477CHAPTER 42 Physiology of the Respiratory System measure of the elastic properties of the respiratory system and is called elastance (E) E 5 PEL/V When lung volume is plotted on the y axis and PEL i[.]
CHAPTER 42 Physiology of the Respiratory System 34 Legend a = end-exhalation b = beginning of flow c = end-inhalation bd – ac difference = intrinsic PEEP 30 25 Airway pressure (cmH2O) 477 20 15 10 10000 5000 Flow (mL/min) –5000 –8000 17 16 c a Esophageal 15 pressure (Pes) (cmH2O) 14 13 12 Change in esophageal pressure related to overcoming intrinsic PEEP ∆Pes d b Change in esophageal pressure related to delivering tidal gas 11 10 • Fig 42.6 Airway pressure, spirometry, and esophageal pressure tracings for a spontaneously breathing and mechanically ventilated child that has intrinsic positive end-expiratory pressure (PEEP) Esophageal pressure begins to drop at point a as the child attempts to initiate a breath; however, flow does not begin until point b The area demarcated in gray represents the pressure work that the child must to overcome intrinsic PEEP before any inspiratory flow can occur The blue shading is the pressure work related to inspiring airflow The double-headed arrow represents the total change in esophageal pressure +15 +15 +15 +15 +2 +15 +15 +15 +15 +15 +15 No PEEP +15 +15 +15 With PEEP 15 • Fig 42.7 Pressure gradients involved when intrinsic positive end-expiratory pressure (PEEP) is present With no addition of PEEP, a significant reduction in alveolar pressure would be required to facilitate airflow When PEEP is applied to match the intrinsic PEEP, airflow can be facilitated by just reducing alveolar pressure less than the applied PEEP measure of the elastic properties of the respiratory system and is called elastance (E): E PEL/V When lung volume is plotted on the y-axis and PEL is plotted on the x-axis, the slope of the static pressure-volume curve is equivalent to the reciprocal of elastance, called compliance During health, most of the pressure produced during tidal respiration is required to overcome elastic forces and a minimal amount is required to overcome the flow-resistant forces The lung parenchyma is a complex system consisting of alveolar walls composed of collagen, elastin, and proteoglycan macromolecules; an air-liquid interface of surfactant; and cells that have the capacity to act in a contractile fashion, called interstitial cells The energy 478 S E C T I O N V Pediatric Critical Care: Pulmonary expended moving the tissue is called the tissue viscance or resistance When measured during inspiration, the tissue resistance increases with increasing lung volume, whereas airway resistance falls Tissue resistance comprises approximately 65% of respiratory system resistance at FRC in mechanically ventilated animals and increases to as much as 95% at higher lung volumes.21 The contribution of tissue resistance to respiratory system resistance in humans under the same circumstances is unknown The other part of elastic recoil depends on the surface tension at the alveolar gas-liquid interface (surface forces) Surface tension is produced by the interface between air in the alveolus and the thin film of liquid that covers the alveolar surface Surface tension in the alveolus is created by interacting water molecules that direct a force inward and could cause alveoli to collapse This action is described by La Place’s equation, in which the pressure inside a bubble exceeds the pressure outside the bubble by twice the surface tension divided by the radius In other words, the smaller a bubble, the more the pressure inside exceeds the pressure on the outside La Place’s equation is defined as P 2T/r where P is the internal pressure, T is the tension in the wall of the structure, and r is the radius When comparing two different alveoli with the same surface tension, the smaller the radius, the greater the pressure created by a given surface tension When the alveoli are in communication, air will flow from high pressure (small alveoli) to lower pressure (larger alveoli) Thus, smaller alveoli are more likely to collapse Surfactant contains a mixture of lipids and proteins; it exists as a monolayer on top of the alveolar subphase22 and acts to lower surface tension at the alveolar airliquid interface, thereby decreasing elastic recoil of the lungs.23 Furthermore, surfactant reduces the interstitial pressure and transcapillary gradient, preventing pulmonary edema.24 Respiratory System and Lung Compliance Recall that compliance is the inverse of elastance Compliance is how much a compartment will expand if the pressure in that compartment is changed The compliance (C) is determined by the change in pressure (DP) produced by a change in volume (DV): C DV/DP As described earlier, the two major forces contributing to lung compliance are tissue elastic forces and surface tension forces In respiratory physiology, it is important to remember that the compliance properties of the respiratory system are a function of both the lung and the chest wall, and are related by the equation 1/ CRS 1/ CL 1/ CCW The compliance of the lungs (CL), chest wall (CCW), and respiratory system (CRS) can be determined individually by measuring the change in distending pressure and the associated change in volume Measurement of these elastic properties must be done under conditions of no airflow; otherwise, one cannot distinguish between flow-resistive and tissue-elastic components in the equation of motion of the respiratory system During mechanical ventilation, this is done by employing inspiratory (and expiratory) holds where flow is zero For each of the components discussed earlier, the compliance is calculated as the change in volume (tidal volume) divided by the transmural pressure across that structure For the lung, this pressure is the transpulmonary driving pressure (Palv Ppl), where Palv is the alveolar pressure and Ppl is the pleural pressure Alveolar pressure can be estimated from airway pressure during conditions of no airflow (inspiratory and expiratory hold); pleural pressure can be estimated from esophageal pressure Unfortunately, these pressures are not possible to measure directly in routine clinical practice; thus, surrogates are frequently used, with some limitations.25,26 For the chest wall, the transchest wall pressure is (Ppl Pbs), where Pbs is body surface pressure and is typically atmospheric pressure For the entire respiratory system, it is the airway driving pressure (Palv Pbs): CL 5 DV/D(Palv Ppl) CCW DV/D(Ppl Pbs) CRS DV/D(Palv Pbs) Pulmonary compliance changes with growth and maturation depending on the number of expanded air spaces, size and geometry of the air spaces, characteristics of the surface lining layer, and properties of the lung parenchyma This shift is represented by changes in the shape of the volume-pressure curve The developmental change in shape of the volume-pressure curve represents the maturation of alveoli and, hence, differences in the elastincollagen ratio with age.27 End-Expiratory Lung Volume and Compliance In the intact thorax, the inward recoil of the lungs is opposed by the outward recoil of the chest wall (when it is below or at its resting volume) However, as the chest volume increases above its resting volume, both the lungs and chest wall recoil inward and act as though arranged in series The pressure required to balance the elastic recoil of the lungs, chest wall, and respiratory system (elastic recoil pressure) may be determined by having a subject exhale in increments from total lung capacity to residual volume At each volume, the subject relaxes against a fixed obstruction with glottis open; the pressure difference across the lung, chest wall, and entire respiratory system is then recorded.28 The static pressure-volume curves of the respiratory system, lung, and chest wall are different during inspiration and expiration Thus, lung volume at a given transpulmonary pressure is higher during deflation than during inflation This phenomenon is called hysteresis Hysteresis is the failure of a system to follow identical paths of response on application and withdrawal of a forcing agent, as occurs during inspiration and expiration Hysteresis in the respiratory system depends on viscoelasticity, such as stress adaptation (i.e., rate-dependent phenomenon), and on plasticity (i.e., a rate-independent phenomenon) In the lungs, hysteresis is due primarily to surface properties and alveolar recruitment-derecruitment In comparison, the chest wall hysteresis is related to the action of both muscles and ligaments because both skeletal muscles and elastic fibers exhibit hysteresis Hysteresis is negligible when volume changes are minimal, such as during quiet breathing The area of the hysteresis loop represents energy lost from the system The resting volume of the respiratory system, the functional residual capacity (FRC), is the volume at which the elastic recoil of the lungs and the chest wall exactly balance each other Above and below this equilibrium point, progressively increasing pressure is required to change the volume of the respiratory system The total pressure required at each volume is the sum of the pressures required to overcome the elastic recoil of the lungs and chest wall Hence, it is at a mechanical advantage to remain at FRC, as this is where compliance is maximized and resistance is minimized CHAPTER 42 Physiology of the Respiratory System Functional Residual Capacity, Closing Capacity, and Age of breathing, therefore, this is the function of pressure volume If a patient is breathing spontaneously with no ventilator assistance, the pressure is best characterized by changes in pleural pressure throughout the breath, and the volume is the tidal volume If the patient is not spontaneously breathing and is on a ventilator, this pressure is characterized by changes in airway pressure throughout the breath, and the volume is the tidal volume Here, the patient has no work of breathing—the ventilator performs the work In assisted ventilation, the change in pleural pressure can be used to estimate patient contribution to work, while changes in airway pressure are used to estimate ventilator contributions It is important to remember that this total work represents both flow-resistive and tissue-elastic properties of the airways, lungs, and chest wall This work of breathing relationship is often calculated from the Campbell diagram, which allows for theoretical attribution of the various components of work However, in cases in which there are changes in pressure without volume displacement (i.e., isometric work), such as during severe upper or lower airway obstruction, the impact to the patient may be underestimated from the work of breathing calculation In general, if flow-resistive work predominates (i.e., airway obstruction), it is more efficient to breathe less often but with a higher tidal volume, as the resistance to airflow in the intrathoracic airways reduces with increasing volume In contrast, when elastic work predominates (i.e., parenchymal lung disease), it is more efficient to breathe more often with lower tidal volume, as elastic work increases further as volume increases (Fig 42.8).29 Life begins with a small number of alveoli, only about 10% of what adults will have From infancy until about years of age, there is rapid growth of alveoli size and number Each alveolus has a critical closing capacity based on the particular elastance properties of that alveolus Much like a balloon, when the volume falls below a critical level, the alveoli collapse In healthy adults, the critical closing capacity for most alveoli is much lower than FRC; thus, small losses in alveolar volume not result in alveolar collapse During infancy, the chest wall is very compliant and the elastic recoil of the lungs results in a much smaller resting volume (FRC) For infants, the critical closing capacity of many alveoli may actually lie above FRC This, coupled with the fact that infants lack collateral ventilation pathways that older children and adults have, makes them particularly prone to respiratory failure In fact, spontaneously breathing infants attempt to counteract this by stopping exhalation before reaching airway closure through laryngeal breaking (sometimes termed auto-PEEP [positive endexpiratory pressure]), as an attempt to maintain a higher FRC Work of Breathing Returning to the equation of motion of the respiratory system, we again see that the pressure that needs to be generated to promote airflow is a function of both the resistive and elastic properties of the respiratory system: PRS (V/C) RQ If the patient is on a mechanical ventilator, the pressure that is generated is shared between the patient and the ventilator depending on the degree of spontaneous effort and synchronization: Extrathoracic Space At normal FRC, the mechanical forces of the chest wall and lung are balanced, with a slightly negative pleural pressure The total transmural pressure across the respiratory system is at end expiration (Palv Pbs), as both alveolar pressure and body surface pressure (atmospheric pressure) are zero This is balanced by the pressure across the lung (transpulmonary pressure, Palv Ppl), which is slightly positive because baseline pleural pressure is PRS PApplied PMUS (V/C) RQ However, from a respiratory mechanics standpoint, both the pressure and volume are important when considering the energy required for the system to function In physics terms, this is described by the concept of work, or the force distance For work Work of breathing (arbitrary units) Normal Increased elastic resistance Increased air flow resistance Total Total El as Total El tic El as tic as tic low ow rfl 10 Ai low Airf Airf 15 20 479 10 15 20 10 15 20 Respiratory rate (breaths/min) • Fig 42.8 Elastic work, work related to airflow resistance, and total work as a function of respiratory rate under the same minute ventilation When elastic work is increased, the total work is lowest at a higher respiratory rate This changes when work related to airflow resistance predominates and it is more efficient to breathe with a lower respiratory rate and higher tidal volume 480 S E C T I O N V Pediatric Critical Care: Pulmonary typically 25 and across the chest wall, which is slightly negative However, under circumstances in which the chest wall elastance is increased (i.e., chest wall compliance is decreased), the pleural pressure rises to less negative or even positive values This rise in pleural pressure results in negative transpulmonary pressure, leading to alveolar collapse at end exhalation The result is increased elastic work from the mechanical properties of the chest wall and loss of end expiratory lung volume (FRC) with reduced lung compliance In these circumstances, the important therapeutic principle is normalization of transpulmonary pressures at end exhalation to prevent alveolar collapse.25 This is typically accomplished with positive-pressure ventilation and PEEP in particular However, if chest wall elastance is high, then going back to the equation of motion of the respiratory system, additional pressure needs to be generated by either the patient (spontaneous breathing) or the ventilator In these circumstances, the transpulmonary driving pressure may remain low, as this pressure is transmitted to the pleural space to move the chest wall out of the way Gas Exchange With an understanding of the principles that affect movement of gas into and out of the lungs, we can now focus on the necessary function of the respiratory system to supply oxygen to the body and to remove excess CO2 The following are the essential steps involved in this process: Ventilation, the exchange of gas between the atmosphere and alveoli Diffusion across the alveolar-capillary membrane Transport of gases in the blood Diffusion of the gases from the capillaries of the systemic circulation to the cells of the body Use of oxygen and production of CO2 within the cells as a by-product of metabolism In the alveoli, air is exposed to a thin film of blood at the alveolarcapillary membrane Oxygen diffuses across the alveolar-capillary membrane, enters the blood, and combines with hemoglobin Simultaneously, CO2 diffuses from the blood and enters the alveolar gas In this way, the mixed venous blood entering the lungs is altered through the addition of oxygen and removal of CO2 This is the process of gas exchange The partial pressure of oxygen (Po2) and CO2 (Pco2) in the arterial blood—and therefore the adequacy of gas exchange—is dependent on a number of factors These factors include the composition of the alveolar gas and the extent to which equilibrium is reached between the alveolar gas and pulmonary capillary blood The alveolar gas composition is, in turn, dependent on the content of the inspired air and mixed venous blood, the quantity of air (ventilation) and blood (perfusion) reaching the alveoli, and the ratio of alveolar ventilation to perfusion ( V˙a/Q) Of the factors determining the adequacy of gas exchange, the structure and function of the lungs primarily influence the ventilation-perfusion relationships, alveolar ventilation, and diffusion of oxygen and CO2 Alveolar ventilation and oxygenation are related by the alveolar gas equation The alveolar gas equation for calculating Pao2 is essential to understanding disease states and hypoxemia Pao2 Fio2 (PB PH2O) Paco2/RQ Where Pao2 is the alveolar partial pressure of oxygen, Fio2 is the fraction of inspired gas that is oxygen (expressed as a decimal), PB is barometric pressure, PH2O is the saturated vapor pressure of water at body temperature and the prevailing atmospheric pressure, Paco2 is the arterial partial pressure of carbon dioxide, and RQ is the respiratory quotient or respiratory coefficient (the ratio of CO2 produced to the oxygen consumed), whose value is typically 0.8 Ventilation-Perfusion Relationships In the normal, upright lung, both alveolar ventilation and perfusion increase from the apex to the bases largely because of the effects of gravity Blood flow increases more rapidly from apex to ˙ a/Q ratios are high at the apex base than ventilation; therefore, V and decrease progressively toward the base of the lungs The regional differences in perfusion are called West’s zones of perfusion.30–32 West’s zone I occurs when mean pulmonary arterial pressure is less than or equal to alveolar pressure; thus, no blood flow occurs In zone I, the apices of the lung of an upright adult, there are unperfused yet ventilated alveoli, which is dead space ventilation (Bronchial arterial flow nourishes the lung.) In zone II, which consists of the midlung, pulmonary artery pressure is greater than alveolar pressure Conditions in this zone are governed by the fact that blood flow is not influenced by venous pressure but rather by the difference between arterial and alveolar pressures, which is a function of (hydrostatic) height In zone III, the lower zone of the lung, pressure at the alveolus is exceeded by the pressures in both the pulmonary artery and vein Flow in this zone is a function of pulmonary artery and pulmonary venous pressures At the base of the lung, because of higher perivascular pressures and reduced lung expansion, flow is again diminished.33 Any disorder affecting the airways or lung parenchyma will result in an increased imbalance between ventilation and perfusion There are two extremes of this V/Q mismatch Shunt refers to areas where there is no ventilation but there is perfusion This is represented as a V/Q ratio of Here, the alveolar gas most represents mixed-venous blood, with a Pco2 of 45 mm Hg and a Po2 of 40 mm Hg This is because no fresh gas is inspired into that alveolus The opposite side is dead space, where there is ventilation, but no perfusion (V/Q ratio of infinity) Here, alveolar gas most represents inspired air (whether it be room air or with supplemental oxygen) Under normal conditions, if the patient is breathing room air at sea level, the alveolar Po2 is typically 150, with no Pco2 The presence of varying V˙a/Q (whether ,1 or 1) highlights the presence of ventilation-perfusion mismatch Hypoxemia When faced with a hypoxemic patient, an algorithmic approach can be used to help identify the cause of hypoxemia In health, the partial pressure of oxygen in the alveolus (Pao2) is a primary determinant of arterial oxygen tension (Pao2): Pao25 [(PB – PH2O) Fio2] – Paco2/RQ Substituting normal values for an individual breathing room air at sea level, the Pao2 is approximately 100 mm Hg As oxygen crosses the alveolar membrane into the pulmonary capillary network, a negligible amount of oxygen tension is lost (around 10 mm Hg, although this fluctuates with age) By examining the alveolar gas equation closely, one can see that three conditions can cause a decrease in Pao2, which will make the patient hypoxemic: altitude (low Pb), hypoxic gas mixture (low Fio2), and hypoventilation (high Paco2) In these circumstances, there is no CHAPTER 42 Physiology of the Respiratory System increase in the arterial Po2 (A – a Do2) gradient In most circumstances, the degree of hypoxemia from any of these three sources can be easily overcome with a small increase in supplemental oxygen Hypoxemia is more commonly a reflection of shunt or V/Q mismatch with regions with V/Q ratios less than In these circumstances, there is a marked elevation in the arterial Po2 (A – a DO2) gradient Alternatively, one can also try to quantify the ˙ 0, using the degree of true intrapulmonary shunt, where V shunt equation This is calculated with simultaneous arterial and mixed venous blood gases (requires a pulmonary artery catheter), with the patient exposed to 1.0 Fio2, and is given by Qs/Qt: Qs/Qt (Cc Ca)/(Cc Cv) where Cc, Ca, and Cv are the O2 contents of pulmonary end-capillary, arterial, and mixed venous blood, respectively This requires knowing the hemoglobin and using the alveolar gas equation to calculate Pao2 for computing the end-capillary CaO2 When the shunt fraction is calculated on an Fio2 of less than 1.0, this is sometimes referred to as the venous-admixture method, which gives information regarding shunt, V/Q regions less than 1, and diffusion limitation Hypercarbia The respiratory system also eliminates CO2 from the blood Arterial CO2 tension (Paco2) is directly proportional to minute ventilation (Ve), where Ve respiratory rate tidal volume Ve fVt It is worth noting that Vt is composed of dead space volume (Vd) and alveolar volume (Va) Dead space volume is the portion of the tidal breath that does not participate in gas exchange with pulmonary capillaries Dead space is composed of anatomic dead space and nonanatomic dead space (sometimes called functional, physiologic, or alveolar dead space) Anatomic dead space is found within the conducting airways—the nose, mouth, oropharynx, trachea, bronchi, and bronchioles—and accounts for approximately 20% to 30% of a tidal breath,34 although it is relatively larger in infants Nonanatomic (alveolar) dead space approaches zero in healthy individuals, as most lung units are equivalently ventilated and perfused However, in infants and children with respiratory disease, total dead space may approach 60% to 70% of a tidal breath.35 In contrast, alveolar volume is the portion of inspired breath that arrives at the alveoli and participates in gas exchange with pulmonary capillaries Therefore, it is more accurate to state that Paco2 is proportional to alveolar minute ventilation (MVa): MVa f (Vt – Vd) Hence, an elevated Paco2 can arise from a decrease in respiratory rate, a decrease in tidal volume, or an increase in dead space The alveolar ventilation is an important determinant of gas exchange because it, along with the rate at which tissue metabolism produces CO2 (V˙co2), determines the Pco2 of arterial blood: Pco2 V˙co2/ V˙a ˙ co2 is constant, Pco2 varies inversely with V˙a It When V is evident that at given minute ventilation, the Pco2 will vary directly with the amount of dead space As dead space changes, 481 the Pco2 can be kept constant only by increasing or decreasing V˙e by an identical amount The measurement of dead space has evolved from the original description by Bohr in 1891, when dead space was considered simply the gas from the conducting airways One can calculate the physiologic (or total) dead space as Vd/Vt (PaCO2 PĒCO2)/PaCO2 where PĒCO2 is mean expired Pco2 Increasingly, volumetric capnography has been used to measure not only total dead space fraction Vd/Vt but also to differentiate alveolar dead space from airway dead space.35–37 Physiologic dead space increases in a variety of pathophysiologic situations that compromise pulmonary blood flow, such as pulmonary embolus, microvascular thrombosis, pulmonary hypertension, impaired cardiac output, and regional overdistension of lung units with excessive ventilation Diffusion of Oxygen and Carbon Dioxide Gas must travel through a number of barriers between the alveolus and blood These barriers include the alveolar epithelial lining, basement membrane, capillary endothelial lining, plasma, and red blood cell The amount of gas (Q) diffusing through a membrane is directly proportional to the surface area available for diffusion (S), the pressure difference for the gas on either side of the membrane (p1 p2), and a constant (K) that depends on the solubility coefficient of the gas, membrane characteristics, and liquid used This association is defined by the Fick principle of the diffusion state as follows: Q/min Kl(p1 p2)/d where Q is inversely proportional to the distance it has to diffuse and K is proportional to the solubility of the gas and inversely proportional to the square root of the molecular weight In healthy subjects at rest, equilibration of the Po2 and Pco2 of the alveolar gas and pulmonary capillary blood is achieved in approximately 0.75 seconds.38 This is about one-third of the time spent by the blood in the capillary network The rate of pulmonary blood flow can increase greatly, to the point that it prevents equilibration For this reason, diffusion disequilibrium has been demonstrated in healthy persons but only during strenuous exercise at high altitudes In the presence of parenchymal disease, diffusion impairment may occur as a result of thickening of the alveolar-capillary membrane Much more commonly, however, diffusion disequilibrium is associated with destruction of the pulmonary capillary bed This destruction results in a greatly increased blood flow velocity in the remaining capillaries, which may allow insufficient time for equilibration Even when parenchymal disease is severe, however, diffusion disequilibrium usually occurs only when cardiac output— and therefore rate of flow—is markedly increased Key References Akoumianaki E, Maggiore SM, Valenza F, et al The application of esophageal pressure measurement in patients with respiratory failure Am J Respir Crit Care Med 2014;189(5):520-531 Bhalla AK, Belani S, Leung D, Newth CJL, Khemani RG Higher dead space is associated with increased mortality in critically ill children Crit Care Med 2015;43(11):2439-2445 ... breathing and is on a ventilator, this pressure is characterized by changes in airway pressure throughout the breath, and the volume is the tidal volume Here, the patient has no work of breathing—the... is important to remember that this total work represents both flow-resistive and tissue-elastic properties of the airways, lungs, and chest wall This work of breathing relationship is often calculated... seconds.38 This is about one-third of the time spent by the blood in the capillary network The rate of pulmonary blood flow can increase greatly, to the point that it prevents equilibration For this