Neonatal Pulmonary Function

N conatal Pulmonary Function NICHOLAS M. NELSON, M.D.

This essay recounts the intrusion of clinical pediatricians into basic and applied pulmonary physiology. Their orientation has remained clinical, however, and they have for the most part simply adapted the tools of the basic scientist to the newborn babies whose physiology they are trying to understand. This emphasis is reflected in the bibliography, which, by design, cites investigations in babies to the nearly total exclusion of work with animals and adult human beings. One might wonder why clinicians should show such an inordinate interest in such esoterica as pressure-volume curves, the theory of respiratory control and gaseous diffusion. Some have suffered from the simple thirst for basic knowledge, but most, of course, have been driven from the bedside to the laboratory by the need for an understanding of the derangements in cardiopulmonary function that culminate in the respiratory distress syndrome. No claim to comprehensiveness is made, so that the reader interested in greater depth must consult other recent surveys.1, 4, 8, 17, 18, 26, 31, 33, 60 Pathologic states will not be considered, since they are adequately covered in other parts of this volume. Equations and symbols are strictly avoided in order to retain a broad readership. The attempt has been made to integrate what knowledge is available and to indicate where it is not. This effort to give insight may earn the just complaint of unwarranted speculation, for which sin no apologies are offered. Acknowledgments are in order to the dedicated workers who have gathered this information and to the legion of basic physiologists whose brilliant ideas and ingenious methods they have used or adapted. A much greater debt, however, is owed to those babies who have been studied. These "untrained" subjects have proved to be immensely cooperative in the careful hands of patient investigators cognizant of the anesthetic powers of a full stomach. Attached to mask and tube, breathing gases familiar and strange, these uncomplaining infants have graciously divulged some of the secrets of their remarkable adaptation to the rigors of extrauterine respiration. Supported by a United States Public Health Service Research Training Grant (Tl HD 50-07) from the National Institute of Child Health and Human Development.

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The main end of pulmonary function is the arterialization of mixed venous blood presented to the lungs by the right side of the heart, and in order to accomplish such an exchange of respiratory gases, pulmonary capillary blood must be intimately exposed to fresh alveolar gas. Mechanical forces of the lung and thorax are responsible for sucking air into the respiratory tree and distributing it to alveoli. Alveolar ventilation must then be servocontrolled at levels appropriate to the metabolic demands of the body while the physicochemical process of diffusion effects the transfer of gases between alveolus and capillary. Finally, cardiovascular function must be so integrated as to maintain a proper volume of blood perfusing the gas-exchanging surface.

MECHANICS

Mechanics is that branch of physics which considers the action of forces upon stationary (statics) and moving (dynamics) bodies. Pulmonary physiologists have analyzed lung function in similar fashion, since ventilation of the lungs entails the passage of gas molecules into and out of the respiratory tree, and this requires the application of a force (pressure) to a particle (gas molecule). Forces generated by the respiratory apparatus act upon the thoracic bellows to produce the pressure changes which cause gas to flow. Thus during inspiration alveolar pressure is lowered below atmospheric and gas flows into the lung, while during expiration alveolar pressure is greater than atmospheric and gas flows out. Yet in the physiologic as well as in the physical world active forces are opposed by reactive forces. Accordingly, pressure differences tending to produce gas flow in the lung are opposed by resistance to flow through the respiratory tree, while the muscular expansion of the thorax is opposed by the elastic recoil of the lung.

STATICS: PRESSURE-VOLUME CURVES, COMPLIANCE, SURFACTANT

Theory and Methods If a perfectly elastic spring is stretched, the amount of stretch (strain) bears a linear relation to the force (stress) applied. The physicist knows this stress-strain relation as Hooke's Law, and the constant which relates the applied force to the resultant stretch is known as the elastance or bulk modulus of the material under consideration. Similarly, the pressure difference or force applied by muscular activity to the lungs and thoracic bellows is related to the resultant volume change (stretch) by a "constant" known as compliance. Thus ' change in volume produced campIlance = . . pressure difference applied

NEONATAL PULMONARY FUNCTION

771

This respiratory compliance represents the summated effects of the elastic recoil of lung tissue and that of the thoracic cage (which in this context includes the chest wall, diaphragm and underlying gut). In the normal state at end-expiration the elastic recoil of the partly inflated lung tends to produce collapse, while that of the partly compressed thorax tends to produce expansion. These opposing forces of elastic recoil are responsible for the normally negative intrapleural pressure of -2 to -5 cm. of water. Compliance is most commonly measured by inflating the lung-thorax system with known volumes of air and noting the pressure difference across the tissues of concern at each volume. Thus total respiratory compliance of the lungs and chest relates volume change alveolar pressure - atmospheric pressure' whereas lung or pulmonary compliance relates volume change alveolar pressure - intrapleural pressure and thoracic cage compliance relates volume change intrapleural pressure - atmospheric pressure' A typical "relaxation" pressure curve can be inscribed by having a subject inhale gas from a spirometer, hold his breath, and then relax his muscles of respiration while attached to a closed mouthpiece. This procedure allows the unopposed force of elastic recoil of the total respiratory system to apply pressure to the contained gas. Pressure manometers attached to the airway and to an esophageal balloon or catheter estimate alveolar (glottis is open) and intrapleural (nearly) pressure respectively. This is repeated at several different volumes and values plotted as diagrammed in Figure 1. Notice that: ( 1) compliance ( volume c~ange ) is the slope of the pressure-volume curve under pressure c ange consideration and that the higher the slope, the greater the compliance; (2) lung compliance is not constant, but rather decreases at extreme lung volumes, although it is nearly constant in the middle ranges; (3) the equilibrium or "rest volume" tends to occur at about 30 to 40 per cent of total lung capacity, where the elastic recoil tending to collapse the lung is exactly counterbalanced by the elastic recoil tending to expand the thorax. These opposing forces are responsible for the intrapleural negative pressure. Since compliance in one person is not strictly constant at all lung volumes, comparisons between subjects should be made at a specific lung volume. Such a value is termed "specific" compliance or compliance-unit lung volume. Compliance of the lung alone is often measured clinically during respiration by continuously monitoring intraesophageal ("intrapleural") pressure and minute volume, but measuring volume and transpulmonary (atmospheric-intraesophageal) pressure only at end-inspiration when

772

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Figure 1. Static pressure-volume diagram of the neonatal respiratory system. A normal spirogram is shown for volume orientation. Note especially that (1) the chest wall is extremely compliant (high slope); ( 2) the lung compliance decreases (low slope) at extremes of lung volume; and (3) the rest volume of the system is relatively close to the collapse volume of the lung. See text for details.

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Figure 2. Dynamic pressure-volume loops for the neonatal lung. These have been superimposed on the static compliance curve of the lung where "distending" transpulmonary pressure is the difference between atmospheric and intrapleural pressure.

•

NEONATAL PuLMONARY FUNCTION

773

there is no air flow; a static measurement thus can be determined with little error under suspended dynamic conditions and js, therefore, referred to as «dynamic" compliance. A series of such dynamic pulmonary pressure-volume loops is shown in Figure 2 superimposed upon the static pressure-volume curve of the lung. Again, variations of the dynamic compliance (slope of the curve) may be noted at extremes of lung volume. Nearly half of the pressure required to inHate the lung to a given volume is devoted to overcoming those surface tension forces at the alveolar air-liquid interface which tend to produce alveolar collapse. Thus a large share of the elastic recoil of lung tissue is provided by alveolar surface tension, the remainder being due to the true elasticity of stretched lung tissue. The basic role of "pulmonary surfactant" in respiratory mechanics is discussed elsewhere in this volume (see p. 703) and will be treated only briefly here. We may say in summary that changes in pulmonary (lung) compliance indicate changes in the volume and quality of lung tissue. If the factor of lung volume is held constant by comparing subjects at equal lung volume or size (specific compliance), then changes in specific lung compliance may be held due to changes in lung compliance or stiffness secondary to varying degrees of pulmonary vascular congestion, edema, fibrosis, alveolar surface tension, and so on. Measurement and Interpretation Basic work in the intact newborn animal2 , 7 and in postmortem lung preparations from infants29 has elucidated much of the mechanical adjustments being made during this era of life. At rest volume (i.e. neither positive nor negative pressures are being exerted-see Fig. 1) and before air-breathing has commenced, the fetal lung-chest wall complex is at such a volume that the lung is nearly totally collapsed; its alveoli are nearly empty of fluid, and only a small amount can be withdrawn from the airways. Thus deprived of the surface-active and major portion of its elastic recoil, the lung exerts little retractile force against the opposing but weak expansile force of the relatively compliant thoracic cage. Consequently the resultant intrapleural pressure is not negative, but atmospheric. After the first breath, however, surface tension at the curved alveolar air-liquid interface establishes an increased retractile force in pulmonary tissue sufficiently large to create a negative intrapleural pressure at the now increased rest volume of end-expiration. After this initial air expansion of the lung, the peculiar property of lung hysteresis induced by pulmonary surfactant (see p. 703) prevents collapse of alveoli at low lung volumes, and the rest volume of the lung begins to increase to a new and higher equilibrium point. Nevertheless the rest volume of the lung at end-expiration (called the functional residual capacity) is still suffiCiently close to lung collapse volume that air-

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trapping in some alveoli is a regular occurrence. 42 This phenomenon is partly the result of the very compliant and nonossified thorax of the newborn, a circumstance probably dictated by the logistics of passage through a narrow birth canal. The relatively wet lung of the fetus loses water rapidly in the first few hours after birth. Two mechanisms may be responsible for this: (1) the increased absorption gradient established in pulmonary capillaries as their perfusing pressure drops below colloid osmotic pressure after ventilation; (2) the greatly increased rate of lung lymph flow that follows birth. 10 Most of these phenomena are now well documented in the human newborn by many different workers. The pressure-volume curve of the apneic and anesthetized newborn baby has been measured preoperatively by inflating the lung at various known tracheal pressures and measuring the passively expired gas in a spirometer. 53 The total lung-thorax pressure curve so described has a compliance slope remarkably close to the "dynamic" compliance slope for the lung alone measured in other babies at comparable lung volumes. 13 , 20, 22, 52, 63 The latter is usually measured by recording "intrapleural" pressure changes by means of an intraesophageal catheter and appropriate manometers and relating them to simultaneous volume changes recorded from whole body or reverse plethysmographs (see below) or other techniques. 63 This near equality of total lung-thorax compliance and that of the lung alone reinforces the conclusion that the thoracic cage in the newborn is exceedingly compliant,2,7 since the three values are related by the expression: 1 total compl.

=

1 lung compl.

+

1 chest compl.

Reported values for lung and total compliance have ranged around a value of 0.05 to 0.06 ml. per centimeter of water per milliliter of lung volume and may show a slow but significant increase in the first days of life, by which time pulmonary compliance is remarkably close to that of the adult (see Table 1). An increase in specific compliance occurs between three and eight hours of age,16 presumably as fluid is absorbed from the lung interstitium through vascular and lymphatic channels. 7,l0

DYNAMICS: PULMONARY, AIRWAY AND THORACIC RESISTANCE

Theory and Methods Any body moved by a force offers resistance to that force, but if the force is successful in moving the body a finite distance against that resistance, then physical work is done (work equals force times dis-

775

NEONATAL PULMONARY FUNCTION

tance ). We are familiar with the electrical equivalent that electromotive force propels a How of electrons or current against a resistance offered by the conductor. This is summarized in Ohm's Law, whereby

11

volts amperes

driving pressure difference

or, more genera y, resistance = ---=-.c=---'fln-----ow Similarly the driving force of the respiratory apparatus encounters an impedance to ventilation offered by resistance to gas How through the airways and by viscous (frictional) resistance of the moving pulmonary tissue in addition to the elastic resistance or recoil (compliance) which we have already considered as a static phenomenon. Airway resistance is defined as the ratio of driving pressure along airway (mouth-alveolus) airway gas How • The determinants of this resistance to gas How through the respiratory tubes are the viscosity of the gas, its degree of turbulence, and the length and radii of the tubes (Poiseuille's and Reynold's Laws). Of these factors, the radius of the conducting tube is the most important, since resistance varies inversely with the fourth power of the radius. Hence bronchi of small diameter will offer greatly increased resistance to ventilation. Since airway diameter varies directly with lung volume, it follows that the airway resistance in a given lung will increase greatly (by a power of 4) as lung volume decreases. Airway conductance (the reciprocal of resistance) varies directly with lung volume. Because of this variance of conductance or resistance with lung volume, comparisons are best made of "specific" conductance or resistance at a specific lung volume.

resistance

=

Table 1.

Respiratory Mechanics ADULT

Total respiratory compliance (

INFANT

100

0.02-0.035"

4.9

0.061"

m!. m!. ) cm. H20 cm. H20/L. lung vo!' Chest compliance Lung compliance

200 200

0.04-0.07 0.04-0.07

22-52 • 5.2

0.06516.22,29,35,37,

Io/c"

5.5

100%23, "

68

100%"

1.0 4.5 2.8 1.6 0.1

16% 84% 54% 29% 1%

18. 50 6 42 2-

I

T ata I IIow reSIstance . (cm. H20 -L./sec. Chest wall Pulmonary Nose Airway

0 InSpIratory resist.)

Lung tissue Time constant of mechanical impedance *. (sec.) Respiratory frequency (breaths per min.)

Airway conductance (L./sec./cm. H20/L. lung vo!.) --.

0.24-0.58'

26%' 74%13,20,35.37.61

9%'· 62%46". 3%-

0.643• 20 0.24'·

0.33' 40 0.28"

4.7'· 16-5020 67%

0.030-0.050" 1 .5-2.013, 20 S6, 37 50-70%13.20 36,37

Expiratory flow rate

Mean (L./sec.) Total pulmonary work (kg,-cm./min.) Elastic work (per cent)

* Calculated. * * Total compliance •• * ExcJ uding nose.

X total resistance.

sa

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Airway resistance may be measured in the body plethysmograph, which is essentially an airtight box containing the subject. As breathing proceeds, air in the box surrounding the subject is alternately compressed and expanded by the moving thorax, and these pressure changes are sensed by delicate manometers. Gas flow is simultaneously monitored by suitable flowmeters (pneumotachygraphs). The box pressure changes can be related to the alveolar-mouth pressure gradient (driving pressure) giving all the information necessary for calculation of airway resistance. This has been done in the newborn with results as summarized in Table 1, wherein is apparent the greater relative importance of airway resistance in babies (62 per cent pulmonary flow resistance versus 29 per cent in adults). The total pulmonary resistance is defined as the ratio of transpulmonary driving pressure (mouth-intrapleural) air gas flow and is a simpler measurement to make than that of airway resistance alone because only intrapleural pressure changes need be monitored. Flow may be derived as before from a pneumotachygraph or by differentiating (graphically or electrically) the volume trace versus time from a body plethysmograph. Many such studies have been performed in the newborn, and they are also summarized in Table l. Considerable variation in pulmonary resistance measurements has been noted, premature infants tending to have rather higher values than term infants,13 as would be expected in view of the smaller airways. Expiratory resistance is generally higher than inspiratory resistance because bronchi partially collapse during expiration. Since the respiratory musculature applies pressure ( force) against several resistances (elastic and nonelastic) to change lung volume (distance ), it performs true physical work (force times distance). This is depicted in Figure 3, in which the "pressure-volume loop" of a single respiration has been superimposed on the lung compliance line (see Fig. 1). Since "work" is defined as force times distance, pressure (distending force) times volume (distance distended) is defined as pressure work, and hence the areas enclosed by the various curves represent pulmonary pressure work done against the various resistances. Thus during inspiration the area ABC represents the work done in overcoming the static elastic resistance (compliance). This energy remains stored as the retractive force of the lung to be tapped during the ensuing passive expiration; i.e. passive expiration will require no further work. Area ADC E represents the additional inspiratory work that must be performed against the dynamic frictional (viscous) resistance of the lung tissue. Finally, area ACD represents the work done in overcoming the much larger resistance to gas flow through the airways. Such curves of total pulmonary resistance may be inscribed on an oscilloscope or

777

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Figure 3. Pressure-volume loop and pulmonary pressure work. Pressure-volume loop (cf. Fig. 2) is diagrammed and its area divided to show relative amounts of work. Area ABC represents the pressure work done against the elastic recoil of the lung during inspiration; area ACD represents work done in overcoming gas How-resistance in the airways; area ADC E represents work done in overcoming viscous resistance in lung tissue. Flow resistance is the more significant part of total pulmonary resistance.

X-y recorder by attaching the plethysmograph manometer to record volume change while the intraesophageal manometer records pressure change. The appropriate areas are measured graphically or calculated mathematically. Measurements and Interpretation Notice in Table 1 that after correction to equivalent lung volumes, "specific" lung compliance and airway conductance (

.1 ) in the resIstance infant are similar to those in the adult. The rapid decrease in pulmonary resistance and inspiratory work noted in the first minutes after birth35 are almost certainly a result of the rapid increase in resting lung volume. Thus, although the much smaller airways of the newborn dictate a large absolute increase in airway and over-all pulmonary resistance, when considered in the light of the lungs' ability to move air (conductance), the newborn seems not to be particularly disadvantaged. The product of total respiratory compliance times total respiratory resistance defines the "time constant of mechanical impedance to oscillatory air flow." This time constant is the prime determinant of respiratory frequency, and it is geared to the minimal average force of respiratory muscles. 3s The short time constant for infants listed in Table 1 dictates the need for a respiratory frequency of approximately 40

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breaths per minute, which is, of course, the average observed value in normal newborns. Summary The fetal thorax is a very compliant structure. This fact in combination with the poor retractile force of the fluid-filled lung ensures a lack of negative intrapleural pressure during fetal life. After initial ventilation has expanded the lung within the first few minutes after birth, airway resistance decreases rapidly as lung compliance increases. A negative intrapleural pressure is established as the retractile force of the lung increases after development of alveolar air-liquid surface tension subsequent to these first breaths. The balance between lung retraction and chest expansion is tenuous, however, and air-trapping in some alveoli often occurs until the chest wall begins to ossify, thus decreasing its compliance. In the absence of pulmonary surfactant activity, the retractile force of the lung becomes excessive and collapse of alveoli occurs, leading to diminished lung volume and compliance, while the average intrapleural pressure becomes more negative. These aberrations are basic in the pathogenesis of the respiratory distress syndrome. VENTILATION

Having described how the forces generated by the respiratory apparatus move air from mouth to alveoli, we must now consider how and where it is distributed throughout the lung.

STATIC LUNG VOLUMES: TOTAL, RESIDUAL AND TIDAL VOLUMES; FUNGrIONAL RESIDUAL CAPACITY

Theory and Methods As is apparent from Figure 4, all the lung volumes except functional residual capacity are measurable if one can record gas volume changes during quiet respiration (tidal volume), maximal inhalation (inspiratory reserve volume) and maximal exhalation (expiratory reserve volume). Volume changes may be recorded directly by spirometry or plethysmography. The spirometer (cylinder of the familiar basal metabolism apparatus) is simply a bell which rises above the surface of the water in which it is immersed in direct proportion to the amount of gas trapped under it. Appropriate mechanical or electrical recorders are attached. Exhaled gas is led from the subject to the spirometer by a system of one-way valves (an "open" circuit) usually attached to the newborn infant by a nasal coupling. 39 Standard plethysmography entails placing

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NEONATAL PULMONARY FUNCTION

the subject within an airtight box with only the face communicating to the exterior,13· 19.21.36 The seal used in work with infants is usually in the form of an inflatable rubber ring which surrounds the face. Thoracic movements compress or expand the gas surrounding the subject's body, and these changes are sensed by appropriate volume or pressure recorders. Alternatively, the subject may rebreathe through a tightly fitting mask connected to an airtight box (reverse plethysmography) ,22. 35 but this allows build-up of exhaled carbon dioxide to stimulate respiration in unphysiologic fashion and is hence unsuitable for long-term recording. Volume changes may also be recorded indirectly by integrating the electrical output of a gas-flow transducer, the pneumotachygraph. 63 Newer electrical methods of recording respiration (impedance plethysmography) give promise of freeing the baby from rather unwieldy and unphysiologic apparatus, since only two small electrodes are attached to the thoracic skin. These methods, however, must be calibrated in each subject against one of the standard techniques. "Maximal" inspiration and expiration are produced by encouraging the baby to cry ("crying vital capacity"3.62), a measurement which, although crude, is remarkably reproducible. Functional residual capacity is measured separately by dilution of a tracer gas such as helium or nitrogen. In a closed (rebreathing) circuit a known amount of helium in air or other diluent gas is rebreathed by the subject until equilibrium is established between the subject's lungs and the external apparatus. 28 From the change in helium concentration and the known volume of the external circuit, the unknown volume (subject's lungs and airways) can be deduced. If the dilutional process began precisely at end-expiration, then functional residual capacity will have been determined (Fig. 4). Similarly, in an open (nonrebreathing) circuit, the nitrogen normally present in the lungs of an air-breathing baby may be quantitatively displaced ("washed out") into .",

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Static lung volumes. A normal spirogram is shown for reference.

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NICHOLAS

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a spirometer by oxygen-breathing,42. 61 and the original lung volume calculated from the amount of nitrogen exhaled. Finally, a different kind of lung volume may be measured. This is the "thoracic gas volume" or the total amount of gas contained in the thorax, whether communicating with the airways or not. Normally, thoracic gas volume is the same as the functional residual capacity (which is in communication with the airways); but should some gas be "trapped," as in a group of alveoli or a cyst, and barred access to ventilating airways, then the thoracic gas volume will be registered as greater than the functional residual capacity by the volume of gas so trapped. 42 The method makes use of Boyle's Law, which states that the volume of a given number of gas molecules varies inversely with the pressure applied. The airway of a subject is suddenly and brieRy obstructed at end-expiration so that as respiratory movements continue against the obstruction, the thoracic gas is alternately compressed and expanded. The thoracic gas pressure changes are sensed by an airway manometer and the thoracic gas volume changes by a body plethysmograph. If these changes are related to the airway pressure just before obstruction (atmospheric), then the unknown thoracic gas volume can be derived. 3 • 13. 36 Measurements and Interpretation All these volumes have now been determined in newborn infants by several groups of investigators, with results as summarized in Table 2. Several points concerning these average values bear closer scrutiny. First, the tidal volume-functional residual capacity ratio is similar in infant and adult. This ratio determines the stability of alveolar gas composition: if the ratio is too high, there will be a large variation of alveolar gas tensions with each inspiration, and the buffering action of the functional residual capacity will be compromised. Second, the vital capacity and total lung capacity (derived from functional residual capacity and vital capacity) are rather smaller in babies than in adults. Although this could indicate that the determination of "crying vital capacity" underestimates the true value, the measurement is at least remarkably constant in individual babies 62 and in different laboratories. 3 • 62 If it is, in fact, accurate, the low vital capacity and total lung capacity may be explained by the compliant chest wall which, in the newborn infant, may lack sufficient "stiffness" to provide the optimum mechanical leverage necessary for full inspiration. Third, the diminished expiratory reserve volume-total lung capacity ratio suggests that the resting volume of the chest-lung at end-expiration (functional residual capacity) is close to the collapse volume of the lung (approximately the residual volume). This impression is bolstered by the fact that the average thoracic gas volume is 6 m!. per kilogram greater than the functional residual capacity (Table 2), indicating that some gas may be

781

NEONATAL PULMONARY FUNCTION

Table 2.

Lung Volumes INFANT

Total lung capacitv . . . . . , . (ml./kg.) Vital capacity. . . . . . . . . . (ml./kg.) Thoracic gas volume ........ (ml. /kg.) Functional residual capacity .. (ml./kg.) Tidal volume .............. (m!. /kg.) Expiratory reserve volume/vital capacity ...... . Functional residual capacity/total lung capacity ..... . Residual volume/total lung capacity. . . . . . .. . ....... . Tidal volume/functional residual capacity ... Expiratory reserve volume/total lung capacity ................ .

86 52 34 34

63 3 33 62 363,16,42

3028 ,42

7

617.

0.25

0.30 0.48 0.33 0.20

0.40 0.20 0.20 0.20

21, .9, 6f

0.17

trapped in alveoli isolated from the airways. Finally, the high functional residual capacity-total lung capacity and residual volume-total lung capacity ratios might suggest expiratory obstruction in "overblown" or emphysematous lungs secondary to high expiratory resistance in young infants. Yet the normal specific conductance of the infant's airway indicates that he suffers relatively no more expiratory obstruction than does the adult. Consequently we must look elsewhere for an explanation of the relatively (to total lung capacity) high resting volume of the lungthorax in babies. It has been observed that functional residual capacity per unit of body weight actually decreases with increasing body weight (and hence maturity) .16, 42 Since maturation involves generation of increasing numbers of alveoli and a consequent increase in total alveolar surface tension, it appears likely that more mature infants should have greater total retractive force in their pulmonary tissue. It thus seems probable that infants of greater gestational age have lungs which "seek" a smaller rest volume in balance with the outward-expanding chest wall. The typical adult balance at a rest volume of 40 per cent of total lung capacity is probably not struck until alveolar generation has ceased and the thoracic cage has been completely ossified. Summary The functional residual capacity is rapidly established after birth at a resting lung volume considerably greater than that in fetal life. This volume is sufficiently large to provide adequate buffering of alveolar gas composition. A tenuous balance exists, however, between the retractive forces of the lung and the weakly expansive forces of the compliant chest wall. This potential instability may lead to collapse of certain areas of the infant's lung with trapping of air in alveoli thus isolated from the airway. These factors appear to pose no particular problem to the normal term infant, but could further embarrass the immature newborn with alveolar instability secondary to lack of pulmonary surfactant activity (i.e. the respiratory distress syndrome).

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DYNAMIC LUNG VOLUMES: ALVEOLAR VENTILATION AND DEAD SPACE

Theory and Methods Not all the gas inhaled into the lungs is useful ventilation in the sense that it brings fresh air into contact with mixed venous blood. Consider the end of an exhalation which has left gas of alveolar composition (high carbon dioxide, low oxygen) stagnant in the conducting airways. The subsequent inhalation reconducts this stagnant alveolar gas back to the alveoli followed by a bolus of fresh air (high oxygen, no carbon dioxide). The efficiency of each tidal volume is consequently diminished by the amount of alveolar air rebreathed. Thus "dead space" may be thought of as any portion of the respiratory tract which is ventilated with gas, but which does not contribute to the arterialization of pulmonary capillary blood. The "anatomic" dead space is that portion of the tidal volume which is not in alveoli; "alveolar" dead space is that portion of the tidal volume which is in alveoli that are not perfused; "physiologic" dead space is the sum of anatomic and alveolar dead space. That portion of ventilation directed to the total physiologic dead space is termed "wasted ventilation." Each total tidal volume is directed through the dead space to the alveoli and is thereby fractionated into the alveolar tidal volume and the dead space tidal volume. Hence the total minute ventilation (total tidal volume per breath times respiratory frequency) is the sum of the dead space ("wasted") ventilation and the alveolar ventilation. Alveolar ventilation is closely controlled by the integrated respiratory servomechanism to maintain a constant arterial and hence alveolar carbon dioxide tension. Since arterial carbon dioxide tension is determined by the ratio of carbon dioxide production to alveolar ventilation, and since carbon dioxide production is directly related by the respiratory quotient to metabolic needs or oxygen consumption, there is a direct relation between oxygen consumption and alveolar ventilation. This relath e ra t'10 0 f alveolar ventilation. II d the "ventl'latwn . equw. · t lOn, . ,IS ca e oxygen consumptIOn alent" and is remarkably constant at all ages and at all levels of metabolic demand. In states of hyperventilation (beyond metabolic needs) the ratio is elevated, and alveolar (and arterial) carbon dioxide tension is depressed. Conversely, states of hypoventilation lead to opposite changes. Total ventilation may be conveniently measured by collecting and measuring all the gas expired during a timed period. Alternatively, each tidal volume may be measured in a spirometer or plethysmograph and then summed over a timed period. Alveolar ventilation may then be calculated by measuring carbon dioxide production (carbon dioxide

783

NEONATAL PuLMONARY FUNCTION

Table 3.

Alveolar Ventilation ADULT I7 • 18

Alveolar ventilation (ml./kg./min.)... ........ Alveolar ventilation/oxygen uptake (ml./ml.). . . . . . . Alveolar ventilation (L./square meter/min.). .. . . . . . . Dead space (ml./kg.). . . . . . . . . .......... Dead space/tidal volume. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Alveolar ventilation/dead space

(~) .................. mIn. 1

INFANT

60 19 2.4 2.2 0.3

100-15040 23 40 2.3 40 2.2 19 • 40. 0.3 19 • 40.

23

100 39 • 40

64 64

content of expired gas times volume of expired gas) and dividing by the alveolar carbon dioxide content. The latter is obtained from an alveolar (end-tidal) sample or derived from the arterial carbon dioxide tension in normal infants. lB. 19.40,50 It is also possible to measure the dead space independently by special techniques 59 and then subtract this from the total tidal volume in order to obtain the alveolar tidal volume of each of many breaths which are then summed. Measurements and Interpretation It is apparent in Table 3 that on the basis of body weight the infant is overventilating by comparison with the adult. Nevertheless it has been noted above that ventilatory needs are a function of metabolic rate or oxygen consumption. This is in turn most nearly a function of body surface area (or approximately body weight to the % power) .32 Thus, on the basis of body surface area, alveolar ventilation at rest is relatively unchanged throughout life at 2.3 liters per square meter per minute. Anatomic dead space, on the other hand, is indeed related to body weight (approximately 1 m!. per pound), whereas the proportion of wasted to total ventilation is constant throughout life at approximately 30 per cent. The alveolar ventilation-dead space ratio together with the time constant of mechanical impedance to respiration (see Table 1) determines the rate of respiration, and both factors dictate an increasing respiratory frequency as body size diminishes.

Summary By increasing respiratory rate to about 40 breaths per minute, the newborn infant compensates for the slight relative increase in mechanical impedance to ventilation dictated by the small size of his lungs. This maintains alveolar ventilation adequate to his metabolic needs at a minimal expenditure of muscular effort. He wastes no more effort in ventilating the conducting airways than does the adult. Should respiratory dead space be increased by disease, the rate of total ventilation must increase in order to maintain alveolar ventilation constant. This increase in total ventilation necessarily entails more

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pulmonary pressure work, which further increases metabolic demand for increased alveolar ventilation, thus closing a vicious circle.

DISTRIBUTION OF VENTILATION

Theory and Methods Although alveolar ventilation thus appears adequate in infants on the basis of total measurements, poor distribution of ventilation might seriously vitiate the effort. For instance, if because of bronchospastic, mucous or other obstruction, only 20 per cent of the alveoli were adequately ventilated and thus received 99 per cent of the total ventilation to the lungs, but if all the alveoli (ventilated or not) were perfused to an equal degree, then, obviously, nearly 80 per cent of the perfusing blood would be incompletely arterialized during passage through the lungs. In a "perfect" lung where each alveolar tidal volume is equally distributed throughout all alveoli (rather than being directed to only 20 per cent of the alveoli as above), it can be shown that a gaseous label such as helium should be washed in or out of the lungs in exponential fashion; i.e. a plot of the logarithm of changing alveolar helium concentration versus time on a linear abscissa should be a straight line. Departures from this mathematical ideal can be quantified to define conceptual groups of alveoli which are slowly or rapidly ventilated. The lung also demonstrates typical behavior during the analysis of single breaths. Thus in a lung all of whose alveoli fill and empty in perfect unison, the instantaneous plot of carbon dioxide excretion at the mouth versus time (measured with a rapid-responding meter) during a single expiration will describe (1) a flat portion of 0 per cent carbon dioxide as the fresh air-containing airways are washed out by the advancing wave of alveolar gas; (2) a sharp inflection as the "square wave" of alveolar gas hits the detector; (3) a definite "plateau" at about 5 per cent carbon dioxide as true alveolar gas passes the detector. On the other hand, lungs with poor distribution of ventilation to the alveoli demonstrate a slow increase to a poor and rising plateau because gas from the better ventilated alveoli containing less carbon dioxide is blown off first and then followed by gas from poorly ventilated alveoli containing more carbon dioxide. Measurements and Interpretation Such tests in the normal newborn infant reveal him to be equipped with lungs whose ventilation is remarkably well distributed to all alveoli (Table 4),41.61.64 Although a "slowly" ventilated compartment of the lung is detectable, it accounts for only 18 per cent of total lung tissue, and there is over-all only about a 4 per cent departure ("pulmonary

785

NEONATAL PULMONARY FUNCTION

Table 4.

Distribution

crt Ventilation ADULT12, 18,27

INFANT41, 69, 61, 64

Plateau

Single breath and end-tidal test ....................... Plateau

Nitrogen Washout Test Rapidly ventilated alveoli

Per cent of total lung ............................ 48% Per cent of total ventilation. . . . . . . . . . . . . . . . . . . . .. 65% Rate of ventilation (mi./min./mI.). . . . . . . ......... 4

82% 87% 8

Slowly ventilated alveoli

Per cent of total lung . . . . . . . . . . . . . . . . . . . . . . . . . . .. 52 % Per cent of total ventilation. . . . . . . . . . . . . . . 35 % Rate of ventilation (mi./min./mI.). . . . . . . . . 1 Pulmonary clearance delay (per cent).. . . . . . ........ 0-37%

18% 13% 2 4(0-20)%

clearance delay") from a perfectly exponential washout of test gas (which was in these studies the nitrogen washed out of the lungs by oxygen breathing). Indeed, the only real difference between infant and adult appears to be the more rapid alveolar ventilation of the baby. We have seen above, however, that in terms of oxygen need per unit of body surface area even this factor is not really different. Summary The total ventilation is almost perfectly distributed to all alveoli in the normal newborn infant. The seemingly greater alveolar ventilation of the infant is appropriate for his particular metabolic needs and body size. Airway obstruction on a functional (spasm) or mechanical (e.g. meconium) basis might redistribute adequate total alveolar ventilation sufficiently to cause incomplete arterialization of the venous blood.

CONTROL OF VENTILATION: CENTRAL AND PERIPHERAL CHEMORECEPTORS

Theory and Methods This field of pulmonary physiology is still under extremely active investigation and discussion, but a consensus has been reached along the following lines. The respiratory servomechanism is geared toward homeostasis of arterial carbon dioxide tension and cerebrospinal fluid pH. Rapid response to change in arterial carbon dioxide tension appears to be vested in the peripheral chemoreceptors of the aortic and carotid bodies, whereas the responses of the central (medullary) centers are slower. The peripheral chemoreceptors of man breathing air at sea level are

786

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under some degree of constant anoxic stimulus. This is demonstrated by the. immediate hypoventilation occurring during oxygen breathing. Such an anoxic stimulus, however, becomes considerably greater when arterial oxygen saturation decreases below about 80 per cent. This response appears to be rather in the nature of an emergency mechanism, whereas the usual operational control of ventilation resides in carbon dioxide responses. The peripheral (aortic and carotid body) chemoreceptors have a threshold of activity at about 38 mm. of mercury arterial carbon dioxide tension in adults and appear most sensitive to respiratory oscillations of arterial carbon dioxide tension of about 5 to lO mm. of mercury in amplitude. Having been stimulated by a rising, oscillating arterial carbon dioxide tension, the typical sensitivity is such that for every 1 mm. increase in arterial carbon dioxide tension, there is an increase in ventilation of about 0.04 liter per kilogram. This degree of sensitivity can be increased by hypoxia as mentioned above. Slow adaptions of respiration to changing environmental and internal conditions seem more the responsibility of the central chemoreceptors located on the ventral medullary surface. These receptors are specifically pH-sensitive. In a situation of acute carbon dioxide retention after the peripheral chemoreceptors have been stimulated by elevated arterial carbon dioxide tension, the freely diffusible gaseous carbon dioxide molecules enter the cerebrospinal fluid from the blood. Because cerebrospinal fluid lacks the efficient intravascular buffers of hemoglobin and other proteins and contains only bicarbonate as a buffer, the carbon dioxide produces a relatively large and immediate decrease in cerebrospinal fluid pH below the normal 7.25. This in turn produces a direct stimulus to the medullary chemoreceptor and hyperventilation results. Such centrally stimulated hyperventilation is sustained until the relatively slow process of active transport of bicarbonate ion from blood across the blood-brain barrier can readjust cerebrospinal fluid pH. Measurement and Interpretation After some years of discussion it has recently been confirmedl l that the peripheral chemoreceptor response to arterial oxygen tension is active in the newborn. The response to a shift from air to oxygen breathing is an immediate decrease in ventilation, and this "physiological denervation" demonstrates a significant degree of hypoxic chemoreceptor stimulus to normal respiration just as in the adult. After the initial depression of ventilation by oxygen breathing, there ensues a slight rise in alveolar carbon dioxide tension possibly attended by secondary hyperventilation. Further, there seems little doubt that the peripheral chemoreceptors in the fetus and the newborn are responsible to oscillation of arterial p C02' 6 Indeed, it has been suggested that. the reason why the normal

]

787

NEONATAL PULMONARY FUNCTION

fetus does not gasp in utero is that oscillations of uterine arterial carbon dioxide tension with maternal respiration are damped in the large intervillous blood pool behind the placenta so that the umbilical venous ("fetal arterial") carbon dioxide tension is nonoscillatory.6 After birth and the first breath, however, oscillations of neonatal arterial carbon dioxide tension probably do occur and thus stimulate respiration. The familiar periodic respiration of premature infants has been shown to be associated with just such oscillations of P 002. 15 Table 5 indicates that although the "sensitivity" of the chemoreceptors is similar in infant and adult, the "set-point" (the value toward which homeostasis is aimed) of the resting arterial carbon dioxide tension is different. In fact, the plasma acid-base status of the newborn infant is similar to that of his pregnant mother and reflects a compensated (normal pH) respiratory alkalosis (arterial carbon dioxide tension less than 40). Low plasma bicarbonate is the hallmark of such a status and represents the effects of renal and other ion transport adjustments. Since the hyperventilation of pregnancy is fairly clearly the result of respiratory stimulation by progesterone,30 it is perhaps disappointing that there is no apparent stimulation of neonatal respiration by progesterone. 57 It is, however, possible that the intrauterine exposure to low maternal bicarbonate has set up an equilibrium status such that the fetal and neonatal cerebrospinal fluid bicarbonate concentration is low. As independent respiration occurs after birth and arterial carbon dioxide tension rises,45,51 rapid diffusion of carbon dioxide into the cerebrospinal fluid should occur. This should produce a rapid decrease in cerebrospinal fluid pH (since the bicarbonate buffer is probably depleted) with consequent stimulation of the medullary chemoreceptors. The "set-point" of resting arterial carbon dioxide tension in the newborn may, therefore, be lower than that of the adult because of decreased bicarbonate stores in the blood and cerebrospinal fluid of infants. If true, and proof is certainly wanting, then the resting arterial carbon dioxide tensions of babies cannot rise until ion transport mechanisms in at least the renal tubule and choroid plexus allow for conservation of bicarbonate and its transfer to cerebrospinal fluid with subsequent decrease in ventilatory stimulus. The few long-term studies of arterial Table 5.

Control oj Ventilation ADULT 17

Alveolar {arterial} Peo2 at rest (mm. Hg) ........ 38-40 Plasma bicarbonate (mEq./L.) ................ 24-28 Arterial blood pH.. . . . . . .. . . . . .. . . . . . . . . . . . .. 7 . 38 Ventilatory "sensitivity" to CO2 {L./min./mm. Hg Peo/kg.)................. 0.042 Ventilatory response to O 2 • • • • • • • . • . • . • . • Initial decrease Subsequent increase

INFANT

32-3545, 4D, 51 17-22 49 7.38 45 ,49,51 0.047 5 ,57 Initial decrease ll Subsequent increase"

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carbon dioxide tension available13 , 50, 54 indicate that this adjustment may require several months. Summary There is abundant evidence for central and peripheral chemoreceptor activity in the newborn infant. These chemoreceptor responses may explain (1) the lack of active respiration by the normal fetus; (2) sustained breathing after birth; (3) the periodic breathing of premature infants; (4) the normally low arterial carbon dioxide tension of newborn infants. Body bicarbonate stores in the infant appear to be low, probably as the result of long-term residence in a hyperventilating hostess. This limitation may seriously compromise the newborn baby's ability to compensate for the acidosis of asphyxia.

DIFFUSION DIFFUSING CAPACITY FOR OXYGEN AND CARBON MONOXIDE

Theory and Methods Once oxygen has been inspired and distributed evenly to the alveoli, it must diffuse through the alveolar wall into the pulmonary capillary blood, there to combine with hemoglobin. Carbon dioxide, a highly diffusible gas, traverses the same path (much more readily) in the opposite direction, and the combined process accomplishes the basic purpose of pulmonary function, namely, arterialization of the mixed venous blood which is presented to the lungs through the pulmonary artery. The diffusing respiratory gases encounter How resistance offered by the alveolar wall, the interstitial space, the capillary endothelium, the plasma and most importantly the speed of the chemical combination with hemoglobin. These resistances retard the How of gas in series and may, therefore, be added as in an electrical circuit: total resistance to gas How equals "membrane resistance" plus "chemical resistance." Since resistance is

1 , this relation might be restated as: conductance

1 1 1

alveolar gas pressure -

capillary gas pressure'

:! 2 i222i.! I 789

NEONATAL PULMONARY FUNCTION

Oxygen uptake is readily determined by measuring minute volume and the oxygen contents of inspired and expired gas. The denominator is derived by a computational process of integration from knowledge of the oxygen-dissociation curve and measurements of alveolar and arterial oxygen tension during breathing of slightly hypoxic gas mixtures. This procedure is, however, difficult and tedious. For this reason it is more usual to measure the diffusing capacity for carbon monoxide (which bears a direct relation to the diffusing capacity for oxygen) by breathing small and entirely nontoxic concentrations of carbon monoxide in air or oxygen. In this case, because of the extreme affinity of carbon monoxide for hemoglobin, the capillary carbon monoxide pressure is nearly (but not completely) negligible. Alveolar carbon monoxide pressure is measured directly from "alveolar" (end-tidal) samples or derived by separate measurements of the respiratory dead space. By measuring the decreasing lung diffusing capacity for carbon monoxide at several increasing levels of inspired oxygen concentration (which competes with carbon monoxide for combination with hemoglobin), it is possible to compute separately the "membrane" diffusing capacity and the "chemical" diffusing capacity. This latter term is the product of a well defined constant (expressing the speed of combination of carbon monoxide with hemoglobin) and the amount of hemoglobin in pulmonary capillaries. The pulmonary capillary blood volume so assayed is, moreover, only that which is in effective (gas-exchanging) contact with ventilated alveoli. This measurement specifically does not include the total and much larger pulmonary blood volume. Measurements and Interpretation The available data concerning transfer of respiratory gases from alveolus to capillary are set out in Table 6, wherein it is apparent that the newborn infant has a diminished ability to transfer gases compared to that of the adult. Both the effective pulmonary capillary blood volume and membrane diffusing capacity are relatively low; the former represents a smaller gas-exchanging surface between ventilated alveoli and

Table 6.

Diffusion ADULT 17 ,18

INFANT

10-16 30-40 12-24 600

5-8 44 ,66

Total lung diffusing capacity for CO* ....................... . "Membrane" diffusing capacity * ............................ . Total lung diffusing capacity for O 2 * ........................ . Total pulmonary blood volume (mI.) ................. . (mI./kg.) .............. . Pulmonary capillary blood volume (m!.) .................... . (mI. /square meter) ........ .

* M!./min./mm.

Hg/square meter ("steady-state" at rest).

7-1144

4-5 43

9

70-90 40-50

3-544 10-30 44

790

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perfused capillaries, whereas the latter indicates an increased "thickness" through the alveolar-capillary membrane. These physiologic facts would appear to confirm anatomic observations of the growth of several postnatal generations of alveoli28 whose walls become thinner with consequent over-all increase in gas-exchanging surface area. Diffusing capacity does not attain adult levels until several years of age. 58 This small but measurable "impairment" of diffusion presents no clinical threat, and it causes no significant decrease in arterialization of the blood. 48 PERFUSION

Detailed consideration of the pulmonary circulation is beyond the scope of this essay, and more complete discussion will be found elsewhere in this volume. It is apparent, however, that the complete pulmonary function of arterialization of venous blood cannot be carried out unless pedusion, like ventilation, of the lung is adequate in volume and uniform in distribution. Moreover, for any group of alveoli blood flow must be matched to gas flow lest incomplete arterialization of blood occur. The following brief outline of postnatal vascular events is now generally held to be well established. The first breaths of life produce a considerable increase in pulmonary blood flow as mechanical impedance decreases and active vasomotor tone lessens under the influence of rising arterial oxygen tension. Consequently the pulmonary artery pressure drops sharply even though the low adult levels are not reached until 10 to 14 days after birth. The ratio of pulmonary-systemic resistance thus decreases, and the fetal right-to-Ieft flow through the ductus arteriosus reverses. As pulmonary venous return to the left atrium increases, sufficient pressure is built up within that chamber to shut the foramen ovale, thereby cutting off the fetal right-to-Ieft shunt at this level. The foramen is usually closed within 90 minutes after birth, but the ductus arteriosus remains patent and shunting left-to-right for approximately 12 hours. Both the foramen ovale and the ductus arteriosus may under appropriate stress revert to their fetal function of shunting blood past the lungs, thereby depriving the alveoli of sufficient nutritive blood flow to maintain adequate activity of pulmonary surfactant. It is evident that, however helpful, this broad outline contains regrettably little information as to the quality of distribution of the increasing pulmonary blood flow. It is conceivable that, for a time at least, much of it is rushing through preferential arteriovenous channels rather than intimately perfusing the whole pulmonary capillary bed Fortunately, these relations are susceptible of analysis by recently developed techniques discussed below.

[

- ---

~~--

NEONATAL PULMONARY FUNCTION

u 791

NONUNIFORMITY OF VENTILATION AND PERFUSION ALVEOLAR-ARTERIAL GAS TENSION DIFFERENCES: CARBON DIOXIDE, NITROGEN, OXYGEN

Theory and Methods

If the gas of each alveolar tidal volume were evenly distributed to each alveolus, and if this ideal alveolar ventilation were perfectly matched by the flow of capillary blood past the alveoli, then gas exchange would be ideal, and the oxygen and carbon dioxide tensions of arterial blood would exactly equal those in the alveoli. This is not the case, however, largely because gravity effects cause blood to pool in the dependent portions of the lung where perfusion is consequently increased. Conversely, ventilation tends to be better in the upper areas of the lung. Thus the many millions of alveoli have a spectrum of ventilation-perfusion ratios. Normally the range of this spectrum is fairly narrow, and its average value is nearly unity. At this mean ventilationperfusion ratio of 0.9, the lung is performing minimal blood and gas flow work. In diseased lungs the spectrum of ventilation-perfusion ratios is considerably widened, and the mean mayor may not be 0.9. Consequently such lungs are less efficient in performing ventilatory and circulatory work. It can be shown that alveoli whose ventilation-perfusion ratios are, because of excess ventilation or decreased perfusion, much greater than 0.9 will establish a significant difference between the carbon dioxide pressure of the mixed alveolar gas and capillary blood (arterial-alveolar carbon dioxide pressure difference),l7· 18 The relative excess of gas flow over blood flow represents ventilation wasted in supplying extra gas either to alveoli whose blood is already arterialized or to alveoli which have no perfusion at all. The volume of such wasted ventilation is termed "alveolar" dead space. On the other hand, alveoli with low ventilation-perfusion ratios are those with gas flow insufficient to arterialize completely all the capillary blood perfusing them. These alveoli act as "virtual" or "capillary" shunts. In such alveoli the continually perfusing blood extracts more and more oxygen from and contributes more and more carbon dioxide to their poorly replenished gas contents. Since, on balance, the average infant or adult excretes fewer carbon dioxide molecules than the number of oxygen molecules taken up (respiratory quotient less than 1), the inert gas molecules of nitrogen fill in the voids to maintain constant volume. Consequently the nitrogen concentration or pressure in such alveoli increases. This sort of process tends to establish arterial-alveolar nitrogen pressure differences, so that a subject whose lungs contain many alveoli exhibiting decreased ventilation-perfusion ratios will be characterized by a greater than average arterial-alveolar nitrogen pres-

ma

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Figure 5. Various ventilatory units. The normal unit has a ventilation-perfusion ratio of nearly unity. The silent unit without ventilation or perfusion is not detectable by physiologic means. The nonperfused unit with a high ventilation-perfusion ratio behaves as (alveolar) dead space and contributes to the arterial-alveolar carbon dioxide pressure difference. The poorly ventilated unit with a low ventilation-perfusion ratio behaves as a (capillary) shunt and contributes both to the alveolar-arterial oxygen pressure difference and to the arterial-alveolar nitrogen difference. The mixed capillary blood is further desaturated by the anatomic shunt of venous blood. (Adapted from Bendixen et al.: Respiratory Care. St. Louis, C. V. Mosby Company, 1965.)

sure difference. 24 It should be noted, however, that such evidence may indicate relative underventilation or overperfusion, or both, since the nitrogen difference indicates only that the ratio of ventilation-perfusion is decreased. These various ventilation-perfusion relations are diagrammed in Figure 5. Alveolar-arterial pressure differences for oxygen are more complex, for they represent the summed effects of (1) areas of the lung with low ventilation-perfusion; (2) impairment of diffusion (thickened membrane or decreased surface area for diffusion); and (3) true anatomic shunts from right to left bypassing the alveoli or the lung (Fig. 5) altogether. True shunts normally occur in the vasa vasorum and the bronchial circulation in addition to whatever blood perfuses totally unventilated or atelectatic alveoli. The newborn baby may further shunt venous blood directly into the arterial circuit across the foramen ovale and the ductus arteriosus. Exact localization of these shunts requires catheterization of the specific vascular sites concerned, but the summed effects of all sources of veno-arterial shunting may be estimated by noting the arterial oxygen pressure during oxygen breathing. Oxygen breathing will overcome any arterial desaturation due to diffusion impairment and the

-

"

---

...

~--

- -- ---

-

.

793

NEONATAL PULMONARY FUNCTION

capillary shunts in alveoli which are underventilated or overperfused. It cannot, however, correct desaturation due to true anatomic shunts. Measurements and Interpretations Table 7 summarizes the available data concerning blood gas tensions in babies. Remembering that carbon dioxide differences largely repre-

sent areas of the lung with high ventilation-perfusion, whereas nitrogen differences mainly signify low ventilation-perfusion ratios, we note that neither the normal infant nor the normal adult has remarkably wide variation of ventilation-perfusion ratios. The emphysematous adult, however, often has nitrogen differences of 20 to 60 mm. of mercury. The wider oxygen difference in the infant is accounted for by increased venoarterial shunting occurring (largely) through the foramen ovale.41 This also accounts for the difference between the total gas pressure in the alveolus and in the artery.14 The total oxygen difference can be fractionated into its three main components (capillary shunt, anatomic shunt, diffusion component) by analyzing the oxygen tensions in the alveolus and artery during studies Table 7.

Alveolar-Arterial Gas Tensions (mm. Hg)* ADULT 14

~NFANT

Alv.

Art.

DiJf·

Alv.

Art.

DiJf.

HsO ............ 47 0 •.............. 105 CO•............ 40

47 95 41 575 758

0 +10 -1 -7 +2

47 105 35 573 760

47 80 36 583 746

0 +25 41 _1 40 -10 24 • 44 +14

N •...•.......... 568 Total ........... 760

.. Breathing air at sea level.

Table 8.

Alveolar-Arterial Oxygen Differences (mm. Hg) ADULT9, 18

Breathing 14% D.; differences due to: Capillary shunt ........................................... <1 Anatomic shunt .......................................... < 1 Diffusion component. .••.................................. ~ Total.. .........•..................................... 7 Breathing 21 % D. (air); differences due to: Capillary shunt ........................................... 1-2 Anatomic shunt. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8 Diffusion component ...................................... ~ Total ................................................. 10 Breathing 100% O 2; differences due to: Capillary shunt. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 0 Anatomic shunt. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37 Diffusion component. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. 0 Total ................•................................ 37

INFAN~1. 4a

<1 5

10 15 1-2 23 <1

25 0 311 0 311

794

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at various levels of oxygenation (Table 8). During hypoxic ventilation the oxygen difference is mainly due to the (artificially increased) diffusion component, whereas during hyperoxic ventilation it is entirely due to the true shunt component. During air breathing the total oxygen difference is mostly the result again of "physiologic shunting" (anatomic). In the adult this is mainly through the bronchial circulation and amounts to 2 to 3 per cent of total cardiac output. In the infant the bronchial vessels, the foramen ovale and the ductus arteriosus are the main sites for such shunting, which involves roughly 20 to 30 per cent of total cardiac output and is the reason for the lower arterial oxygen tension in newborn babies. Despite this lowered arterial oxygen tension, the greater affinity of fetal hemoglobin for oxygen ensures adequate oxygen saturation of the normal infant's blood.

INTEGRATED POSTNATAL CARDIOPULMONARY ADAPTATION

The Blood Gases Since the main purpose of pulmonary function is the arterialization of the venous blood, the composition of the arterial blood gases reRects the adequacy of lung ventilation, diffusion and perfusion to that purpose. Sufficient longitudinal investigations of many of these factors have been performed to give a fairly clear picture of the immediate postnatal establishment of independent respiration. After the first breath of life has been taken in response to a number of chemical and somatic stimuli,33, 47, 55 the rest volume of the lung increases rapidly to establish a fairly stable functional residual capacity by eight to 10 minutes of age (Fig. 6). Continuing adequate ventilation is accompanied by decreasing pulmonary vascular resistance and an increasing peripheral vascular resistance as the placental circuit is subtracted by clamping the cord. These factors lead to increased pulmonary perfusion, while local regulation of gas and blood Row within the lung tends to eliminate nonuniform distribution of both elements. As the pulmonary vascular bed expands, pulmonary capillary pressure drops considerably below that of plasma osmotic pressure, thus ensuring absorption of Ruid from the still wet lung. This absorptive process, however, abetted by the increased Row of lymph out of the lung, takes time, so that the increase in specific compliance of the lung is delayed and reaches its maximum about 24 hours of age. The development of maximum air conductance is similarly delayed, presumably as a result of a relatively slow relaxation of bronchospasm and clearance of Ruid from the airways. The effects of these events on the blood gases are depicted in Figure 7, wherein is noted the normal state of relative asphyxia (hypo-

22

"'Q 70 Q;

~ 60

"0 >

go :>

-

50

E

"-

oN

"-

oN J:

J:

40

40 E

30

30=

u "u

E

u

"-

'" .!!:

E LUN G VOLUME

AT REST

20

10

OLI--~----4~--~--~--~--~~~--~--~~~--~2~4~3~6~4~B~hr~0

Figure 6. Respiratory mechanics after birth. The functional residual capacity (resting lung volume) is rapidly established. There appears to be a distinct lag, however, in the development of maximal specific lung compliance (ml./cm.H20/ml. lung volume) because the removal of lung fluid requires time. The similar lag in specific conductance may be related to wet or spastic airways. (Constructed from smoothed data of references 3, 16, 20, 35, 36, 47, 48, 49.) 7.4 ARTERIAL pH

.=120

E "-

ALVEOLAR VENTILATION

!1

30

7.3

25

7.2 a.

20

7.1

":>

~

J:

"-

6u

~IOO TOTAL PLASMA CO 2 CONTENT

!!

:; E

BO ARTERIAL ~ TENSION

60

'"E 40

J:

ARTERIAL CO2 TENSION

E 20 ARTERIAL-ALVEOLAR C02 DIFFERENCE

o 4

15

30

60 min 2

4

B

12

24 36 48 hours

AGE

Figure 7. Blood gas and acid-base adjustments following birth. Birth asphyxia is reflected in the hypoxemia and respiratory acidosis (high arterial carbon dioxide tension, low pH, high normal carbon dioxide content) that characterize the first hour of life. These defects are rapidly compensated, however, and by 4 to 12 hours of age pulmonary function (ventilation, diffusion, perfusion) is sufficiently well established to support normal homeostasis of the blood gases. The persistent low arterial oxygen tension (and high alveolar-arterial oxygen difference) indicates a continuing venoarterial shunt. (Constructed from smoothed data of references 45, 49, 51, 65.)

795

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NICHOLAS

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xemia and hypercapnia with acidosis) in the :first few moments after birth. This asphyctic state represents the "hypoventilation" produced by the recurrent interruption of uterine, placental and umbilical blood flow that is caused by normal labor and delivery. The high arterial carbon dioxide tension and normal carbon dioxide content reveal the acidosis as being purely respiratory and acute. The acidosis is rapidly corrected by "blowing off" the carbon dioxide accumulated during the asphyctic period. By one hour of age the pH is normal and alveolar ventilation stable. The normal carbon dioxide difference demonstrates that by one hour of age there are few areas of significant alveolar dead space. Although the stable oxygen difference and carbon dioxide tension indicate that few large areas of hypoventilation remain after two to four hours of age, the total physiologic shunt is still considerably larger than in the adult. This increased shunt occurs most probably at the level of the ductus arteriosus and the foramen ovale, which will not close functionally until left-sided pressures remain larger than right-sided pressures throughout all phases of the cardiac cycle. Thus the arterial oxygen tension, although reaching a stable plateau by two to four hours after birth, remains depressed relative to that of the adult for a considerable period of time.

CONCLUSIONS

1. Although intimate study of pulmonary function in the newborn infant has revealed some differences from the adult, these are principally related to size. 2. The cardiorespiratory apparatus of the term fetus is awesomely developed to a state entirely appropriate for his needs after birth. 3. The asphyctic episode of normal labor and delivery is rapidly compensated soon after independent respiration has been established. 4. Further development of pulmonary reserve occurs as growth progresses. 5. In certain areas (stability of lung volume, defense against acidosis, preservation of adequate pulmonary perfusion) the newborn infant may exhibit significant diminution of cardiopulmonary reserve.

REFERENCES 1. Adams, F. H.: Fetal and Neonatal Cardiovascular and Pulmonary Function. Ann. Rev. Physiol., 27:257,1965. 2. Agostoni, E.: Volume-Pressure Relationships of the Thorax and Lung in the Newborn. J. Appl. Physiol., 14:909, 1959. 3. Auld, P. A. M., Nelson, N. M., Cherry, R. B., Rudolph, A. J., and Smith, C. A.:

-

NEONATAL PuLMONARY FUNCTION

4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29.

-----.

-_.

4.tt-. Li.hM 797

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