Guyton and Hall Physiology Chapter 38 - Pulmonary Ventilation PDF

CHAPTER 38 UNIT VII Pulmonary Ventilation The main functions of respiration are to provid...

CHAPTER 38 UNIT VII Pulmonary Ventilation The main functions of respiration are to provide oxygen allowing the sternum to fall backward toward the verte- to the tissues and remove carbon dioxide. The four major bral column. When the rib cage is elevated, however, the components of respiration are the following: (1) pulmo- ribs project almost directly forward, so the sternum also nary ventilation, which means the inflow and outflow of moves forward, away from the spine, making the antero- air between the atmosphere and the lung alveoli; (2) dif- posterior thickness of the chest about 20% greater during fusion of oxygen (O2) and carbon dioxide (CO2) between maximum inspiration than during expiration. Therefore, the alveoli and the blood; (3) transport of oxygen and car- all the muscles that elevate the chest cage are classified as bon dioxide in the blood and body fluids to and from the muscles of inspiration, and the muscles that depress the body’s tissue cells; and (4) regulation of ventilation and chest cage are classified as muscles of expiration. other facets of respiration. This chapter is a discussion of The most important muscles that raise the rib cage are pulmonary ventilation; the subsequent five chapters cover the external intercostals, but others that help are the fol- other respiratory functions plus the physiology of special lowing: (1) sternocleidomastoid muscles, which lift upward respiratory abnormalities. on the sternum; (2) anterior serrati, which lift many of the ribs; and (3) scaleni, which lift the first two ribs. MECHANICS OF PULMONARY The muscles that pull the rib cage downward during VENTILATION expiration are mainly the following: (1) the abdominal recti, which have the powerful effect of pulling downward on the lower ribs at the same time that they and other MUSCLES THAT CAUSE LUNG EXPANSION abdominal muscles also compress the abdominal con- AND CONTRACTION tents upward against the diaphragm; and (2) the internal The lungs can be expanded and contracted in two ways: intercostals. (1) by downward or upward movement of the diaphragm Figure 38-1 also shows the mechanism whereby the to lengthen or shorten the chest cavity; and (2) by eleva- external and internal intercostals act to cause inspiration tion or depression of the ribs to increase or decrease the and expiration. To the left, the ribs during expiration are anteroposterior diameter of the chest cavity. Figure 38-1 angled downward, and the external intercostals are elon- shows these two methods. gated forward and downward. As they contract, they pull Normal quiet breathing is accomplished almost the upper ribs forward in relation to the lower ribs, which entirely by movement of the diaphragm. During inspi- causes leverage on the ribs to raise them upward, thereby ration, contraction of the diaphragm pulls the lower causing inspiration. The internal intercostals function in surfaces of the lungs downward. Then, during expi- the opposite manner, functioning as expiratory muscles ration, the diaphragm simply relaxes, and the elastic because they angle between the ribs in the opposite direc- recoil of the lungs, chest wall, and abdominal structures tion and cause opposite leverage. compresses the lungs and expels the air. During heavy PRESSURES THAT CAUSE MOVEMENT OF breathing, however, the elastic forces are not powerful AIR IN AND OUT OF THE LUNGS enough to cause the necessary rapid expiration, so extra force is achieved mainly by contraction of the abdominal See Video 38-1. The lung is an elastic structure that col- muscles, which pushes the abdominal contents upward lapses like a balloon and expels all its air through the tra- against the bottom of the diaphragm, thereby compress- chea whenever there is no force to keep it inflated. Also, ing the lungs. there are no attachments between the lung and walls of The second method for expanding the lungs is to the chest cage, except where it is suspended at its hilum raise the rib cage. Raising the rib cage expands the lungs from the mediastinum, the middle section of the chest because, in the natural resting position, the ribs slant cavity. Instead, the lung “floats” in the thoracic cavity, downward, as shown on the left side of Figure 38-1, thus surrounded by a thin layer of pleural fluid that lubricates 491 UNIT VII Respiration EXPIRATION INSPIRATION Increased vertical diameter Elevated Increased rib cage AP diameter External intercostals contracted Internal intercostals Diaphragmatic relaxed contraction Figure 38-1 Contraction and expan- sion of the thoracic cage during expi- Abdominals ration and inspiration, demonstrating contracted diaphragmatic contraction, function of the intercostal muscles, and elevation and depression of the rib cage. AP, An- teroposterior. Volume change (liters) movement of the lungs within the cavity. Furthermore, Lung volume 0.50 continual suction of excess fluid into lymphatic channels maintains a slight suction between the visceral surface of the lung pleura and the parietal pleural surface of the tho- 0.25 racic cavity. Therefore, the lungs are held to the thoracic wall as if glued there, except that they are well lubricated 0 and can slide freely as the chest expands and contracts. Pleural Pressure and Its Changes During Respira- +2 Alveolar pressure tion. Pleural pressure is the pressure of the fluid in the thin space between the lung pleura and chest wall pleura. 0 This pressure is normally a slight suction, which means Pressure (cm H2O) a slightly negative pressure. The normal pleural pressure –2 at the beginning of inspiration is about −5 centimeters of Transpulmonary pressure water (cm H2O), which is the amount of suction required –4 to hold the lungs open to their resting level. During nor- mal inspiration, expansion of the chest cage pulls outward –6 on the lungs with greater force and creates more negative Pleural pressure pressure to an average of about −7.5 cm H2O. –8 These relationships between pleural pressure and Inspiration Expiration changing lung volume are demonstrated in Figure 38-2; in the lower panel shows the increasing negativity of the Figure 38-2 Changes in lung volume, alveolar pressure, pleural pres- pleural pressure from −5 to −7.5 cm H2O during inspira- sure, and transpulmonary pressure during normal breathing. tion and in the upper panel an increase in lung volume of 0.5 liter. Then, during expiration, the events are essentially es to about −1 cm H2O. This slight negative pressure is reversed. enough to pull 0.5 liter of air into the lungs in the 2 sec- onds required for normal quiet inspiration. Alveolar Pressure—Air Pressure Inside the Lung Al- During expiration, alveolar pressure rises to about +1 veoli. When the glottis is open and no air is flowing into cm H2O, which forces the 0.5 liter of inspired air out of or out of the lungs, the pressures in all parts of the respira- the lungs during the 2 to 3 seconds of expiration. tory tree, all the way to the alveoli, are equal to atmos- pheric pressure, which is considered to be zero reference Transpulmonary Pressure—Difference between Al- pressure in the airways—that is, 0 cm H2O pressure. To veolar and Pleural Pressures. Note in Figure 38-2 that cause inward flow of air into the alveoli during inspira- the transpulmonary pressure is the pressure difference be- tion, the pressure in the alveoli must fall to a value slightly tween that in the alveoli and that on the outer surfaces of below atmospheric pressure (below 0). The second curve the lungs (pleural pressure); it is a measure of the elastic (labeled “alveolar pressure”) of Figure 38-2 demonstrates forces in the lungs that tend to collapse the lungs at each that during normal inspiration, alveolar pressure decreas- instant of respiration, called the recoil pressure. 492  Chapter 38 Pulmonary Ventilation Saline-filled Air-filled 0.50 Lung volume change (liters) Lung volume change (liters) 0.50 Expiration UNIT VII Expiration 0.25 0.25 Inspiration Inspiration 0 0 –2 –4 –6 –8 0 Pleural pressure (cm H2O) –4 –5 –6 Figure 38-4 Comparison of the compliance diagrams of saline-filled Pleural pressure (cm H2O) and air-filled lungs when the alveolar pressure is maintained at at- Figure 38-3 Compliance diagram in a healthy person. This diagram mospheric pressure (0 cm H2O) and pleural pressure is changed to shows changes in lung volume during changes in transpulmonary change the transpulmonary pressure. pressure (alveolar pressure minus pleural pressure). Compliance of the Lungs diagram of the lungs when filled with saline solution and The extent to which the lungs will expand for each unit when filled with air. When the lungs are filled with air, increase in transpulmonary pressure (if enough time is there is an interface between the alveolar fluid and the air allowed to reach equilibrium) is called the lung compli- in the alveoli. In lungs filled with saline solution, there is ance. The total compliance of both lungs together in the no air-fluid interface and, therefore, the surface tension normal adult averages about 200 ml of air/cm H2O trans- effect is not present; only tissue elastic forces are opera- pulmonary pressure. That is, every time the transpulmo- tive in the lung filled with saline solution. nary pressure increases by 1 cm H2O, the lung volume, Note that transpleural pressures required to expand after 10 to 20 seconds, will expand 200 ml. air-filled lungs are about three times as great as those required to expand lungs filled with saline solution. Thus, one can conclude that the tissue elastic forces tending to Compliance Diagram of the Lungs. Figure 38-3 is a di- cause collapse of the air-filled lung represent only about agram relating lung volume changes to changes in pleural one-third of the total lung elasticity, whereas the fluid-air pressure, which, in turn, alters transpulmonary pressure. surface tension forces in the alveoli represent about two- Note that the relationship is different for inspiration and thirds. expiration. Each curve is recorded by changing the pleu- The fluid-air surface tension elastic forces of the lungs ral pressure in small steps and allowing the lung volume also increase tremendously when the substance called to come to a steady level between successive steps. The surfactant is not present in the alveolar fluid. two curves are called, respectively, the inspiratory com- pliance curve and the expiratory compliance curve, and Surfactant, Surface Tension, and Collapse the entire diagram is called the compliance diagram of the of the Alveoli lungs. Principle of Surface Tension. When water forms a sur- The characteristics of the compliance diagram are face with air, the water molecules on the surface of the determined by the elastic forces of the lungs. These forces water have an especially strong attraction for one anoth- can be divided into two parts: (1) elastic forces of the lung er. As a result, the water surface is always attempting to tissue; and (2) elastic forces caused by surface tension of contract. This is what holds raindrops together—a tight the fluid that lines the inside walls of the alveoli and other contractile membrane of water molecules around the lung air spaces. entire surface of the raindrop. Now, let us reverse these The elastic forces of the lung tissue are determined principles and see what happens on the inner surfaces of mainly by elastin and collagen fibers interwoven among the alveoli. Here, the water surface is also attempting to the lung parenchyma. In deflated lungs, these fibers contract. This tends to force air out of the alveoli through are in an elastically contracted and kinked state; then, the bronchi and, in doing so, causes the alveoli to try to when the lungs expand, the fibers become stretched and collapse. The net effect is to cause an elastic contractile unkinked, thereby elongating and exerting even more force of the entire lungs, which is called the surface ten- elastic force. sion elastic force. The elastic forces caused by surface tension are much more complex. The significance of surface tension is Surfactant and Its Effect on Surface Tension. Sur- shown in Figure 38-4, which compares the compliance factant is a surface-active agent in water, which means 493 UNIT VII Respiration that it greatly reduces the surface tension of water. It is is fatal if not treated with strong measures, especially prop- secreted by special surfactant-secreting epithelial cells erly applied continuous positive pressure breathing. called type II alveolar epithelial cells, which constitute about 10% of the surface area of the alveoli. These cells are EFFECT OF THE THORACIC CAGE ON granular, containing lipid inclusions that are secreted in LUNG EXPANSIBILITY the surfactant into the alveoli. Thus far, we have discussed the expansibility of the lungs Surfactant is a complex mixture of several phospholip- alone, without considering the thoracic cage. The tho- ids, proteins, and ions. The most important components racic cage has its own elastic and viscous characteristics are the phospholipid dipalmitoyl phosphatidylcholine, and, even if the lungs were not present in the thorax, surfactant apoproteins, and calcium ions. The dipalmitoyl muscular effort would still be required to expand the phosphatidylcholine and several less important phospho- thoracic cage. lipids are responsible for reducing the surface tension. They perform this function by not dissolving uniformly Compliance of Thorax and Lungs in the fluid lining the alveolar surface. Instead, part of Together the molecule dissolves while the remainder spreads over The compliance of the entire pulmonary system (the the surface of the water in the alveoli. This surface has lungs and thoracic cage together) is measured while from one-twelfth to one-half the surface tension of a pure expanding the lungs of a totally relaxed or paralyzed water surface. subject. To measure compliance, air is forced into the Quantitatively, the surface tension of different water lungs a little at a time while recording lung pressures and fluids is approximately the following: pure water, 72 volumes. To inflate this total pulmonary system, almost dynes/cm; normal fluids lining the alveoli but without twice as much pressure is required compared with the surfactant, 50 dynes/cm; normal fluids lining the alveoli same lungs after removal from the chest cage. Therefore, and with normal amounts of surfactant included, between the compliance of the combined lung-thorax system is 5 and 30 dynes/cm. almost exactly half that of the lungs alone—110 ml/cm Pressure in Occluded Alveoli Caused by Surface Ten- H2O pressure for the combined system, compared with sion. If the air passages leading from the alveoli of the lungs 200 ml/cm H2O for the lungs alone. Furthermore, when are blocked, the surface tension in the alveoli tends to col- the lungs are expanded to high volumes or compressed lapse the alveoli. This collapse creates positive pressure in to low volumes, the limitations of the chest become the alveoli, attempting to push the air out. The amount of extreme. When near these limits, the compliance of the pressure generated in this way in an alveolus can be calcu- combined lung-thorax system can be less than 20% of lated from the following formula: that of the lungs alone.  ° 4VSGBDF UFOTJPO 1SFTTVSF  Work of Breathing 3BEJVT PG BMWFPMVT For the average-sized alveolus with a radius of about We have already pointed out that during normal quiet 100 micrometers and lined with normal surfactant, this breathing, all respiratory muscle contraction occurs during calculates to be about 4 cm H2O pressure (3 mm Hg). If the inspiration; expiration is almost entirely a passive process alveoli were lined with pure water without any surfactant, caused by elastic recoil of the lungs and chest cage. Thus, the pressure would be calculated as about 18 cm H2O pres- under resting conditions, the respiratory muscles normally sure—4.5 times as great. Thus, one sees the importance of perform “work” to cause inspiration but not to cause expi- surfactant in reducing alveolar surface tension and there- ration. fore also reducing the effort required by the respiratory The work of inspiration can be divided into three frac- muscles to expand the lungs. tions: (1) that required to expand the lungs against the Pressure Caused by Surface Tension Is Inversely Related lung and chest elastic forces, called compliance work or to Alveolar Radius. Note from the preceding formula that elastic work; (2) that required to overcome the viscosity of the smaller the alveolus, the greater the alveolar pressure the lung and chest wall structures, called tissue resistance caused by the surface tension. Thus, when the alveoli have work; and (3) that required to overcome airway resistance half the normal radius (50 instead of 100 micrometers), the to movement of air into the lungs, called airway resistance pressures noted earlier are doubled. This phenomenon is work. especially significant in small premature infants, many of Energy Required for Respiration. During normal quiet whom have alveoli with radii less than 25% that of an adult respiration, only 3% to 5% of the total energy expended by person. Furthermore, surfactant does not normally begin the body is required for pulmonary ventilation. However, to be secreted into the alveoli until between the sixth and during heavy exercise, the amount of energy required can seventh months of gestation and, in some cases, even later. increase as much as 50-fold, especially if the person has any Therefore, many premature infants have little or no sur- degree of increased airway resistance or decreased pulmo- factant in the alveoli when they are born, and their lungs nary compliance. Therefore, one of the major limitations have an extreme tendency to collapse, sometimes as much on the intensity of exercise that can be performed is the as six to eight times that in a normal adult person. This situ- person’s ability to provide enough muscle energy for the ation causes respiratory distress syndrome of the newborn. It respiratory process alone. 494  Chapter 38 Pulmonary Ventilation PULMONARY VOLUMES AND Table 38-1 Average Pulmonary Volumes and CAPACITIES Capacities for Healthy, Young Adult Men and Women Pulmonary Volumes and Capacities Men Women RECORDING CHANGES IN PULMONARY Volume (ml) VOLUME—SPIROMETRY UNIT VII Tidal volume 500 400 Pulmonary ventilation can be studied by recording the Inspiratory reserve volume 3000 1900 volume movement of air into and out of the lungs, a Expiratory volume 1100 700 method called spirometry. A typical basic spirometer is Residual volume 1200 1100 shown in Figure 38-5. It consists of a drum inverted over Capacities (ml) a chamber of water, with the drum counterbalanced by Inspiratory capacity 3500 2400 a weight. In the drum is a breathing gas, usually air or Functional residual capacity 2300 1800 oxygen; a tube connects the mouth with the gas chamber. When the person breathes into and out of the chamber, Vital capacity 4600 3100 the drum rises and falls, and an appropriate recording is Total lung capacity 5800 4200 made. Figure 38-6 shows a spirogram indicating changes in lung volume under different conditions of breathing. For ease in describing the events of pulmonary ventilation, Pulmonary Volumes the air in the lungs has been subdivided in this diagram Figure 38-6 lists four pulmonary lung volumes that when into four volumes and four capacities, which are the aver- added together, equal the maximum volume to which the ages for a young adult man. Table 38-1 summarizes the lungs can be expanded. The lung volumes shown are for average pulmonary volumes and capacities for healthy average adult males, but lung volumes vary considerably men and women. depending on physical fitness, age, height, sex, and other factors, such as the altitude at which a person resides. The significance of each of these lung volumes is the following: 1. The tidal volume is the volume of air inspired or ex- Floating drum pired with each normal breath; it amounts to about 500 ml in the average healthy man. Oxygen Recording 2. The inspiratory reserve volume is the extra volume chamber drum of air that can be inspired over and above the nor- mal tidal volume when the person inspires with full Water Mouthpiece force; it is usually equal to about 3000 ml. Counterbalancing weight 3. The expiratory reserve volume is the maximum extra volume of air that can be expired by forceful expira- tion after the end of a normal tidal expiration; this Figure 38-5 Spirometer. volume normally amounts to about 1100 ml in men. 4. The residual volume is the volume of air remaining 6000 in the lungs after the most forceful expiration; this volume averages about 1200 ml. 5000 Pulmonary Capacities Inspiratory Inspiratory Vital Total lung reserve capacity capacity capacity In describing events in the pulmonary cycle, it is some- Lung volume (ml) 4000 volume times useful to consider two or more of the volumes Tidal together. Such combinations are called pulmonary capac- 3000 volume ities. To the right in Figure 38-6 are listed the important pulmonary capacities, which can be described as follows: 1. The inspiratory capacity equals the tidal volume 2000 Expiratory Functional residual plus the inspiratory reserve volume. This capacity reserve volume capacity is the amount of air (≈3500 ml) that a person can 1000 breathe in, beginning at the normal expiratory level Residual volume and distending the lungs to the maximum amount. 2. The functional residual capacity equals the expira- Time tory reserve volume plus the residual volume. This Figure 38-6 Respiratory excursions during normal breathing and capacity is the amount of air that remains in the during maximal inspiration and maximal expiration. lungs at the end of normal expiration ≈2300 ml). 495 UNIT VII Respiration 3. The vital capacity equals the inspiratory reserve vol- Table 38-2 Abbreviations and Symbols for Pulmonary ume plus the tidal volume plus the expiratory re- Function serve volume. This capacity is the maximum amount Abbreviation Function of air a person can expel from the lungs after first VT Tidal volume filling the lungs to their maximum extent and then FRC Functional residual capacity expiring to the maximum extent (≈4600 ml). 4. The total lung capacity is the maximum volume to ERV Expiratory reserve volume which the lungs can be expanded with the greatest RV Residual volume possible effort (≈5800 ml); it is equal to the vital ca- IC Inspiratory capacity pacity plus the residual volume. IRV Inspiratory reserve volume Most pulmonary volumes and capacities are usually TLC Total lung capacity about 20% to 30% less in women than in men, and they VC Vital capacity are greater in large and athletic people than in small and asthenic people. Raw Resistance of the airways to flow of air into the lung ABBREVIATIONS AND SYMBOLS USED IN C Compliance PULMONARY FUNCTION STUDIES VD Volume of dead space gas Spirometry is only one of many measurement procedures VA Volume of alveolar gas that pulmonary physicians use daily. Many of these pro- VI Inspired volume of ventilation per minute cedures depend heavily on mathematical computations. To simplify these calculations, as well as the presentation VE Expired volume of ventilation per minute of pulmonary function data, several abbreviations and VS Shunt flow symbols have become standardized. The more important of these are given in Table 38-2. Using these symbols, VA Alveolar ventilation per minute we present here a few simple algebraic equations show- VO2 Rate of oxygen uptake per minute ing some of the interrelationships among the pulmonary volumes and capacities; the student should think through VCO2 Amount of carbon dioxide eliminated per minute and verify these interrelationships. VCO Rate of carbon monoxide uptake per minute 7$  *37 75 &37 DLO2 Diffusing capacity of the lungs for oxygen 7$  *$ &37 DLCO Diffusing capacity of the lungs for carbon monoxide 5-$  7$ 37 PB Atmospheric pressure Palv Alveolar pressure 5-$  *$ '3$ Ppl Pleural pressure PO2 Partial pressure of oxygen '3$  &37 37  PCO2 Partial pressure of carbon dioxide PN2 Partial pressure of nitrogen DETERMINATION OF FUNCTIONAL PaO2 Partial pressure of oxygen in arterial blood RESIDUAL CAPACITY, RESIDUAL VOLUME, AND TOTAL LUNG CAPACITY—HELIUM PaCO2 Partial pressure of carbon dioxide in arterial blood DILUTION METHOD PAO2 Partial pressure of oxygen in alveolar gas The functional residual capacity (FRC), which is the vol- PACO2 Partial pressure of carbon dioxide in ume of air that remains in the lungs at the end of each alveolar gas normal expiration, is important to lung function. Because PAH2O Partial pressure of water in alveolar gas its value changes markedly in some types of pulmonary R Respiratory exchange ratio disease, it is often desirable to measure this capacity. The spirometer cannot be used in to measure the FRC directly Q Cardiac output because the air in the residual volume of the lungs cannot CaO2 Concentration of oxygen in arterial blood be expired into the spirometer, and this volume consti- CVO2 Concentration of oxygen in mixed venous tutes about half of the FRC. To measure FRC, the spirom- blood eter must be used in an indirect manner, usually by means SO2 Percentage saturation of hemoglobin with of a helium dilution method, as follows. oxygen A spirometer of known volume is filled with air SaO2 Percentage saturation of hemoglobin with mixed with helium at a known concentration. Before oxygen in arterial blood 496  Chapter 38 Pulmonary Ventilation breathing from the spirometer, the person expires nor- 80 mally. At the end of this expiration, the remaining vol- ume in the lungs is equal to the FRC. At this point, the gen concentration tro Inspiration of pure oxygen 60 Percent nitrogen ni subject immediately begins to breathe from the spirom- rded eter, and the gases of the spirometer mix with the gases UNIT VII Reco of the lungs. As a result, the helium becomes diluted by 40 the FRC gases, and the volume of the FRC can be calcu- lated from the degree of dilution of the helium, using the following formula: 20   $J)F '3$  å  7J4QJS 0 $G)F 0 100 200 300 400 500 Air expired (ml) where FRC is functional residual capacity, CiHe is the Figure 38-7 Record of the changes in nitrogen concentration in the initial concentration of helium in the spirometer, CfHe is expired air after a single previous inspiration of pure oxygen. This the final concentration of helium in the spirometer, and record can be used to calculate dead space, as discussed in the text. ViSpir is the initial volume of the spirometer. DEAD SPACE AND ITS EFFECT ON Once the FRC has been determined, the residual vol- ALVEOLAR VENTILATION ume (RV) can be determined by subtracting expiratory reserve volume (ERV), as measured by normal spirom- Some of the air a person breathes never reaches the gas etry, from the FRC. Also, the total lung capacity (TLC) exchange areas but simply fills respiratory passages, such can be determined by adding the inspiratory capacity (IC) as the nose, pharynx, and trachea, where gas exchange to the FRC. That is: does not occur. This air is called dead space air because it is not useful for gas exchange. 37  '3$ å &37 On expiration, the air in the dead space is expired first, and before any of the air from the alveoli reaches the atmo- 5-$  '3$ *$ sphere. Therefore, the dead space is very disadvantageous for removing the expiratory gases from the lungs. MINUTE RESPIRATORY VOLUME EQUALS Measurement of Dead Space Volume. A simple method RESPIRATORY RATE TIMES TIDAL for measuring dead space volume is demonstrated by the VOLUME graph in Figure 38-7. In making this measurement, the sub- ject suddenly takes a deep breath of 100% O2, which fills the The minute respiratory volume is the total amount of entire dead space with pure O2. Some oxygen also mixes with new air moved into the respiratory passages each min- the alveolar air but does not completely replace this air. Then ute and is equal to the tidal volume times the respiratory the person expires through a rapidly recording nitrogen meter, rate per minute. The normal tidal volume is about 500 which makes the record shown in the figure. The first portion ml, and the normal respiratory rate is about 12 breaths/ of the expired air comes from the dead space regions of the min. Therefore, the minute respiratory volume averages respiratory passageways, where the air has been completely re- about 6 L/min. A person can live for a short period with placed by O2. Therefore, in the early part of the record, only O2 a minute respiratory volume as low as 1.5 L/min and a appears, and the nitrogen concentration is 0. Then, when al- veolar air begins to reach the nitrogen meter, the nitrogen con- respiratory rate of only 2 to 4 breaths/min. centration rises rapidly because alveolar air containing large The respiratory rate occasionally rises to 40 to 50 amounts of nitrogen begins to mix with the dead space air. breaths/min, and the tidal volume can become as great as After still more air has been expired, all the dead space air has the vital capacity, about 4600 ml in a young man. This can been washed from the passages and only alveolar air remains. give a minute respiratory volume greater than 200 L/min, Therefore, the recorded nitrogen concentration reaches a pla- or more than 30 times normal. Most people cannot sus- teau level equal to its concentration in the alveoli, as shown at tain more than half to two-thirds of these values for longer the right in the figure. The gray area represents the air that has than 1 minute. no nitrogen in it and is a measure of the volume of dead space air. For exact quantification, the following equation is used: (SBZ BSFB ° 7& ALVEOLAR VENTILATION 7%  1JOL BSFB (SBZ BSFB The ultimate importance of pulmonary ventilation is to where VD is dead space air and VE is the total volume renew the air in the gas exchange areas of the lungs con- of expired air. tinually, where air is in proximity to the pulmonary blood. Let us assume, for example, that the gray area on the These areas include the alveoli, alveolar sacs, alveolar graph is 30 square centimeters, the pink area is 70 square ducts, and respiratory bronchioles. The rate at which new centimeters, and the total volume expired is 500 ml. The air reaches these areas is called alveolar ventilation. dead space would be 497 UNIT VII Respiration  °    NM VA = Freq × ( VT − VD ) <   where V A is the volume of alveolar ventilation per min- Normal Dead Space Volume. The normal dead space air ute, Freq is the frequency of respiration per minute, Vt is in a young man is about 150 ml. Dead space air increases the tidal volume, and Vd is the physiological dead space slightly with age. volume. Anatomical Versus Physiological Dead Space. The Thus, with a normal tidal volume of 500 ml, a normal method just described for measuring the dead space meas- dead space of 150 ml, and a respiratory rate of 12 breaths/ ures the volume of all the space of the respiratory system other than the alveoli and their other closely related gas ex- min, alveolar ventilation equals 12 × (500 − 150), or 4200 change areas; this space is called the anatomic dead space. ml/min. On occasion, some of the alveoli are nonfunctional or only Alveolar ventilation is one of the major factors deter- partially functional because of absent or poor blood flow mining the concentrations of oxygen and carbon dioxide through the adjacent pulmonary capillaries. Therefore, in the alveoli. Therefore, almost all discussions of gaseous these alveoli must also be considered dead space. When the exchange in the following chapters on the respiratory sys- alveolar dead space is included in the total measurement tem focus on alveolar ventilation. of dead space, this is called the physiological dead space, in contradistinction to the anatomical dead space. In a person Functions of Respiratory Passageways with healthy lungs, the anatomical and physiological dead Trachea, Bronchi, and Bronchioles spaces are nearly equal because all alveoli are functional in Figure 38-8 highlights the respiratory passageways. The air the normal lung but, in a person with partially functional is distributed to the lungs by way of the trachea, bronchi, or nonfunctional alveoli in some parts of the lungs, the and bronchioles. physiological dead space may be as much as 10 times the One of the most important challenges in the respiratory volume of the anatomical dead space, or 1 to 2 liters. These passageways is to keep them open and allow easy passage problems are discussed further in Chapter 40 in relation to of air to and from the alveoli. To keep the trachea from col- pulmonary gaseous exchange and in Chapter 43 in relation lapsing, multiple cartilage rings extend about five-sixths of to certain pulmonary diseases. the way around the trachea. In the walls of the bronchi, less extensive curved cartilage plates also maintain a reasonable RATE OF ALVEOLAR VENTILATION amount of rigidity yet allow sufficient motion for the lungs Alveolar ventilation per minute is the total volume of new to expand and contract. These plates become progressively air entering the alveoli and adjacent gas exchange areas less extensive in the later generations of bronchi and are each minute. It is equal to the respiratory rate times the gone in the bronchioles, which usually have diameters less than 1.5 millimeters. The bronchioles are not prevented amount of new air that enters these areas with each breath: CO2 O2 Alveolus Conchae O2 O2 Pharynx CO2 CO2 Glottis Epiglottis Pulmonary capillary Larynx, vocal cords Esophagus Trachea Pulmonary arteries Pulmonary veins Alveoli Figure 38-8 Respiratory passages. 498  Chapter 38 Pulmonary Ventilation from collapsing by the rigidity of their walls. Instead, they Local Secretory Factors May Cause Bronchiolar Constric- are kept expanded mainly by the same transpulmonary tion. Several substances formed in the lungs are often active pressures that expand the alveoli. That is, as the alveoli en- in causing bronchiolar constriction. Two of the most impor- large, the bronchioles also enlarge, but not as much. tant of these are histamine and slow reactive substance of Muscular Wall of the Bronchi and Bronchioles. In all anaphylaxis. Both these substances are released in the lung UNIT VII areas of the trachea and bronchi not occupied by cartilage tissues by mast cells during allergic reactions, especially plates, the walls are composed mainly of smooth mus- those caused by pollen in the air. Therefore, they play key cle. Also, the walls of the bronchioles are almost entirely roles in causing airway obstruction in allergic asthma; this is smooth muscle, with the exception of the most terminal especially true of the slow reactive substance of anaphylaxis. bronchiole, called the respiratory bronchiole, which is The same irritants that cause parasympathetic constric- mainly pulmonary epithelium and underlying fibrous tissue tor reflexes of the airways—smoke, dust, sulfur dioxide, and plus a few smooth muscle fibers. Many obstructive diseases some of the acidic elements in smog—may also act directly of the lung result from narrowing of the smaller bronchi on the lung tissues to initiate local, non-nervous reactions and larger bronchioles, often because of excessive contrac- that cause obstructive constriction of the airways. tion of the smooth muscle. Resistance to Airflow in the Bronchial Tree. Under nor- Mucus Lining the Respiratory Passageways and Cilia mal respiratory conditions, air flows through the respira- Action to Clear the Passageways tory passageways so easily that less than 1 cm H2O pressure All the respiratory passages, from the nose to the terminal gradient from the alveoli to the atmosphere is sufficient bronchioles, are kept moist by a layer of mucus that coats to cause enough airflow for quiet breathing. The greatest the entire surface. The mucus is secreted partly by individual amount of resistance to airflow occurs not in the tiny air mucous goblet cells in the epithelial lining of the passages and passages of the terminal bronchioles but in some of the partly by small submucosal glands. In addition to keeping the larger bronchioles and bronchi near the trachea. The rea- surfaces moist, the mucus traps small particles out of the in- son for this high resistance is that there are relatively few of spired air and keeps most of these particles from ever reach- these larger bronchi in comparison with the approximately ing the alveoli. The mucus is removed from the passages in 65,000 parallel terminal bronchioles, through each of which the following manner. only a minute amount of air must pass. The entire surface of the respiratory passages, in the nose In some disease conditions, the smaller bronchioles play and the lower passages, down as far as the terminal bronchi- a far greater role in determining airflow resistance because oles, is lined with ciliated epithelium, with about 200 cilia on of their small size and because they are easily occluded each epithelial cell. These cilia beat continually at a rate of 10 by the following: (1) muscle contraction in their walls; (2) to 20 times/sec by the mechanism explained in Chapter 2, and edema in the walls; or (3) mucus collecting in the lumens the direction of their “power stroke” is always toward the phar- of the bronchioles. ynx. That is, the cilia in the lungs beat upward, whereas those Nervous and Local Control of the Bronchiolar Muscu- in the nose beat downward. This continual beating causes the lature—Sympathetic Dilation of the Bronchioles. Direct coat of mucus to flow slowly, at a velocity of a few millime- control of the bronchioles by sympathetic nerve fibers is ters per minute, toward the pharynx. Then the mucus and its relatively weak because few of these fibers penetrate to the entrapped particles are swallowed or coughed to the exterior. central portions of the lung. However, the bronchial tree is very much exposed to norepinephrine and epinephrine Cough Reflex released into the blood by sympathetic stimulation of the The bronchi and trachea are so sensitive to light touch that adrenal gland medullae. Both these hormones, especially slight amounts of foreign matter or other causes of irritation epinephrine because of its greater stimulation of beta- initiate the cough reflex. The larynx and carina (the point where adrenergic receptors, cause dilation of the bronchial tree. the trachea divides into the bronchi) are especially sensitive, and Parasympathetic Constriction of the Bronchioles. the terminal bronchioles and even the alveoli are sensitive to A few parasympathetic nerve fibers derived from the va- corrosive chemical stimuli such as sulfur dioxide gas or chlorine gus nerves penetrate the lung parenchyma. These nerves gas. Afferent nerve impulses pass from the respiratory passages secrete acetylcholine and, when activated, cause mild to mainly through the vagus nerves to the medulla of the brain. moderate constriction of the bronchioles. When a disease There, an automatic sequence of events is triggered by the neu- process such as asthma has already caused some bronchi- ronal circuits of the medulla, causing the following effects. olar constriction, superimposed parasympathetic nervous 1. Up to 2.5 liters of air are rapidly inspired. stimulation often worsens the condition. When this situa- 2. The epiglottis closes, and the vocal cords shut tightly to tion occurs, administration of drugs that block the effects entrap the air within the lungs. of acetylcholine, such as atropine, can sometimes relax the 3. The abdominal muscles contract forcefully, pushing respiratory passages enough to relieve the obstruction. against the diaphragm while other expiratory muscles, Sometimes the parasympathetic nerves are also acti- such as the internal intercostals, also contract forcefully. vated by reflexes that originate in the lungs. Most of these Consequently, the pressure in the lungs rises rapidly, to reflexes begin with irritation of the epithelial membrane as much as 100 mm Hg or more. of the respiratory passageways, initiated by noxious gases, 4. The vocal cords and epiglottis suddenly open widely, so dust, cigarette smoke, or bronchial infection. Also, a bron- that air under this high pressure in the lungs explodes chiolar constrictor reflex often occurs when microemboli outward. Sometimes this air is expelled at velocities occlude small pulmonary arteries. ranging from 75 to 100 miles/hour. 499 UNIT VII Respiration Importantly, the strong compression of the lungs col- example, the particles of cigarette smoke are about 0.3 mi- lapses the bronchi and trachea by causing their noncarti- crometer. Almost none of these particles are precipitated in laginous parts to invaginate inward, so the exploding air the respiratory passageways before they reach the alveoli. actually passes through bronchial and tracheal slits. The Unfortunately, up to one-third of them do precipitate in the rapidly moving air usually carries with it any foreign matter alveoli by the diffusion process, with the balance remaining that is present in the bronchi or trachea. suspended and expelled in the expired air. Many of the particles that become entrapped in the al- Sneeze Reflex veoli are removed by alveolar macrophages, as explained in The sneeze reflex is very much like the cough reflex, except Chapter 34, and others are carried away by the lung lym- that it applies to the nasal passageways instead of the lower phatics. An excess of particles can cause growth of fibrous respiratory passages. The initiating stimulus of the sneeze tissue in the alveolar septa, leading to permanent debility. reflex is irritation in the nasal passageways; the afferent im- pulses pass in the fifth cranial nerve to the medulla, where Vocalization the reflex is triggered. A series of reactions similar to those Speech involves not only the respiratory system but also for the cough reflex takes place, but the uvula is depressed, the following: (1) specific speech nervous control centers in so large amounts of air pass rapidly through the nose, thus the cerebral cortex, discussed in Chapter 58; (2) respiratory helping clear the nasal passages of foreign matter. control centers of the brain; and (3) the articulation and resonance structures of mouth and nasal cavities. Speech Normal Respiratory Functions of the Nose is composed of two mechanical functions: (1) phonation, As air passes through the nose, three distinct normal respira- which is achieved by the larynx; and (2) articulation, which tory functions are performed by the nasal cavities: (1) the air is achieved by the structures of the mouth. is warmed by the extensive surfaces of the conchae and sep- Phonation. The larynx, shown in Figure 38-9A, is es- tum, a total area of about 160 square centimeters (see Figure pecially adapted to act as a vibrator. The vibrating elements 38-8); (2) the air is almost completely humidified, even before are the vocal folds, commonly called the vocal cords. The it passes beyond the nose; and (3) the air is partially filtered. vocal cords protrude from the lateral walls of the larynx These functions together are called the air-conditioning func- toward the center of the glottis; they are stretched and po- tion of the upper respiratory passageways. Ordinarily, the sitioned by several specific muscles of the larynx itself. temperature of the inspired air rises to within 1°F of body tem- Figure 38-9B shows the vocal cords as they are seen perature and to within 2% to 3% of full saturation with water when looking into the glottis with a laryngoscope. During vapor before it reaches the trachea. When a person breathes normal breathing, the cords are wide open to allow easy pas- air through a tube directly into the trachea (as through a tra- sage of air. During phonation, the cords move together so cheostomy), the cooling and especially the drying effect in the that passage of air between them will cause vibration. The lower lung can lead to serious lung crusting and infection. pitch of the vibration is determined mainly by the degree Filtration Function of the Nose. The hairs at the entrance of stretch of the cords, but also by how tightly the cords are to the nostrils are important for filtering out large particles. approximated to one another and by the mass of their edges. Much more important, though, is the removal of particles by Figure 38-9A shows a dissected view of the vocal folds turbulent precipitation. That is, the air passing through the after removal of the mucous epithelial lining. Immediately in- nasal passageways hits many obstructing vanes—the con- side each cord is a strong elastic ligament called the vocal liga- chae (also called turbinates, because they cause turbulence ment. This ligament is attached anteriorly to the large thyroid of the air), the septum, and the pharyngeal wall. Each time cartilage, which is the cartilage that projects forward from the air hits one of these obstructions, it must change its direc- anterior surface of the neck and is called the Adam’s apple. tion of movement. The particles suspended in the air, having Posteriorly, the vocal ligament is attached to the vocal pro- far more mass and momentum than air, cannot change their cesses of two arytenoid cartilages. The thyroid cartilage and direction of travel as rapidly as the air can. Therefore, they the arytenoid cartilages articulate from below with another continue forward, striking the surfaces of the obstructions, cartilage (not shown in Figure 38-9), the cricoid cartilage. and are entrapped in the mucous coating and transported by The vocal cords can be stretched by forward rotation of the cilia to the pharynx to be swallowed. the thyroid cartilage or posterior rotation of the arytenoid Size of Particles Entrapped in the Respiratory Passag- cartilages, activated by muscles stretching from the thyroid es. The nasal turbulence mechanism for removing particles cartilage and arytenoid cartilages to the cricoid cartilage. from air is so effective that almost no particles larger than 6 Muscles located in the vocal cords lateral to the vocal liga- micrometers in diameter enter the lungs through the nose. ments, the thyroarytenoid muscles, can pull the arytenoid This size is smaller than red blood cells. cartilages toward the thyroid cartilage and, therefore, loos- Of the remaining particles, many that are between 1 and en the vocal cords. Also, slips of these muscles in the vocal 5 micrometers settle in the smaller bronchioles as a result cords can change the shapes and masses of the vocal cord of gravitational precipitation. For example, terminal bron- edges, sharpening them to emit high-pitched sounds and chiolar disease is common in coal miners because of settled blunting them for the more bass sounds. dust particles. Some of the still smaller particles (