679

Chapter 17 - Respiratory Physiology and Respiratory Function during Anesthesia

William C. Wilson

Jonathan L. Benumof

RESPIRATORY PHYSIOLOGY

Anesthesiologists require an extensive knowledge of respiratory physiology to care for patients in the operating room and the intensive care unit. Mastery of the normal respiratory physiologic processes is a prerequisite to understanding the mechanisms of impaired gas exchange that occur during anesthesia and surgery and with disease. This chapter is divided into two sections. The first section reviews the normal (gravity-determined) distribution of perfusion and ventilation, the major nongravitational determinants of resistance to perfusion and ventilation, transport of respiratory gases, and the pulmonary reflexes and special functions of the lung. In the second section of this chapter, these processes and concepts are discussed in relation to the general mechanisms of impaired gas exchange during anesthesia and surgery. The text has been updated to reflect recent developments in cellular physiology and molecular biology (e.g., the mechanisms of hypoxic pulmonary vasoconstriction). The interested reader is referred to other chapters in this book to review the topics of pulmonary function testing ( Chapter 26 ) and pulmonary pharmacology (including control of breathing and effects of anesthetic gases— Chapter 6 ).

Normal (Gravity-Determined) Distribution of Perfusion, Ventilation, and the Ventilation-Perfusion Ratio

Distribution of Pulmonary Perfusion

Contraction of the right ventricle imparts kinetic energy to the blood in the main pulmonary artery. As the kinetic energy in the main pulmonary artery is dissipated in climbing a vertical hydrostatic gradient, the absolute pressure in the pulmonary artery (Ppa) decreases by 1 cm H₂ O per centimeter of vertical distance up the lung ( Fig. 17-1 ). At some height above the heart, Ppa becomes zero (atmospheric), and still higher in the lung, Ppa becomes negative.^[1]

680

Figure 17-1 Schematic diagram showing the distribution of blood flow in the upright lung. In zone 1, alveolar pressure (PA) exceeds pulmonary artery pressure (Ppa), and no flow occurs because the intra-alveolar vessels are collapsed by the compressing alveolar pressure. In zone 2, Ppa exceeds PA, but PA exceeds pulmonary venous pressure (Ppv). Flow in zone 2 is determined by the Ppa-PA difference (Ppa - PA) and has been likened to an upstream river waterfall over a dam. Because Ppa increases down zone 2 whereas PA remains constant, perfusion pressure increases, and flow steadily increases down the zone. In zone 3, Ppv exceeds PA, and flow is determined by the Ppa-Ppv difference (Ppa - Ppv), which is constant down this portion of the lung. However, transmural pressure across the wall of the vessel increases down this zone, so the caliber of the vessels increases (resistance decreases), and therefore flow increases. Finally, in zone 4, pulmonary interstitial pressure becomes positive and exceeds both Ppv and PA. Consequently, flow in zone 4 is determined by the Ppa-interstitial pressure difference (Ppa - PISF). (Redrawn with modification from West JB: Ventilation/Blood Flow and Gas Exchange, 4th ed. Oxford, Blackwell Scientific, 1970.)

Further down the lung, absolute Ppa becomes positive, and blood flow begins when Ppa exceeds PA (zone 2, Ppa > PA > Ppv). At this vertical level in the lung, PA exceeds Ppv, and blood flow is determined by the mean Ppa - PA difference rather than by the more conventional Ppa - Ppv difference (see later).^[3] The zone 2 blood flow-alveolar pressure relationship has the same physical characteristics as a waterfall flowing over a dam. The height of the upstream river (before reaching the dam) is equivalent to Ppa, and the height of the dam is equivalent to PA. The rate of water flow over the dam is proportional to only the difference between the height of the upstream river and the dam (Ppa - PA), and it does not matter how far below the dam the downstream riverbed (Ppv) is. This phenomenon has various names, including the waterfall, Starling resistor, weir (dam made by beavers), and "sluice" effect. Because mean Ppa increases down this region of the lung but mean PA is relatively constant, the mean driving pressure (Ppa - PA) increases linearly, and therefore mean blood flow increases linearly. However, respiration and pulmonary blood flow are cyclic phenomena. Therefore, absolute instantaneous Ppa, Ppv, and PA are changing continuously, and the relationships among Ppa, Ppv, and PA are dynamically determined by the phase lags between the cardiac and respiratory cycles. Consequently, a given point in zone 2 may actually be in either a zone 1 or a zone 3 condition at a given moment, depending on whether the patient is in respiratory systole or diastole or in cardiac systole or diastole.

Still lower in the lung, there is a vertical level at which Ppv becomes positive and also exceeds PA. In this region, blood flow is governed by the pulmonary arteriovenous pressure difference (Ppa - Ppv) (zone 3, Ppa > Ppv > PA), for here both these vascular pressures exceed PA, and the capillary systems are thus permanently open and blood flow is continuous. In descending zone 3, gravity causes both absolute Ppa and Ppv to increase at the same rate, so perfusion pressure (Ppa - Ppv) is unchanged. However, the pressure outside the vessels, namely, pleural pressure (Ppl), increases less than Ppa and Ppv, so the transmural distending pressures (Ppa - Ppl and Ppv - Ppl) increase down zone 3, the vessel radii increase, vascular resistance decreases, and blood flow therefore increases further.

Finally, whenever pulmonary vascular pressure (PVR) is extremely high, as it is in a severely volume-overloaded patient, in a severely restricted and constricted pulmonary vascular bed, in an extremely dependent lung (far below the vertical level of the left atrium), and in patients with pulmonary embolism or mitral stenosis, fluid may transude out of the pulmonary vessels into the pulmonary interstitial compartment. In addition, pulmonary interstitial edema can be caused by extremely

681

When the flow of fluid into the interstitial space is excessive and cannot be cleared adequately by the lymphatics, it accumulates in the interstitial connective tissue compartment around the large vessels and airways and forms peribronchial and periarteriolar edema fluid cuffs. The transuded pulmonary interstitial fluid fills the pulmonary interstitial space and may eliminate the normally present negative and radially expanding interstitial tension on the extra-alveolar pulmonary vessels. Expansion of the pulmonary interstitial space by fluid causes pulmonary interstitial pressure (PISF) to become positive and exceed Ppv (zone 4, Ppa > PISF > Ppv > PA). ^{[6] [7]} In addition, the vascular resistance of extra-alveolar vessels may be increased at a very low lung volume (i.e., residual volume); at such volumes the tethering action of the pulmonary tissue on the vessels is also lost, and as a result, PISF increases positively (see the lung volume discussion later).^{[8] [9]} Consequently, zone 4 blood flow is governed by the arteriointerstitial pressure difference (Ppa - PISF), which is less than the Ppa - Ppv difference, and therefore zone 4 blood flow is less than zone 3 blood flow. In summary, zone 4 is a region of the lung from which a large amount of fluid has transuded into the pulmonary interstitial compartment or is possibly at a very low lung volume. Both these circumstances produce positive interstitial pressure, which causes compression of extra-alveolar vessels, increased extra-alveolar vascular resistance, and decreased regional blood flow.

It should be evident that as Ppa and Ppv increase, three important changes take place in the pulmonary circulation, namely, recruitment or opening of previously unperfused vessels, distention or widening of previously perfused vessels, and transudation of fluid from very distended vessels.^{[10] [11]} Thus, as mean Ppa increases, zone 1 arteries may become zone 2 arteries, and as mean Ppv increases, zone 2 veins may become zone 3 veins. The increase in both mean Ppa and Ppv distends zone 3 vessels according to their compliance and decreases the resistance to flow through them. Zone 3 vessels may become so distended that they leak fluid and become converted to zone 4 vessels. In general, recruitment is the principal change as Ppa and Ppv increase from low to moderate levels, distention is the principal change as Ppa and Ppv increase from moderate to high levels, and finally, transudation is the principal change when Ppa and Ppv increase from high to very high levels.

Distribution of Ventilation

Gravity also causes differences in vertical Ppl, which in turn causes differences in regional alveolar volume, compliance, and ventilation. The vertical gradient of Ppl can best be understood by imagining the lung as a plastic bag filled with semifluid contents; in other words, it is a viscoelastic structure. Without the presence of a supporting chest wall, the effect of gravity on the contents of the bag would cause the bag to bulge outward at the bottom and inward at the top (it would assume a globular shape). With the lung inside the supporting chest wall, the lung cannot assume a globular shape. However, gravity still exerts a force on the lung to assume a globular shape; this force creates relatively more negative pressure at the top of the pleural space (where the lung pulls away from the chest wall) and relatively more positive pressure at the bottom of the lung (where the lung is compressed against the chest wall) ( Fig. 17-2 ). The density of the lung determines the magnitude of this pressure gradient. Because the lung has about one fourth the density of water, the gradient of Ppl (in cm H₂ O) is about one fourth the height of the upright lung (30 cm). Thus, Ppl increases positively by 30/4 = 7.5 cm H₂ O from the top to the bottom of the lung.^[12]

Because PA is the same throughout the lung, the Ppl gradient causes regional differences in transpulmonary distending pressure (PA - Ppl). Ppl is most positive (least negative) in the dependent basilar lung regions, so alveoli in these regions are more compressed and are therefore considerably smaller than the superior, relatively noncompressed apical alveoli (there is an approximately fourfold volume difference). ^[13] If regional differences in alveolar volume are translated to a pressure-volume curve for normal lung ( Fig. 17-3 ), the dependent small alveoli are on the midportion and the nondependent large alveoli are on the upper portion of the S-shaped pressure-volume curve.

Figure 17-2 Schematic diagram of the lung within the chest wall showing the tendency of the lung to assume a globular shape because of gravity and the lung's viscoelastic nature. The tendency of the top of the lung to collapse inward creates a relatively negative pressure at the apex of the lung, and the tendency of the bottom of the lung to spread outward creates a relatively positive pressure at the base of the lung. Thus, alveoli at the top of the lung tend to be held open and are larger at end-exhalation, whereas those at the bottom tend to be smaller and compressed at end-exhalation. Pleural pressure increases by 0.25 cm H₂ O per centimeter of lung dependency.

682

Figure 17-3 Pleural pressure increases by 0.25 cm H₂ O every centimeter down the lung. The increase in pleural pressure causes a fourfold decrease in alveolar volume from the top of the lung to the bottom. The caliber of the air passages also decreases as lung volume decreases. When regional alveolar volume is translated over to a regional transpulmonary pressure-alveolar volume curve, small alveoli are on a steep (large slope) portion of the curve, and large alveoli are on a flat (small slope) portion of the curve. Because the regional slope equals regional compliance, the dependent small alveoli normally receive the largest share of the tidal volume. Over the normal tidal volume range (lung volume increases by 500 mL from 2500 mL [normal functional residual capacity] to 3000 mL), the pressure-volume relationship is linear. The lung volume values in this diagram are derived from the upright position.

Distribution of the Ventilation-Perfusion Ratio

Both blood flow and ventilation (both on the left-hand vertical axis of Fig. 17-4 ) increase linearly with distance down the normal upright lung (horizontal axis, reverse polarity). ^[14] Because blood flow increases from a very low value and more rapidly than ventilation does with distance down the lung, the ventilation-perfusion (V̇A/) ratio (right-hand vertical axis) decreases rapidly at first and then more slowly.

The V̇A/ ratio best expresses the amount of ventilation relative to perfusion in any given lung region. Thus, alveoli at the base of the lung are overperfused in relation to their ventilation (V̇A/ < 1). Figure 17-5 shows the calculated ventilation (V̇A) and bloow flow () in liters per minute, the V̇A/ ratio, and the alveolar partial pressure of oxygen (PAO₂ ) and partial pressure of carbon dioxide (PACO₂ ) in mm Hg for horizontal slices from the top (7% of lung volume), middle (11% of lung volume), and bottom (13% of lung volume) of the lung.^[15] PAO₂ increases by more than 40 mm Hg from 89 mm Hg at the base to 132 mm Hg at the apex, whereas PCO₂ ) decreases by 14 mm Hg from 42 mm Hg at the bottom to 28 mm Hg at the top. Thus, in keeping with the regional V̇A/ ratio, the bottom of the lung is relatively hypoxic and hypercapnic as compared with the top of the lung.

V̇A/ inequalities have different effects on arterial PCO₂ (PaCO₂ ) than on arterial PO₂ (PaO₂ ). Blood passing through underventilated alveoli tends to retain its CO₂ and does not take up enough O₂ ; blood traversing overventilated alveoli gives off an excessive amount of CO₂ but cannot take up a proportionately increased amount of O₂ because of the flatness of the oxygen-hemoglobin (oxy-Hb) dissociation

Figure 17-4 Distribution of ventilation and blood flow (left-hand vertical axis) and the ventilation-perfusion ratio (V̇A/, right-hand vertical axis) in normal upright lung. Both blood flow and ventilation are expressed in liters per minute per percentage of alveolar volume and have been drawn as smoothed-out linear functions of vertical height. The closed circles mark the V̇A/ ratios of horizontal lung slices (three of which are shown in Fig. 17-5 ). A cardiac output of 6 L/min and a total minute ventilation of 5.1 L/min were assumed. (Redrawn with modification from West JB: Ventilation/Blood Flow and Gas Exchange, 4th ed. Oxford, Blackwell Scientific, 1970.)

683

Figure 17-5 Ventilation-perfusion ratio (V̇A/) and the regional composition of alveolar gas. Values for regional flow (), ventilation (V̇A), PO₂ , and PCO₂ were derived from Figure 17-4 . PN₂ was obtained by what remains from total gas pressure (which, including water vapor, equals 760 mm Hg). The volumes [Vol. (%)] of the three lung slices are also shown. When compared with the top of the lung, the bottom of the lung has a low V̇A/ ratio and is relatively hypoxic and hypercapnic. (Redrawn from West JB: Regional differences in gas exchange in the lung of erect man. J Appl Physiol 17:893, 1962.)

In 1974, Wagner and colleagues^[16] described a method of determining the continuous distribution of V̇A/ ratios within the lung based on the pattern of elimination of a series of intravenously infused inert gases. Gases of differing solubility are dissolved in physiologic saline solution and infused into a peripheral vein until a steady state is achieved (20 minutes). Toward the end of the infusion period, samples of arterial and mixed expired gas are collected, and total ventilation and cardiac output (T) are measured. For each gas, the ratio of arterial to mixed venous concentration (retention) and the ratio of expired to mixed venous concentration (excretion) are calculated, and retention-solubility and excretion-solubility curves are drawn. The retention- and excretion-solubility curves can be regarded as fingerprints of the particular distribution of V̇A/ ratios that give rise to them.

Figure 17-6 shows the type of distributions found in young, healthy subjects breathing air in the semirecumbent position.^[17] The distributions of both ventilation and

Figure 17-6 A, Average distribution of ventilation-perfusion ratios (V̇A/) in normal young semirecumbent subjects. The 95% range covers from 0.3 to 2.1 (between dashed lines). B, Corresponding variations in PO₂ and PCO₂ in alveolar gas. (Redrawn from West JB: Blood flow to the lung and gas exchange. Anesthesiology 41:124, 1974.)