, the airway pressure has decreased from 90 to 60 cm H₂O). This point, known as the EPP, is the point at which transmural pressure across the airway is 0. Use part B of Animated Figure 4-13 to view the change in pressures during a forced expiration starting from TLC (only shown up through development of the initial EPP), and pay special attention to the location where the airway pressure first becomes equal to pleural pressure. If the airway were an infinitely flexible tube, as we examined with the Starling resistor, the airway would now collapse, and flow would cease. Pressure in the airway would then equalize with the alveolus (static conditions in place), the transmural pressure would become positive, the airway would reopen, and flow would be reinstituted. As soon as flow of gas was restarted, however, the EPP would reappear, and the cycle would repeat.

As soon as the EPP has been established, further increases in pleural pressure (i.e., blowing more forcefully) does not lead to an increase in expiratory flow. Although the increase in pleural pressure will increase the alveolar pressure and thus, the intra-airway pressure, it also increases the pressure surrounding the airway (see Fig. 4-14). Consequently, transmural pressure is not altered. To the extent that further increases in pleural pressure do not yield greater expiratory flow, these conditions are sometimes termed effort independence. At the EPP, the driving pressure is no longer the alveolar pressure minus the pressure at the airway opening. As noted in the Starling resistor analogy, the driving pressure is now the alveolar pressure minus the pleural pressure.

The concept of the EPP depends on conceptualizing the airways as highly flexible, similar to a Starling resistor. However, we know from Chapter 2 that the central airways of the lung, especially the trachea, are supported by cartilaginous rings that help resist deformation when transmural pressure is negative (i.e., pressure outside greater than pressure inside the airway). What determines whether the EPP occurs within a flexible peripheral airway or a supported central airway?

The key factor in determining where along the airway the EPP will occur for a given pulmonary resistance and pulmonary compliance is the difference between the alveolar pressure and the pleural pressure. When the difference between these pressures is large, gas will travel a long distance toward the mouth before losing sufficient pressure to achieve EPP. Alternatively, if the alveolar pressure and the pleural pressure are nearly the same, a small decrease in pressure will result in EPP. The difference between alveolar pressure and pleural pressure is the elastic recoil pressure. For a given lung, elastic recoil pressure changes in concert with the volume of the lung; at higher lung volumes, elastic recoil pressure is greater. Therefore, EPP tends to occur toward the supported, central airways when gas is exiting the alveolus at high lung volumes and in the peripheral, unsupported airways when gas exits the alveolus at low lung volumes. Take another look at Animated Figure 4-13, this time paying special attention to the lung elastic recoil pressure (shown above each lung). Note how the lower elastic recoil pressure in part C leads to an EPP in the more peripheral, unsupported airways.

Flow Limitation and the Flow–Volume loop

Given what you have just learned, reexamine Figure 4-17. The vast majority of the expiratory flow–volume loop (the portion to the right of the peak flow) is constrained by the principles of flow limitation. What does this mean? Pick a point on the maximal expiratory flow curve to the right of the peak flow. At that flow and that lung volume, further increases in expiratory effort (or pleural pressure) will not result in a higher flow. If you pick a point near RV, the flow at which flow limitation is present is very low, much lower than at a volume near FRC. Stated differently, the same expiratory effort at FRC may yield a greater flow than at RV. As discussed, this is largely because of the differences in the elastic recoil pressure at these two lung volumes. New experimental data suggest that even at lung volumes near TLC, we may be flow limited as well.

Emphysema and the Flow–Volume loop

In emphysema, lung tissue is destroyed and the elastic recoil of the lung is reduced. This process has several effects on the factors that determine expiratory flow. As you may recall, the small, flexible, peripheral airways are supported by the recoil of the lung tissue through which they pass (review Animated Figure 4-9). This support helps to prevent narrowing of the airways when transmural pressure is negative, as occurs during a forced exhalation. With the weakening of these supports, the small airways are more likely to collapse under these circumstances.

Elastic recoil pressure is one of the major determinants of alveolar pressure. Therefore, a reduction in elastic recoil reduces the driving pressure during exhalation. Furthermore, the location of the EPP (i.e., whether it will occur toward the more central airways or be found in the small, peripheral airways) is largely determined by the difference between the alveolar pressure and the pleural pressure. A smaller difference, which results from a lower elastic recoil pressure, predisposes to the movement of the EPP toward the alveolus regardless of the lung volume. Both of these factors contribute to the development of dynamic compression (reversible narrowing of airways that results from changes in transmural pressures during exhalation) of the airways at higher lung volumes than is seen in normal individuals. Consequently, in a patient with emphysema, flow limitation may exist at any given lung volume between TLC and RV.

The flow–volume loop also takes a different shape in patients with emphysema. The initial peak flow is lower than normal because of the reduced driving pressure seen in the alveolus at TLC and because, even at TLC, there may be dynamic compression of the airways. In addition, the expiratory flows decrease rapidly at lung volumes below TLC because of further narrowing of the airways. As a result, the expiratory curve, rather than appearing fairly linear from the peak flow to RV, takes on a concave-upward appearance, termed expiratory coving (Fig. 4-18).

The inspiratory portion of the curve is relatively normal in appearance. During inspiration, transmural pressure across the airways is positive. Therefore, the loss of elastic recoil does not disturb inspiratory flow.

Time Constants ↑

A time constant is a measure of how well gas is moved in and out of alveoli. A large time constant implies that it takes a long time to exchange gas between the atmosphere and the alveolus; a short time constant implies a rapid exchange. The time constant can be conceptualized as the product of the airway resistance and the lung compliance.

An area of lung in which the airway resistance is high will have a large time constant because it will take longer for air to move into and out of that region of the lung for any given driving pressure (i.e., flow will be reduced). An area of lung with a high compliance (i.e., with reduced elastic recoil) will have a large time constant because the elastic recoil of the lung is a primary determinant of the driving pressure during exhalation; expiratory flow will be reduced.

Let us consider a clinical example to demonstrate the implications of this concept. You ask a person to breathe 100% oxygen. What happens to the mixture of gases in the alveolus? Just before the first breath of oxygen, the alveolus contains mostly nitrogen, some oxygen, and a small amount of carbon dioxide. The amount of gas in the lungs at FRC may be 3 to 4 L, depending on the size and age of the person. The individual now inhales a tidal volume (approximately 0.5 L) of 100% oxygen. Even if the lungs are normal, the gas in the alveolus will not immediately reflect the change in the concentration of gases in the inspired air. It will take several minutes before the nitrogen has been washed out of the lungs (recall the nitrogen washout technique for measuring FRC in Chapter 3). If the time constant of the lungs is very high, it may take 15 to 20 minutes before the gas in the alveoli reflects the change in the concentrations of the inspired gases.

The notion of time constants is used to conceptualize certain properties of the lung (you will never be asked to calculate the time constant in a clinical setting). Because most diseases of the lung are heterogeneous in their distribution, we tend to speak of the time constant for a region of lung rather than the lung as a whole. For example, a patient with emphysema has some areas of the lung that are relatively normal and other areas that are quite abnormal because of the disease process.

The concept of time constants offers us another physiologic explanation for the shape of the flow–volume loop in a patient with emphysema (see Fig. 4-18). Assuming a heterogeneous distribution of time constants throughout the lung, the units with a relatively normal time constant will have high expiratory flows and will empty first during the forced exhalation (the high flows near TLC). Next, the units that are only mildly affected will empty with intermediate flows. Finally, the most diseased units will empty very slowly with low flows (the flows seen near RV).