Abstract
A thorough understanding of the basics of respiratory physiology is essential for any clinician caring for patients in the cardiovascular intensive care unit (CVICU). Distribution of ventilation, pulmonary blood flow, ventilation/perfusion matching, and the physiology of gas exchange are all essential and foundational concepts necessary for the treatment and care of the cardiac patient. Developmental changes and normal growth from infancy through young adulthood can have tremendous effects on these basic principles. Cardiac anatomy can vary tremendously with the observation that physiology that is normal and expected for one type of defect represents severe derangement in another. Although there are certainly some universal observations that can be said across the spectrum of congenital heart disease, there are numerous special exceptions in cardiopulmonary interactions that must be appreciated and appropriately addressed when caring for the cardiac patient.
Key Words
congenital heart disease, cardiopulmonary interactions, congenital heart surgery, respiratory mechanics, ventilation, perfusion, airway
Respiratory mechanics and physiology affect the broad spectrum of cardiac physiologies encountered in the cardiovascular intensive care unit (CVICU) in many interconnected and complex ways. Said differently, the patient affected by cardiac disease is often vulnerable to alterations in lung function, and the converse is also true: alterations in cardiac function and anatomy affect respiratory physiology in often dramatic ways. It is therefore imperative for the clinician to be aware of how normal and abnormal respiratory mechanics can create excessive demands on cardiac output, and how they can adversely affect both short- and long-term somatic growth. The mechanisms by which this detriment to cardiac output and somatic growth occurs are multifactorial and truly merit a multivolume textbook dedicated to just this subject. We present to the reader in this chapter an introductory discussion of some of these concepts and mechanisms.
Distribution of Ventilation
Gravity-Dependent Determinants of Ventilation
The lung is a viscoelastic structure that is located inside and is supported by the chest wall. Gravity causes the lung to assume a globular shape with a relatively more negative pressure at the top and a more positive pressure at the base of the lung. The magnitude of the pleural pressure (P pl ) gradient depends on the density of the lung. P pl normally increases 7.5 cm H 2 O from the top to the bottom of the adult lung.
In normal lungs the pressure of the air in the alveolus (alveolar pressure [P A ]) is equal throughout the lung, and the P pl gradient results in regional differences in transpulmonary pressure (P A − P pl ). Where P pl is most positive (i.e., least negative), the transmural pressure differences result in the alveoli being compressed and smaller than the apical alveoli. Thus the small alveoli located in the basal areas of the lung are on the midportion of a normal pressure-volume curve of the lung, and the larger alveoli of the apices of the lung are on the upper portion ( Fig. 14.1 ). Dependent alveoli are relatively more compliant (have a greater volume change for a given change in pressure [i.e., on the steep slope of the pressure-volume curve]), whereas nondependent alveoli are relatively less compliant (on the flatter slope). Therefore the majority of the tidal volume during normal ventilation is preferentially distributed to dependent alveoli because these alveoli expand more per unit pressure change than do nondependent alveoli.
Gravity-Independent Determinants of Ventilation
Muscles of Respiration.
In order for gas exchange to occur at the level of the alveoli, inspired air must travel into the lung through the airways. The muscles of respiration, which include the diaphragm and the external intercostal muscles, actively constrict during inspiration to allow air in, whereas quiet expiration occurs passively via elastic recoil of the system. Accessory muscles of inspiration, such as the scalene and sternocleidomastoid muscles, aid respiration during exercise. Expiration also becomes active during exercise with the contraction of muscles of the abdominal wall (i.e., rectus abdominis, internal and external oblique muscles and transversus abdominis), and the internal intercostal muscles.
Lung Volumes and Airway Closure.
Functional residual capacity (FRC) is defined as the volume of gas remaining in the normal lungs at the end of an expiration, when P A equals ambient pressure (P ambient ). FRC depends on the balance of the lungs’ intrinsic elastic properties that favor reduction in volume and the natural tendency of the chest wall to recoil outward. Changes in the elastic properties of either of these components of the respiratory system alter FRC.
Total lung capacity (TLC) is the entire gas volume of the maximally spontaneously inflated pulmonary parenchyma and airways in the thorax. It provides the reference point for all other lung volumes and capacities ( Fig. 14.2 ). Vital capacity defines the volume obtained by maximal expiration from TLC and is the maximum volume possible during spontaneous ventilation. As such, it provides a measure of ventilatory reserve.
A critical relationship occurs between the volume of gas remaining in the normal lungs at the end of expiration (FRC) and the volume of gas in the lung at the point at which conducting airways collapse, which is called the closing capacity (CC). Using the inert gas washout technique during maximal inspiratory and expiratory maneuvers, the CC can be identified as the point at which conducting airways in dependent lung regions begin to collapse. If end-expiratory lung volume (EELV) falls below CC, or conversely CC is elevated above EELV, these areas of lung collapse and do not participate in gas exchange.
Compliance.
The relationship between the change in volume (ΔV) and change in distending pressure (ΔP) defines compliance.
C = Δ V / Δ P
During certain modes of positive or negative pressure lung inflation, the transthoracic pressure gradient first increases to a peak value and then decreases to a lower plateau value. The peak transthoracic pressure is the pressure required to overcome both elastic and airway resistance (see later). The transthoracic pressure decreases to a plateau value because gas redistributes over time to alveoli with longer time constants. As the gas redistributes into an increased number of alveoli, less pressure is generated by the same volume of gas, and the pressure decreases. Therefore two measures of compliance can be made, dynamic and static. During positive pressure ventilation, dynamic compliance can be estimated by calculating the volume change (tidal volume) divided by the peak inspiratory pressure minus the end-expiratory pressure (positive end-expiratory pressure [PEEP]). As such, dynamic compliance makes an accounting for the movement of gas through the system. In contrast, static compliance can be approximated by measuring the change in volume divided by the plateau inspiratory pressure minus the end-expiratory pressure. Plateau pressure falls below peak inspiratory pressure because of gas redistribution; therefore static compliance is greater than dynamic compliance. Static compliance is a better evaluation of the entire respiratory system, because the measurement reflects more of the gas-exchanging alveoli.
The compliance relationship of the chest wall and lung units is sigmoidal. At the extremes of lung volumes, compliance decreases, and a larger increase in peak inspiratory pressure is required to obtain similar changes in volume. Underinflation (atelectasis, hypoventilation, EELV < FRC) and overexpansion (asthma, excessive PEEP, EELV > FRC) should thus be avoided because they require greater peak pressures to change lung volume.
An additional force that contributes to the elastic recoil of the lung is surface tension . Surface tension is a force generated by the stronger attraction between adjacent liquid molecules than between molecules of liquid and gas. Because of this force, liquid assumes the shape of a sphere, which provides the smallest possible surface area for a given volume. The liquid that lines the alveolus exerts surface tension and is described by Laplace’s law, in which pressure (P) to inflate an alveolus is directly proportional to the surface tension (T) of the fluid lining the alveolus and inversely proportional to the radius (R) of the alveolus:
P = 2 T / R
Using this relationship, the pressure inside small alveoli would be higher than inside large alveoli. Because small alveoli would have greater pressure than large ones, small alveoli would empty into larger ones, until theoretically, one gigantic alveolus would be left ( Fig. 14.4A ). This phenomenon does not occur in the lung because of the alterations in alveolar surface tension.
In the normal healthy lung, tension is reduced by the presence of surfactant, which is a mixture of phospholipids, neutral lipids, and proteins produced by type II pneumocytes. It greatly reduces surface tension in the alveoli due to the mixed property of its phospholipid molecule being hydrophilic at one end and hydrophobic at the other. By reducing surface tension and therefore the pressure needed to inflate the alveolus, surfactant increases lung compliance. Surfactant also allows stabilization of smaller alveoli, inhibiting them from discharging their contents into large alveoli (see Fig. 14.4B ). Pulmonary edema can be exacerbated as surface tension forces draw fluid from the capillaries in the alveoli. By reducing surface tension, surfactant prevents transudation of fluid by reducing the hydrostatic driving force for pulmonary edema.
For preterm infants incapable of producing adequate amounts of endogenous surfactant, exogenous surfactant replacement has been used for many years with great reduction of morbidity and mortality. In addition to bovine- and porcine-derived surfactant, synthetic surfactant has also become available. Newer studies are investigating the effectiveness of minimally invasive surfactant administration techniques, such as nebulization, which would allow administration in nonintubated infants.
Alterations in chest wall and lung compliance are important conditions that require continuous evaluation in critically ill children. Although both an increase and a decrease in compliance can result in a change in lung volume, a reduction in compliance requires prompt identification and intervention. A decrease in intrinsic compliance of the lungs and/or chest wall will result in decreased total compliance and a reduction of lung volume for a given P A and a decrease in FRC. In many clinical instances this may necessitate the application of additional distending pressure (P A ) in the form of positive pressure ventilation and/or continuous positive airway pressures (continuous positive airway pressure [CPAP]/PEEP) to reestablish normal lung volumes.
Resistance.
For gas flow to occur, a pressure gradient must be generated to overcome the nonelastic airway resistance of the lungs. Mathematically, resistance (R) is defined by the pressure gradient (ΔP) required to generate a given flow of gas ( V̇ ). Physically, resistance results from the friction during movement of gas molecules within the airways (airway resistance) and friction from motion of the lung and chest wall (tissue viscous resistance). These components make up the total nonelastic resistance of the respiratory system. Normally airway resistance accounts for approximately 75% of total nonelastic resistance. However, in conditions in which respiratory pathophysiology alters tissue viscous resistance, airway resistance may be altered.
The pressure gradient (ΔP) along the airway is dependent upon the caliber of the airway and the rate and pattern of airflow. During laminar flow the pressure drop down the airway is proportional to the flow. When flow exceeds a critical velocity, it becomes turbulent, and the pressure drop down the tube becomes proportional to the square of the flow. As flow becomes more turbulent, pressure increases more than flow, and resistance increases. Increased airway resistance requires a larger pressure gradient between the airway opening and the alveoli to maintain flow. During positive pressure ventilation this requires the generation of higher inspiratory pressures to achieve similar ventilation, whereas during spontaneous breathing a more negative intrapleural and alveolar pressure must be achieved to maintain similar ventilation. In both cases the work required to produce adequate gas flow is increased.
Resistance of the airways is approximated by the diameter of the airway, the velocity of airflow, and the properties of inhaled gases. Resistance is determined by Poiseuille’s law, which governs the laminar flow of gas in nonbranching tubes:
P = V ˙ ( 8 L η ′ / π r 4 )
Airway resistance is also dependent on alterations in lung volume. When lung volume is increased above FRC, airway resistance increases by only a small amount. In contrast, when lung volume is decreased below FRC, airway resistance increases dramatically. Airway resistance is also dependent on conducting airway patency. During normal negative pressure ventilation, intrathoracic conducting airways have a tendency to narrow on exhalation and open on inspiration. The result is an increase in airway resistance during exhalation. In conditions in which total cross-sectional area is reduced and airway resistance increased, small airways collapse, and flow limitations occur during expiration.
Time Constants.
The interaction between compliance and resistance largely determines the distribution of ventilation within the lungs. This relationship is defined as the product of the resistance (R) and compliance (C), which is the time constant (τ), measured in seconds:
τ = R ( cm H 2 O L / sec ) × C ( L cm H 2 O )
The time constant defines the time required for each compartment to achieve a change in volume following the application or withdrawal of a constant distending pressure. It also describes the time required for the pressure within alveoli to equilibrate. As an example, a constant distending pressure applied to the airway overcomes airway resistance and expands the lung (elastic forces). The component of the distending pressure overcoming resistance to airflow is maximal initially and declines exponentially as airflow decreases. The component overcoming elastic forces increases in proportion to the change in lung volume. Thus the pressure required to overcome compliance is initially minimal, then increases exponentially with increasing lung volume. Lung volume approaches equilibrium according to an exponential function with the time course of change in these exponential curves being described by their time constant. Mathematically, 63% of lung inflation (or deflation) occurs in one time constant ( Fig. 14.5 ).
Most causes of respiratory failure have widespread abnormalities in pulmonary resistance and compliance, resulting in striking inhomogeneity in regional time constants. Consequently, with normal tidal breathing, certain compartments fill and empty rapidly (short time constants) while others fill and empty slowly (long time constants). This inhomogeneity of time constants results in marked irregularities in the distribution of ventilation with abnormal gas exchange. Under these conditions, successful positive pressure ventilation may require manipulation of inspiratory and expiratory time to allow more uniform distribution (“homogeneity”) of ventilation among lung compartments. This strategy, described elsewhere, frequently improves ventilation/perfusion (V/Q) matching.
Work of Breathing.
Work of breathing is defined as the energy necessary to perform tidal ventilation over a set unit of time. The work of breathing is determined by the pressure-volume characteristics (compliance and resistance) of the respiratory system ( Fig. 14.6 ). During breathing, work must be done to overcome the tendency of the lungs to collapse and the chest wall to spring out (see Fig. 14.6 , area ADC) and the frictional resistance to gas flow that occurs in the airways (see Fig. 14.6 , area ABC). Work of breathing (see Fig. 14.6 , area ABCD) is increased by conditions that increase resistance or decrease compliance or when respiratory frequency increases.
If minute volume is constant, the “compliance” component of work is increased when tidal ventilation is large and respiratory rate slow. The “resistance” component of work is increased when the respiratory rate is rapid and tidal ventilation decreased. When the two components are summated and the total work plotted against the respiratory frequency, an optimal respiratory frequency that minimizes the total work of breathing can be obtained ( Fig. 14.7 ). In children with restrictive lung disease (EELV < FRC, low compliance) and short time constants, the optimal respiratory frequency is increased, whereas children with obstructive lung diseases (EELV > FRC, high resistance) with long time constants have a lower optimal respiratory frequency.
Distribution of Pulmonary Blood Flow
The pulmonary vasculature can be modeled as having two components: (1) a fixed component that is the primary determinant of regional perfusion and (2) a variable component that acts on top of the fixed structure and is affected by local factors. The fixed structures can best be characterized using fractal geometry, a new mathematical science used to describe “natural objects.” The variable component of the vasculature can be influenced by passive and active regional factors such as recruitment and/or distention due to changing hydrostatic or driving pressures. Active factors such as vasomotion in response to shear stress or hypoxic vasoconstriction will influence regional perfusion. The relative contribution of both the fixed and variable components of the pulmonary circulation to pulmonary perfusion heterogeneity can be quantified.
Passive Pulmonary Blood Flow
Passive alterations in pulmonary vascular resistance (PVR) and blood flow are the primary determinants of the distribution of pulmonary blood flow. In the majority of critically ill patients the primary emphasis in critical care is placed on altering active pulmonary blood flow without a clear appreciation of the importance of passive pulmonary blood flow. Active pulmonary blood flow, however, cannot be fully appreciated without a sound understanding of the passive relationship that occurs between pulmonary artery pressure, P A , and cardiac output.
Gravity-Dependent Determinants of Blood Flow.
For many years it has been held that the primary determinant of the distribution of pulmonary blood flow is gravity. The right ventricle imparts kinetic energy to blood during systole and ejects a stroke volume into the pulmonary artery. The kinetic energy is dissipated in the lungs as blood in the pulmonary artery climbs a vertical column in the gravity-dependent lung. The pulmonary artery pressure therefore decreases by 1 cm H 2 O per centimeter vertical distance up the lung ( Fig. 14.8 ). The distribution of pulmonary blood flow to different lung segments is dependent upon the differences between three pressures in the lung: (1) intraalveolar pulmonary artery pressure (P pa ) or pulmonary capillary pressure, (2) P A , and (3) venous pressure (P pv ). At some height above the heart the absolute pressure in the pulmonary artery (P pa ) becomes less than zero (atmospheric). At that point, P A exceeds P pa and P pv . In this region the pulmonary vessels are collapsed due to the higher P A , and blood flow ceases (West zone 1, P A > P pa > P pv ). Lung that undergoes ventilation but no perfusion does not contribute to gas exchange and is referred to as physiologic dead space . Normally, very few of the lung units function as zone 1. Any factor that alters the P pa /P A relationship supporting the collapse of pulmonary vessels (i.e., P A > P pa or P pa /P A < 1) will result in an increase in zone 1 lung. These conditions include an increase in P A (application of positive pressure to the airways) or a reduction of P pa (decreased cardiac output, shock, pulmonary emboli).
In regions of the lung where P pa exceeds P A and P A exceeds P pv , perfusion occurs (West zone 2, P pa > P A > P pv ). Pulmonary arterial flow to this region is determined by the mean pulmonary artery versus alveolar pressure difference (P pa − P A ). Blood flow is independent of the venous (P pv ) or left atrial pressure. Because mean P pa increases down the lung while mean P A remains constant, the mean driving pressure (P pa − P A ) increases, and blood flow in the lower portions of the lung increases. In inferior segments of the lung, P pv exceeds P A , and blood flow is governed by the pulmonary arteriovenous pressure difference (P pa − P pv ) (West zone 3, P pa > P pv > P A ). The effects of gravity are equal on pulmonary artery and pulmonary venous pressure, and both P pa and P pv increase at the same rate; thus the capillaries are permanently open, and the perfusion pressure (P pa − P pv ) is constant. However, because the increase in P pl is less than the increase in P pa and P pv , the transmural distending pressure (P pa − P pl and P pv − P pl ) increases down zone 3. Therefore the resistance is decreased, and for a given driving pressure, flow increases. Thus flow increases at lower lung levels in zone 3. It must be realized that ventilation and pulmonary blood flow are constantly changing forces and any given portion of the lung may actually move in and out of zone 2 conditions and become either zone 1 or zone 3, depending upon whether the patient is in cardiac systole or diastole, inspiration or expiration, or spontaneous or positive pressure ventilation.
When pulmonary vascular pressures are extremely high, as in volume or pressure loading of the pulmonary arteries, fluid transudate forms in the interstitial space. When fluid flow into the interstitial space exceeds the lymphatic clearance rate, fluid accumulates. This eliminates the normally present negative tension on the extraalveolar vessels. Pulmonary interstitial pressure (P int ) eventually becomes positive and exceeds P pv (West zone 4, P pa > P int > P pv > P A ). In zone 4, pulmonary blood flow is regulated by the arterial-interstitial pressure difference (P pa − P int ). The arterial-interstitial pressure difference in zone 4 is less than the zone 3 difference (P pa − P pv ); therefore zone 4 blood flow is less than zone 3 blood flow.
Alterations of P pa and P pv not only cause changes in regional blood flow but also affect the microcirculation. Three gradual changes take place in the pulmonary circulation when P pa and P pv increase: (1) recruitment or opening of previously nonperfused vessels, (2) distention or widening of previously perfused vessels (increased cross-sectional area, less resistance), and (3) transudation of fluid at the capillary level. Recruitment occurs when P pa and P pv are increased from low to moderate levels, distension occurs when P pa and P pv are increased from moderate to high levels, and finally, transudation occurs when P pa and P pv are increased from high to very high levels.
Gravity-Independent Determinants of Blood Flow.
The first study to demonstrate that the geometry of the vascular bed is an important determinant of pulmonary blood flow distribution was made by Reed and Wood. Later techniques providing high-resolution measurements of pulmonary perfusion have confirmed a large degree of spatial heterogeneity, likely based on the architecture of the vasculature. Neighboring regions of lung have similar magnitudes of flow (i.e., high-flow regions are adjacent to other high-flow regions, and low-flow regions are adjacent to other low-flow regions). This relationship can be quantified using correlation coefficients between flows to pairs of lung regions. The spatial correlation [ρ(d)] is the correlation between blood flow to one region at one position and blood flow to a second region displaced by distance d. The correlation can range from 1 (perfect positive correlation) to −1 (perfect negative correlation) with 0 indicating random association between pairs. When the spatial correlation of perfusion is determined for regional pulmonary perfusion, a positive correlation is found for neighboring regions. This spatial correlation is best modeled using fractal methods. When extended to three dimensions, this fractal model is able to explain the high local correlations in blood flow and the decreasing correlation as distance increases. Pulmonary perfusion has also been shown to have temporal variability.
Recent studies using these high-resolution methods as well as experiments performed in both microgravity and macrogravity settings have demonstrated that pulmonary perfusion is far more heterogeneous than can be explained by gravity alone. Although multiple studies in different species have confirmed gravity-independent perfusion heterogeneity, these observations have not been made in man. Some investigators suggest that gravity is not an important determinant of pulmonary blood flow distribution in quadrupeds (a characteristic common to all species in these studies) because their posture produces smaller lung volumes. Quadrupeds also have a more muscularized vascular system with a smaller proportion of their vascular resistance in the microvascular segments. In an attempt to overcome these potential problems, high-resolution methods were recently used in baboons (a species with pulmonary structures and physiology remarkably similar to man). With the use of multiple-stepwise regression, gravity-dependent perfusion heterogeneity was estimated at 7%, 5%, and 25% in the supine, prone, and upright positions, respectively. Therefore these recent high-resolution experiments continue to suggest that gravity is an important, but not predominant, determinant of pulmonary perfusion heterogeneity.
PVR and blood flow are dependent on a variety of physiologic conditions, including lung volume. As discussed earlier, FRC is the lung volume at the end of an expiration in normal lungs, when P A equals P atm . Total PVR is increased when lung volume is either increased above or decreased below FRC ( Fig. 14.9 ). The increase in total PVR at lung volumes above FRC is due to a large increase in vascular resistance contributed by the small intraalveolar vessels, which are extended and compressed by the expanded alveolus and surrounding lung. In contradistinction, the increase in total PVR at lung volumes below FRC is due to hypoxic pulmonary vasoconstriction (HPV), which occurs in collapsed alveoli and the tortuous course of the large extraalveolar vessels at low lung volumes.
FRC can therefore be understood as the lung volume at which PVR is minimized, an observation that should be leveraged when optimizing positive pressure ventilation. It is worth noting that lung compliance and resistance are also optimized at FRC, with compliance being the highest at FRC and resistance being the lowest. Thus in normal lungs EELV is the same as FRC, and the work of ventilation and of perfusion is minimized.
The relationship between lung volume and FRC is obviously variable. Tidal ventilation occurs from EELV (FRC in normal lungs), and thus PVR, airway resistance, and lung compliance cycle dynamically with ventilation. In disease states, EELV can be increased above FRC (obstructive lung disease) or decreased below FRC (restrictive lung disease). This pathologic EELV (i.e., when EELV does not equal FRC) will alter PVR, compliance, and resistance. For these reasons, mechanical ventilation applied during diseased states should be tailored to allow for tidal volume at or near FRC.
Active Pulmonary Blood Flow
Total PVR expresses the relationship between flow and driving pressure (Ohm’s law). In the pulmonary circulation the vessels are not rigid tubes but expand as flow increases. Therefore PVR is flow dependent and decreases as flow increases. In addition, previously nonperfused vessels are recruited (opened) as cardiac output increases. Because of these physiologic principles, PVR is not precisely measured in the pulmonary circulation, and the relationship between flow and pressure must be carefully assessed. Two situations, however, can occur in which PVR changes can be accurately measured. One condition is active pulmonary vasoconstriction, which occurs when cardiac output is decreased and P pa remains constant or is increased. Another is active pulmonary vasodilation, which can occur when cardiac output increases and P pa remains constant or decreases.
A variety of physiologic or pharmacologic stimuli may cause alterations of the pulmonary circulation. One of the most frequently encountered is alveolar hypoxia. Alveolar hypoxia of a whole lung, lobe, or lobule of lung causes localized pulmonary vasoconstriction (see Chapter 23 ), referred to as a hypoxic pulmonary vasoconstriction (HPV). HPV is present in all mammalian species. The mechanisms by which alveolar hypoxia causes pulmonary vasoconstriction remain unclear, although two theories have been proposed. First, alveolar hypoxia may change the balance between vasoconstrictor substance(s) and vasodilator substance(s) elaborated from multiple potential sources (e.g., endothelium, smooth muscle), with the net result of vasoconstriction. Recent evidence suggests that HPV may in part be a result of a reduction of endothelium-derived nitric oxide. Second, hypoxia may stimulate the metabolic activity of pulmonary vascular smooth muscle, partially depolarizing the cell membrane, influencing excitation coupling, and causing ion fluxes that cause vasoconstriction. Thus HPV appears to be due to hypoxia-induced modulation of vasoactive substances and/or a direct action on the pulmonary vascular smooth muscle. HPV may involve the entire lung or be limited to localized regions of the lung, depending on whether there is global or regional alveolar hypoxia. Regional alveolar hypoxia causes locally increased vascular resistance and shunts blood toward normoxic lung with lower vascular resistance, thereby improving V/Q matching. Global alveolar hypoxia results in an elevated mean P pa and an increased workload for the right ventricle. Regional HPV is therefore a protective mechanism designed to optimize V/Q matching, whereas global HPV is a maladaptive response and can lead to right ventricular dysfunction and failure.
Ventilation/Perfusion Matching.
Matching of lung ventilation (V) and perfusion (Q) at the alveolar level is necessary for optimal gas exchange to occur. The ratio of ventilation to perfusion (V/Q) expresses the amount of ventilation relative to perfusion in any given lung region. In the normal healthy lung the idealized lung region has perfectly matched ventilation to perfusion, where V/Q equals 1. Both pulmonary blood flow and ventilation increase with distance down the normal upright lung in a gravity-dependent manner (as discussed previously). However, because blood flow increases more rapidly and from a much lower value than ventilation, V/Q decreases exponentially.
V/Q mismatch alters both arterial oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) tensions. Blood flows from underventilated alveoli (with V/Q < 1) tend to have increased PaCO 2 and decreased PaO 2 . Blood flows from overventilated alveoli (with physiologic dead space and with V/Q > 1) have lower PaCO 2 but cannot increase the PaO 2 due to the flat upper portion of the oxygen-hemoglobin dissociation curve. Thus in conditions with V/Q inequalities, carbon dioxide can be eliminated from the overventilated alveoli to compensate for the underventilated alveoli, but large alveolar to arterial oxygen gradients can occur. In fact, V/Q mismatching is the major cause of hypoxemia associated with respiratory diseases. PaCO 2 may be normal or even low in response to compensatory hyperventilation for the hypoxemia.
V/Q inequality can be altered by a variety of respiratory interventions, which include increasing inspired oxygen or application of positive pressure to the airway. Increasing the concentration of inspired oxygen overcomes the alveolar arterial gradient in poorly ventilated alveoli (i.e., low V/Q lung compartments), resulting in improved oxygen content of the blood.
Physiology of Gas and Fluid Exchange
Gas Properties
The primary function of the respiratory system is to transfer oxygen and carbon dioxide across the alveolar-capillary membrane. This process occurs in the terminal gas exchange unit (alveoli). The transfer of oxygen and carbon dioxide represents the summation of multiple interactions at the level of the alveoli and represents the fundamental process of gas exchange between inspired gases and pulmonary capillary blood. For a more thorough evaluation of these complex interactions, excellent reviews are available. The purpose of this section is not to be comprehensive but rather to provide enough background to convey the basic principles of gas exchange.
The behavior of gases and the principles of gas exchange can be expressed by certain laws. The pressure exerted by a gas and its components is observed by Dalton’s law. Dalton’s gas law states that the pressure exerted by a group of gases is the sum of the partial pressure of these gases. This property defines the pressure exerted by the individual components of a gas mixture. At standard temperature (37°C) and at sea level (atmospheric pressure P B = 760 mm Hg), air consists of 20.93% oxygen. Therefore the partial pressure exerted by oxygen in air is:
P air O 2 = ( % O 2 in air ) × atmospheric pressure ( P B ) P air O 2 = 0.2093 × 760 = 159 mm Hg
The partial pressure of oxygen, however, is altered before gas exchange at the alveolar level. When a gas is inhaled, it is warmed and saturated with water vapor. The partial pressure exerted by water vapor must be accounted for and varies with the temperature of the humidified gas; it is independent of pressure. At 37°C the partial pressure of water vapor is 47 mm Hg. Therefore by the time an inhaled gas has reached the level of the alveoli, the partial pressure of the gas has been reduced to 149 mm Hg (0.2093 × 760 − 47 mm Hg).
At the alveolar level the percentage of carbon dioxide in the alveolus is normally approximately 5.6%, and the partial pressure of alveolar carbon dioxide would be:
P A CO 2 = ( % CO 2 in alveolus ) × ( P B − P water vapor ) P A CO 2 = 0.056 × ( 760 − 47 mm Hg ) = 40 mm Hg
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