- Respiration: Applied Anatomy and Pathophysiological Considerations
- Oxygen Delivery Devices
- Approach to the Patient with Hypoxemia
- Approach to the Patient with Hypercapnia
- Noninvasive Ventilation
- Mechanical Ventilators
- Mechanical Ventilation in Specific Clinical Scenarios
- Graphic Analysis of Mechanical Ventilation
- Patient-Ventilator Asynchrony
- Monitoring O2 and CO2 during Mechanical Ventilation
- Lung Recruitment Maneuvers
- Heart Lung Interactions during Mechanical Ventilation
- Monitoring Pressures during Mechanical Ventilation
- Inspiratory Effort Assessment in Ventilated Patient
- Ventilator-induced Lung Injury
- Ventilator-induced Diaphragm Dysfunction
- Weaning from Mechanical Ventilation
- Aerosol Drug Delivery in Ventilated Patient
- Extracorporeal Membrane Oxygenation
- Extracorporeal Membrane Carbon Dioxide Removal
- High Frequency Oscillatory Ventilation
The macroscopic and microscopic anatomy of the respiratory tract is inseparable from its physiological function, and has significant relevance to the study of human respiratory pathophysiology. Applied respiratory anatomy and physiology is of fundamental importance to critical care, given the prevalence of respiratory conditions and complications among critically ill patients, and the frequency of the need for interventions directed at the respiratory system. This chapter focuses on those aspects of respiratory tract anatomy and physiology which are most relevant to the routine practice of critical care medicine, and which have the greatest impact on the management of a patient with severe respiratory pathology.
MACROSCOPIC AND MICROSCOPIC STRUCTURAL ELEMENTS OF THE RESPIRATORY TRACT
The respiratory tract consists of mouth, nose, pharynx, larynx, trachea, bronchi, alveoli, and pulmonary vessels. Of these structural components, many have important roles which are not directly involved in respiration and gas exchange. For instance, the mouth and tongue have important roles in speech and swallowing, the nose in humidification, the trachea in the cough reflex, and the alveoli in the synthesis of angiotensin-converting enzyme (ACE).
The upper airway trachea and bronchi form the “conductive portion” of the respiratory system, so named because the function of these structures is not directly related to gas exchange. The macroscopic and microscopic structure of these components bears a direct relationship to their role as rigid conduits for gas, and the defenders of the delicate lower structures from thermal and physical insult. The “respiratory portion” of the respiratory tract consists of respiratory bronchioles and alveoli. These structures serve to maintain a low resistance to airflow as well as participating directly in gas exchange.
The histological structure of the respiratory tract is no less relevant to function and also calls for a detailed discussion. The mucosa of the upper respiratory tract is well-supplied with capillary blood flow and is an important route of drug delivery. Moreover, its epithelial layer harbors immunoglobulin molecules (predominantly IgA), numerous quiescent lymphocytes, and dendritic antigen-presenting cells (APCs), playing an important role in specific cellular and humoral immunity. Mucous glands and Bowman's glands in the epithelium produce secretions which moisturize the cellular layer and contribute to the humidification of the inspired gas. Lower airways are well-supplied with ciliated columnar epithelium to promote the outward movement of mucus, assisting in the clearance of small particles (Figs. 1A to C).
The respiratory portion of the respiratory tract consists of microscopic respiratory bronchioles and alveoli, the histology of which bears a direct relationship to the function of gas exchange. Respiratory bronchioles contain the smooth muscle, which acts as an important target for bronchodilators. Understanding the cellular structure of alveoli is of paramount importance to the understanding of gas exchange. The physical properties of alveoli and the actions of alveolar surfactant (secreted by Type 2 alveolar cells) are vital to the understanding of clinical approaches to the mechanical ventilation for acute respiratory distress syndrome (ARDS), as well as complications of mechanical ventilation such as barotrauma and biotrauma.
ORAL CAVITY AND THE PHARYNX
The evolution of the human airway from precursor structures in earlier animals and fish has led to a single cavity that serves the purposes of speech, air intake, and swallowing.1
As such this cavity is a complex organ complete with multiple motor and sensory systems, which permit the isolation of these functions, with the resulting inability of human beings to speak, swallow, and breathe at the same time. The motor innervation of the oral cavity and pharynx enjoys a significant amount of central control. From the point of view of the critical care physician, the most important pathophysiological implications of this control is the loss of protective airway reflexes and pharyngeal muscle tone which is associated with a decreased level of consciousness.
The Effect of Depressed Consciousness on Oropharyngeal Patency
The fact that a depressed level of consciousness can give rise to asphyxia due to airway obstruction is a well-recognized feature of advanced life support training. The pathophysiological mechanism underlying such airway obstruction is complex. Though relaxation of the tongue plays a role in obstruction at the level of the pharynx, closure of the laryngeal entrance by the epiglottis is the main cause of airway closure associated with unconsciousness. Cadaveric studies where the tongue was removed had demonstrated that an airtight seal could be achieved by the closure of the epiglottis alone.2 The most important implication of this finding in critical care is the observation that elevation of the mandible-hyoid apparatus by jaw thrust relieves both causes of obstruction.
The nasal cavity turbinates serve to increase the turbulence of air flow, thereby increasing the contact of inspired air with the nasal mucosa. The effect of this is to increase the temperature and humidity of inspired air, protecting the mucosa of lower passages from dehydration.
The anterior nares feature coarse hairs, called vibrissae (though the term usually applies to mammalian sensory hairs from which human nasal hair differs in both structure and function). These hairs arise from follicles which are similar to hair follicles elsewhere on the skin, and are neither richly innervated nor mapped onto the somatosensory cortex, in contrast to the mystacial vibrissae of mammals. These hairs are thought to serve the purpose of increasing the turbulence of nasal airflow as well as trapping inhaled macroscopic particles. The importance of these hairs in the critical care environment is seen in the context of airway burns; singed vibrissae are a signal that inhaled gas or smoke was sufficiently hot to be associated with a high risk of airway burns.3
The Role of the Upper Airway in Humidification
The upper airway is able to warm and humidify inspired air over an enviable range of temperatures and ambient humidity levels. By the time it reaches the carina, inspired gas may be heated by 20–30°C during its passage through the upper airways, and inspired air as cold as −100°C achieves core body temperature and 100% humidity by the time it reaches the alveoli.4 This exchange of heat and moisture occurs in both directions: On expiration, heat and moisture are reclaimed by the mucosa, and expired air has its temperature reduced from 37°C at the alveoli to 32°C at the nares. The expired air remains 100% saturated with water vapor, but as its temperature decreases, so does its absolute water content.5
The efficiency of heat and moisture exchange in the nasopharynx is increased by means of turbulent convection. Turbulence increases the contact between inspired air and nasopharyngeal mucosa, promoting increased heat exchange. At the same time, increased contact with inspired air promotes the evaporation of water from the mucosa. As heat is exchanged and inspired air increases in temperature, its capacity to “hold” water vapor also increases, until an equilibrium is reached where the inspired air is isothermic with the mucosa, and 100% saturated. This occurs at the “isothermic saturation boundary”, at a level just below the carina during normal quiet breathing. At this level, the absolute humidity is 47 g/m3.
The importance of maintaining humidification of the respiratory gases is twofold. It maintains the health and barrier integrity of the respiratory mucosa, and allows effective gas exchange. This has implications for the critical care environment, where mechanical ventilation often requires the use of piped gas supplies. The administration of dry cold gas (for instance, oxygen directly from the compressed gas storage system) leads to the inspissation of secretions, dehydration of the nasal mucosa, failure of the mucosal barrier function, an increased risk of epistaxis, as well as the thickening of the lower respiratory tract mucus layer, and the impairment of mucosal ciliary motility.6
For these reasons, in mechanically ventilated patients, humidification of inspired gas mixtures needs to be maintained, particularly if the upper airways have been bypassed by endotracheal intubation or tracheostomy. This can be accomplished by means of passive heat and moisture exchange filters which replicate the functions of the upper airway mucosa, or by active humidifiers which pass the inspired gas mixture across a heated water bath. In order to maintain mucosal integrity and enhance secretion clearance, a humidity output of 30 g/m3 is recommended for long-term intensive care unit (ICU) use and 20 g/m3 for short-term perioperative ventilation.7
The larynx is a cartilaginous tubular structure which acts as the entrance to the trachea and functions to occlude the airway. In evolutionary terms, it had developed from the airways of the lungfish, and had served to protect the air-filled cavities of the respiratory system during feeding and perfusion of the gills with water.8 Similarly, the human larynx has multiple functions all of which in some way involve occluding or obstructing the flow of air in and out of the trachea. These functions include phonation (the laryngeal component of speech), effort closure (for forceful expulsion of lung air, as in coughing), and swallowing (where the larynx is elevated and epiglottis closes the laryngeal inlet, directing the food bolus backward into the esophagus).
The anatomy of the larynx as relevant to the practice of gaining airway access has paramount importance to the critical care physician. Figure 2 demonstrates the anatomical features of the adult larynx from the point of view of direct laryngoscopy. Anatomically, the larynx extends from the tip of the epiglottis to the inferior border of the cricoid cartilage. It is suspended from the hyoid bone, and is found at the level of the C3–C6 cervical vertebrae. Its rigid structural components consist of three single cartilages (thyroid, epiglottic, and cricoid) and three paired cartilages (arytenoid, cuneiform, and corniculate). In terms of importance to airway access, the most important cartilaginous structure is the epiglottic cartilage, a long teardrop-shaped cartilage which is attached anteriorly to the hyoid bone by the hyoepiglottic ligament.9 Pressure in the vallecula during direct laryngoscopy elevates the epiglottis and affords a direct view of the vocal cords. Position of the epiglottis during laryngoscopy describes the difficulty of intubation by the Cormack–Lehane descriptive system,10 ranging from Grade 4 (where not even the epiglottis is visible) to Grade 1 (where the epiglottis is completely elevated and most of the glottis can be visualized).
The larynx moves under the influence of intrinsic muscles that control the vocal cords and the extrinsic muscles which change the position of the larynx in relation to the hyoid and sternum to assist in swallowing.9 Of the intrinsic muscles, all receive motor innervation from the recurrent laryngeal nerve except for the cricothyroid muscle (which increases tension on the vocal cords, and for which is motor innervation is supplied by the external branch of the superior laryngeal nerve). Damage to the recurrent laryngeal nerve produces paralysis of the ipsilateral intrinsic muscles, sparing the cricothyroid muscle. The resulting unopposed tension on the vocal cords can give rise to hoarseness or stridor with unilateral lesions and airway obstruction with bilateral recurrent laryngeal nerve injuries. Outside of surgical scenarios such as thyroid surgery, a likely cause of recurrent laryngeal nerve injury in the ICU is an endotracheal tube cuff which has been inflated in the subglottic larynx. The recurrent laryngeal nerve enters this area between the cricoid and the thyroid cartilage, and is susceptible to injury where an inflated cuff can compress it against the overlying thyroid cartilage.11
Laryngospasm and Protection from Aspiration
The larynx is richly innervated by the superior laryngeal nerve and the recurrent laryngeal nerve, both are the branches of the vagus nerve.12 Sensory innervation to the glottis and the glottic vestibule is supplied by the internal branch of the superior laryngeal nerve. The lower glottis sensory and motor innervation comes from the recurrent laryngeal nerve. The density of laryngeal sensory chemoreceptors and mechanoreceptors is greatest at the laryngeal opening, which allows rapid protective responses.
The stimulation of these receptors leads to the reflexive closure of the glottis by adduction of the vocal cords, which functions to protect the lower airways from foreign material. When this adduction response is long-lived, it may render ventilation impossible. Such a sustained closure of the true vocal cords (or both true and false cords) is described as “laryngospasm”.13 Failure of the afferent or efferent components of the laryngeal closure reflex (e.g. following stroke) may give rise to aspiration of upper airway secretions and subsequent pneumonitis.
The Effect of Endotracheal Intubation on Cough
A normal cough sequence consists of deep inspiration, glottic closure, increase in transpulmonary pressure by forceful contraction of respiratory muscles, and ultimately glottis opening with an abrupt increase in airway gas flow. The tracheal lumen collapses and in the narrowed trachea the high peak air flow results in the expulsion of tracheal secretions. In the intubated state, glottis closure is not available, and normal cough efficiency is altered by the disruption of normal flow and pressure timing. The intubated patient is still able to transport secretions to the trachea, but failure of the trachea to collapse prevents the necessary high flows from being generated, with the resulting accumulation of secretions near the distal end of the endotracheal tube.14 This has significant implications for secretion control and management of pulmonary infection in intubated patients.
The Effect of Tracheostomy on Swallowing Function
A key function of the laryngeal apparatus is to permit airway closure during swallowing by the elevation of the larynx. The laryngeal inlet is both closed and physically removed from the path of the food bolus by action of a number of muscles, which are grouped under the term “laryngeal strap muscles” and which contribute to the suspension of the larynx.15 This movement is permitted by the natural elasticity and mobility of the trachea. The presence of a tracheostomy tethers the larynx by immobilizing the trachea against the skin and strap muscles of the neck, inhibiting the normal upward excursion of the larynx.16
Trachea and Bronchi—The Conductive Airways
The tracheobronchial tree is a series of tubular respiratory passages consisting of complete and incomplete cartilaginous rings as well as smooth muscle and the striated trachealis muscle. The tree branches into 23 “generations” of successively narrower airways with a progressive increase in the total cross-sectional area, from the 1.8 cm diameter of the trachea (generation 0) to the respiratory bronchioles (generations 17–19), which are approximately 0.4 mm in diameter (Fig. 3). As the total cross-sectional area of the lower airways may be up to 100 times that of the upper airways, the resistance to air flow in these regions is usually minimal.
Among the functions and structural properties of the tracheobronchial tree, of greatest pathophysiological importance to the critical care physician is the immune function of the mucociliary escalator and the role of bronchial smooth muscle tone in generating resistance to air flow.
The “mucociliary escalator” consists of a ciliated epithelial layer, which extends from the larynx to the terminal bronchioles (the 16th division of the tracheobronchial tree). This ciliated layer is the primary defense mechanism of the lower respiratory tract against inhaled particulate matter. The cells of this layer consist of ciliated columnar epithelial cells (each featuring approximately 200 cilia) and mucus-secreting goblet cells (Fig. 4). The secretions of the cells (4% mucus and 96% water by weight) form a layer over the cilated epithelium. Rather than a continuous mucus layer that covers the epithelium like a blanket, discrete islands of respiratory mucus float on a layer of periciliary sol like lilies on water; the sol forms a thinner fluid that allows the cilia to beat and thus propel the mucus islands up the airway.17 The coordinated movement of the cilia is a surprisingly powerful force and can carry masses up to 10 g cm−2 against gravity,18 at velocities of approximately 5–20 mm per minute.
Increased susceptibility to pneumonia among ventilated patients has been attributed an impairment of the mucociliary escalator action. Intubated patients have slowed mucociliary clearance (down to 1 mm/min), and mucous flow may even be reversed in the semirecumbent position, which may contribute to the pathogenesis of atelectasis and ventilator-associated pneumonia.19,20 High oxygen concentrations, poor humidification, systemic inflammatory response, colonization by bacteria, suction catheter damage to the mucosa, and bacterial colonization have all been implicated as possible causes of this mucociliary clearance impairment.
The Role of Bronchial Smooth Muscle in Bronchospasm
Bronchi and bronchioles (generations 4–14) feature crisscrossing helical bands of muscle, the thickness of which is proportionally greatest at the level of the bronchioles.21 These bands of muscle can alter the diameter of the small airways in response to local cellular factors, mechanical and chemical stimuli, and neural control or humoral circulating factors. The cross-sectional area of the distal bronchi may decrease by 50–80% at maximal bronchoconstriction; the degree of bronchoconstriction increases with increasing bronchial generations,22 which has implications for drug delivery. Inhaled bronchodilator particle size needs to be sufficiently small in order to penetrate to these deeper structures.
Alveolar Ducts and Alveoli
The terminal bronchioles are the last generation of conductive airways. Beyond these, the airway branches into respiratory bronchioles, alveolar ducts, and alveolar sacs. Like the terminal bronchioles, the respiratory bronchioles have a well-defined smooth muscle layer; however, with increasing generations respiratory bronchiole walls gradually increase in the number of mural alveoli. The alveolar ducts differ from respiratory bronchioles by having no walls (i.e. their walls consist only of the openings of mural alveoli). Alveolar sacs are the terminal branches of the respiratory tract. Approximately half of all alveoli take their origin from alveolar sacs, the other half originating from alveolar ducts. The total number of the alveoli is on average approximately 480 million, and each is approximately 0.2 mm in diameter at functional residual capacity (FRC). Each alveolus is usually polyhedral rather than spherical; the septa between alveoli are stretched tight by the tension of the elastic fibers they contain as well as by the surface tension created by the air–fluid interface. These septa contain pores of Kohn, microscopic fenestrations which permit the movement of gas between alveoli (Fig. 5). The alveolar septa also contain the pulmonary capillaries, which bulge into the airspace. The thickness of the active membrane here is 0.2–0.3 µm, and there is virtually no interstitial space.
Alveolar epithelial cells (Type I cells) have a flat sheet-like structure, mostly devoid of organelles and of approximately 0.1 µm in thickness. They are joined together by tight junctions, which prevent the escape of large proteins into the alveolar space. These cells do not have the capacity to undergo mitosis. Type II cells are the stem cells from which Type I cells arise; these serve to replenish the alveolar epithelium as well as being sources of alveolar surfactant.
Alveolar surfactant is a surface-active material, which is responsible for maintaining the low surface tension of alveolar fluid. Surfactant consists of one main active ingredient (dipalmitoylphosphatidylcholine, a phospholipid) as well as carbohydrates and a small amount of surfactant proteins (2% by weight).
Surfactant is released by Type II cells, has a half-life of 15–30 hours, and is degraded by reuptake into Type II cells. The clinical relevance of surfactant is apparent in surfactant-deficient pathological states, of which the prototypic model is a preterm neonatal lung. Severe respiratory failure with atelectasis tends to develop in premature infants who are yet to secrete enough surfactant23 and those suffering from hereditary disorders of surfactant protein synthesis.24 The presence of surfactant in bronchoalveolar lavage fluid can be confirmed by the presence of foam in the retrieved fluid, and indicates a deep lavage. However, the excessive washout of surfactant can give rise to postlavage hypoxia and atelectasis. Lastly, pulmonary surfactant interacts destructively with lipopeptide antibiotics such as daptomycin, resulting in their deactivation.25
Ventilator-associated Lung Injury at the Alveolar Level
The alveolar septa derive their durability from a basement membrane layer (the lamina densa) composed of Type IV collagen fibers. This layer is approximately 50 nm thick and is adherent to the epithelial (respiratory) and endothelial (vascular) cells on either side by a network of attachment proteins called laminins. These proteins interact with the cytoskeleton of endothelial and epithelial cells, regulating the permeability of the membrane.
Mechanical ventilation with high pressures can damage the alveolar septa. Microscopically, there is damage to both alveolar epithelium and pulmonary capillary endothelium. At ventilation with pressures greater than 30 cm H2O, there is flattening of alveolar capillaries, and visible disruption of the epithelial and endothelial layers. The basement membrane usually remains intact (and may be the sole remaining barrier between gas and blood). However, the diffusion of gases is still impaired because the membrane is usually thickened (up to 1 µm) due to cellular damage and resulting interstitial edema. At higher pressures (up to 50 cm H2O) the basement membrane can also be damaged, and microscopy of alveoli ventilated at such pressures reveals a full-thickness of red blood cells in the alveolar spaces.26 It would appear that the elastic collagen-rich basement membrane has a greater tolerance for mechanical stress, but the damage to endothelial and epithelial cells manifests at lower pressures. This cellular damage then gives rise not only to a degraded gas diffusion due to increasing membrane thickness, but also to a release of proinflammatory mediators into the systemic circulation. The systemic effects of such cytokine release are seen in mechanically ventilated patients with ARDS; the phenomenon has been called “biotrauma” and can lead to multi-organ dysfunction.27
APPLIED ANATOMY AND PATHOPHYSIOLOGY OF THE PULMONARY CIRCULATION
The anatomical distinction between the pulmonary and systemic circulation lies in the different pressures between these two systems. The blood pressure within the pulmonary circulation is approximately 15–20% of the systemic arterial blood pressure. Consequently, pulmonary vessels have significantly less smooth muscle; in fact, the larger vessels are composed mainly of elastic connective tissue. Muscular layers become dominant in pulmonary arteries below 1mm diameter. In contrast to systemic arterioles, pulmonary arterioles have minimal smooth muscle tissue in their walls, and are structurally indistinguishable from pulmonary venules. Pulmonary arterioles and venules frequently have small (25–50 µm) anastomoses which remain closed under normal conditions and only open into shunts under conditions of increased cardiac output or with the use of inotrope agents.28 Shunt, pulmonary hypertension, and their management are discussed in greater detail elsewhere.
Pulmonary capillaries form a dense network in the alveolar septa, and a capillary network may span several alveoli before emptying into a pulmonary venule. Pulmonary venules run along segmental septa. Pulmonary vessels and bronchi are surrounded by a network of pulmonary lymphatics, which occupy potential spaces between these structures and the rest of the lung parenchyma. During episodes of pulmonary edema, these potential spaces become distended with fluid, giving rise to the characteristic peribronchial cuffing seen on chest radiographs. Lymphatic drainage occurs in the direction of the hilum, also giving rise to the perihilar hazing and “bat-wing” appearance of acute pulmonary edema. Tracheobronchial lymph nodes accept drainage from pulmonary lymphatics, and these groups of nodes (particularly the subcarinal nodes) become attractive targets for bronchoscopic biopsy sampling.
Ventilation and Perfusion Relationship
In ideal circumstances, alveolar ventilation (V) and alveolar capillary perfusion (Q) would be perfectly matched; i.e. the ideal alveolus is ventilated with the perfect amount of air in order to completely saturate all hemoglobin molecules passing through its capillaries. In reality, there is a regional variation of blood flow and ventilation which varies with posture, disease states, drug effects, and mechanical ventilation.
Perfusion is maximal in dependent regions of lung, which in the upright position are the lung bases. According to this “gravitational model”, in upright man the perfusion of the lung apices can be attributed to the difference in hydrostatic pressure between the apices and the bases, which may be 30–40 cm H2O.29
Ventilation is also maximal in the bases of the lungs, where the rib cage expands to the greatest extent in inspiration, and where diaphragmatic excursion contributes to the change in volume. Furthermore, lung tissue has a significant mass and therefore the weight of the tissue above compresses the tissue below; the dependent lung is therefore more compressed, has higher compliance and therefore better ventilation. In the upright position, the measured ratio of apical to basal ventilation is approximately 1:1.5 by volume at resting ventilation, and 1:3 at inspiration to full vital capacity.
Zones of the Lung, Dead Space and Shunt
Regional differences in ventilation and perfusion give rise to three distinct patterns, which are known as Wests’ Zones. Because the pulmonary circulation is a low pressure system, in the apices the pulmonary capillary pressure may be lower than alveolar pressure; this results in areas of lung which are ventilated but not perfused, referred to as alveolar dead space. This region is referred to as Wests Zone 1; the pattern of V/Q mismatch described by this zone does not occur in normal physiological states, but may be seen in critically ill patients suffering from extreme hypovolemia or hemorrhagic shock.30 It can also be seen in circumstances where alveolar pressure is artificially increased, for instance in the context of mechanical ventilation with high pressures.
Wests Zone 2 describes a region which has pulsatile blood flow which is generated by the fact that pulmonary venous pressure is lower than pulmonary arterial pressure. In this region, flow occurs intermittently, when arterial pressure cyclically increases to a point where it overcomes the obstruction to venous flow. After the pressure is relieved, the system returns to a low pressure state and flow ceases again.
Wests Zone 3 describes an area of the lung where the capillaries enjoy constant blood flow because both arterial and venous pressure is higher than the alveolar pressure. This relationship describes blood flow in the dependent basal regions of the lung. Because there is an uninterrupted column of blood between the pulmonary arteries and the pulmonary veins in this region, Zone 3 makes an ideal position for measuring pulmonary capillary wedge pressures using a pulmonary artery catheter.
In disease states such as atelectasis or pneumonia, regions of lung will have minimal ventilation due to physical compression, bronchial obstruction, or copious secretions. In this case, the affected regions of lung will have perfusion, but no ventilation. Pulmonary veins returning from such regions will carry hypoxic blood back into the systemic circulation, and the addition of this hypoxic blood will reduce the oxygen saturation of arterial blood in the systemic circulation. This phenomenon is referred to as intrapulmonary shunting, and the resulting incompletely oxygenated percentage of cardiac output is described as the shunt fraction.
LUNG VOLUME AND CAPACITIES
Static lung volumes and capacities have standard definitions (Fig. 6), where a “capacity” refers to a measurement consisting of more than one “volume”.
The total lung capacity (TLS) is the volume of gas in the lungs at the end of a maximal inspiration. The residual volume (RV) is the volume which remains after a maximal expiration. The functional residual capacity (FRC) is the volume of gas which remains in the lungs after an expiration during normal breathing. Lung volumes are affected by age, gender, ethnicity, posture, obesity, and pregnancy; they change in linear proportion with the height of a patient. During mechanical ventilation, tidal volume is usually calculated with reference to the ideal body weight, which is indexed to height.
Volume-Related Airway Collapse and Closing Capacity
Lung volumes influence the diameter of smaller airways, particularly those beyond generation 11 (as these have minimal cartilage and rely instead on the traction from lung tissue for their patency). As lung volume decreases in expiration, the volume of all air-filled cavities and passages decreases proportionally, which includes the smaller airways. As lung volume decreased toward RV, some of these smaller airways begin to close, which results in an increase in their resistance to airflow.32 At some critical volume, these small airways collapse completely; the volume at which this occurs is referred to as closing capacity, and the effect of lung volume on increasing airway resistance is referred to as volume-related airway collapse. Closing capacity increases with age; it is well below the FRC in young patients, but becomes equal to FRC in patients over 70, even in the upright posture.33 With the closing capacity exceeding FRC, during a period of expiration some of the alveoli will be perfused with pulmonary blood but not ventilated because of airway closure, which represents a shunt by definition. This is most marked in dependent regions of lung and in situations where the FRC is decreased (e.g. in obese patients, in pregnancy or when the patient is in a supine position). One of the effects of positive end-expiratory pressure (PEEP) is to increase the FRC above closing capacity, thereby decreasing shunt and improving oxygenation.
Flow-Related Airway Collapse and Closing Capacity
Gas flow influences the diameter of smaller airways; even the trachea changes diameter with high expiratory gas flow velocity.34 During forceful expiration, the normally negative intrathoracic pressure becomes positive with the effort of expiratory muscles, resulting in a high velocity gas flow out of the lung. Along the path of gas flow out of the lung, there is a pressure drop (as the resistance to airflow decreases with decreasing generations of airways). Therefore, at a point in the airway, the airway pressure will be equal to the intrathoracic pressure (this point is referred to as the equal pressure point). Beyond that point, intrathoracic pressure may be greater than the airway pressure, which (unless the airway is endowed with rigidity by structural cartilage) will result in airway collapse. This effect is most prominent in airways already narrowed by disease (e.g. asthma), in dependent regions of lung, and at small lung volumes near closing capacity, where airway diameter is already decreased. One of the effects of PEEP is to oppose positive intrathoracic pressure (e.g. due to “intrinsic PEEP” in asthma), thereby allowing airways to remain open.
APPLIED ANATOMY AND PATHOPHYSIOLOGY OF RESPIRATORY MECHANICS
“Respiratory mechanics” is a term conventionally applied to the interaction of pressure and flow in determining respiratory function. Pressure and flow are determinants from which a variety of indices may be derived, such as volume, compliance, resistance, and work of breathing. These parameters are of substantial importance in the critical care setting, where they are amenable to manipulation by means of mechanical ventilation.35
The respiratory system is composed of several interacting anatomical components, which can be functionally divided into airways, lungs, chest wall, and abdomen. Gas flow through the respiratory system is determined by pressure gradients, which are generated by the interaction of these anatomical elements. In order for gas flow to occur there needs to be a pressure gradient between the atmosphere and the alveoli. This pressure gradient across the lung (PL) represents the difference between pressure at the airway (Pao) and pressure in the pleural space (Ppl). As there is no convenient method to monitor pleural pressure directly, esophageal balloon manometry may be used as an acceptable surrogate.36 For the intents and purposes of bedside physiology, Ppl = Pes. Thus,
PL = Pao– Pes
Thus, a negative pleural pressure must be generated by the respiratory muscles in order to produce a flow of atmospheric gas into the system. In the mechanically ventilated patient, positive pressure applied at the airway opening produces a positive pressure gradient which drives the flow of gas. Outward flow during expiration occurs passively, and is the consequence of elastic structures recoiling into their resting state (these structures include the lung parenchyma, chest wall, and the abdomen). The amount of pressure which needs to be generated by the patient (or applied by the ventilator) in order to produce gas flow is determined by pulmonary compliance and respiratory system resistance.
Respiratory system compliance is determined by the equation,
where ΔV is the change in volume, Pplat is the plateau airway ΔV pressure, and C is compliance expressed in terms of volume per unit pressure (classically as mL/cm H2O). Normal static compliance in a mechanically ventilated patient is generally held to be 50–100 mL/cm H2O.
Response of the respiratory system to distending pressure is nonlinear, and can be represented by a sigmoid curve. Ventilation typically occurs in the range of tidal volumes where compliance of the respiratory system is high (the “steep” portion of the pressure–volume curve); ventilation with higher volumes or higher pressures may lead to overdistension and a loss of lung compliance is seen, i.e. higher pressures produce a smaller increase in volume (Fig. 7).
Compliance may be further divided into static and dynamic compliance. Conventionally, discussions of compliance address static compliance alone, in the context of a respiratory system inflated with a static volume of gas. However, the process of mechanical ventilation is a dynamic process where inward and outward flow is constantly alternating. The compliance of this system is described by the term “dynamic compliance”, which is described by the equation,
where Ppeak represents the peak inspiratory pressure. Peak inspiratory pressure is the sum of pressure generated in overcoming lung compliance and pressure generated in overcoming respiratory resistance.
The anatomical and physiological determinants of static compliance are the elasticity of lung tissue and alveolar surface tension. These may be altered in disease states. For instance, decreased respiratory compliance is seen in states of surfactant deficiency (for instance, in premature neonates, or in patients recovering from bronchoscopic lavage). Pulmonary disease which decreases compliance may do so in a diffuse manner (e.g. the effects of ARDS) or by decreasing the total lung capacity by obliterating aeration of whole regions of lung (e.g. the effects of lung consolidation). Destructive pulmonary parenchymal disease may also have the effect of increasing lung compliance, as in the case of emphysema. Unique approaches to the management of mechanical ventilation in states of extremely poor lung compliance (such as ARDS) are discussed in later chapters.
Resistance, broadly speaking, is a resistance to motion. The respiratory system is resistant to the flow of gas. The determinants of this resistance and their proportional contributions are friction against airway surfaces (80%), tissue resistance (19%), and forces of inertia (1%). The resistance to airflow is, therefore, determined largely by the resistance of airways.
The relationship of airway diameter to airway resistance and the pressure generated thereby is described by Poiseuille's Law:
where ΔP is the change in pressure generated by the resistance, Q is the flow rate of the gas, η is the viscosity of the gas, L is the length of the airway, and r is the radius of the airway (which is assumed to be cylindrical in cross-section). By this relationship, the greatest airway resistance is to be expected at the transition point between lobar and segmental bronchi (generations 3, 4, and 5) where the total cross-section of the airways is the smallest (Fig. 3). Measurement and imaging of airways37 has confirmed that 80% of total airway resistance is generated at this level.
Physiological changes in the respiratory system can influence airway resistance. For instance, airway resistance is inversely proportional to lung volume. Beyond the conducting airways, airflow resistance becomes dependent on lung volume. In inspiration, the expanding lung also puts distending pressure on the smallest airways by traction, therefore increasing their diameter and decreasing their resistance. Conversely, forced expiration increases airflow resistance by increasing pressure on these small airways, forming flow-limiting segments.
Pathological states can also influence airway resistance. Notably, asthma and anaphylaxis can give rise to marked reversible increases in airway resistance. Irreversible or incompletely reversible increases in airway resistance are associated with disease states such as chronic obstructive pulmonary disease (COPD). Unique approaches to the management of bronchospasm and mechanical ventilation in states of extremely high airway resistance are discussed in later chapters.
Idealised models of lung function behold the lung as a perfectly elastic solid, which instantly expands by a volume (ΔV) in response to the distending pressure (ΔP). The properties of lung in vivo are not ideal, and lung tissue takes some time to distend to ΔV. The time required to distend the lung up to 63% of the maximal inflation or deflation is referred to as the time constant (τ), and is described mathematically as:
τ = C × R
where C represents compliance and R represents resistance. The value of this constant varies across lung units, and between inspiration and expiration. Lung units with a high compliance and high resistance (e.g. emphysema and COPD) fill slowly, empty even more slowly, and this is represented by a longer time constant (τ) value. Conversely, lung units with poor compliance and low resistance (e.g. pulmonary fibrosis, ARDS) have a quick τ value, filling and emptying rapidly.
The concept of time constant has relevance with relation to positive pressure ventilation. As the lung is distended during a mechanical breath, the greatest part of the tidal volume will be distributed into lung units with the lowest (quickest) τ value. Even if the ventilator has cycled to inspiratory pause or expiration, gas may continue to redistribute from these “quick” lung units into “slow” lung units, a process referred to as pendelluft. This has the effect of reducing dynamic lung compliance and worsening oxygenation. As lung units with poor compliance and low airflow resistance fill the fastest, they will contribute to a rapid rise in pressure with the initiation of the mechanical breath. Gas, which subsequently redistributes from these units, has already participated in gas exchange and therefore will have a higher PCO2 and a lower PO2, diluting fresh gas and thereby impairing effective gas exchange.38 Though likely to have minimal adverse influence on gas exchange physiology in the healthy subject, time constant may play a significant role in the physiology of the critically ill patient, particularly hypoxemic patients with severe COPD. This has implications for the approach to ventilation in such patients; classically a prolonged expiratory phase is programmed into the ventilator in order to allow for the lung units with low time constant to empty.
Work of Breathing
The definition of work is the product of force and distance, or in the case of the respiratory system the product of pressure and volume. The commonly used term “work of breathing” is something of a misnomer as it is usually used to describe the power of breathing, which is defined as work per unit time, and where the respiratory rate is also incorporated. Work of breathing can be expressed in joules per liter, which is energy required during one breath cycle divided by the tidal volume in liters. Alternatively, power of breathing can be expressed in joules per minute, which is the energy in joules per breath cycle multiplied by the minute respiratory rate. The work and power of breathing of a normal healthy patient is approximately 0.35 J/L, or 2.4 J/min.39 The main determinants of the work of breathing are elastic recoil of the respiratory system and the resistance to airflow.40
Work against the elastic recoil of the respiratory system is used to expand the chest and distend the lung parenchyma. During normal quiet breathing, approximately half of the energy is spent on this (and is stored as potential energy, to be used during the passive expiratory phase) and the other half is dissipated as heat in the process of overcoming frictional forces.
Work against airway resistance is spent to overcome the frictional resistance to airflow. Additional negative intrathoracic pressure needs to be generated in order to create a sufficient pressure gradient and overcome resistance to inspiratory flow.
Under normal conditions, only the inspiratory muscles perform any work (by storing the work against elastic recoil in elastic tissues, the work of expiration is completely transferred to expiratory muscles). Work against elastic recoil increases with slow and deep breathing, whereas work against airway resistance increases with rapid shallow breathing (i.e. where flow rates are increased). Patients with normal lung physiology who are at rest will trend toward a respiratory rate which is a compromise between these two competing sources of impedance, and which minimizes the work of breathing.
With normal quiet breathing the total oxygen consumption of the respiratory muscles is approximately 1 mL per liter of minute volume or 2% of the total body oxygen consumption.31 When the minute volume increases to 10 L/min in the absence of lung pathology, the oxygen cost of work of breathing accounts for 5% of total body oxygen consumption. In disease states which affect pulmonary compliance or airway resistance the oxygen cost of breathing can increase markedly. In COPD patients with poor lung function, the oxygen cost of the work of breathing at rest has been found to be in excess of 16 mL/L, or up to 50% of the total body oxygen consumption.41 Mechanical ventilation can significantly decrease the demands on a failing heart by assuming some or all of the respiratory workload.
The work of breathing can be measured by integrating the area under the pressure/volume diagram of a breath, where the measured pressure is the pleural pressure or next most convenient surrogate, e.g. esophageal pressure as measured by esophageal manometry.42 Measurement of pleural pressure and esophageal manometry are not often available at the bedside, but the pressure and volume graphics of a mechanical ventilator are effective surrogate measures for ventilated patients on volume control mode of ventilation with a constant inspiratory gas flow.43 During a mechanical breath a patient may perform part of the work of breathing, with the remainder being performed by the ventilator device. It is possible to calculate the level of ventilator dependence by comparing the work of breathing required for unsupported breaths and assisted breaths.
- The respiratory tract consists of conductive (upper airway trachea and bronchi) and respiratory portions (respiratory bronchioles and alveoli), of which only the latter participate in gas exchange.
- The roles of the upper airway include humidification and heating of inspired gas, protection of the lower airway from foreign material, phonation, swallowing, immune defence, and the maintenance of low resistance to air flow.
- Alveolar surfactant is a surface-active material, which is responsible for maintaining the low surface tension of alveolar fluid and thereby preventing alveolar atelectasis.
- The pulmonary circulation is a low-resistance system, where the pressure is 15–20% of the systemic pressure and the vessels have significantly less smooth muscle.
- The relationships of pressure volume and flow describe the mechanical properties of the respiratory system, such that compliance is the change in volume per unit pressure and resistance is the change in pressure per unit flow.
- The relationship of compliance and resistance describe the time constant (τ), defined as the time required to distend the lung up to 63% of the maximal inflation.
- The work of breathing is the energy required to generate a tidal volume, and can expressed in joules per liter of breath volume, or as power of breathing in Joules per minute.
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