472 SECTION V Pediatric Critical Care Pulmonary Extrathoracic Upper Airways When evaluating the extrathoracic upper airways, the physiology and pathophysiology typically follow airway anatomy Therefor[.]
472 S E C T I O N V Pediatric Critical Care: Pulmonary release H1, resulting in stimulation of these central chemoreceptors The parafacial retrotrapezoid nucleus (RTN), which contains Phox2b-expressing glutamatergic neurons, has been identified as a likely location for the chemoreceptors that sense CO2 in the central nervous system, as a mutation in Phox2b is a risk factor for developing congenital hypoventilation syndrome, where severe hypoventilation occurs during sleep or sedation.3,4 The peripheral chemoreceptors consist of the carotid bodies located at the bifurcation of the common carotid artery and aortic bodies located in the aortic arch The carotid bodies are the primary oxygen chemoreceptor They become activated when partial pressure of arterial oxygen (Pao2) falls below 100 mm Hg and can be modulated further by changes in CO2 and H1 in arterial blood.2 The aortic bodies respond to reductions in arterial pH There is a link between central and peripheral chemoreceptors with Phox2b neurons, which consequently increases or decreases the slope of the central CO2 ventilatory response when the peripheral chemoreceptors are stimulated.5 Pulmonary mechanoreceptors sense the adequacy of lung stretch and send afferent messages back to the respiratory centers Within the tracheobronchial superficial mucosal layer are rapidly adapting pulmonary stretch receptors that when activated result in elevated airway resistance, reflex apnea, and coughing Within the tracheobronchial smooth muscle layer are the slowly adapting pulmonary stretch receptors that when activated send messages through the vagal afferent myelinated fibers to terminate inspiration This reflex to end inspiration, which is driven by these pulmonary stretch-sensitive mechanoreceptors, is termed the HeringBreuer inflation reflex This alone can relieve feelings of dyspnea from unsatisfied inspiration independent of arterial blood gas concentration Receptors that sense injury to tissues (nociceptors) exist in the respiratory system In the upper respiratory tract, irritants on the mucosal surface triggered by mechanical touch can initiate a rapid cough In the lower respiratory tract, bronchopulmonary C-fibers, which are slower-acting unmyelinated fibers housed near the pulmonary interstitium, are activated by inflammation and can trigger defensive mechanisms such as apnea, rapid shallow breathing, mucus secretion, bronchoconstriction, and cough.2,6 Higher States Level of consciousness can further modulate respiratory drive In the sleeping or obtunded patient, control is dominated by chemoreceptor feedback Chemoreception with the RTN manages a large portion of the drive to breathe during non–rapid eye movement (REM) sleep; during REM sleep, the contribution of the RTN is still present but affects only some components of breathing During wakefulness and non-REM sleep, the RTN regulates both respiratory rate and tidal volume During REM sleep, however, the RTN regulates only tidal volume.7 Opioid drugs, such as morphine and fentanyl, reduce motor control and attention, which can alter sleep Respiratory rhythm generation is highly influenced by the pre-Botzinger complex in the ventrolateral medulla; this site is greatly inhibited by opioids, which reduce respiratory rate without a significant change in tidal volume (although this can also occur during high doses).8 Volatile anesthetics and propofol can suppress breathing by blunting chemoreception, inhibiting motor neurons, and by eliminating the wakefulness state During anesthesia, the response to hypoxic drive is blunted even prior to a loss of consciousness.9 During sleep, respiratory rate is left unchanged or increased while the tidal volume and response to oxygen chemoreception is decreased.10 Extrathoracic Upper Airways When evaluating the extrathoracic upper airways, the physiology and pathophysiology typically follow airway anatomy Therefore, it is useful to compartmentalize the upper airway into supraglottic regions (i.e., the nasopharynx and oropharynx), the region near the glottis (i.e., vocal cords and folds), and subglottic region (i.e., the extrathoracic trachea) Given the anatomic considerations of the pediatric airway—as well as physiologic concepts relating the relationship between airway caliber, resistance, and flow— children are particularly prone to develop respiratory failure related to upper airway obstruction from lesions in any one of the three extrathoracic compartments Anatomic Considerations for the Pediatric Upper Airway Anatomically, the configuration of the airway changes considerably as a child develops from infancy to adulthood The infant’s airway is characterized by a relatively small mandible and flat roof of the nasopharynx.11–13 As the child develops, the mandible descends and moves forward, and the roof of the pharynx becomes more rounded Moreover, the tongue is relatively large compared to the bony structures in the mouth, and the normal anterior displacement of the tongue with inspiration is relatively blunted in the young infant As a result, loss of airway tone from sedation, sleep, or CNS dysfunction is more likely to result in obstruction of the posterior pharynx in a young child than in an adult.14 Compared with the adult, the infant’s larynx is high in the neck; at birth, the epiglottis often overlaps the soft palate at the level of the first cervical vertebrae The epiglottis separates from the soft palate by approximately months of age and descends to the third cervical vertebrae It reaches the adult position, at the fifth or sixth cervical vertebrae, by adolescence The infant’s epiglottis is rounder and softer than the adult epiglottis and is more prone to occlude the airway Finally, it has been a longstanding belief that the airway of an infant tapers in a funnel shape and becomes narrowest at the cricoid cartilage, in the subglottic space, and it remains this way until about to 10 years of age.12 However, more recent evidence that has examined computed tomography scans and ultrasound of pediatric patients questions some of these findings Nevertheless, the area at highest risk for injury from endotracheal intubation does appear to be below the vocal cords, in the subglottic space.15 Ohm’s Law and Poiseuille’s Law Air moving through the upper airway can be modeled as a fluid moving through a pipe The rate of flow through a tube is a function of the resistance and pressure gradient, which can be modified from Ohm’s law, where voltage (V) equals the current (I) multiplied by resistance (R) In physiologic considerations of airflow, V represents the pressure gradient across the system (ΔP), and I represents the flow (Q), yielding the relationship Q ΔP /R The resistance in the airway can be modeled from Poiseuille’s law, where length (l) of the pipe, its radius (r), and the viscosity of gas (h) affect the resistance (R 8hl/πr4) Since the radius term is in the denominator and is raised to the fourth power, the effect of an internal radius reduction of one-half can increase the resistance by 16-fold under laminar conditions and even more so during turbulent flow Since the internal lumen of the pediatric airway is much smaller than an adult airway, the resistance to flow is already exponentially higher Further reductions in the cross-sectional area of the airway (such as from croup) lead to an even more significant increase in airway resistance CHAPTER 42 Physiology of the Respiratory System Turbulent Versus Laminar Flow (Reynolds Number) When flow is turbulent rather than laminar, the relationship between pressure and flow is no longer linear, making the resistance more difficult to estimate directly Nevertheless, most believe that a modification of Poiseuille’s law can be applied, but the radius term in the denominator is now raised to the fifth power instead of the fourth, making the impact of airway caliber even more critical during conditions of turbulent flow Laminar versus turbulent flow is primarily determined from the Reynolds number (Re) which is given by Obstructed – Re ƥvd/m where d is the diameter, v is the mean velocity, ƥ is the density of the gas, and m is the viscosity Higher Reynolds numbers (.4000) result in turbulent flow whereas lower numbers (,2000) result in laminar flow, with a point of transition in between Hence, conditions that increase mean velocity (i.e., increased flow), increase the density of the gas, or decrease the viscosity will promote turbulent flow This is the physiologic principle behind heliox, as replacing nitrogen with helium—a gas of much lower density but similar viscosity—reduces the Reynolds number Transmural Pressure (Collapse of Upper Airway) Airway caliber changes dynamically throughout the respiratory cycle because of changes in transmural pressures Transmural pressure is defined as the pressure inside a structure minus the pressure outside When considering the upper airway, negative pressure during inspiration within the airway relative to atmospheric pressure outside the airway will result in a slightly negative transmural pressure and a tendency of the airway walls to collapse inward This reverses during exhalation, with pressure within the airway being slightly positive relative to the atmospheric pressure The degree of airway caliber change during inspiration depends on both the magnitude of the transmural pressure and airway wall compliance During normal conditions, airway caliber changes minimally However, as airway pressure becomes more negative (i.e., in an attempt to overcome an area of increased airway resistance), airway caliber is further reduced at the point distal to the obstruction This is classically seen in cases such as viral croup, in which there is further dynamic collapse of the upper airway typically just below the area of inflammation (Fig 42.2) The opposite occurs during exhalation, which is typically why croup manifests predominantly with inspiratory stridor Inspiratory Flow Limitation When inspiration and expiration are unobstructed, flow steadily increases during inspiration, reaches peak flow, and begins to decelerate as it approaches zero just before exhalation begins Volume increases with this flow, giving rise to the classic appearance of a flow-volume loop (Fig 42.3A) However, this pattern is altered in the presence of upper airway obstruction In circumstances of extrathoracic, dynamic obstruction (such as croup), the flow-volume loop shows flattening of inspiratory flow over a large range of volume with inspiratory flow limitation (Fig 42.3B), where no further increase in flow is possible due to the lesion itself in combination with dynamic airway collapse Truly identifying inspiratory flow limitation mandates knowing that patient effort is continuing, but flow cannot be increased Thus, if one combines a measure of patient effort— such as an esophageal catheter that provides a surrogate for pleural pressure—with a measure of flow, one can see no rise (or minimal rise) in inspiratory flow with significant patient effort 473 – – – – – – – – – – – • Fig 42.2 Extrathoracic upper airway obstruction Transmural pressure distal to the obstruction is very negative, resulting in dynamic airway collapse during inspiration (Fig 42.3C–D) This appears as a flat portion on the top of the flow-pressure plot Furthermore, one can also pinpoint the location of the obstruction by evaluating whether changes in airway positioning improve flow limitation In general, supraglottic lesions respond to changes in airway position, such as a jaw thrust (Esmarch maneuver) In circumstances of poor airway wall compliance (such as subglottic stenosis or complete tracheal rings), there is less dynamic collapse of the upper airway during inspiration Here there is both inspiratory and expiratory flow limitation, with minimal change in airway caliber from inspiration to exhalation Intrathoracic Compartment Flow Resistance of the Respiratory System The response of the lung to movement is governed by the physical impedance of the respiratory system The impedance can be categorized into (1) elastic resistance between the alveolar gas/liquid interface and tissue, and (2) frictional resistance to gas flow Under static conditions (no flow), pressure is required only to oppose the elastic recoil of the respiratory system However, when the lungs and chest wall are in motion and movement of air into and out of the lungs occurs, pressure also must be provided to overcome the frictional or viscous forces The ratio of this additional pressure (P) and the rate of airflow (Q) that it produces is defined as the resistance: R P/Q In other words, the flow (Q) measured at the mouth depends on the change in pressure across the respiratory system (i.e., the pressure difference between alveoli [Palv] and mouth [Pmo] during spontaneous breathing) and the airway resistance (Raw): Q (Pmo Palv)/Raw Raw is the sum of the peripheral airway resistance (peripheral intrathoracic airways ,2 mm diameter [Rawp]), the central airway resistance (large intrathoracic airways mm diameter [Rawc]), 474 Inspiration 30 30 20 20 Flow (L/min) 400 40 10 Exhalation 500 40 300 200 100 –10 Tidal volume (mL) 10 Exhalation 500 400 300 Inspiration 200 100 –10 Tidal volume (mL) –20 –20 –30 –30 A B –40 Normal 18 12 12 –6 Exhalation –12 Inspiration Flow (L/min) Inspiration Flow (L/min) –40 Abnormal 18 Exhalation –6 –12 –18 C Flow (L/min) S E C T I O N V Pediatric Critical Care: Pulmonary –18 –30 –20 –10 10 Pressure cmH2O D –30 –20 –10 10 Pressure cmH2O • Fig 42.3 Normal flow-volume (A) and flow-pressure (C) loops versus abnormal loops seen during extra- thoracic upper airway obstruction (B and D) Flow is normal during exhalation and then limited during inspiration during dynamic airway collapse and the extrathoracic airway resistance (especially glottis [Rext]) In healthy people, Rext accounts for 50% of the total Raw and Rawp for about 15%, although this relationship fluctuates as a function of age as more peripheral airways develop into adulthood In fact, peripheral and central airway resistance is nearly equal for infants and toddlers, with a fall in peripheral airway resistance typically around years of age.16 While airway resistance is most commonly altered in disease states, total respiratory resistance (Rrs) consists of the resistance of the airways (Raw), resistance of the lung (RL), and resistance of the chest wall (Rcw): and therefore increase airway diameter, which decreases Raw The specific relationship between Raw (or its reciprocal conductance Gaw [5 1/Raw]) and volume is mirrored by the specific Raw (sRaw) and specific Gaw (sGaw): Rrs Rcw RL Raw Raw 5 (Pao Palv)/Q RL 5 (Pao Ppl)/Q Rcw (Ppl Pbs)/Q RRS (Pao Pbs)/Q In older children, Rcw and RL represent only 10% to 20% of Rrs.17 However, in newborns, RL could be higher.18 During quiet breathing, Raw accounts for greater than 50% of the total respiratory system resistance.19 As flow increases, airway resistance contributes further to total respiratory system resistance Increased flow can also result in nonlinear flow-resistance characteristics that lead to progressively more turbulent flow and therefore larger increases in airway resistance, as discussed in the upper airway compartment section For patients who are breathing quietly by mouth, total airway resistance is divided almost equally between the upper and lower airways As flow rate increases, the ratio of upper to lower airway resistance progressively increases as well There is also a volume dependency for Raw because higher lung volumes give higher elastic recoil properties of the chest wall (Pel) sRaw Raw/V The resistance of the airways (Raw), lungs (airway and parenchyma [RL]), chest wall (Rcw), and entire respiratory system (RRS) can be calculated by measuring the rate of airflow and associated transstructural pressure by subtracting from the total pressure the amount required to overcome elastic recoil: where Pao, Palv, Ppl, and Pbs represent the pressure at the airway opening, alveolar pressure, pleural pressure, and pressure at the body surface, respectively The resistance of the lung parenchyma may be derived by subtracting airway from total lung resistance Anatomic Considerations for Pediatric Lower Airways The lower airways are composed of a series of branches, including the main bronchi, lobar bronchi, segmental bronchi (to designated bronchopulmonary segments), and so on, to the smallest bronchioles, the terminal bronchioles The luminal diameter of a branch is related to the number of alveoli at the end of that branch (axial and lateral pathways) Because the longer airways CHAPTER 42 Physiology of the Respiratory System with more branches and more alveoli usually have a wider lumen, allowing greater airflow, under conditions of health, newly inspired air reaches all of the alveoli throughout both lungs at the same time and in approximately the same amount This may change in circumstances of disease (see later section about time constants) Although the base airway diameter decreases with branching, the overall or total cross-sectional diameter increases tremendously to keep peripheral airway resistance low While the conductance (1/resistance) of the conducting airways does not change too much across the age spectrum, the peripheral airway conductance increases dramatically (resistance falls) after about years of age.16 This age-dependent change is also attributed to the development of collateral ventilation paths, which dramatically increases the surface area of the respiratory system Consequently, children younger than years have a very high peripheral airway resistance Therefore, they are most susceptible to developing respiratory failure when exposed to conditions that may further increase lower airway resistance (such as bronchiolitis) Reactivity of Lower Airways The lower airways are surrounded by a layer of smooth muscle that receives sympathetic impulses to relax and parasympathetic impulses to contract Airway dilation may occur as a result of sympathomimetic agents (e.g., epinephrine or adrenaline) Airway constriction is mediated by efferent autonomic nerve control and can also occur as a result of irritants (e.g., dust, smoke, or cold), hyperventilation, and vasoactive agents (e.g., acetylcholine, histamine, or bradykinin) Constriction of these smooth muscles increases peripheral airway resistance and is typified in disease states such as asthma and occasionally bronchiolitis, although the degree of airway reactivity in bronchiolitis is variable Transmural Pressure in the Presence of Lower Airway Obstruction Like the upper airway compartment, the lower airways are subject to transmural pressure gradients during inspiration and exhalation Thus, when considering the intrathoracic lower airways, the pressure inside is airway pressure, whereas the pressure outside is the interstitial pressure, which is approximately equal to the pleural pressure For normal, healthy patients at end expiration, alveolar and airway pressure is and pleural pressure is, on average, 25 This results in a slightly positive-pressure transmural pressure across the intrathoracic airways and alveoli During inspiration, pleural pressure becomes even more negative than both alveolar and airway pressure, resulting in a more positive transmural pressure in the lower airways during inspiration, causing the airways to dilate At the end of inspiration, respiratory muscles relax; the elastic recoil of the respiratory system produces a slightly less negative pleural pressure and slightly positive alveolar pressure to enable a pressure gradient for airflow During exhalation in healthy individuals, a positive transmural pressure is maintained across the intrathoracic lower airways (although slightly less positive than at end exhalation and much less positive than during inspiration), which prevents lower airway collapse During routine exercise (when the expiratory muscles are active), both pleural pressure and airway pressure become positive during exhalation (but airway pressure is more positive than pleural pressure) Thus, as long as there is no point of obstruction in the lower airways, there will be no airway collapse, as the transmural pressure remains positive However, if there is a point of intrathoracic lower airway obstruction, then a few important phenomena occur First, air becomes trapped in the alveoli during exhalation, in part because the transmural pressure is less positive during exhalation than inspiration in the intrathoracic airways This progressive air trapping results in a transition point for the airway pressure during exhalation, where it is more positive in the airways distal to the obstruction (secondary to air trapping) and less positive in airways proximal to the obstruction To help overcome this increase in airway resistance during exhalation, expiratory muscles are recruited and pleural pressure becomes more positive to help force out air Subsequently, the pleural pressure during exhalation exceeds the airway pressure at the point proximal to the obstruction, resulting in dynamic collapse of the airway from a very negative transmural pressure and expiratory flow limitation (Fig 42.4) Atmospheric pressure Airway pressure Equal pressure points +12 Cartilaginous rings of large airways –5 –5 +0.5 +1 –5 –5 A During normal quiet breathing • Fig +13 Alveolar pressure +1 +33 +13 Pleural pressure +20 475 +33 +18 +20 +13 +40 +13 B During routine exercise +0.5 +34 +33 +34 +40 +33 C During forced expiration 42.4 Pressure gradients involved with lower airway obstruction during normal quiet breathing (A), routine exercise (B), and forced expiration (C) Airway patency depends on airway transmural pressure During forced expiration, pleural pressure may exceed airway pressure at the point proximal to the obstruction This results in very negative transmural pressure, dynamic airway collapse, and expiratory flow limitation 476 S E C T I O N V Pediatric Critical Care: Pulmonary 50 40 30 20 Flow (L/min) 10 Exhalation Inspiration –10 –20 Normal Diseased After response to bronchodilator –30 –40 500 400 300 200 100 Tidal volume (mL) • Fig 42.5 Flow-volume loop of an unaffected child compared with a child with asthma before and after a bronchodilator Flow and volume are reduced during both inspiration and exhalation, with a scooped-out appearance during exhalation Administering a bronchodilator increases both flow and volume and results in a more normal-appearing exhalation Identifying Expiratory Flow Limitation Airway obstruction that is severe enough can be identified during tidal breathing However, if the obstruction is mild, then forced expiratory maneuvers are necessary For cooperative patients who are not on mechanical ventilation, this is classically done with spirometry Children with severe lower airway obstruction often have lower flow and volume (even on inspiration) than healthy children However, the biggest abnormalities are seen during exhalation (above the y-axis), where the peak flow is lower than normal, and there is a typical scooped-out appearance to the flowvolume loop (Fig 42.5) This improves after administration of a bronchodilator in this example from a child with asthma For children on mechanical ventilation, these flow-volume loops are standard in most ventilators In many ventilators, inspiration is above the y-axis and exhalation below the y-axis (opposite of spirometry loops on spontaneously breathing patients not on a ventilator) At times, this obstruction cannot be detected during tidal breathing, particularly if the tidal volume is low (i.e., 4–6 mL/kg) In these circumstances, increasing the tidal volume or performing a forced deflation maneuver during neuromuscular blockade (where airway pressure is taken to 140 cm H2O to simulate total lung capacity and then subsequently exposed to a tank with a negative pressure of 240 cm H2O) can be used to quantify the severity of obstruction Administration of Positive End Expiratory Pressure to Prevent Collapse While it may seem counterintuitive to administer PEEP to a child with air trapping and lower airway disease, the use of PEEP can be helpful for a variety of reasons in children with lower airway obstruction First, if there is significant dynamic collapse of the lower airways during exhalation (this occurs more commonly in chronic obstructive pulmonary disease, bronchopulmonary dysplasia, and bronchomalacia than in asthma), then applying PEEP helps keep the transmural pressure proximal to the area of obstruction slightly positive during exhalation, preventing collapse As long as the applied PEEP is kept less than the intrinsic PEEP, it does not appear that alveolar pressure is increased Second, although lower airway obstruction is commonly thought of as an expiratory disease, these patients often have high inspiratory work as well This is because the high end-expiratory lung volume (EELV) results in lower respiratory system compliance (see later discussion) and because during inspiration subjects must lower alveolar pressure below atmospheric pressure for airflow to occur Hence, if alveolar pressure remains at 110 at the end of exhalation, then a subject must lower alveolar pressure by at least 10 cm H2O before airflow occurs, resulting in high inspiratory work of breathing to overcome this intrinsic PEEP (Fig 42.6) The application of PEEP now raises the downstream pressure (i.e., instead of needing to make alveolar pressure lower than atmospheric pressure, one now simply needs to make alveolar pressure less than PEEP) This can be accomplished through invasive or noninvasive ventilation by setting PEEP or the continuous positive airway pressure level high enough to overcome the level of intrinsic PEEP (Fig 42.7) Time Constants The other crucial element in the mechanics of intrathoracic lower airways is the time constant (t) of the respiratory system Time constant is defined as the time it takes for volume in the respiratory system to be reduced by 63% when the respiratory system is allowed to empty passively.25 If we use a model of the respiratory system with a single compartment with a constant compliance and constant resistance, then the following occurs: t5R3C where R is the total respiratory system resistance, and C is the total respiratory system compliance This time constant can be measured during passive exhalation by evaluating the slope of the expiratory portion of the flow-volume loop In a single-compartment model, the volume-time profile can be represented by exponential decay, where 63% of the lung is emptied with one time constant, 92% with two time constants, and 97% with three time constants In circumstances in which compliance is reduced (such as parenchymal lung disease), the time constant is shorter than in health Conversely, in conditions in which resistance is increased (such as lower airway obstruction), the time constant is longer than in health For this reason, patients with lower airway obstruction require more time for exhalation Individual alveolar/ airway units may have different time constants This occurs frequently during critical illness with heterogenous pulmonary parenchymal disease (such as acute respiratory distress syndrome or pneumonia), or lower airway disease (both asthma and bronchiolitis) This affects mechanical ventilation strategies Elastic Properties of the Respiratory System The respiratory system is composed of a collection of elastic structures The response to a force applied to the elastic structure of the respiratory system is to resist deformation by producing an opposing force—known as elastic recoil—to return the structure to its relaxed state.20 In the respiratory system, this is the elastic recoil pressure (PEL) The PEL divided by the lung volume (V) gives a ... (opposite of spirometry loops on spontaneously breathing patients not on a ventilator) At times, this obstruction cannot be detected during tidal breathing, particularly if the tidal volume is low... just before exhalation begins Volume increases with this flow, giving rise to the classic appearance of a flow-volume loop (Fig 42.3A) However, this pattern is altered in the presence of upper airway... identified during tidal breathing However, if the obstruction is mild, then forced expiratory maneuvers are necessary For cooperative patients who are not on mechanical ventilation, this is classically