Ventilation

Robert L. Chatburn and Ehab G. Daoud

Key Terms

airway resistance

alveolar dead space

compliance

dynamic compression

dynamic hyperinflation (air trapping)

elastance

elasticity

equal pressure point (EPP)

hyperventilation

hypoventilation

hysteresis

physiologic dead space

transairway pressure (P_TAW)

transalveolar pressure (P_TA)

trans–chest wall pressure (P_TCW)

transpulmonary

transpulmonary pressure difference (P_TP)

transrespiratory

transrespiratory pressure (P_TR)

transthoracic

transthoracic pressure difference (P_TT)

ventilation

The primary functions of the lungs are to supply the body with oxygen (O₂) and to remove carbon dioxide (CO₂). To perform these functions, the lungs must be adequately ventilated. Ventilation is the process of moving gas (usually air) in and out of the lungs. Ventilation is to be distinguished from respiration, which involves complex physiologic processes at the blood and cellular levels.

In health, ventilation is regulated to meet the body’s needs under a wide range of conditions. In disease, this process can be markedly disrupted. Inadequate ventilation or increased work of breathing often results. Respiratory care is often directed toward restoring adequate and efficient ventilation. Respiratory care modalities try to reduce the work of breathing and provide artificial ventilation if necessary. Providing effective respiratory care requires an understanding of normal ventilatory processes and of how various diseases may affect ventilation.

Mechanics of Ventilation

Normal ventilation is a cyclic activity that has two phases: inspiration and expiration. During each cycle, a volume of gas moves in and out of the respiratory tract. This volume, measured during either inspiration or expiration, is called the tidal volume (V_T). The normal V_T refreshes the gas present in the lung removing CO₂ and supplying O₂ to meet metabolic needs. The V_T must be able to meet changing metabolic demands, such as during exercise or sleep. The vital capacity and its subdivisions provide the necessary reserves for increasing ventilation (see Chapter 19).

Ventilation can be related to a simplified version of the equation of motion for the respiratory system:

Pressure=VolumeCompliance+(Resistance×Flow)

where:

Pressure = Force generated by the respiratory muscles or a mechanical ventilator, or both, during inspiration

Volume = Volume change (e.g., V_T)

Elastance = Distensibility of the lungs and thorax (Δpressure/Δvolume); elastance is the reciprocal of compliance (Δvolume/Δpressure)

Resistance = Airflow and tissue resistance (Δpressure/Δflow)

Flow = Volume change per unit of time

In this equation, the terms (elastance × volume) and (resistance × flow) have units of pressure and represent the elastic and resistive loads against which the respiratory muscles or ventilator must work to ventilate the lungs. In healthy lungs, this work is minimal and performed during the inspiratory phase. Expiration is normally passive (i.e., no muscle force involved).

Pressure Differences During Breathing

The equation of motion is a mathematical model describing the behavior of a graphic model of the lungs. The graphic model is shown in Figure 10-1.¹ The model lumps all the resistive properties of the many airways into a single flow-conducting tube and lumps all the elastic properties of the alveoli and airways into a single elastic compartment. Surrounding the “lungs” is another elastic compartment representing the chest wall. This graphic representation of the respiratory system allows us to define points in space where pressures may be measured (or inferred) as defined in Table 10-1. Mathematical models relating pressure, volume, and flow corresponding to this graphic model are constructed using pressure differences between the points. The various components of the graphic model are defined as everything that exists between these points in space. The respiratory system is everything that exists between the pressure measured at the airway opening (P_AO) and the pressure measured at the body surface (P_BS). The associated pressure difference is transrespiratory pressure (P_TR):

TABLE 10-1

Measurable Pressures Used in Describing Respiratory System Mechanics

Name	Symbol	Definition
Pressure at the airway opening	P_AO	Pressure measured at the opening of the respiratory system airway (e.g., mouth and nose, tracheostomy opening, and distal end of endotracheal tube)
Pleural pressure	P_pl	Pressure measured in the pleural space, changes in which are often estimated by measuring pressure changes in the esophagus
Alveolar pressure	P_A	Pressure in the alveolar (gas space) region of the lungs
Body surface pressure	P_BS	Pressure measured at the body surface

PTR=PAO−PBS

The term P_AO comes before the term P_BS in the equation. This order is dictated by the direction of flow. For inspiration, P_AO is higher than P_BS, and P_TR is calculated by subtracting P_BS from P_AO. The same general principle applies to all the other pressure differences described subsequently.

The components of transrespiratory pressure correspond to the components of the graphic model (i.e., airways, lungs, and chest wall). The airways are whatever exists between pressure measured at the airway opening and pressure measured in the alveoli of the lungs (P_A). The graphic model makes the lungs look like one giant alveolus, which means that alveolar pressure represents an average pressure over all alveoli in real lungs. The associated pressure difference is transairway pressure (P_TAW):

PTAW=PAO−PA

The alveolar region is whatever exists between pressure measured in the model alveolus and pressure measured in the pleural space (P_pl). The associated pressure difference is transalveolar pressure (P_TA):

PTA=PA−Ppl

The chest wall exists between pressure measured in the pleural space and the pressure on the body surface. The associated pressure difference is trans–chest wall pressure (P_TCW):

PTCW=Ppl−PBS

Some of these components can be combined to get respiratory subsystems. Most commonly, the pulmonary system (airways and alveolar region) is defined in terms of the transpulmonary pressure difference (P_TP):

PTP=PAO−Ppl

The literature is very confused regarding the definition of transpulmonary pressure. Authors often define P_TP as P_A − P_pl. The confusion arises from the fact that P_TA = P_A − P_pl but only under static conditions. Static conditions can be imposed during mechanical ventilation by using an inspiratory hold maneuver. This situation should be considered a special case of P_TP, however; the general case is P_TP = P_AO − P_pl, which shows what pressures must be measured to derive the mechanical properties of the pulmonary system under either static or dynamic (breathing) conditions. If we want to evaluate the elastance and resistance of the pulmonary system, we substitute P_TP for P in the equation of motion. Alternatively, if we want to evaluate total respiratory system elastance and resistance, we substitute P_TR for P.

Sometimes it is useful to define transthoracic pressure difference (P_TT) as:

PTT=PA−PBS

Table 10-2 summarizes these equations.

TABLE 10-2

Pressure Differences Used in Describing Respiratory System Mechanics

Definition	Name	Symbol
P_AO − P_BS	Transrespiratory pressure difference	ΔP_TR
P_AO − P_A	Transairway pressure difference	ΔP_TAW
P_AO − P_pl	Transpulmonary pressure difference	ΔP_TP
P_A − P_pl	Transalveolar pressure difference	ΔP_TA
P_A − P_BS	Transthoracic pressure difference	ΔP_TT
P_pl − P_BS	Trans–chest wall pressure difference	ΔP_TCW
	Global muscle pressure difference	ΔP_mus

The transrespiratory pressure gradient causes gas to flow into and out of the alveoli during breathing. For a spontaneously breathing subject, P_A is subatmospheric in the beginning of inspiration compared with P_AO causing air to flow into the alveoli. The opposite happens in the beginning of exhalation; P_A is higher than P_AO causing air to flow out of the airway opening.

During a normal breathing cycle, the glottis remains open. P_BS and P_AO remain at zero (i.e., atmospheric) throughout the cycle; only changes in P_A and P_pl are of interest. Before inspiration, pleural pressure is approximately −5 cm H₂O (i.e., 5 cm H₂O below atmospheric pressure), and alveolar pressure is 0 cm H₂O. The transpulmonary pressure gradient is also approximately 5 cm H₂O in the resting state, that is, P_TP = P_AO − P_pl = 0 − (−5) = 5. This positive end expiratory P_TP maintains the lung at its resting volume (i.e., functional residual capacity [FRC]). Airway opening and alveolar pressures are both zero, so the transairway pressure gradient also is zero. No gas moves into or out of the respiratory tract.

Inspiration begins when muscular effort expands the thorax. Thoracic expansion causes a decrease in pleural pressure. This decrease in pleural pressure causes a positive change on expiratory P_TP and P_TA, which induces flow into the lungs. The inspiratory flow is proportional to the positive change in transairway pressure difference; the higher the change in P_TA, the higher the flow.

Pleural pressure continues to decrease until the end of inspiration. Alveolar filling slows when alveolar pressure approaches equilibrium with the atmosphere, and inspiratory flow decreases to zero (Figure 10-2). At this point, called end-inspiration, alveolar pressure has returned to zero, and the intrapleural pressure—and hence transpulmonary pressure gradient—reaches the maximal value (for a normal breath) of approximately 10 cm H₂O.

FIGURE 10-2 Waveforms for normal breathing. *Red,* change in pleural pressure relative to end expiratory value (cm H₂O, scaled times ten); *blue,* alveolar pressure (cm H₂O, scaled times ten); *green,* flow (L/min, scaled times ten); *purple,* volume (ml).

As expiration begins, the thorax recoils, and P_pl starts to increase, and the transpulmonary pressure difference starts to decrease. Because transpulmonary pressure difference is decreasing (e.g., from 10 cm H₂O to 5 cm H₂O), the opposite of inspiration, flow is in the opposite (negative) direction. The equation of motion shows this, setting the driving pressure, P_mus, to zero:

Pmus=0=(Elastance×Volume)+(Resistance×Flow)

Rearranging, we get:

(Elastance×Volume)=−(Resistance×Flow)=Resistance×(−Flow)

This equation says two important things: (1) Flow is negative, indicating expiration, and (2) the driving force (transthoracic pressure, equal to elastance × volume) for expiratory flow is the energy stored in the combined elastances of lungs and chest wall (the total elastance is the sum of the chest wall and lung elastances).

These events occur during normal V_T excursions. Similar pressure changes accompany deeper inspiration and expiration. The magnitude of the pressure changes is greater with deeper breathing. Pleural pressures are always negative (subatmospheric) during normal inspiration and exhalation. During forced inspiration with a big down movement of the diaphragm, the pleural pressure can decrease to −50 cm H₂O, whereas during a forced expiration, pleural pressure may increase above atmospheric pressure to 50 to 100 cm H₂O.

Forces Opposing Inflation of the Lung

The lungs have a tendency to recoil inward, whereas the chest wall tends to move outward; these opposing forces keep the lung at its resting volumes (FRC). To generate the above-described pressure gradients, the lungs must be distended. This distention requires several opposing forces to be overcome for inspiration to occur. Normal expiration is passive, using the energy stored during inspiration. As indicated in the equation of motion, the forces opposing lung inflation may be grouped into two categories: elastic forces and frictional forces. Elastic forces involve the tissues of the lungs, thorax, and abdomen, along with surface tension in the alveoli. Frictional forces include resistance caused by gas flow through the airways (natural and artificial) and tissue movement during breathing.

Elastic Opposition to Ventilation

Elastin and collagen fibers are found in the lung parenchyma. These tissues give the lung the property of elasticity. Elasticity is the physical tendency of an object to return to an initial state after deformation. When stretched, an elastic body tends to return to its original shape. The tension developed when an elastic structure is stretched is proportional to the degree of deformation produced (Hooke’s law). An example is a simple spring (Figure 10-3). When tension on a spring is increased, the spring lengthens. However, the ability of the spring to stretch is limited. When the point of maximal stretch is reached, further tension produces little or no increase in length. Additional tension may break the spring.

FIGURE 10-3 Graphic representation of the force-length relationship applied to a simple spring (increase in length with increase in force). With increasing force, or weight in this example, the spring lengthens from A to B, but at the point of maximal stretch, further force produces no additional increase in length (B to C).

In the respiratory system, inflation stretches tissue. The elastic properties of the lungs and chest wall oppose inflation. To increase lung volume, pressure must be applied. This property may be shown by subjecting an excised lung to changes in transpulmonary pressure and measuring the associated changes in volume (Figure 10-4). To simulate the pressures during breathing, the lung is placed in an airtight jar. The force to inflate the lung is provided by a pump that varies the pressure around the lung inside the jar, simulating P_pl. This action mimics the pleural pressure changes associated with thoracic expansion and contraction. The changes in transpulmonary pressure are made in discrete steps, allowing the lungs to come to rest in between so that all of the applied pressure opposes elastic forces and none of it opposes resistive forces (i.e., flow is zero when the measurements are made). The amount of stretch (inflation) is measured as volume by a spirometer. Changes in volume resulting from changes in transpulmonary pressure are plotted on a graph.

FIGURE 10-4 Measurement of the pressure-volume curve of an excised lung. The lung is placed in a sealed jar and connected to a spirometer (to measure volume). A pump generates subatmospheric pressure around the lung while its volume is measured. The curve plotting the relationship between pressure and volume is nonlinear and flattens at high expanding pressures (subatmospheric). The inflation and deflation curves are not the same. This difference is called *hysteresis.* (Modified from West JB: Respiratory physiology: the essentials, ed 7, Baltimore, 2005, Williams & Wilkins.)

During inspiration in this model, increasingly greater negative pleural pressures are required to stretch the lung to a larger volume. As the lung is stretched to its maximum (total lung capacity [TLC]), the inflation “curve” becomes flat. This flattening indicates increasing opposition to expansion (i.e., for the same change in transpulmonary pressure, there is less change in volume).²

As with a spring when tension is removed, deflation occurs passively as pressure in the jar is allowed to return toward atmospheric. Deflation of the lung does not follow the inflation curve exactly. During deflation, lung volume at any given pressure is slightly greater than it is during inflation. This difference between the inflation and deflation curves is called hysteresis.² Hysteresis indicates that factors other than simple elastic tissue forces are present. The major factor, particularly in sick lungs, is the opening of collapsed alveoli during inspiration that tend to stay open during expiration until very low lung volumes are reached.

Chest wall and lung elastances are connected in series, meaning that they both experience the same flow and change in volume, but they do not have the same pressure differences. Series elastances are simply additive. The elastance of the respiratory system is the sum of lung (pulmonary) elastance (E_L) and chest wall elastance (E_CW):

ERS=EL+ECW

Expressed in terms of compliance:

CRS=CL×CCWCL+CCW

The resistance of the natural and artificial airways (e.g., endotracheal tube) is also in series so that the total system resistance is simply the sum of resistance of the components.

Surface Tension Forces

Part of the hysteresis exhibited by the lung is a result of surface tension forces in the alveoli. If a lung is filled with fluid such as saline, the pressure-volume curves look much different than the pressure-volume curves of an air-filled lung (Figure 10-5). Less pressure is needed to inflate a fluid-filled lung to a given volume. This phenomenon indicates that a gas-fluid interface in the air-filled lung changes its inflation-deflation characteristics.

FIGURE 10-5 Static pressure-volume curves of saline-filled and air-filled excised lungs. In the saline-filled lung, the distending pressure is the same during inflation and deflation. The air-filled lung shows hysteresis (i.e., higher pressure for a given volume on inflation compared with deflation). The hysteresis results in part from the effects of surface tension forces caused by the air-liquid interface in the alveoli. (Modified from Slonim NB, Hamilton LH: Respiratory physiology, ed 5, St Louis, 1987, Mosby.)

The recoil of the lung is a combination of tissue elasticity and these surface tension forces in the alveoli. During inflation, additional pressure is needed to overcome surface tension forces. During deflation, surface tension forces are reduced, resulting in altered pressure-volume characteristics (i.e., the leftward shift seen in Figure 10-4). In the intact lung (i.e., within the chest), the volume history also affects the degree of hysteresis that occurs. Factors such as the initial volume, the tidal excursion, and whether the lungs have been previously inflated or deflated help determine the volume history and the shape of the pressure-volume curves of the lung.

Mini Clini

Surfactant Replacement Therapy and Lung Mechanics

Problem

If an infant is born prematurely, the lungs may be unable to produce adequate amounts of pulmonary surfactant. How does this condition affect lung mechanics, and what effect does surfactant replacement therapy have on lung compliance and the work of breathing?

Discussion

The liquid molecules that line each alveolus attract one another. This attraction creates a force called surface tension, which tends to shrink the alveolus. Pulmonary surfactant molecules have weak intramolecular attractive forces. When surfactant molecules are mixed with other liquid molecules that have higher intramolecular attraction, the surfactant molecules are pushed to the surface of the liquid, where they form the air-liquid interface. Because of the weak intramolecular attraction between these surfactant molecules at the surface, the liquid lining of the alveoli exhibits much less surface tension than it would in the absence of pulmonary surfactant. A premature infant with inadequate surfactant has abnormally high intraalveolar surface tension; this produces a collapsing force that increases lung recoil and reduces lung compliance. Greater muscular effort is required to overcome increased recoil during inspiration, and the work of breathing is increased. The infant may eventually become fatigued and develop ventilatory failure. Instillation of artificial surfactant into the lungs reduces surface tension to its normal level. Lung compliance is increased, elastic recoil is reduced, and the muscular work required to inflate the lung is reduced.

A phospholipid called pulmonary surfactant reduces surface tension in the lung. Alveolar type II cells probably produce pulmonary surfactant (see Chapter 8). In contrast to typical surface-active agents, pulmonary surfactant changes surface tension according to its area.³ The ability of pulmonary surfactant to reduce surface tension decreases as surface area (i.e., lung volume) increases. Conversely, when surface area decreases, the ability of pulmonary surfactant to reduce surface tension increases. This property of changing surface tension to match lung volume helps stabilize the alveoli. Any disorder that alters or destroys pulmonary surfactant can cause significant changes in the work of distending the lung.

Lung Compliance

Tissue elastic forces and surface tension oppose lung inflation. Compliance is the reciprocal of elastance:

Compliance=1Elastance=ΔVΔP

Compliance is defined as volume change per unit of change in the pressure difference across the structure. It is usually measured in milliliters per centimeter of water.

A graph of change in lung volume versus change in transpulmonary pressure (Figure 10-6, A) is the compliance curve of the lungs. Figure 10-6, B compares a normal lung compliance curve with curves that might be observed in patients who have emphysema (obstructive lung disease) or pulmonary fibrosis (restrictive lung disease). The curve from a patient with emphysema is steeper and displaced to the left. The shape and position of this curve represent large changes in volume for small pressure changes (increased compliance). Increased compliance results primarily from loss of elastic fibers, which occurs in emphysema. The lungs become more distensible so that the normal transpulmonary pressure results in a larger lung volume. The term hyperinflation is used to describe an abnormally increased lung volume. A distinctly opposite pattern is seen in pulmonary fibrosis. Interstitial fibrosis is characterized by an increase in connective tissue. The compliance curve of a patient with pulmonary fibrosis is flatter than the normal curve, shifted down and to the right. As a result, there is a smaller volume change for any given pressure change (decreased compliance). Consequently, the lungs become stiffer, usually with a reduced volume.

FIGURE 10-6 A, Compliance measurement (deflation curve). After swallowing an esophageal balloon, the subject inhales a full breath and then exhales slowly. At specific lung volumes, he holds his breath with the glottis open, ensuring an alveolar pressure of zero. Lung volume is plotted against esophageal pressure (which essentially equals P_pl), generating a compliance curve. B, Compliance curves. Normal lung compliance is approximately 0.2 L/cm H₂O (measured from the lower portion of the curve, near resting lung volume). Compliance is increased in emphysema because of the destruction of elastic tissue; conversely, it is decreased in pulmonary fibrosis because of increased elastic recoil. (Modified from Martin L: Pulmonary physiology in clinical practice: the essentials for patient care and evaluation, St Louis, 1987, Mosby.)

Chest Wall Compliance

Inflation and deflation of the lung occur with changes in the dimensions of the chest wall (see Chapter 8). The relationship between the lungs and the chest wall can be illustrated by plotting their relaxation pressure curves separately and combined (Figure 10-7). In the intact thorax, the lungs and chest wall recoil against each other. The point at which these opposing forces balance determines the resting volume of the lungs, or functional residual capacity. This is also the point at which alveolar pressure equals atmospheric pressure. The normal FRC is approximately 40% of the TLC. If the normal lung–chest wall relationship is disrupted, the lung tends to collapse to a volume less than the FRC, and the thorax expands to a volume larger than the FRC.

FIGURE 10-7 Relationship between the lungs and chest wall. Volumes of the lungs, thorax, and lungs and thorax combined are plotted as a percentage of vital capacity against intrapulmonary pressure (recoil pressure). The combined lung-thorax relaxation curve *(solid line)* is the sum of the individual lung and thorax curves. Equilibrium (zero pressure) occurs where the lung and thoracic recoil forces balance (a + b = 0). This point determines the FRC (lung B). Lung A represents low lung volume with greater recoil pressure exerted by the chest wall. Lung C shows a chest wall recoil of zero at approximately 70% of TLC. When lung volume is greater than 70% of TLC, greater pressures are required to distend both the lungs and the thorax (lung D). (Modified from Beachey W: Respiratory care anatomy and physiology, ed 2, St Louis, 2007, Mosby.)

Rule of Thumb

The lungs and chest wall each have their own compliance, or distensibility. In healthy adults, the compliance of the lungs and chest wall are approximately equal at 0.2 L/cm H₂O. However, because the lungs are contained within the thorax, the two systems act as springs pulling against each other. This action reduces the compliance of the system to approximately half that of the individual components, or 0.1 L/cm H₂O. This rule has many practical implications, particularly for mechanical ventilation of the lungs. Any disease process that alters the compliance of the lungs or chest wall can seriously disrupt the normal mechanics of ventilation.

The lung–chest wall system may be compared with two springs that are pulling against each other. The chest wall spring tends to expand, whereas the lung spring tends to contract. At the resting level, the forces of the chest wall and lungs balance. The tendency of the chest wall to expand is offset by the contractile force of the lungs. This balance of forces determines the resting lung volume, or FRC. The opposing forces between the chest wall and lungs are partially responsible for the subatmospheric pressure in the intrapleural space. Diseases that alter the compliance of either the chest wall or the lung often disrupt the balance point, usually with a change in lung volume.

Inhalation occurs when the balance between the lungs and chest wall shifts. Energy from the respiratory muscles (primarily the diaphragm) overcomes the contractile force of the lungs. At the beginning of the breath, the tendency of the chest wall to expand facilitates lung expansion. When lung volume nears 70% of the vital capacity, the chest wall reaches its natural resting level. To inspire to a lung volume greater than about 70% of TLC, the inspiratory muscles must overcome the recoil of both the lungs and the chest wall (see Figure 10-7).

For exhalation, potential energy “stored” in the stretched lung (and chest wall at high volumes) during the preceding inspiration causes passive deflation. To exhale below the resting level (FRC), muscular effort is required to overcome the tendency of the chest wall to expand. The expiratory muscles (see Chapter 8) provide this energy.

Compliance of the chest wall, similar to lung compliance, is a measure of distensibility. The compliance of the normal chest wall is similar to that of the lungs (0.2 L/cm H₂O). Obesity, kyphoscoliosis, ankylosing spondylitis, and many other abnormalities can reduce chest wall compliance and lung volumes.

R_aw in nonventilated patients is usually measured in a pulmonary function laboratory (see Chapter 19). Flow () is measured with a pneumotachometer. Alveolar pressures are determined in a body plethysmograph, an airtight box in which the patient sits. By momentarily occluding the patient’s airway and measuring the pressure at the mouth, alveolar pressure can be estimated (i.e., mouth pressure equals alveolar pressure under conditions of no flow). By relating flow and alveolar pressure to changes in plethysmograph pressure, airway resistance can be calculated.