Chapter 2. Mechanics of Breathing

The reader understands the mechanical properties of the lung and the chest wall during breathing.

• Describes the generation of a pressure gradient between the atmosphere and the alveoli.
• Describes the passive expansion and recoil of the alveoli.
• Defines the mechanical interaction of the lung and the chest wall, and relates this concept to the negative intrapleural pressure.
• Describes the pressure-volume characteristics of the lung and the chest wall, and predicts changes in the compliance of the lung and the chest wall in different physiologic and pathologic conditions.
• States the roles of pulmonary surfactant and alveolar interdependence in the recoil and expansion of the lung.
• Defines the functional residual capacity (FRC), and uses his or her understanding of lung-chest wall interactions to predict changes in FRC in different physiologic and pathologic conditions.
• Defines airways resistance and lists the factors that contribute to or alter the resistance to airflow.
• Describes the dynamic compression of airways during a forced expiration.
• Relates changes in the dynamic compliance of the lung to alterations in airways resistance.
• Lists the factors that contribute to the work of breathing.
• Predicts alterations in the work of breathing in different physiologic and pathologic states.

Air, like other fluids, moves from a region of higher pressure to one of lower pressure.

Under normal circumstances, inspiration is accomplished by causing alveolar pressure to fall below atmospheric pressure. When the mechanics of breathing are being discussed, atmospheric pressure is conventionally referred to as 0 cm H2O, so lowering alveolar pressure below atmospheric pressure is known as negative-pressure breathing. As soon as a pressure difference sufficient to overcome the resistance to airflow offered by the conducting airways is established between the atmosphere and the alveoli, air flows into the lungs. It is also possible to cause air to flow into the lungs by raising the pressure at the nose and mouth above alveolar pressure. This positive-pressure ventilation is generally used on patients unable to generate a sufficient pressure difference between the atmosphere and the alveoli by normal negative-pressure breathing. Air flows out of the lungs when alveolar pressure is sufficiently greater than atmospheric pressure to overcome the resistance to airflow offered by the conducting airways.

During normal negative-pressure breathing, alveolar pressure is made lower than atmospheric pressure. This is accomplished by causing the muscles of inspiration to contract, which increases the volume of the alveoli, thus lowering the alveolar pressure according to Boyle law. (See Appendix II: The Laws Governing the Behavior of Gases.)

Passive Expansion of Alveoli

Negative Intrapleural Pressure

The pressure in the thin space between the visceral and parietal pleura is normally slightly subatmospheric, even when no inspiratory muscles are contracting. This negative intrapleural pressure (sometimes also referred to as negative intrathoracic pressure) of –3 to –5 cm H2O is mainly caused by the mechanical interaction between the lung and the chest wall. At the end of expiration, when all the respiratory muscles are relaxed, the lung and the chest wall are acting on each other in opposite directions.

Initially, before any airflow occurs, the pressure inside the alveoli is the same as atmospheric pressure—by convention 0 cm H2O. Alveolar pressure is greater than intrapleural pressure because it represents the sum of the intrapleural pressure plus the alveolar elastic recoil pressure:

Alveolar pressure = intrapleural pressure + alveolar elastic recoil pressure

The muscles of inspiration act to increase the volume of the thoracic cavity. The outside of the lung (the visceral pleura) adheres to the inside of the chest wall (the parietal pleura). As the inspiratory muscles contract, expanding the thoracic volume and increasing the outward stress on the lung, the intrapleural pressure becomes more negative. Therefore, the transmural pressure difference tending to distend the alveolar wall (sometimes called the transpulmonary pressure) increases as shown in Figure 2–1, and the alveoli enlarge passively. Increasing alveolar volume lowers alveolar pressure and establishes the pressure gradient for airflow into the lung. In reality, only a small percentage of the total number of alveoli are directly exposed to the intrapleural surface pressure, and at first thought, it is difficult to see how alveoli located centrally in the lung could be expanded by a more negative intrapleural pressure. However, analysis has shown that the pressure at the pleural surface is transmitted through the alveolar walls to more centrally located alveoli and small airways. This structural interdependence of alveolar units is depicted in Figure 2–2.

Note that in Figure 2–1, the inward alveolar elastic recoil calculated by the equation above is equal to the transmural pressure difference. This is true under static conditions, but they may differ slightly during a breath as the alveoli are stretched.

The Muscles of Respiration

Inspiratory Muscles

The muscles of inspiration include the diaphragm, the external intercostals, and the accessory muscles of inspiration, which include the sternocleidomastoid, the trapezius, and the muscles of the vertebral column.

The Diaphragm

The diaphragm is a large (about 250 cm2 in surface area) dome-shaped muscle that separates the thorax from the abdominal cavity. As mentioned in Chapter 1, the diaphragm is considered to be an integral part of the chest wall and must always be considered in the analysis of chest wall mechanics.

The diaphragm is the primary muscle of inspiration. When a person is in the supine position, the diaphragm is responsible for about two thirds of the air that enters the lungs during normal quiet breathing (which is called eupnea). (When a person is standing or seated in an upright posture, the diaphragm is responsible for only about one third to one half of the tidal volume.) It is innervated by the 2 phrenic nerves, which leave the spinal cord at the third through the fifth cervical segments.

The muscle fibers of the diaphragm are inserted into the sternum and the 6 lower ribs and into the vertebral column by the two crura. The other ends of these muscle fibers converge to attach to the fibrous central tendon, which is also attached to the pericardium on its upper surface (Figure 2–3). During normal quiet breathing, contraction of the diaphragm causes its dome to descend 1 to 2 cm into the abdominal cavity, with little change in its shape. This elongates the thorax and increases its volume. These small downward movements of the diaphragm are possible because the abdominal viscera can push out against the relatively compliant abdominal wall. During a deep inspiration, the diaphragm can descend as much as 10 cm. With such a deep inspiration, the limit of the compliance of the abdominal wall is reached, abdominal pressure increases, and the indistensible central tendon becomes fixed against the abdominal contents. After this point, contraction of the diaphragm against the fixed central tendon elevates the lower ribs (Figure 2–3).

If one of the leaflets of the diaphragm is paralyzed (eg, because of transection of one of the phrenic nerves), it will “paradoxically” move up into the thorax as intrapleural pressure becomes more negative during a rapid inspiratory effort.

The External Intercostals

When they are stimulated to contract, the external intercostal, parasternal intercostal, and scalene muscles raise and enlarge the rib cage. The parasternal muscles, which are usually considered part of the internal intercostals, are inspiratory muscles and may be partly responsible for raising the lower ribs. The scalene muscles appear to contract in normal quiet breathing and are therefore not accessory muscles. Figure 2–4 demonstrates how contraction of these muscles increases the anteroposterior dimension of the chest as the ribs rotate upward about their axes and also increases the transverse dimension of the lower portion of the chest. These muscles are innervated by nerves leaving the spinal cord at the first through the 11th thoracic segments. During inspiration, the diaphragm and inspiratory rib cage muscles contract simultaneously. If the diaphragm contracted alone, the rib cage muscles would be pulled inward (this is called retraction). If the inspiratory muscles of the rib cage contracted alone, the diaphragm would be pulled upward into the thorax.

The Accessory Muscles of Inspiration

The accessory muscles of inspiration are not involved during normal quiet breathing but may be called into play during exercise; during the inspiratory phase of coughing or sneezing; or in a pathologic state, such as asthma. For example, the sternocleidomastoid elevates the sternum and helps increase the anteroposterior and transverse dimensions of the chest. Dyspnea, the feeling that breathing is difficult, may sometimes result from fatigue of the inspiratory muscles. Other potential causes of dyspnea will be discussed in Chapter 9.

Expiratory Muscles

Expiration is passive during normal quiet breathing, and no respiratory muscles contract. As the inspiratory muscles relax, the increased elastic recoil of the distended alveoli is sufficient to decrease the alveolar volume and raise alveolar pressure above atmospheric pressure. Now the pressure gradient for airflow out of the lung has been established.

Although the diaphragm is usually considered to be completely relaxed during expiration, it is likely that some diaphragmatic muscle tone is maintained, especially when one is in the horizontal position. The inspiratory muscles may also continue to contract actively during the early part of expiration, especially in obese people. This so-called braking action may help maintain a smooth transition between inspiration and expiration. It may also be important during speech production.

Active expiration occurs during exercise, speech, singing, the expiratory phase of coughing or sneezing, and in pathologic states such as chronic bronchitis. The main muscles of expiration are the muscles of the abdominal wall, including the rectus abdominis, the external and internal oblique muscles, the transversus abdominis, and the internal intercostal muscles.

The Abdominal Muscles

When the abdominal muscles contract, they increase abdominal pressure and push the abdominal contents against the relaxed diaphragm, forcing it upward into the thoracic cavity. They also help depress the lower ribs and pull down the anterior part of the lower chest.

The Internal Intercostal Muscles

Contraction of the internal intercostal muscles depresses the rib cage downward in a manner opposite to the actions of the external intercostals.

Summary of the Events Occurring during the Course of a Breath

The events occurring during the course of an idealized normal quiet breath, which are summarized in Table 2–1, are shown in Figure 2–5. For the purpose of clarity, inspiration, and expiration are considered to be of equal duration, although during normal quiet breathing, the expiratory phase is 2 to 3 times longer than the inspiratory phase, that is, the normal I:E ratio is 1:2 to 1:4 in eupneic breathing.

The volume of air entering or leaving the lungs can be measured with a spirometer, as will be described in Chapter 3 (Figure 3–4). Airflow can be measured by breathing through a pneumotachograph, which measures the instantaneous pressure difference across a fixed resistance. The intrapleural pressure can be estimated by having a subject swallow a balloon into the intrathoracic portion of the esophagus. The pressure then measured in the balloon is nearly equal to intrapleural pressure. Alveolar pressures are not directly measurable and must be calculated.

Initially, alveolar pressure equals atmospheric pressure, and so no air flows into the lung. Intrapleural pressure is –5 cm H2O. Contraction of the inspiratory muscles causes intrapleural pressure to become more negative as the lungs are pulled open and the alveoli are distended. Note the 2 different courses for changes in intrapleural pressure. The dashed line (which would not really be straight for reasons discussed in the next section) predicts the changes in intrapleural pressure necessary to overcome the elastic recoil of the alveoli. The solid line is a more accurate representation of intrapleural pressure because it also includes the additional pressure work that must be done to overcome the resistance to airflow and tissue resistance discussed later in this chapter. As the alveoli are distended, the pressure inside them falls below atmospheric pressure and air flows into the alveoli, as seen in the tidal volume panel. As the air flows into the alveoli, alveolar pressure returns to 0 cm H2O and airflow into the lung ceases. At the vertical line (at 2 seconds), the inspiratory effort ceases and the inspiratory muscles relax. Intrapleural pressure becomes less negative, and the elastic recoil of the alveolar walls (which is increased at the higher lung volume) compresses the alveolar gas. This raises alveolar pressure above atmospheric pressure so that air flows out of the lung until an alveolar pressure of 0 cm H2O is restored. At this point, airflow ceases until the next inspiratory effort.

The relationship between changes in the pressure distending the alveoli and changes in lung volume is important to understand because it dictates how easily the lung inflates with each breath. As mentioned before, the alveolar-distending pressure is often referred to as the transpulmonary pressure. Strictly speaking, the transpulmonary pressure is equal to the pressure in the trachea minus the intrapleural pressure. Thus, it is the pressure difference across the whole lung. However, the pressure in the alveoli is the same as the pressure in the airways—including the trachea—at the beginning or end of each normal breath, that is, end-expiratory or end-inspiratory alveolar pressure is 0 cm H2O (Figure 2–5). Therefore, at the beginning or end of each lung inflation, alveolar-distending pressure can be referred to as the transpulmonary pressure.

Compliance of the Lung and the Chest Wall

The pressure-volume characteristics of the lung can be inspected in several ways. One of the simplest is to remove the lungs from an animal or a cadaver and then graph the changes in volume that occur for each change in transpulmonary pressure the lungs are subjected to (Figure 2–6).

Figure 2–6 shows that as the transpulmonary pressure increases, the lung volume increases.

The slope between 2 points on a pressure-volume curve is known as the compliance. Compliance is defined as the change in volume divided by the change in pressure. Lungs with high compliance have a steep slope on their pressure-volume curves; that is, a small change in distending pressure will cause a large change in volume. It is important to remember that compliance is the inverse of elastance, elasticity, or elastic recoil. Compliance denotes the ease with which something can be stretched or distorted; elastance refers to the tendency for something to oppose stretch or distortion, as well as to its ability to return to its original configuration after the distorting force is removed.

There are several other interesting things to note about an experiment like that illustrated in Figure 2–6. The curve obtained is the same whether the lungs are inflated with positive pressure (by forcing air into the trachea) or with negative pressure (by suspending the lung, except for the trachea, in a closed chamber and pumping out the air around the lung). So when the lung alone is considered, only the transpulmonary pressure is important, not how the transpulmonary pressure is generated. As was seen in Figure 2–2A and B, when the lungs and chest wall are considered together, generation of the transmural pressure difference by positive pressure does have effects different from generation of the transmural pressure difference by negative pressure. A second feature of the curve in Figure 2–6 is that there is a difference between the pressure-volume curve for inflation and the curve for deflation, as shown by the arrows. Such a difference is called hysteresis. One possible explanation for this hysteresis is the stretching on inspiration and the compression on expiration of the film of surfactant that lines the air-liquid interface in the alveoli (discussed later in this chapter). Surfactant has less effect on decreasing surface tension during inspiration than during expiration because of movement of surfactant molecules from the interior of the liquid phase to the surface during inspiration. Another explanation is that some alveoli or small airways may open on inspiration (“recruitment”) and close on expiration (“derecruitment”); the recruitment of collapsed alveoli or small airways requires energy and may be responsible for the lower inflection point seen on some inspiratory pressure-volume curves (see the air inflation curve in Figure 2–8). Finally, it is helpful to think of each alveolus as having its own pressure-volume curve like that shown in Figure 2–6, although some researchers believe that lung volume changes primarily by recruitment and derecruitment of alveoli rather than by volume changes of individual alveoli.

It may be surprising that there is no general agreement about what happens to alveoli as lung volume changes. As was shown in Figure 2–2, all alveoli could expand approximately equally during inspiration or some could expand more than others (eg, those closest to the pleura during negative-pressure breathing; those more centrally located during positive-pressure ventilation). As stated above, some researchers believe that most of the changes in lung volume during normal breathing occur by recruitment and derecruitment of unopened alveoli, with little change in volume of those already open, or by changes in the size of alveolar ducts with little change in alveolar volume at all. Whether alveoli expand by simply increasing the length of alveolar septae or opening folded areas or pleats is also not agreed upon.

Clinical Evaluation of the Compliance of the Lung and the Chest Wall

The compliance of the lung and the chest wall provides very useful data for the clinical evaluation of a patient’s respiratory system because many diseases or pathologic states affect the compliance of the lung, of the chest wall, or both. The lung and the chest wall are physically in series with each other, and therefore their compliances add as reciprocals:

Conversely, the elastances of the lung and chest wall add directly.

Compliances in parallel add directly. Therefore, both lungs together are more compliant than either one alone; 2 alveoli in parallel are similarly more compliant than 1 alone.

To make clinical determinations of pulmonary compliance, one must be able to measure changes in pressure and in volume. Volume changes can be measured with a spirometer, but measuring pressure changes is more difficult because changes in the transmural pressure difference must be taken into account. For the lungs, the transmural pressure difference is transpulmonary pressure (alveolar minus intrapleural); for the chest wall, the transmural pressure difference is intrapleural pressure minus atmospheric pressure. As described previously, intrapleural pressure can be measured by having the patient swallow an esophageal balloon. The compliance curve for the lung can then be generated by having the patient take a very deep breath and exhale in stages, stopping periodically for pressure and volume determinations. During these determinations, no airflow is occurring; alveolar pressure therefore equals atmospheric pressure, 0 cm H2O. Similar measurements can be made as the patient inhales in stages from a low lung volume to a high lung volume. Such curves are called static compliance curves because all measurements are made when no airflow is occurring. The compliance of the chest wall is normally obtained by determining the compliance of the total system and the compliance of the lungs alone and then calculating the compliance of the chest wall according to the above formula. Dynamic compliance, in which pressure-volume characteristics during the breath are considered, will be discussed later in this chapter.

Representative static compliance curves for the lungs are shown in Figure 2–7. Note that these curves correspond to the expiratory curve in Figure 2–6. Many pathologic states shift the curve to the right (ie, for any increase in transpulmonary pressure there is less of an increase in lung volume). A proliferation of connective tissue called fibrosis may be seen in sarcoidosis or after chemical or thermal injury to the lungs. Such changes will make the lungs less compliant, or “stiffer,” and increase alveolar elastic recoil. Similarly, pulmonary vascular engorgement or areas of collapsed alveoli (atelectasis) also make the lung less compliant. Other conditions that interfere with the lung’s ability to expand (such as the presence of air, excess fluid, or blood in the intrapleural space) will effectively decrease the compliance of the lungs. Emphysema increases the compliance of the lungs because it destroys the alveolar septal tissue that normally opposes lung expansion.

The compliance of the chest wall is decreased in obese people, for whom moving the diaphragm downward and the rib cage up and out is much more difficult. People suffering from a musculoskeletal disorder that leads to decreased mobility of the rib cage, such as kyphoscoliosis, also have decreased chest wall compliance. Other conditions that can decrease the compliance of the chest wall include ossification of costal cartilage, skin scars from burn injuries, and abdominal distension.

Because they must generate greater transpulmonary pressures to breathe in the same volume of air, people with decreased compliance of the lungs must do more work to inspire than those with normal pulmonary compliance. Similarly, more muscular work must be done by someone with decreased chest wall compliance than by a person with normal chest wall compliance. In both cases, the person would be likely to breathe at a greater rate with a smaller tidal volume (the volume of air coming into and out of the respiratory system per breath).

As noted in the beginning of this section, lung compliance is volume-dependent. It is greater at low lung volumes and lower at high lung volumes. For this reason, the term specific compliance is often used to denote compliance with reference to the original lung volume.

The total compliance of a normal person near the normal end-expiratory lung volume (the functional residual capacity [FRC]) is about 0.1 L/cm H2O. The compliance of the lungs is about 0.2 L/cm H2O; that of the chest wall is also about 0.2 L/cm H2O.

Elastic Recoil of the Lung

The elastic recoil of the lungs is partly due to the elastic properties of the pulmonary parenchyma itself. Elastin is more compliant or distensible and is important at low or normal lung volumes. Collagen is less compliant or distensible and is not usually stressed until lung volume is large. However, there is another component of the elastic recoil of the lung besides the elastin, collagen, and other constituents of the lung tissue. That other component is the surface tension at the air-liquid interface in the alveoli.

Surface tension is a force that occurs at any gas-liquid interface (or even interfaces between 2 immiscible liquids) and is generated by the cohesive forces between the molecules of the liquid. These cohesive forces balance each other within the liquid phase but are unopposed at the surface of the liquid. Surface tension is what causes water to bead and form droplets. It causes a liquid to shrink to form the smallest possible surface area. The unit of measurement of surface tension is dynes per centimeter (dyn/cm).

The role of the surface tension forces in the elastic recoil of the lung can be demonstrated in an experiment such as that shown in Figure 2–8.

In this experiment, a pressure-volume curve for an excised lung was generated as was done in Figure 2–6. Because the lung was inflated with air, an air-liquid interface was present in the lung, and surface tension forces contributed to alveolar elastic recoil. Then, all the gas was removed from the lung, and it was inflated again, this time with saline instead of with air. In this situation, surface tension forces are absent because there is no air-liquid interface. The elastic recoil is due only to the elastic recoil of the lung tissue itself. Note that there is no hysteresis with saline inflation. Whatever causes the hysteresis appears to be related to surface tension in the lung. To recapitulate, the curve at left (saline inflation) represents the elastic recoil due to only the lung tissue itself. The curve at right demonstrates the recoil due to both the lung tissue and the surface tension forces. The difference between the 2 curves is the recoil due to surface tension forces.

The demonstration of the large role of surface tension forces in the recoil pressure of the lung led to consideration of how surface tension affects the alveoli. One traditional way of thinking about this has been to consider the alveolus to be a sphere hanging from the airway, as in Figure 2–9. The relationship between the pressure inside the alveolus and the wall tension of the alveolus would then be given by Laplace’s law (units in parentheses).

This can be rearranged as

The surface tension of most liquids (such as water) is constant and not dependent on the surface area of the air-liquid interface. Consider what this would mean in the lung, where alveoli of different sizes are connected to each other by common airways and collateral ventilation pathways (described in Chapter 1). If 2 alveoli of different sizes are connected by a common airway (Figure 2–10) and the surface tension of the 2 alveoli is equal, then according to Laplace’s law, the pressure in the small alveolus must be greater than that in the larger alveolus and the smaller alveolus will empty into the larger alveolus. If surface tension is independent of surface area, the smaller the alveolus on the right becomes, the higher the pressure in it.

Thus, if the lung were composed of interconnected alveoli of different sizes (which it is) with a constant surface tension at the air-liquid interface, it would be expected to be inherently unstable, with a tendency for smaller alveoli to collapse into larger ones. Normally, this is not the case, which is fortunate because collapsed alveoli require very great distending pressures to reopen, partly because of the cohesive forces at the liquid-liquid interface of collapsed alveoli. At least 2 factors cause the alveoli to be more stable than this prediction based on constant surface tension. The first factor is a substance called pulmonary surfactant, which is produced by specialized alveolar cells, and the second is the structural interdependence of the alveoli.

Pulmonary Surfactant

The surface tension of a liquid can be measured with an apparatus like that shown in Figure 2–11.

The liquid to be inspected is placed in the trough. The movable barrier (denoted by the arrow at right) allows a determination of the role of the surface area of the air-liquid interface on surface tension. The surface tension is measured by the downward force on the platinum strip, which is suspended from the force transducer.

The results of a series of such experiments are shown in Figure 2–12. The surface tension properties of water, water after the addition of detergent, and lung extract are plotted with respect to the relative surface area of the trough seen in Figure 2–11. Water has a relatively high surface tension (about 72 dyn/cm) that is completely independent of surface area of the air-liquid interface. Addition of detergent to the water decreases the surface tension, but it is still independent of surface area. “Lung extract,” which was obtained by washing out with saline the liquid film that lines the alveoli, displays both low overall surface tension and a great deal of area dependence. Its maximum surface tension is about 45 dyn/cm, which occurs at high relative surface areas. At low relative areas, the surface tension falls to nearly 0 dyn/cm. Furthermore, the lung extract also displays a great deal of hysteresis, similar to that seen in Figures 2–6 and 2–8.

From these data, it can be concluded that the alveolar surface contains a component that lowers the elastic recoil due to surface tension, even at high lung volumes.

The surface-active component of the lung extract is called pulmonary surfactant. It is a complex consisting of about 85% to 90% lipids and 10% to 15% proteins. The lipid portion is about 85% phospholipid, approximately 75% of which is phosphatidylcholine, mainly dipalmitoyl phosphatidylcholine. There are 4 specific surfactant proteins: SP-A, SP-B, SP-C, and SP-D. Surfactant is manufactured by specialized alveolar cells known as type II alveolar epithelial cells (see Chapters 1 and 10). SP-A and SP-D do not appear to be important in surfactant’s function of decreasing surface tension, but seem to be important components of the host defense response of innate immunity. Both bind to bacteria, viruses, mycobacteria, and fungi, and enhance phagocytosis and the release of mediators of the immune response by macrophages. Surfactant B, which is necessary for surfactant function, helps arrange phospholipids into lamellar bodies, form tubular myelin and surface films, and assists the entry of phospholipids into the surface monolayer as the alveoli expand during inspiration (see Figure 10–6). The function of SP-C is not known. Pulmonary surfactant appears to be continuously produced in the lung, but it is also continuously used up in or cleared from the lung. Some pulmonary surfactant is taken back into the type II cells (reuptake), where it is recycled and secreted again, or it is degraded and used to synthesize other phospholipids. Other surfactant is cleared from the alveoli by alveolar macrophages, absorption into the lymphatics, or migration up to the small airways and the mucociliary escalator (see Chapter 10). Although the alveolar surface is usually considered to be completely lined with liquid, some studies have shown that the surface consists of both dry areas and wet areas.

The clinical consequences of a lack of functional pulmonary surfactant can be seen in several conditions. Surfactant is not produced by the fetal lung until about the fourth month of gestation, and it may not be fully functional until the seventh month or later. Prematurely born infants who do not have functional pulmonary surfactant experience great difficulty in inflating their lungs, especially on their first breaths. Even if their alveoli are inflated for them, the tendency toward spontaneous collapse is great because their alveoli are much less stable without pulmonary surfactant. Therefore, the lack of functional pulmonary surfactant in a prematurely born neonate may be a major factor in the infant respiratory distress syndrome. Pulmonary surfactant may also be important in maintaining the stability of small airways.

Hypoxia or hypoxemia (low oxygen in the arterial blood), or both, may lead to a decrease in surfactant production, surfactant inactivation, or an increase in surfactant destruction. This condition may be a contributing factor in the acute respiratory distress syndrome (also known as adult respiratory distress syndrome or “shock-lung syndrome”) seen in patients after trauma or surgery. One thing that can be done to help maintain patients with acute or infant respiratory distress syndrome is to ventilate their lungs with positive-pressure ventilators and to keep their alveolar pressure above atmospheric pressure during expiration (this is known as positive end-expiratory pressure). This process opposes the increased elastic recoil of the alveoli and the tendency for spontaneous atelectasis to occur because of a lack of pulmonary surfactant. Exogenous pulmonary surfactant is now administered directly into the airway of neonates with infant respiratory distress syndrome.

In summary, pulmonary surfactant helps decrease the work of inspiration by lowering the surface tension of the alveoli, thus reducing the elastic recoil of the lung and making the lung more compliant. Surfactant also helps stabilize the alveoli by lowering even further the surface tension of smaller alveoli, equalizing the pressure inside alveoli of different sizes.

Alveolar Interdependence

A second factor tending to stabilize the alveoli is their mechanical interdependence, which was discussed at the beginning of this chapter. Alveoli do not hang from the airways like a “bunch of grapes” (the translation of the Latin word “acinus”), and they are not spheres. They are mechanically interdependent polygons with flat walls shared by adjacent alveoli. Alveoli are not normally held open by positive airway pressure, as suggested by Figures 2–9 and 2–10; they are held open by the chest wall pulling on the outer surface of the lung, as shown in Figure 2–2. If an alveolus, such as the one in the middle of Figure 2–13, were to begin to collapse, it would increase the stresses on the walls of the adjacent alveoli, which would tend to hold it open. This process would oppose a tendency for isolated alveoli with a relative lack of pulmonary surfactant to collapse spontaneously. Conversely, if a whole subdivision of the lung (such as a lobule) has collapsed, as soon as the first alveolus is reinflated, it helps to pull other alveoli open by its mechanical interdependence with them. Thus, both pulmonary surfactant and the mechanical interdependence of the alveoli help stabilize the alveoli and oppose alveolar collapse (atelectasis).

The interaction between the lung and the chest wall was discussed earlier in this chapter. The inward elastic recoil of the lung normally opposes the outward elastic recoil of the chest wall, and vice versa. If the integrity of the lung-chest wall system is disturbed by breaking the seal of the chest wall (eg, by a penetrating knife wound), the inward elastic recoil of the lung can no longer be opposed by the outward recoil of the chest wall, and their interdependence ceases. Lung volume decreases, and alveoli have a much greater tendency to collapse, especially if air moves in through the wound until intrapleural pressure equalizes with atmospheric pressure and abolishes the transpulmonary pressure gradient. At this point nothing is tending to hold the alveoli open and their elastic recoil is causing them to collapse. Similarly, the chest wall tends to expand because its outward recoil is no longer opposed by the inward recoil of the lung.

When the lung-chest wall system is intact and the respiratory muscles are relaxed, the volume of gas left in the lungs is determined by the balance of these 2 opposing forces. The volume of gas in the lungs at the end of a normal tidal expiration, when no respiratory muscles are actively contracting, is known as the functional residual capacity (FRC). For any given situation, the FRC will be that lung volume at which the outward recoil of the chest wall is equal to the inward recoil of the lungs. The relationship between lung elastic recoil and chest wall elastic recoil is illustrated in static (or “relaxation”) pressure-volume curves (Figure 2–14).

In the studies from which these data were taken, participants breathed air from a spirometer so that lung volumes could be determined. Intrapleural pressure was measured with an esophageal balloon, and pressure was also measured at the person’s nose or mouth. The subjects were instructed to breathe air into or from the spirometer to attain different lung volumes. A stopcock in the spirometer tubing near the subject’s mouth was then closed, and the subject was instructed to suddenly relax his or her respiratory muscles. The pressure then measured at the nose or mouth (which is equal to alveolar pressure at this point when no airflow is occurring) is the sum of the recoil pressure of both lungs and the chest wall. It is represented by the dashed line labeled “system” (respiratory system) in Figure 2–14. The individual recoil pressures of the lung and the chest wall can be calculated because the intrapleural pressure is known. Lung recoil pressure is labeled “lungs” on the graphs; chest wall recoil pressure is labeled “chest wall” on the graphs. The graph on the left was drawn from data obtained when participants were sitting up; the graph on the right was drawn from data obtained when participants were lying on their backs.

The left graph in Figure 2–14 shows that the pressure measured at the mouth (system) is equal to 0 cm H2O at the point where lung recoil pressure is equal and opposite to chest wall recoil pressure. Therefore, alveolar pressure is also 0 cm H2O. The lung volume at this point is the person’s FRC.

As the person increases his or her lung volume, the total system recoil pressure becomes positive because of 2 factors: the increased inward elastic recoil of the lung because of the stretched alveoli and the decreased outward elastic recoil of the chest wall. In fact, at high lung volumes the recoil pressure of the chest wall is also positive (note the point where the chest wall line crosses the 0 pressure line). This is because at high lung volumes, above about 70% of the total lung capacity (TLC), when a person is in an upright posture, the chest wall also has inward elastic recoil. Seventy percent of the TLC is approximately equal to 60% of the vital capacity (VC—defined later in this chapter) seen in the left panel of Figure 2–14. In other words, if one could imagine a relaxed intact chest wall with no lungs in it, the resting volume of the thorax would be about 70% of the volume of the thorax when the lungs are maximally (voluntarily) expanded; the relaxed volume of the chest wall of a 70-kg man is about 1 L greater than the FRC. At thoracic volumes below about 70% of the TLC, the chest wall elastic recoil is outward; at thoracic volumes above 70% of the TLC, the recoil is inward. The chest wall is analogous to a rigid coiled spring with spaces between the coils: if it is stretched, it has inward elastic recoil, if it is compressed, it has outward elastic recoil. Therefore, at high lung volumes the mouth pressure is highly positive because both lung and chest wall elastic recoil are inward.

At lung volumes below the FRC, the relaxation pressure measured at the mouth is negative because the outward recoil of the chest wall is greater than the reduced inward recoil of the lungs.

The point of this discussion can be seen in the right-hand graph of Figure 2–14, in which the data collected were from supine subjects. Although the elastic recoil curve for the lung is relatively unchanged, the recoil curves for the chest wall and the respiratory system are shifted to the right. The reason for this shift is the effect of gravity on the mechanics of the chest wall, especially the diaphragm. When a person is standing up or sitting, the contents of the abdomen are being pulled away from the diaphragm by gravity. When the same person lies down, the abdominal contents are pushing inward against the relaxed diaphragm. This decreases the overall outward recoil of the chest wall and displaces the chest wall elastic recoil curve to the right. Because the respiratory system curve is the sum of the lung and chest wall curves, it is also shifted to the right.

The lung volume at which the outward recoil of the chest wall is equal to the inward recoil of the lung is much lower in the supine subject, as can be seen at the point where the system line crosses the 0 recoil pressure line. In other words, the FRC decreased appreciably just because the person changed from the sitting to the supine position. Figure 2–15 shows the effect of body position on the FRC.

Several factors besides the elastic recoil of the lungs and the chest wall must be overcome to move air into or out of the lungs. These factors include the inertia of the respiratory system, the frictional resistance of the lung and chest wall tissue, and the frictional resistance of the airways to the flow of air. The inertia of the system is negligible. Pulmonary tissue resistance is caused by the friction encountered as the lung tissues move against each other or the chest wall as the lung expands. The airways resistance plus the pulmonary tissue resistance is often referred to as the pulmonary resistance. Pulmonary tissue resistance normally contributes about 20% of the pulmonary resistance, with airways resistance responsible for the other 80%. Pulmonary tissue resistance can be increased in such conditions as pulmonary sarcoidosis, silicosis, asbestosis, and fibrosis. Because airways resistance is the major component of the total resistance and because it can increase tremendously both in healthy people and in those suffering from various diseases, the remainder of this chapter will concentrate on airways resistance.

Laminar, Turbulent, and Transitional Flow

Generally, the relationship among pressure, flow, and resistance is stated as

Therefore,

This means that resistance is a meaningful term only during flow. When airflow is considered, the units of resistance are usually cm H2O/L/s.

The resistance to airflow is analogous to electrical resistance in that resistances in series are added directly:

Resistances in parallel are added as reciprocals:

Understanding and quantifying the resistance to airflow in the conducting system of the lungs is difficult because of the nature of the airways themselves. It is relatively easy to inspect the resistance to airflow in a single, unbranched, indistensible tube; however, the ever-branching, narrowing, distensible, and compressible system of airways complicates the analysis of the factors contributing to airways resistance. Therefore, equations can only approximate clinical situations.

Airflow, like that of other fluids, can occur as either laminar or turbulent flow.

As seen in Figure 2–16, laminar flow (or streamline flow) consists of a number of concentrically arranged cylinders of air flowing at different rates. This telescope like arrangement is such that the cylinder closest to the wall of the vessel has the slowest velocity because of frictional forces with the wall; the pathway in the center of the vessel has the highest velocity.

When a fluid such as air flows through rigid, smooth-bore tubes, its behavior is governed by Poiseuille’s law. The pressure difference is directly proportional to the flow times the resistance if flow is laminar:

where ΔP is the pressure difference,

According to Poiseuille’s law, the resistance is directly proportional to the viscosity of the fluid and the length of the tube and is inversely proportional to the fourth power of the radius of the tube:

where η is the viscosity of fluid, l is the length of tube, and r is the radius of tube.

Note that if the radius is cut in half, the resistance is multiplied by 16 because the resistance is inversely proportional to the radius to the fourth power.

Flow changes from laminar to turbulent when Reynold’s number exceeds 2000. Reynold’s number is a dimensionless number equal to the density of the fluid times the velocity of the fluid times the diameter of the tube divided by the viscosity of the fluid:

where ρ is the density of fluid, Ve is the linear velocity of fluid, D is the diameter of tube, and η is the viscosity of fluid.

During turbulent flow, the relationship among the pressure difference, flow, and resistance changes. Because the pressure difference is proportional to the flow squared, much greater pressure differences are required to generate the same airflow. The resistance term is influenced more by the density than it is by the viscosity during turbulent flow:

Transitional flow is a mixture of laminar and turbulent flow. This type of flow often occurs at branch points or points distal to partial obstructions.

Turbulent flow tends to occur if airflow is high, gas density is high, the tube radius is large, or all 3 conditions exist. During turbulent flow, flow is inversely proportional to gas density, but viscosity is unimportant as the concentric cylinders of flow (the lamina) break down. True laminar flow probably occurs only in the smallest airways, where the linear velocity of airflow is extremely low. Linear velocity (cm/s) is equal to the flow (cm3/s) divided by the cross-sectional area. The total cross-sectional area of the smallest airways is very large (see Chapter 1), and so the linear velocity of airflow is very low. The airflow in the trachea and larger airways is usually either turbulent or transitional.

Distribution of Airways Resistance

In a normal adult about 35% to 50% of the total resistance to airflow is located in the upper airways: the nose, nasal turbinates, oropharynx, nasopharynx, and larynx. Resistance is higher when one breathes through the nose than when one breathes through the mouth.

The vocal cords open slightly during normal inspirations and close slightly during expirations. During deep inspirations, they open widely. The muscles of the oropharynx also contract during normal inspirations, which dilates and stabilizes the upper airway. During deep forced inspirations, the development of negative pressure could cause the upper airway to be pulled inward and partly or completely obstruct airflow. Reflex contraction of these pharyngeal dilator muscles normally keeps the airway open (see Figure 2–25).

As for the tracheobronchial tree, the component with the highest individual resistance is the smallest airway, which has the smallest radius. Nevertheless, because the smallest airways are arranged in parallel, their resistances add as reciprocals, so that the total resistance to airflow offered by the numerous small airways is extremely low during normal, quiet breathing. Therefore, under normal circumstances the greatest resistance to airflow resides in the large to medium-sized bronchi.

Control of Bronchial Smooth Muscle

The smooth muscle of the airways from the trachea down to the alveolar ducts is under the control of efferent fibers of the autonomic nervous system. Stimulation of the cholinergic parasympathetic postganglionic fibers causes constriction of bronchial smooth muscle as well as increased glandular mucus secretion. The preganglionic fibers travel in the vagus. Stimulation of the adrenergic sympathetic fibers causes dilation of bronchial and bronchiolar smooth muscle as well as inhibition of glandular secretion. This dilation of the airways smooth muscle is mediated by beta2 (β2) receptors, which predominate in the airways. Selective stimulation of the alpha (α) receptors with pharmacologic agents causes bronchoconstriction. Adrenergic transmitters carried in the blood may be as important as those released from the sympathetic nerves in causing bronchodilation. The bronchial smooth muscle is normally under greater parasympathetic than sympathetic tone.

Inhalation of chemical irritants, smoke, or dust; stimulation of the arterial chemoreceptors; and substances such as histamine cause reflex constriction of the airways. Decreased CO2 in the branches of the conducting system causes a local constriction of the smooth muscle of the nearby airways; increased CO2 or decreased O2 causes a local dilation. This may help balance ventilation and perfusion (see Chapter 5). Many other substances can have direct or indirect effects on airway smooth muscle (Table 2–2). Leukotrienes usually cause bronchoconstriction, as do some prostaglandins.

Lung Volume and Airways Resistance

Airways resistance decreases with increasing lung volume, as shown in Figure 2–17 (normal curve). This relationship is still present in an emphysematous lung (“Abnormal” in Figure 2–17), although in emphysema the resistance is higher than that in a healthy lung, especially at low lung volumes.

There are 2 reasons for this relationship; both mainly involve the small airways, which, as described in Chapter 1, have little or no cartilaginous support. The small airways are therefore rather distensible and also compressible. Thus, the transmural pressure difference across the wall of the small airways is an important determinant of the radius of the small airways: Since resistance is inversely proportional to the radius to the fourth power, changes in the radii of small airways can cause dramatic changes in airways resistance, even with so many parallel pathways. To increase lung volume, a person breathing normally takes a “deep breath,” that is, makes a strong inspiratory effort. This effort causes intrapleural pressure to become much more negative than the –7 or –10 cm H2O seen in a normal, quiet breath. The transmural pressure difference across the wall becomes much more positive, and small airways are distended.

A second reason for the decreased airways resistance seen at higher lung volumes is that the so-called traction on the small airways increases. As shown in the schematic drawing in Figure 2–18 (see also the alveolar duct in Figure 1–3), the small airways traveling through the lung form attachments to the walls of alveoli. As the alveoli expand during the course of a deep inspiration, the elastic recoil in their walls increases; this elastic recoil is transmitted to the attachments at the airway, pulling it open.

Dynamic Compression of Airways

Airways resistance is extremely high at low lung volumes, as can be seen in Figure 2–17. To achieve low lung volumes, a person must make a forced expiratory effort by contracting the muscles of expiration, mainly the abdominal and internal intercostal muscles. This effort generates positive intrapleural pressure, which can be as high as 120 cm H2O during a maximal forced expiratory effort. (Maximal inspiratory intrapleural pressures can be as low as –80 cm H2O.)

The effect of this high positive intrapleural pressure on the transmural pressure gradient during a forced expiration can be seen at right in Figure 2–19, a schematic drawing of a single alveolus and airway.

At this instant, during the course of a forced expiration, the muscles of expiration are generating a positive intrapleural pressure of +25 cm H2O. Pressure in the alveolus is greater than intrapleural pressure because of the alveolar elastic recoil pressure of +10 cm H2O, which together with intrapleural pressure, gives an alveolar pressure of +35 cm H2O. The alveolar elastic recoil pressure decreases at lower lung volumes because the alveolus is not as distended. In the figure, a gradient has been established from the alveolar pressure of +35 cm H2O to the atmospheric pressure of 0 cm H2O. If the airways were rigid and incompressible, the large expiratory pressure gradient would generate very high rates of airflow.

The situation during a normal passive expiration at the same lung volume (note the same alveolar elastic recoil pressure) is shown in the left part of Figure 2–19. The transmural pressure gradient across the smallest airways is

tending to hold the airway open. During the forced expiration at right, the transmural pressure gradient is 30 cm H2O − 25 cm H2O, or only 5 cm H2O holding the airway open. The airway may then be slightly compressed, and its resistance to airflow will be even greater than during the passive expiration. This increased resistance during a forced expiration is called dynamic compression of airways.

Consider what must occur during a maximal forced expiration. As the expiratory effort is increased to attain a lower and lower lung volume, intrapleural pressure is getting more and more positive, and more and more dynamic compression will occur. Furthermore, as lung volume decreases, there will be less alveolar elastic recoil pressure and the difference between alveolar pressure and intrapleural pressure will decrease.

One way of looking at this process is the equal pressure point hypothesis. (Another explanation of flow limitation during forced expiration, the wave speed flow-limiting mechanism, is too complex to discuss here.) At any instant during a forced expiration, there is a point along the airways where the pressure inside the airway is just equal to the pressure outside the airway. At that point the transmural pressure gradient is 0 (note the arrows in Figure 2–19). Above that point, the transmural pressure gradient is negative: The pressure outside the airway is greater than the pressure inside it, and the airway will collapse if cartilaginous support or alveolar septal traction is insufficient to keep it open.

As the forced expiratory effort continues, the equal pressure point is likely to move down the airway toward the alveoli from larger to smaller airways. This occurs because, as the muscular effort increases, intrapleural pressure increases and because, as lung volume decreases, alveolar elastic recoil pressure decreases. As the equal pressure point moves down the airway, dynamic compression increases and the airways ultimately begin to collapse. This airways closure can be demonstrated only at especially low lung volumes in healthy subjects, but the closing volume may occur at higher lung volumes in patients with emphysema, as will be discussed at the end of this chapter. (Note that the point at which airways resistance approaches infinity occurs at a much higher volume in the “abnormal” lungs in Figure 2–17.) The closing volume test itself will be discussed in Chapter 3.

Consider the pressure gradient for airflow during a forced expiration. During a passive expiration the pressure gradient for airflow

Thus, during a forced expiration, when intrapleural pressure becomes positive and dynamic compression occurs, the effective driving pressure for airflow from the lung is the alveolar elastic recoil pressure. Alveolar elastic recoil is also important in opposing dynamic compression of the airways because of its role in the traction of the alveolar septa on small airways, as shown in Figure 2–18. The effects of alveolar elastic recoil on airflow during a forced expiration are illustrated in Figure 2–20.

The Bernoulli principle may also play a role in dynamic compression of the airways. For an ideal fluid with no viscosity, as the linear velocity of the fluid flow increases, the pressure exerted by the fluid on the walls of the vessel (the “lateral pressure”) decreases. Therefore, as the velocity of airflow in the small compressible airways increases during a forced expiration, the pressure inside the vessel decreases. This could contribute to a decreased or more negative transmural pressure difference across the vessel wall.

Assessment of Airways Resistance

The resistance to airflow cannot be measured directly but must be calculated from the pressure difference and airflow during a breath:

This formula is an approximation because it presumes that all airflow is laminar, which is not true. But there is a second problem: How can the pressure gradient be determined? To know the pressure gradient, the alveolar pressure—which also cannot be measured directly—must be known. Alveolar pressure can be calculated using a body plethysmograph, an expensive piece of equipment described in detail in the next chapter, but this procedure is not often done. Instead, airways resistance is usually assessed indirectly. The assessment of airways resistance during expiration will be emphasized because it is of interest in patients with emphysema, chronic bronchitis, and asthma.

Forced Vital Capacity

One way of assessing expiratory airways resistance is to look at the results of a forced expiration into a spirometer, as shown in Figure 2–21. This measurement is called a forced vital capacity (FVC). The VC is the volume of air a subject is able to expire after a maximal inspiration to the total lung capacity (TLC). An FVC means that a maximal expiratory effort was made during this maneuver.

In an FVC test, a person makes a maximal inspiration to the TLC. After a moment, he or she makes a maximal forced expiratory effort, blowing as much air as possible out of the lungs. At this point, only a residual volume (RV) of air is left in the lungs. (The lung volumes will be described in detail in the next chapter.) This procedure takes only a few seconds, as can be seen on the time scale.

The part of the curve most sensitive to changes in expiratory airways resistance is the first second of expiration. The volume of air expired in the first second of expiration (the FEV1, or forced expiratory volume in 1 second), especially when expressed as a ratio with the total amount of air expired during the FVC, is a good index of expiratory airways resistance. In normal young subjects, the FEV1/FVC is greater than 0.80; that is, at least 80% of the FVC is expired in the first second. An FEV1/FVC of 75% would be more likely in an older person. A patient with airway obstruction caused by an episode of asthma, for example, would be expected to have an FEV1/FVC far below 0.80, as shown in the middle and bottom panels in Figure 2–21.

The bottom panel of Figure 2–21 shows similar FVC curves that would be obtained from a commonly used rolling seal spirometer. The curves are reversed right to left and upside down if they are compared with those in the top and middle panels. The TLC is at the bottom left, and the RVs are at the top right. The time scale is left to right. Note the calculations of the FEV1 to FVC ratios.

Another way of expressing the same information is the FEF25%–75%, or forced (mid) expiratory flow rate (formerly called the MMFR, or maximal midexpiratory flow rate). This variable is simply the slope of a line drawn between the points on the expiratory curve at 25% and 75% of the FVC. In cases of airway obstruction, this line is not nearly as steep as it is on a curve obtained from someone with normal airways resistance. The FEV1/FVC is usually considered to represent larger airways, the FEF25%–75%, smaller to medium-sized airways.

The main concept underlying these pulmonary function tests is that elevated airways resistance takes time to overcome.

Isovolumetric Pressure-Flow Curve

The isovolumetric pressure-flow technique is not used clinically because intrapleural pressure must be determined and the data obtained are tedious to plot. Analysis of the results obtained from this test, however, demonstrates several points we have already discussed. Isovolumetric pressure-flow curves are obtained by having a subject make repeated expiratory maneuvers with different degrees of effort. Intrapleural pressures are determined with an esophageal balloon, lung volumes are determined with a spirometer, and airflow rates are determined by using a pneumotachograph. The pressure-flow relationship for each of the expiratory maneuvers of various efforts is plotted on a curve for a particular lung volume. With each expiratory effort, as the lung volume passes through the chosen volume, the intrapleural pressure (approximating the expiratory effort) is plotted against the expiratory flow achieved. For example, the middle curve of Figure 2–22 was constructed by determining the intrapleural pressure and airflow for each expiratory maneuver as the subject’s lung volume passed through 50% of the VC. Therefore, none of the 3 curves in Figure 2–22 is really a continuous line; each curve is constructed from individual data points.

The middle curve in Figure 2–22 demonstrates dynamic compression and supports the equal pressure point hypothesis. At this lung volume, at which elastic recoil of the alveoli should be the same no matter what the expiratory effort, with increasing expiratory effort airflow increases up to a point. Beyond that point, generating more positive intrapleural pressure does not increase airflow: It becomes effort-independent. Airways resistance must be increasing with increasing expiratory effort. Airflow has become independent of effort because of greater dynamic compression with more positive intrapleural pressures. The equal pressure point has moved to compressible small airways and is fixed there. Note that at even lower lung volumes (25% of the VC), at which there is less alveolar elastic recoil to provide traction on small airways, this occurs with lower maximal airflow rates. In other words, because alveolar pressure equals the sum of the intrapleural pressure and the alveolar elastic recoil pressure during a forced expiration at a given lung volume, the driving pressure for airflow becomes independent of expiratory muscle effort because increasing the intrapleural pressure increases the alveolar pressure by the same amount. Only the alveolar elastic recoil, which is constant at a given lung volume, drives air out of the lung. At high lung volumes (75% of VC), airflow increases steadily with increasing effort. It is entirely effort-dependent because alveolar elastic recoil pressure is high (which increases both the alveolar septal traction on small airways and the pressure gradient for airflow) and because highly positive intrapleural pressures cannot be attained at such high lung volumes with the airway wide open.

Flow-Volume Curves

These same principles are demonstrated in the expiratory portion of flow-volume curves (Figure 2–23).

A family of flow-volume curves such as those depicted in Figure 2–23 is obtained in the same way as were the data in Figure 2–22, only in this case flow rates are plotted against lung volume for expiratory efforts of different intensities. Intrapleural pressures are not necessary. Because such curves can be plotted instantaneously, this test is often used clinically. There are 2 interesting points about this family of expiratory (upper portion) curves, which corresponds to the 3 curves in Figure 2–22. At high lung volumes, the airflow rate is effort-dependent, which can be seen in the left-hand portion of the curves. At low lung volumes, however, the expiratory efforts of different initial intensities all merge into the same effort-independent curve, as seen in the right-hand portion of the curve. Again, this difference is because intrapleural pressures high enough to cause dynamic compression are necessary to attain very low lung volumes, no matter what the initial expiratory effort. Also, at low lung volumes there is less alveolar elastic recoil pressure, and so there is less traction on the same airways and a smaller pressure gradient for airflow. Note that there is normally no effort independence on inspiratory curves if the subject breathes through the mouth. Patients with upper airway problems such as obstructive sleep apnea or vocal cord paralysis would demonstrate inspiratory effort independence.

The maximal flow-volume curve is often used as a diagnostic tool, as shown in Figure 2–24, because it helps distinguish between 2 major classes of pulmonary diseases—airway obstructive diseases and restrictive diseases, such as fibrosis. Obstructive diseases are those diseases that interfere with airflow; restrictive diseases are those diseases that restrict the expansion of the lung (see the pulmonary function test decision tree in Chapter 6).

Figure 2–24 shows that either obstruction or restriction can cause a decrease in the maximal flow rate that the patient can attain, the peak expiratory flow (PEF; shown in Figure 2–23), but that this decrease occurs for different reasons. Restrictive diseases, which usually entail elevated alveolar elastic recoil, may have decreased PEF because the TLC (and thus the VC) is decreased. The effort-independent part of the curve is similar to that obtained from a person with normal lungs. In fact, the FEV1/FVC is usually normal or even above normal since both the FEV1 and FVC are decreased because the lung has a low volume and because alveolar elastic recoil pressure may be increased. On the other hand, in patients with obstructive diseases, the PEF and FEV1/FVC are both low.

Obstructive diseases—such as asthma, bronchitis, and emphysema—are often associated with high lung volumes, which is helpful because the high volumes increase the alveolar elastic recoil pressure. The RV may be greatly increased if airway closure occurs at relatively high lung volumes. A second important feature of the flow-volume curve of a patient with obstructive disease is the effort-independent portion of the curve, which is depressed inward (concave): Flow rates are low for any relative volume.

Flow-volume curves are very useful in assessing obstructions of the upper airways and the trachea. Flow-volume loops can help distinguish between fixed obstructions (those not affected by the inspiratory or expiratory effort) and variable obstructions (changes in the transmural pressure gradient caused by the inspiratory or expiratory effort result in changes in the cross-sectional area of the obstruction). If the obstruction is variable, flow-volume loops can demonstrate whether the obstruction is extrathoracic or intrathoracic (Figure 2–25). A fixed obstruction affects both expiratory and inspiratory airflow (Figure 2–25A). Both the expiratory and inspiratory flow-volume curves are truncated, with decreased peak expiratory and peak inspiratory flows. The flow-volume loop is unable to distinguish between a fixed extrathoracic and a fixed intrathoracic obstruction, which would usually be determined with a bronchoscope. Fixed obstructions can be caused by foreign bodies or by scarring, usually from a previous intubation or tracheostomy, that makes a region of the airway too stiff to be affected by the transmural pressure gradient.

During a forced expiration, the cross-sectional area of a variable extrathoracic obstruction increases as the pressure inside the airway increases (Figure 2–25B). The expiratory flow-volume curve is therefore nearly normal or not affected. However, during a forced inspiration, the pressure inside the upper airway decreases below atmospheric pressure, and unless the stability of the upper airway is maintained by reflex contraction of the pharyngeal muscles or by other structures, the cross-sectional area of the upper airway will decrease. Therefore, the inspiratory flow-volume curve is truncated in patients with variable extrathoracic obstructions. Variable extrathoracic obstructions can be caused by tumors, fat deposits, weakened or flabby pharyngeal muscles (as in obstructive sleep apnea), paralyzed vocal cords, enlarged lymph nodes, or inflammation.

During a forced expiration, positive intrapleural pressure decreases the transmural pressure gradient across a variable intrathoracic tracheal obstruction, decreasing its cross-sectional area and decreasing the PEF (Figure 2–25C). During a forced inspiration, as large negative intrapleural pressures are generated, the transmural pressure gradient across the variable intrathoracic obstruction increases and its cross-sectional area increases. Thus, the inspiratory flow-volume curve is nearly normal or not affected. Variable intrathoracic obstructions of the trachea are most commonly caused by tumors.

Dynamic Compliance

The dynamic compliance of the lungs is the change in the volume of the lungs divided by the change in the alveolar-distending pressure during the course of a breath. At low breathing frequencies, around 15 breaths/min and lower, dynamic compliance is about equal to static compliance, and the ratio of dynamic compliance to static compliance is 1 (Figure 2–26).

In normal persons, this ratio stays near 1 even at much higher breathing frequencies. However, in patients with elevated resistance to airflow in some of their small airways, the ratio of dynamic compliance to static compliance falls dramatically as breathing frequency is increased. This indicates that changes in dynamic compliance reflect changes in airways resistance as well as changes in the compliance of alveoli.

The effects of increased breathing frequency on dynamic compliance can be explained by thinking of a pair of hypothetical alveoli supplied by the same airway. Consider the time courses of their changes in volume in response to an abrupt increase in airway pressure (a “step” increase) in a situation in which the compliance of each alveolus or the resistance in the branch of the airway supplying it can be arbitrarily altered.

If the resistances and compliances of the 2 units were equal, the 2 alveoli would fill with identical time courses. If the resistances were equal, but the compliance of one were half that of the other, then it would be expected that the alveoli would fill with nearly identical flow rates but that the less compliant one would receive only half the volume received by the other. If the compliances of the 2 units were equal but one was supplied by an airway with twice the resistance to airflow of the one supplying the other, then it would be expected that the 2 units would ultimately fill to the same volume. However, the one supplied by the airway with elevated resistance would fill more slowly than the other because of its elevated resistance. (High resistance units take longer to fill because of lower flow rates; high compliance units take longer to fill because they can hold more volume.) This difference means that at high breathing frequencies the one that fills more quickly than the other will accommodate a larger volume of air per breath.

This situation may also lead to a redistribution of alveolar air after the inflating pressure has ceased because one alveolus has more air in it than the other. But both have equal compliance characteristics. The more distended one therefore has a higher elastic recoil pressure, and because they are joined by a common airway, some air is likely to follow the pressure gradient and move to the other.

Now let’s extrapolate this 2-unit situation to a lung with millions of airways supplying millions of alveoli. In a patient with small-airways disease, many alveoli may be supplied by airways with higher resistance to airflow than normal. These alveoli are sometimes referred to as “slow alveoli” or alveoli with long “time constants.” (The time constant is equal to the resistance times the compliance and it represents the time it takes for the alveolus to fill to 63% of its final volume.) As the patient increases the breathing frequency, the slowest alveoli will not have enough time to fill and will contribute nothing to the dynamic compliance. As the frequency increases, more and more slow alveoli will drop out and dynamic compliance will continue to fall. If this patient were being mechanically ventilated, alveoli may not have enough time to fill or empty (expiration is passive and mainly dependent on alveolar elastic recoil) between breaths. In the latter case “new” air may enter the lung before it has time to empty (“auto PEEP” or “stacked breaths”).

The major points discussed in this chapter can be summarized by considering the work of breathing. The work done in breathing is proportional to the pressure change times the volume change. In eupneic breathing the volume change is the volume of air moved into and out of the lung—the tidal volume.

Note that some of the energy used in the elastic work of breathing during inspiration is stored as potential energy that can be recovered on expiration, but there is no energy stored in the resistive work of breathing—it is lost as heat.

Elastic Work

The elastic work of breathing is the work done to overcome the elastic recoil of the chest wall and the pulmonary parenchyma and the work done to overcome the surface tension of the alveoli. Restrictive diseases are those diseases in which the elastic work of breathing is increased. For example, the work of breathing is elevated in obese patients (who have decreased outward chest wall elastic recoil) and in patients with pulmonary fibrosis or a relative lack of pulmonary surfactant (who have increased elastic recoil of the alveoli).

Resistive Work

The resistive work of breathing is the work done to overcome the tissue resistance and the airways resistance. The tissue resistance may be elevated in conditions such as sarcoidosis, silicosis, and asbestosis. Elevated airways resistance is much more common and is seen in obstructive diseases such as asthma, bronchitis, and emphysema; upper airway obstruction, including obstructive sleep apnea; and accidental aspirations of foreign objects. Normally, most of the resistive work is that done to overcome airways resistance.

The resistive work of breathing can be extremely great during a forced expiration, when dynamic compression occurs. This is especially true in patients who already have elevated airways resistance during normal, quiet breathing. For example, in patients with emphysema, a disease that attacks and obliterates alveolar walls, the work of breathing can be tremendous because of the destruction of the elastic tissue support of their small airways, which allows dynamic compression to occur unopposed. Also, the decreased elastic recoil of alveoli leads to a decreased pressure gradient for expiration.

The oxygen cost of normal, quiet (eupneic) breathing is normally less than 5% of the total body oxygen uptake. This percentage can increase to as much as 30% in normal persons during maximal exercise. In patients with obstructive lung disease, however, the work of breathing can be the factor that limits exercise.

A woman inspires 500 mL from a spirometer. The intrapleural pressure, determined using an esophageal balloon, was – 5 cm H2O before the inspiratory effort and – 10 cm H2O at the end of the inspiration. What is the pulmonary compliance?

The correct answer is:

Remember to use transmural pressure differences in calculations of compliance:

Transmural pressure = pressure inside − pressure outside

Compliance of lungs is

A postoperative patient whose respiratory muscles have been paralyzed with pancuronium bromide, a curare-like drug, is maintained by a positive-pressure respirator. At end expiration (when alveolar pressure equals 0), intrapleural pressure, as measured by an esophageal balloon, is equal to –3 cm H2O. At the peak of inspiration, alveolar pressure is +20 cm H2O and intrapleural pressure is +10 cm H2O. Tidal volume is 500 mL.

a. What is the patient’s pulmonary compliance?

b. What is the patient’s total compliance?

c. What is the patient’s chest wall compliance?

The correct answer is:

a.

b.

where PB = pressure outside the chest wall. It is considered to be 0 cm H2O in this calculation.

c.

From Raff H, Levitzky MG, eds. Medical Physiology: A Systems Approach. New York: McGraw-Hill; 2011:329–330.

A 26-year-old man comes to the Emergency Department because of sudden dyspnea (a feeling that breathing is difficult, also called “shortness of breath”) and pain in the upper part of the left side of his chest. He has no history of any medical problems. He is 183 cm (6 ft 2 in.) tall and weighs about 63.5 kg (140 lb). Blood pressure is 125/80 mm Hg, heart rate is 90/min, and respiratory rate is 22/min (usually 12–15/min in a healthy adult). There are no breath sounds on the left side of his chest, which is hyperresonant (louder and more hollow-sounding) to percussion (the physician tapping on the chest with his or her fingers).

The patient has a pneumothorax. Air has entered the pleural space on the left side of his chest and he is unable to expand his left lung. Therefore there are no breath sounds on the left side of his chest and it is hyperresonant to percussion. In this case, the pneumothorax is a primary spontaneous pneumothorax because it occurred suddenly, and is not attributable to an underlying pulmonary disease (secondary spontaneous pneumothorax) or trauma (traumatic pneumothorax). The inability to ventilate his left lung, combined with pain and anxiety, explain his high respiratory rate, as will be discussed in Chapters 3 and 9.

Primary spontaneous pneumothorax is most common in tall thin males between 10 and 30 years of age, although the reason for this is not known. It is believed to occur when overexpanded alveoli (“blebs”) rupture, perhaps as a result of a cough or sneeze.

If the pneumothorax is mild and the patient is not in too much distress, it may resolve without treatment other than observation. More severe pneumothorax is treated by inserting a catheter or chest tube through the skin and intercostal muscles into the pleural space to allow removal of the air by external suction.

A tension pneumothorax is a potentially life-threatening disorder that most commonly occurs as a result of trauma or lung injury. Air enters the pleural space on inspiration but cannot leave on expiration, progressively increasing intrapleural pressure above atmospheric. This can compress the structures on the affected side of the chest (eg, blood vessels, heart, etc) and eventually the structures on the other side of the chest as well.