Ventilation refers to the bulk transport of air from the atmosphere to the alveolus. The product of tidal volume (Vt) and breathing fre- quency (f) represents the total volume of air delivered to the lung per minute (minute ventilation). However, not all air entering the lung is in contact with gas-exchanging units. The portion of Vt that fills the respiratory zone and alveoli and is available for gas exchange constitutes the alveolar volume (Va), whereas the portion remaining in the conducting airways is the anatomic dead space volume (Vd) (Fig. 15.4). The ratio of Vd to Vt is called the dead space ratio (Vd/
Vt). Normally, one third of a breath is dead space (Vd/Vt = 13).
The amount of fresh air reaching the alveoli is Vt − Vd. With large breaths, the dead space becomes a smaller fraction of the total tidal volume. Therefore, for a given Vt, slow, deep breathing results in greater Va and improved gas exchange compared with rapid, shallow breathing.
The Vd/Vt ratio can be calculated by the Bohr method, as follows:
VD/VT =(PaCO2–PECO2)/PaCO2
where Paco2 is the arterial partial pressure of carbon dioxide and Peco2 is the partial pressure of carbon dioxide in mixed expired gas (i.e., the mixture of CO2-rich gas that enters the alveoli from the pul- monary capillaries and dead space gas, which is devoid of CO2). Peco2 increases during expiration, reaching a plateau at end-expiration. At end-expiration, the Peco2 represents exhaled alveolar gas that has been in equilibrium with pulmonary capillary blood. In healthy individuals, the Peco2 at end-expiration is equivalent to the Paco2.
Ventilation of the dead space is wasted ventilation, because only Va participates in gas exchange. Therefore, as the metabolic rate and carbon dioxide production increase, Va must increase to maintain an arterial Pco2 of 40 mm Hg. The relationship among these variables is described by the alveolar carbon dioxide equation:
PACO2= CO2 production/V˙A
where Paco2 is the partial pressure of carbon dioxide in the alveolus and V˙A is alveolar ventilation. From this equation, one appreciates that the partial pressure of carbon dioxide in the alveolus is inversely pro- portional to alveolar ventilation.
The relationship described by the alveolar oxygen equation is similar:
PAO2= O2consumption/V˙A
However, this relationship is more complicated because Pao2 also is proportional to the fraction of inspired oxygen, the water vapor pres- sure, and the partial pressure of carbon dioxide in the alveolus (dis- cussed later). The implications of the alveolar carbon dioxide and oxygen relationships are that (1) maintenance of a constant alveolar gas composition depends on a constant ratio of ventilation to met- abolic rate; (2) if ventilation is too high (hyperventilation), alveolar Pco2 will be low and alveolar Po2 will be high; and (3) if ventilation is too low (hypoventilation), alveolar Pco2 will be high and alveolar Po2 will be low.
Mechanics of Breathing
Respiratory mechanics is the study of forces needed to deliver air to the lung and how these forces govern the volume and flow of gases.
Mechanically, the respiratory system consists of two structures: the lungs and the chest wall. The lungs are elastic (spring-like) structures that are situated within another elastic structure, the chest wall. At end-expiration, with absent respiratory muscle activity, the inward recoil of the lung is exactly balanced by the outward recoil of the chest wall, representing the equilibrium position of the lung–chest wall unit. Normally, the recoil of the lung is always inward (favoring lung deflation), and the recoil of the chest wall is outward (favoring infla- tion); at high lung volumes, however, the chest wall also recoils inward (Fig. 15.5). The energy required to stretch the respiratory system beyond its equilibrium state (end-expiration during quiet breathing) is provided by the inspiratory muscles. With normal quiet breathing, gas flow out of the lung is usually accomplished by passive recoil of the respiratory system.
During a typical breath, inspiratory muscle contraction lowers the intrapleural pressure, which in turn lowers the intra-alveolar pressure.
Once alveolar pressure becomes subatmospheric, air can flow from the mouth through the airways to the alveoli. At the end of inspiration, the inspiratory muscles are turned off, and the lungs and chest wall recoil passively back to their equilibrium states. This passive recoil of the respiratory system causes alveolar pressure to become positive throughout expiration until the resting position of the lung and chest wall are reestablished and alveolar pressure once again equals atmo- spheric pressure. During quiet breathing, pleural pressure is always subatmospheric, whereas alveolar pressure oscillates below and above zero (atmospheric) pressure (Fig. 15.6).
The major inspiratory muscle is the diaphragm. Others include the sternocleidomastoid muscles, the scalenus muscles, the paraster- nals, and the external intercostals. Diaphragm contraction results in expansion of the lower rib cage and compression of the intra-abdom- inal contents. The latter action results in expansion of the abdominal wall. The expiratory muscles consist of the internal intercostal mus- cles and the abdominal muscles. Expiratory flows can be enhanced by recruiting the expiratory muscles; this occurs during exercise or with cough.
To inflate the respiratory system, the inspiratory muscles must overcome two types of forces: the elastic forces imposed by the lung and the chest wall (elastic loads) and the resistive forces related to air- flow (resistive loads). The elastic loads on the inspiratory muscles result from the respiratory system’s tendency to resist stretch. The elastic forces are volume dependent; that is, the respiratory system becomes more difficult to stretch at volumes greater than the functional resid- ual capacity (FRC) and more difficult to compress at volumes lower than the FRC. The elastic forces can be characterized by examining the relationship between lung volume and recoil pressure (Fig. 15.7).
When either deflated or inflated, the lung and chest wall have charac- teristic recoil pressures. The slope of the relationship between lung vol- ume and elastic recoil pressure of the chest wall or lung represents the 150
350
Anatomic dead space Tidal volume
= 500 mL
Fig. 15.4 Schematic diagram of the inspired volume of air that partici- pates in gas exchange (Va, 350 mL) and the volume of anatomic dead space (Vd, 150 mL), which together provide a tidal breath (Vt) of 500 mL.
compliance of each structure. The sum of the chest wall and lung recoil pressures represents the recoil pressure of the total respiratory system.
The elastic properties of the lung are related to two factors: the elas- tic behavior of collagen and elastin in the lung parenchyma and the surface tension in the alveolus at the air-liquid interface. Both factors contribute equally to lung elastic recoil. A surface-active substance called surfactant is produced by type II alveolar cells and lines the alve- oli. This substance consists primarily of phospholipids. It lowers the surface tension of the air-liquid interface, making it easier to inflate the lung. The lungs are stiff (less compliant) and difficult to inflate in diseases that are characterized by a loss of surfactant (e.g., infant respi- ratory distress syndrome). Diseases such as pulmonary fibrosis, which
are characterized by excessive collagen in the lung, can make the lung stiff and difficult to inflate, whereas those such as emphysema, charac- terized by a loss of elastin and collagen, reduce lung recoil and increase lung compliance (Fig. 15.8). Normally, at FRC, it takes about 1 cm of water pressure (1 cm H2O) to inflate the lungs 200 mL or to inflate the chest wall 200 mL. The lung and chest wall both need to be inflated to the same volume during inspiration, so 2 cm H2O of pressure is required to inflate both to 200 mL. Therefore, normal respiratory sys- tem compliance is roughly 200/2 or 100 mL/cm H2O and compliance of the lung or chest wall compliance is 200/1 or 200 mL/cm H2O at volumes near FRC.
The second set of forces that the inspiratory muscles must over- come to inflate the lungs are flow-dependent forces; namely, tissue viscosity and airway flow resistance, the latter constituting the major component of the flow-dependent forces. Airway resistance during inspiration can be calculated by measuring inspiratory flow and the difference in pressure between the alveolus and the airway opening (ΔPA−ao).
Resistance = ΔPA – ao/V ˙
The airflow velocity, the type of airflow (laminar or turbulent), and the physical attributes of the airway (radius and length) are the key deter- minants of airway resistance. Of the physical properties, the radius of the airways is the major factor. Resistance increases to the fourth power as the diameter decreases under conditions of laminar flow (stream- line flow profile) and to the fifth power under conditions of turbulent flow (chaotic flow profile). Because airway diameter increases as lung volume increases, airway resistance decreases as lung volume increases (Fig. 15.9). Airway diameter also contributes to regional differences in airway resistance. Although the peripheral airways are narrower than the central airways, their total cross-sectional area is much greater than that of the central airways, as described earlier. Consequently, resis- tance to airflow of the peripheral airways is low relative to the central airways (see Fig. 15.3).
The type of airflow is another key determinant of airway resistance.
Resistance is directly proportional to flow rate when flow is laminar.
Resistance is much greater with turbulent flow because it is propor- tional to the square of the flow rate. The velocity of airflow determines, Normal
0 −5 0
Fig. 15.5 Schematic diagram of the lung and chest wall at functional residual capacity (FRC). The arrows show that the expanding elastic force of the chest wall equals the collapsing elastic force of the lung.
The intrapleural pressure is −5 at FRC because both forces are tugging on the pleural space in opposite directions.
0.5
0
B Inspiration Volume
of breath (L)
Intrapleural pressure (cm H2O)
Alveolar pressure (cm H2O)
Expiration
D
A A
0
−5
−8 +
−
C
Fig. 15.6 Volume, intrapleural pressure, and alveolar pressure during a normal breathing cycle. The letters correspond to the various phases of the cycle: A, end-expiration; B, inspiration; C, end-inspiration; and D, expiration. Alveolar pressure is biphasic, with zero crossings at times of no flow (i.e., end-expiration and end-inspiration). Intrapleural pressure remains subatmospheric throughout.
Chest wall Lung TLC Chest wall
and lung
RV FRC
Expanding
Force Collapsing
Force
–40 100
75 50 25
0 –20 0
Pressure (cm H2O)
Vital capacity (%)
20 40
Fig. 15.7 Volume-pressure relationship of the respiratory system and its components, the lung and chest wall. Respiratory system recoil pressure at any volume is the sum of the lung and chest wall recoil pressures. Forces creating negative pressures expand the respiratory system, whereas forces creating positive pressures collapse the respi- ratory system. The slope of the volume-pressure curve represents the compliance of each structure. FRC, Functional residual capacity; RV, residual volume; TLC, total lung capacity.
173 CHAPTER 15 Evaluating Lung Structure and Function
in part, whether the flow pattern is laminar or turbulent. Clinically, increased airway resistance can be seen in diseases associated with air- way obstruction caused by an intrinsic mass, mucus within the airway, airway smooth muscle contraction, or extrinsic compression of the airways.
Lung elastic recoil also influences airway resistance and airflow.
Decreased lung recoil increases resistance by promoting collapse of the small airways (E-Fig. 15.1). Normal resistance when breathing at FRC at low flow rates is in the range of 1 to 2 cm H2O/L per second.
Distribution of Ventilation
The distribution of inhaled volume throughout the lung is unequal. In general, more of the inhaled volume goes to the bases of the lung than to the apex when the individual is inhaling while in an upright body position. This pattern of volume distribution leads to greater ventila- tion of the bases than at the apices. This inhomogeneity of ventilation results largely from regional differences in lung compliance. The alve- oli at the lung apex are relatively more inflated at FRC than the alveoli at the lung base. The difference in alveolar distention from apex to base is related to pleural pressure differences from apex to base. The weight of the lung causes pleural pressure to be more negative at the apex and less negative at the base. The normal difference in pleural pressure from apex to base in an adult is about 8 cm H2O (Fig. 15.10).
Because the apical alveoli are more stretched at FRC, they are operating on a stiffer, less compliant region of their volume-pressure curve than the alveoli at the bases, making them more difficult to inflate than the basilar alveoli. Therefore, at the beginning of inspiration, more volume is directed toward the base than to the apex of the lung.
Control of Ventilation
Maintenance of adequate oxygenation and acid-base balance is accom- plished through the respiratory control system. This system consists of the neurologic respiratory control centers, the respiratory effectors (muscles that provide the power to inflate the lungs), and the respira- tory sensors. The respiratory center that automatically controls inspi- ration and expiration is located in the medulla of the brain stem. The respiratory center in the brain stem has an intrinsic rhythm generator (pacemaker) that drives breathing. The output of this center is mod- ulated by inputs from peripheral and central chemoreceptors, from mechanoreceptors in the lungs, and from higher centers in the brain, including conscious control from the cerebral cortex. The respiratory center in the medulla is primarily responsible for determining the level of ventilation.
Carbon dioxide is the primary factor controlling ventilation.
Carbon dioxide in the arterial blood diffuses across the blood-brain barrier, thereby reducing the pH of the cerebral spinal fluid and stim- ulating the central chemoreceptors. A change in Paco2 above or below normal will increase or decrease ventilation, respectively. During quiet, resting breathing, the level of Paco2 is thought to be the major factor controlling breathing. Only when the Pao2 (i.e., the partial pressure of oxygen dissolved in the blood that is not bound to hemoglobin) falls substantially does ventilation respond significantly. Typically, Pao2 needs to fall to less than 50 mm Hg before ventilation dramatically increases (Fig. 15.11). Low oxygen levels in the blood are not sensed by the respiratory center in the brain but are sensed by receptors in the carotid body. These vascular receptors are located between the internal and external branches of the carotid artery. Changes in Pao2 are sensed by the carotid sinus nerve. Neural traffic projects to the respiratory center through the glossopharyngeal nerve, which serves to modulate ventilation. The carotid body also senses changes in Paco2 and pH.
Nonvolatile acids (e.g., ketoacids) stimulate ventilation through their effects on the carotid body.
The outcome of this complex respiratory control system is that variables such as Pao2, Paco2, and pH are held within narrow lim- its under most circumstances. The respiratory control center also can adjust tidal volume and frequency of breathing to minimize the energetic cost of breathing and can adapt to special circumstances such as speaking, swimming, eating, and exercise. Breathing can be stimulated by artificial manipulation of the Pco2, Po2, and pH. For example, ventilation is increased by rebreathing of carbon dioxide, inhalation of a concentration of low oxygen, or infusion of acid into the bloodstream.
100
60
20
Emphysema
10 20
Transpulmonary pressure (cm H2O)
30 40
Fibrosis Normal
Vital capacity (% total)
Fig. 15.8 Compliance curves for normal individuals and for patients with emphysema or pulmonary fibrosis. The transpulmonary pressure required to achieve a given lung volume is greatest for the patient with pulmonary fibrosis (notice the horizontal dashed line at 60% of the vital capacity). This increases the work of breathing.
4 6 8
4
3
2
1
4
3
2
1
2 0
Lung volume (L)
Airways resistance (cm H2O/ L /sec) Conductance (L/sec/cm H2O)
Conductance AWR
Fig. 15.9 As lung volume increases, the airways are dilated, and air- ways resistance (AWR) decreases. The reciprocal of resistance (con- ductance) increases as lung volume increases.
Normal elastic recoil and
airway resistance
Decreased elastic recoil
and normal airway resistance Normal elastic
recoil with increased airway resistance
Normal airflow
Decreased airflow Decreased
airflow
E-Fig. 15.1 Mechanisms of airflow obstruction.
174 SECTION III Pulmonary and Critical Care Medicine