Vander's Human Physiology PDF - Respiratory Physiology Chapter (2022)

Page 445 CHAPTER 13 Respiratory Physiology Resin cast of the pulmonary art...

Page 445 CHAPTER 13 Respiratory Physiology Resin cast of the pulmonary arteries and bronchi. SPL/Science Source 13.1 Organization of the Respiratory System 13.2 Principles of Ventilation 13.3 Lung Mechanics 13.4 Alveolar Ventilation 13.5 Exchange of Gases in Alveoli and Tissues Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. 13.6 Transport of Oxygen in Blood 13.7 Transport of Carbon Dioxide in Blood 13.8 Transport of Hydrogen Ion Between Tissues and Lungs 13.9 Control of Respiration 13.10 Hypoxia 13.11 Nonrespiratory Functions of the Lungs Chapter 13 Clinical Case Study Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  In the previous chapter, you learned that the major role of the circulatory system is to deliver nutrients and oxygen to the tissues and to remove carbon dioxide and other waste products of metabolism. In this chapter, you will learn how the respiratory system is intimately associated with the circulatory system and is responsible for taking up oxygen from the environment and delivering it to the blood, as well as eliminating carbon dioxide from the blood. Respiration has two meanings: utilization of oxygen in the metabolism of organic molecules by cells, termed internal or cellular respiration, as described in Chapter 3 the exchange of oxygen and carbon dioxide between an organism and the external environment, called pulmonary physiology The adjective pulmonary refers to the lungs. The second meaning is the subject of this chapter. Human cells obtain most of their energy from chemical reactions involving oxygen. In addition, cells must be able to eliminate carbon dioxide, the major end product of oxidative metabolism. Unicellular and some very small organisms can exchange oxygen and carbon dioxide directly with the external environment, but this is not possible for most cells of a complex organism like a human being. Therefore, the evolution of larger animals required the development of specialized structures for the exchange of oxygen and carbon dioxide with the external environment. In humans and other mammals, the respiratory system includes the oral and nasal cavities, the lungs, the series of tubes leading to the lungs, and the chest structures responsible for moving air into and out of the lungs during breathing. Page 446 As you read about the structure, function, and control of the respiratory system, you will encounter numerous examples of the general principles of physiology that were outlined in Chapter 1. The general principle of physiology that physiological processes are governed by the laws of chemistry and physics is demonstrated when describing the binding of oxygen and carbon dioxide to hemoglobin, the handling by the blood of acid produced by Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. metabolism, and the factors that control the inflation and deflation of the lungs. The diffusion of gases is an excellent example of the general principle of physiology that controlled exchange of materials occurs between compartments and across cellular membranes. You will learn how the functional units of the lung, the alveoli, are elegant examples of the general principle of physiology that structure is a determinant of—and has coevolved with— function. Finally, the central nervous system control of respiration is yet another example of the general principle of physiology that homeostasis is essential for health and survival. Table 13.1 lists the different functions of the respiratory system that you will learn about in this chapter. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  TABLE 13.1 Functions of the Respiratory System Provides oxygen to the blood Eliminates carbon dioxide from the blood Regulates the blood’s hydrogen ion concentration (pH) in coordination with the kidneys Forms speech sounds (phonation) Defends against inhaled microbes Influences arterial concentrations of chemical messengers by removing some from pulmonary capillary blood and producing and adding others to this blood Traps and dissolves blood clots arising from systemic veins, such as those in the legs 13.1 Organization of the Respiratory System There are two lungs, the right and left, each divided into lobes. The lungs consist mainly of tiny air-containing sacs called alveoli (singular, alveolus), which number approximately 300 million in an adult. The alveoli are the sites of gas exchange with the blood. The airways are the tubes through which air flows from the external environment to the alveoli and back. Inspiration (inhalation) is the movement of air from the external environment through the airways into the alveoli during breathing. Expiration (exhalation) is air movement in the opposite direction. An inspiration and an expiration constitute a respiratory cycle. During the entire respiratory cycle, the right ventricle of the heart pumps blood through the pulmonary arteries and arterioles and into the capillaries surrounding each alveolus. In a healthy adult at rest, approximately 4 L of fresh air enters and leaves the alveoli per minute, while 5 L of blood, the cardiac output, flows through the pulmonary capillaries. During heavy exercise, the airflow can increase 20-fold, and the blood flow 5- to 6-fold. The Airways and Blood Vessels During inspiration, air passes through the nose or the mouth (or both) into the pharynx, a Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. passage common to both air and food (Figure 13.1). The pharynx branches into two tubes: the esophagus, through which food passes to the stomach, and the larynx, which is part of the airways. The larynx houses the vocal cords, two folds of elastic tissue stretched horizontally across its lumen. The flow of air past the vocal cords causes them to vibrate, producing sounds. The nose, mouth, pharynx, and larynx are collectively termed the upper airways. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Figure 13.1 Organization of the respiratory system. The ribs have been removed in front, and the lungs are shown in a way that makes visible the major airways within them. Not shown: The pharynx continues posteriorly to the esophagus. The larynx opens into a long tube, the trachea, which in turn branches into two bronchi (singular, bronchus), one of which enters each lung. Within the lungs, there are more than 20 generations of branchings, each resulting in narrower, shorter, and more numerous tubes; their names are summarized in Figure 13.2. The walls of the trachea and bronchi contain rings of cartilage, which give them their cylindrical shape and support them. The first airway branches that no longer contain cartilage are termed bronchioles, which branch into the smaller, terminal bronchioles. Alveoli first begin to appear attached to the walls of the respiratory bronchioles. The number of alveoli increases in the alveolar ducts (see Figure 13.2), and the airways then end in grapelike clusters called alveolar sacs that consist entirely of alveoli (Figure 13.3). The bronchioles are surrounded by smooth muscle, which contracts or relaxes to alter bronchiolar radius, in much the same way that the radius of small blood vessels (arterioles) is controlled, as you learned in Chapter 12. Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. Figure 13.2 Airway branching. Asymmetries in branching patterns between the right and left bronchial trees are not depicted. The diameters of the airways and alveoli are not drawn to scale. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Figure 13.3 Relationships between blood vessels and airways. (a) The lung appears transparent so that the relationships are visible. The airways beyond the bronchioles are too small to be seen. (b) An enlargement of a small section of part (a) shows the continuation of the airways and the clusters of alveoli at their ends. Virtually the entire lung, not just the surface, consists of such clusters. Red represents oxygenated blood; blue represents deoxygenated blood. Page 447 The airways beyond the larynx can be divided into two zones. The conducting zone extends from the top of the trachea to the end of the terminal bronchioles. This zone contains no alveoli and does not exchange gases with the blood. The respiratory zone extends from the respiratory bronchioles down. This zone contains alveoli and is the region of gas exchange with the blood. The oral and nasal cavities trap airborne particles in nasal hairs and mucus. The epithelial surfaces of the airways, to the end of the respiratory bronchioles, contain cilia that constantly beat upward toward the pharynx. They also contain glands and individual epithelial cells which secrete mucus, and macrophages, which can phagocytize inhaled pathogens. Particulate matter, such as dust contained in the inspired air, sticks to the mucus, which is continuously and slowly moved by the cilia to the pharynx and then swallowed. This so- called mucous escalator is important in keeping the lungs clear of particulate matter and the many bacteria that enter the body on dust particles. Ciliary activity and number can be Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. decreased by many noxious agents, including the smoke from chronic smoking of tobacco products. This is why smokers often cough up mucus that the cilia would normally have cleared. The airway epithelium also secretes a watery fluid upon which the mucus can ride freely. The production of this fluid is impaired in the disease cystic fibrosis (CF), the most common lethal genetic disease among Whites, in which the mucous layer becomes thick and dehydrated, obstructing the airways. CF is caused by an autosomal recessive mutation in an epithelial chloride channel called the CF transmembrane conductance regulator (CFTR) protein. This results in problems with ion and water movement across cell membranes, which leads to thickened secretions and a high incidence of lung infection. It is usually treated with: Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  therapy to improve clearance of mucus from the lung the aggressive use of antibiotics to prevent pneumonia Although the treatment of CF has improved over the past few decades, median life expectancy is still only about 35 years. Ultimately, lung transplantation may be required. In addition to the lungs, other organs are usually affected—particularly in the secretory organs associated with the gastrointestinal tract (for example, the exocrine pancreas, as described in Chapter 15). Constriction of bronchioles in response to irritation helps to prevent particulate matter and irritants from entering the sites of gas exchange. Another protective mechanism against infection is provided by macrophages that are present in the airways and alveoli. These cells engulf and destroy inhaled particles and bacteria that have reached the alveoli. Macrophages, like the ciliated epithelium of the airways, are injured by tobacco smoke and air pollutants. The physiology of the conducting zone is summarized in Table 13.2. TABLE 13.2 Functions of the Conducting Zone of the Airways Provides a low-resistance pathway for airflow. Resistance is physiologically regulated by changes in contraction of bronchiolar smooth muscle and by physical forces acting upon the airways. Defends against microbes, toxic chemicals, and other foreign matter. Cilia, mucus, and macrophages perform this function. Warms and moistens the air. Participates in sound production (vocal cords). The pulmonary blood vessels generally accompany the airways and also undergo numerous branchings. The smallest of these vessels branch into networks of capillaries that richly supply the alveoli (see Figure 13.3). As you learned in Chapter 12, the pulmonary circulation has a very low resistance to the flow of blood compared to the systemic circulation, and for this reason the pressures within all pulmonary blood vessels are low. This is an important adaptation that minimizes accumulation of fluid in the interstitial spaces of the lungs (see Figure 12.45 for a description of Starling forces and the movement of fluid Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. across capillaries). Page 448 Site of Gas Exchange: The Alveoli The alveoli are tiny, hollow sacs with open ends that are continuous with the lumens of the airways (Figure 13.4a). Typically, a single alveolar wall separates the air in two adjacent alveoli. Most of the air-facing surfaces of the wall are lined by a continuous layer, one cell thick, of flat epithelial cells termed type I alveolar cells. Interspersed between these cells are Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  thicker, specialized cells termed type II alveolar cells (Figure 13.4b) that produce a detergent-like substance called surfactant that, as we will see, is important for preventing the collapse of the alveoli. Figure 13.4 (a) Cross section through an area of the respiratory zone. There are 18 alveoli in this figure, only 4 of which are labeled. Two often share a common wall. (b) Schematic enlargement of a portion of an alveolar wall. Source: Adapted from Gong and Drage. DIG DEEPER What consequences would result if inflammation caused a buildup of fluid in the alveoli and interstitial spaces? Answer found in Appendix A. The alveolar walls contain capillaries and a very small interstitial space, which consists of Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. interstitial fluid and a loose meshwork of connective tissue (see Figure 13.4b). In many places, the interstitial space is absent altogether, and the basement membranes of the alveolar-surface epithelium and the capillary-wall endothelium fuse. Because of this unique anatomical arrangement, the blood within an alveolar-wall capillary is separated from the air within the alveolus by an extremely thin barrier (0.2 μm, compared with the 7 μm diameter of an average red blood cell). The total surface area of alveoli in contact with capillaries is roughly the size of a tennis court. This extensive area and the thinness of the barrier permit the rapid exchange of large quantities of oxygen and carbon dioxide by diffusion. These are excellent examples of two of the general principles of physiology: that physiological processes require the transfer and balance of matter (in this case, oxygen and carbon dioxide) Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  and energy between compartments, and that structure (in this case, the thinness of the diffusion barrier and the enormous surface area for gas exchange) is a determinant of—and has coevolved with—function (the transfer of oxygen and carbon dioxide between the alveolar air and the blood in the pulmonary capillaries). In some of the alveolar walls, pores permit the flow of air between alveoli. This route can be very important when the airway leading to an alveolus is occluded by disease, because some air can still enter the alveolus by way of the pores between it and adjacent alveoli. Page 449 Relation of the Lungs to the Thoracic (Chest) Wall The lungs, like the heart, are situated in the thorax, the compartment of the body between the neck and abdomen. Thorax and chest are synonyms. The thorax is a closed compartment bounded at the neck by muscles and connective tissue and completely separated from the abdomen by a large, dome-shaped sheet of skeletal muscle called the diaphragm (see Figure 13.1). The wall of the thorax is formed by the spinal column, the ribs, the breastbone (sternum), and several groups of muscles that run between the ribs that are collectively called the intercostal muscles. The thoracic wall also contains large amounts of connective tissue with elastic properties. Each lung is surrounded by a completely closed sac, the pleural sac, consisting of a thin sheet of cells called pleura. The pleural sac of one lung is separate from that of the other lung. The relationship between a lung and its pleural sac can be visualized by imagining what happens when you push a fist into a fluid-filled balloon. The arm shown in Figure 13.5 represents the major bronchus leading to the lung, the fist is the lung, and the balloon is the pleural sac. The fist becomes coated by one surface of the balloon. In addition, the balloon is pushed back upon itself so that its opposite surfaces lie close together but are separated by a thin layer of fluid. Unlike the hand and balloon, the pleural surface coating the lung known as the visceral pleura is firmly attached to the lung by connective tissue. Similarly, the outer layer, called the parietal pleura, is attached to and lines the interior thoracic wall and Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. diaphragm. The two layers of pleura in each sac are very close but not attached to each other. Rather, they are separated by an extremely thin layer of intrapleural fluid, the total volume of which is only a few milliliters. The intrapleural fluid totally surrounds the lungs and lubricates the pleural surfaces so that they can slide over each other during breathing. As we will see in the next section, changes in the hydrostatic pressure of the intrapleural fluid—the intrapleural pressure (Pip)—cause the lungs and thoracic wall to move in and out together during normal breathing. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Figure 13.5 Relationship of lungs, pleura, and thoracic wall, shown as analogous to pushing a fist into a fluid-filled balloon. Note that there is no communication between the right and left intrapleural fluids. For purposes of illustration, the volume of intrapleural fluid is greatly exaggerated. It normally consists of an extremely thin layer of fluid between the pleural membrane lining the inner surface of the thoracic wall (the parietal pleura) and the membrane lining the outer surface of the lungs (the visceral pleura). A way to visualize the apposition of the two pleural surfaces is to put a small drop of water between two glass microscope slides. The two slides can easily slide over each other but are very difficult to pull apart. Study and Review 13.1 Respiration: two meanings Cellular (internal) respiration: oxygen utilization by cells Pulmonary respiration: exchange of O2 and CO2 between the lungs and the environment Respiratory system: consists of the lungs, airways (leading to lungs), and chest structures (that induce movement of air into and out of the lungs and airways) conducting zone of the airways (no gas exchange with blood)—composed of upper airways (nose, pharynx, larynx [(location of vocal cords]) → lower airways (trachea, bronchi, and terminal bronchioles) respiratory zone of the airways (gas exchange with blood)—composed of respiratory bronchioles → alveolar sacs containing alveoli Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. Alveoli (sites of gas exchange): lined by epithelial cells, including type I cells and some type II cells (that produce surfactant in a thin layer of a fluid coating) Thorax (chest) (also contains the heart): The thorax includes the skeletal muscles of respiration (drive the respiratory cycle), which are the diaphragm (separates thorax from abdomen) and intercostal muscles (run between ribs). The thorax also is composed of connective tissue (elastic properties). Pleura: two membranous layers covering lungs (visceral pleura) and interior of the thorax (parietal pleura) Intrapleural fluid: extremely thin layer of lubricating fluid between two pleural layers Lungs: elastic structures surrounded by pleura; lung volume depends on: pressure difference across the lungs how compliant (stretchable) the lungs are Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  thin layer of fluid and mucus that coats and protects the airways airway fluid abnormal in cystic fibrosis (CF)–caused by mutation in the (CF) transmembrane conductance regulatory (CFTR) protein Respiratory cycle: Inspiration (inhalation): air moves from environment to respiratory system Expiration (exhalation): air moves from respiratory system to environment Steps involved in respiration are 1. Ventilation: exchange of air by bulk flow 2. Exchange of oxygen and carbon dioxide between alveolar gas and pulmonary capillary blood by diffusion 3. Oxygen and carbon dioxide transport in blood by bulk flow 4. Exchange of oxygen and carbon dioxide between the tissue capillary blood and cells by diffusion 5. Cellular consumption of oxygen and production of carbon dioxide Steady state: occurs when net volumes of oxygen and carbon dioxide exchanged per unit time in the lungs are equal to the net volumes exchanged per unit time in the tissues Review Question: Follow a molecule of oxygen from the inspired air to an alveolus where O2 is absorbed into the blood, naming the major structures it passes. What are the two zones of the respiratory system and what major structures belong to each? What occurs in the steady state? (Answer found in Appendix A.) Page 450 13.2 Principles of Ventilation The next three sections highlight the fact that physiological processes are dictated by the laws of chemistry and physics, one of the general principles of physiology described in Chapter 1. Understanding the forces that control the inflation and deflation of the lung and the flow of air between the lung and the environment requires some knowledge of several fundamental physical laws. Furthermore, an understanding of these forces is necessary to appreciate Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. several pathophysiological events, such as the collapse of a lung due to an air leak into the chest cavity. We begin with an overview of these physical processes and the steps involved in respiration (Figure 13.6) before examining each step in detail. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Figure 13.6 The steps of respiration. Ventilation Ventilation is defined as the exchange of air between the atmosphere and alveoli. Like blood, air moves by bulk flow from a region of high pressure to one of low pressure. Bulk flow can be described by the equation Δ (13-1) Flow (F) is proportional to the pressure difference (ΔP) between two points and inversely proportional to the resistance (R). (Notice that this equation is the same one used to describe the movement of blood through blood vessels, described in Chapter 12.) For airflow into or out of the lungs, the relevant pressures are the gas pressure in the alveoli—the alveolar pressure (Palv)—and the gas pressure at the nose and mouth, normally atmospheric Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. pressure (Patm), which is the pressure of the air surrounding the body: (13-2) Page 451 A very important point must be made here: All pressures in the respiratory system, as in the cardiovascular system, are given relative to atmospheric pressure, which is 760 mmHg at Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  sea level but which decreases in proportion to an increase in altitude. For example, the alveolar pressure between breaths is said to be 0 mmHg, which means that it is the same as atmospheric pressure at any given altitude. From equation 13–2, when there is no airflow, F = 0; therefore, Palv − Patm = 0, and Palv = Patm. That is, when there is no airflow and the airway is open to the atmosphere, the pressure in the alveoli is equal to the pressure in the atmosphere. During ventilation, air moves into and out of the lungs because the alveolar pressure is alternately less than and greater than atmospheric pressure (Figure 13.7). In accordance with equation 13–2 describing airflow, a negative value reflects an inward-directed pressure gradient and a positive value indicates an outward-directed gradient. Therefore, when Palv is less than Patm, Palv − Patm is negative and airflow is inward (inspiration). When Palv is greater than Patm, Palv − Patm is positive and airflow is outward (expiration). These alveolar pressure changes are caused, as we will see, by changes in the dimensions of the chest wall and lungs. Figure 13.7 Relationships required for ventilation. When the alveolar pressure (Palv) is less than atmospheric pressure (Patm), air enters the lungs. Flow (F) is directly proportional to the pressure difference (Palv − Patm) and inversely proportional to airway resistance (R). Black lines show a lung’s position at beginning of inspiration or expiration, and blue lines show position at end of inspiration or expiration. Boyle’s Law To understand how a change in lung dimensions causes a change in alveolar pressure, it is Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. important to learn one more basic physical principle described by Boyle’s law, which is represented by the equation P1V1 = P2V2 (Figure 13.8). At constant temperature, the relationship between the pressure (P) exerted by a fixed number of gas molecules and the volume (V) of their container is as follows: An increase in the volume of the container decreases the pressure of the gas, whereas a decrease in the container volume increases the pressure. In other words, in a closed system, the pressure of a gas and the volume of its container are inversely proportional. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Figure 13.8 Boyle’s law: The pressure exerted by a constant number of gas molecules (at a constant temperature) is inversely proportional to the volume of the container. As the container is compressed, the pressure in the container increases. When the container is decompressed, the pressure inside decreases. It is essential to recognize the correct sequence of events that determine the inspiration and then expiration of a breath. During inspiration and expiration, the volume of the “container”—the lungs—is made to change, and these changes then cause, by Boyle’s law, the alveolar pressure changes that drive airflow into or out of the lungs. Our descriptions of ventilation must focus, therefore, on how the changes in lung dimensions are brought about. Transmural Pressures There are no muscles attached to the lung surface to pull the lungs open or push them shut. Rather, the lungs are passive elastic structures—like balloons—and their volume, therefore, depends on other factors. The first of these is the difference in pressure between the inside and outside of the lung, termed the transpulmonary pressure (Ptp). The second is how stretchable the lungs are, which determines how much they expand for a given change in Ptp. The rest of this section and the next three sections focus on transpulmonary pressure; stretchability will be discussed later in the section on lung compliance. The pressure inside the lungs is the air pressure inside the alveoli (Palv), and the pressure outside the lungs is the pressure of the intrapleural fluid surrounding the lungs (Pip). Thus, Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. (13-3) Compare this equation to equation 13–2 (the equation that describes airflow into or out of the lungs), as it will be essential to distinguish these equations from each other (Figure 13.9). Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Figure 13.9 Pressure differences involved in ventilation. Transpulmonary pressure (Ptp = Palv − Pip) is a determinant of lung size. Intrapleural pressure (Pip) at rest is a balance between the tendency of the lung to collapse and the tendency of the chest wall to expand. Pcw represents the transmural pressure across the chest wall (Pip − Patm). Palv − Patm is the driving pressure gradient for airflow into and out of the lungs. (The volume of intrapleural fluid is greatly exaggerated for visual clarity.) Page 452 Transpulmonary pressure is the transmural pressure that governs the static properties of the lungs. Transmural means “across a wall” and, by convention, is represented by the pressure in the inside of the structure (Pin) minus the pressure outside the structure (Pout). Inflation of a balloonlike structure like the lungs requires an increase in the transmural pressure such that Pin increases relative to Pout. Table 13.3 and Figure 13.9 show the major transmural pressures of the respiratory system. The transmural pressure acting on the lungs (Ptp) is Palv − Pip and, on the chest wall, (Pcw) is Pip − Patm. The muscles of the chest wall contract and cause the chest wall to expand during inspiration; simultaneously, the diaphragm contracts downward, further enlarging the thoracic cavity. As the volume of the thoracic cavity expands, Pip decreases. Ptp becomes more positive as a result and the lungs expand. As this occurs, Palv becomes more negative compared to Patm (due to Boyle’s law), and air flows inward (inspiration, equation 13–2). Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. Therefore, the transmural pressure across the lungs (Ptp) is increased to fill them with air by actively decreasing the pressure surrounding the lungs (Pip) relative to the pressure inside the lungs (Palv). When the respiratory muscles relax, elastic recoil of the lungs drives passive expiration back to the starting point. TABLE 13.3 Two Important Transmural Pressures of the Respiratory System Pin − Transmural Value at Pressure Pout* Rest Explanatory Notes Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Transpulmonary Palv − 0 − [−4] = Pressure difference holding lungs open (opposes inward (Ptp) Pip 4 mmHg elastic recoil of the lung) Chest wall Pip − −4 − 0 = Pressure difference holding chest wall in (opposes (Pcw) Patm −4 mmHg outward elastic recoil of the chest wall) *Pin is pressure inside the structure, and Pout is pressure surrounding the structure. How Is a Stable Balance of Transmural Pressures Achieved Between Breaths? Figure 13.10 illustrates the transmural pressures of the respiratory system at rest—that is, at the end of an unforced expiration when the respiratory muscles are relaxed and there is no airflow. By definition, if there is no airflow and the airways are open to the atmosphere, Palv must equal Patm (see equation 13–2). Because the lungs always have air in them, the transmural pressure of the lungs (Ptp) must always be positive; therefore, Palv > Pip. At rest, when there is no airflow and Palv = 0, Pip must be negative, providing the force that keeps the lungs open and the chest wall in. Figure 13.10 Alveolar (Palv), intrapleural (Pip), transpulmonary (Ptp), and trans-chest-wall (Pcw) pressures (mmHg) at the end of an unforced expiration—that is, between breaths when there is no Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. airflow. The transpulmonary pressure (Palv − Pip) exactly opposes the elastic recoil of the lung, and the lung volume remains stable. Similarly, trans-chest-wall pressure (Pip − Patm) is balanced by the outward elastic recoil of the chest wall. Notice that the transmural pressure is the pressure inside the wall minus the pressure outside the wall. (The volume of intrapleural fluid is greatly exaggerated for clarity.) What are the forces that cause Pip to be negative? The first, the elastic recoil of the lungs, is defined as the tendency of an elastic structure to oppose stretching or distortion. Even at rest, the lungs contain air, and their natural tendency is to collapse because of elastic recoil. The lungs are held open by the positive Ptp, which, at rest, exactly opposes elastic recoil. Second, the chest wall also has elastic recoil, and, at rest, its natural tendency is to expand. At Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  rest, these opposing transmural pressures balance each other out. Page 453 As the lungs tend to collapse and the thoracic wall tends to expand, they move ever so slightly away from each other. This causes an infinitesimal enlargement of the fluid-filled intrapleural space between them. But fluid cannot expand the way air can, so even this tiny enlargement of the intrapleural space—so small that the pleural surfaces still remain in contact with each other—decreases the intrapleural pressure to below atmospheric pressure. In this way, the elastic recoil of both the lungs and chest wall creates the subatmospheric intrapleural pressure that keeps them from moving apart more than a very tiny amount. Again, imagine trying to pull apart two glass slides that have a drop of water between them. The fluid pressure generated between the slides will be lower than atmospheric pressure. The importance of the transpulmonary pressure in achieving this stable balance can be seen when, during surgery or trauma, the chest wall is pierced without damaging the lung. Atmospheric air enters the intrapleural space through the wound, a phenomenon called pneumothorax, and the intrapleural pressure increases from −4 mmHg to 0 mmHg—that is, Pip increases from 4 mmHg lower than Patm to a Pip value equal to Patm. The transpulmonary pressure acting to hold the lung open is eliminated, and the lung collapses (Figure 13.11). Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. Figure 13.11 Pneumothorax. The lung collapses as air enters from the pleural cavity either from inside the lung or from the atmosphere through the thoracic wall. The combination of lung elastic recoil and surface tension causes collapse of the lung when pleural and airway pressures equalize. DIG DEEPER How can a collapsed lung be re-expanded in a patient with a pneumothorax? (Hint: What changes in Pip and Ptp would be needed to re-expand the lung?) Answer found in Appendix A. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  At the same time, the chest wall moves outward because its elastic recoil is also no longer opposed. Also notice in Figure 13.11 that a pneumothorax can result when a hole is made in the lung such that a significant amount of air leaks from inside the lung to the pleural space. This can occur, for example, when high airway pressure is applied during artificial ventilation of a premature infant whose lung surface tension is high and whose lungs are fragile. The thoracic cavity is divided into right and left sides by the mediastinum—the central part of the thorax containing the heart, trachea, esophagus, and other structures—so a pneumothorax is usually unilateral. Inspiration Figure 13.12 and Figure 13.13 summarize the events that occur during normal inspiration at rest. Inspiration is initiated by the neurally induced contraction of the diaphragm and the external intercostal muscles located between the ribs (Figure 13.14). The diaphragm is the most important inspiratory muscle that acts during normal quiet breathing. When activation of the motor neurons within the phrenic nerves innervating the diaphragm causes it to contract, its dome moves downward into the abdomen, enlarging the thorax (see Figure 13.14). Simultaneously, activation of the motor neurons in the intercostal nerves to the inspiratory external intercostal muscles causes them to contract, leading to an upward and outward movement of the ribs and a further increase in thoracic size. Also notice in Figure 13.14 that there are several other sets of muscles that participate in the expansion of the thoracic cavity, which become important during a maximal inspiration. Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. Figure 13.12 Sequence of events during inspiration. Figure 13.13 illustrates these events quantitatively. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Figure 13.13 Summary of alveolar (Palv), intrapleural (Pip), and transpulmonary (Ptp) pressure changes and airflow during a typical respiratory cycle. At the end of expiration 1 , Palv is equal to Patm and there is no airflow. At mid-inspiration 2 , the chest wall is expanding, lowering Pip and making Ptp more positive. This expands the lung, making Palv negative, and results in an inward airflow. At end of inspiration 3 , the chest wall is no longer expanding but has yet to start passive recoil. Because lung size is not changing and the airway is open to the atmosphere, Palv is equal to Patm and there is no airflow. As the respiratory muscles relax, the lungs and chest wall start to passively collapse due to elastic recoil. At mid-expiration 4 , the lung is collapsing, thus compressing alveolar gas. As a result, Palv is positive relative to Patm and airflow is outward. The cycle starts over again at the end of expiration. Notice that throughout a typical respiratory cycle with a normal tidal volume, Pip is negative relative to Patm. In the graph on the left, the difference between Palv and Pip (Palv − Pip) at any point along the curves is equivalent to Ptp. For clarity, the chest-wall elastic recoil (as in Figure 13.10) is not shown. DIG DEEPER How do the changes in Ptp between each step ( 1 – 4 ) explain whether the volume of the lung is increasing or decreasing? Answer found in Appendix A. Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. Figure 13.14 Muscles of respiration during inspiration and expiration. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Page 454 The crucial point is that contraction of the inspiratory muscles, by actively increasing the size of the thorax, upsets the stability set up by purely elastic forces between breaths. As the thorax enlarges, the thoracic wall moves ever so slightly farther away from the lung surface. The intrapleural fluid pressure therefore becomes even more subatmospheric than it was between breaths. This decrease in intrapleural pressure increases the transpulmonary pressure. Therefore, the force acting to expand the lungs—the transpulmonary pressure—is now greater than the elastic recoil exerted by the lungs at this moment, and so the lungs expand further. Note in Figure 13.13 that, by the end of inspiration, equilibrium across the lungs is once again established because the more inflated lungs exert a greater elastic recoil, which equals the increased transpulmonary pressure. In other words, lung volume is stable whenever transpulmonary pressure is balanced by the elastic recoil of the lungs (that is, at the end of both inspiration and expiration when there is no airflow). Therefore, when contraction of the inspiratory muscles actively increases the thoracic dimensions, the lungs are passively forced to enlarge. The enlargement of the lungs causes an increase in the sizes of the alveoli throughout the lungs. By Boyle’s law, the pressure within the alveoli decreases to less than atmospheric (see Figure 13.13). This produces the difference in pressure (Palv < Patm) that causes a bulk flow of air from the atmosphere through the airways into the alveoli. By the end of the inspiration, the pressure in the alveoli again equals atmospheric pressure because of this additional air, and airflow ceases. Page 455 Expiration Figure 13.13 and Figure 13.15 summarize the sequence of events that occur during expiration. At the end of inspiration, the motor neurons to the diaphragm and external intercostal muscles decrease their firing and so these muscles relax. The diaphragm and chest Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. wall are no longer actively pulled outward by the muscle contractions, and so they start to recoil inward to their original smaller dimensions that existed between breaths. This immediately makes the intrapleural pressure less subatmospheric, thereby decreasing the transpulmonary pressure. Therefore, the transpulmonary pressure acting to expand the lungs is now smaller than the elastic recoil exerted by the more expanded lungs and thus the lungs passively recoil to their original dimension. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Figure 13.15 Sequence of events during expiration. Figure 13.13 illustrates these events quantitatively. As the lungs become smaller, air in the alveoli becomes temporarily compressed so that, by Boyle’s law, alveolar pressure exceeds atmospheric pressure (see Figure 13.13). Therefore, air flows from the alveoli through the airways out into the atmosphere. Expiration at rest is passive, depending only upon the relaxation of the inspiratory muscles and the elastic recoil of the stretched lungs. Under certain conditions, such as during exercise, expiration of larger volumes is achieved by contraction of a different set of intercostal muscles and the abdominal muscles, which actively decrease thoracic dimensions (see Figure 13.14). The internal intercostal muscles insert on the ribs in such a way that their contraction pulls the chest wall downward and inward, thereby decreasing thoracic volume. Contraction of the abdominal muscles increases intra-abdominal pressure and forces the relaxed diaphragm up into the thorax. Study and Review 13.2 Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. Bulk flow (F) of air: between the atmosphere and alveoli F = (Palv − Patm)/R where Palv = alveolar pressure, Patm = atmospheric pressure, and R = airway resistance Boyle’s law: P1V1= P2V2 If the volume of a container in state “1” increases, the pressure must decrease leading to state “2” where volume is greater, but the pressure is lower. explains how expanding the lungs lowers the pressure inside the lungs, causing air to move in from the atmosphere Transpulmonary pressure (Ptp) = Palv − Pip Transmural pressure of the lung represents the pressure inside the alveolus (Palv) minus pressure surrounding the lung (intrapleural pressure [Pip]). (Transmural means “across a wall.”) Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  pressure that determines volume inside lung (If Ptp is positive [> 0], there is air in the lung.) Pneumothorax: Air enters the pleural cavity (e.g., through a hole in chest wall) such that Pip = Patm; therefore, Ptp = 0 and lungs collapse because there is no positive transmural pressure holding them open. between breaths: at the end of an unforced expiration just before start of inspiration (called the functional residual capacity [FRC], described in the next section) Patm = Palv, so no air is flowing (no pressure gradient between atmosphere and alveoli). Dimensions of the lungs and thoracic cage are stable (because of opposing elastic forces). Elastic recoil: lung is stretched and attempting to recoil (collapse) chest wall: compressed and attempting to move outward (expand) Subatmospheric intrapleural pressure: “negative” (compared to Patm) due to opposing forces—lungs tend to collapse, and chest well tends to expand (keeps lungs from collapsing) Inspiration: air moving from atmosphere into lungs Contractions of the diaphragm (driven by phrenic nerves) and the inspiratory external intercostal muscles lead to an increase in the volume of the thoracic cage. intrapleural pressure becomes more subatmospheric → transpulmonary pressure increases → lungs expand lung expansion → decreases alveolar pressure (Palv < Patm) via Boyle’s law → air flows into lung Expiration: air moving from lungs to atmosphere Inspiratory muscles cease contracting. Elastic recoil of the lungs returns lung volume to the FRC. It compresses the alveolar air and increases Palv (so Palv > Patm) via Boyle’s law, which forces air out of lungs. forced expirations: The contraction of expiratory intercostal muscles and abdominal muscles causes the chest dimensions to decrease more rapidly, which increases Palv even more and makes the expiration more rapid. Review Question: Between breaths at the end of an unforced expiration (at FRC), in what directions do the lungs and chest wall tend to move? Starting from that state, how is air moved into and out of the lungs? (Answer found in Appendix A.) Page 456 Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. 13.3 Lung Mechanics Lung mechanics characterize the physical interactions of the lungs, diaphragm, and chest wall during breathing and breath holding. As you will see, it includes three major physiological functions: First is the ability to add air to and remove air from the inside of the lungs (compliance). Second, lung mechanics describe the mechanisms for overcoming the surface tension that exists between the air and the extracellular fluid coating the alveoli. Finally, lung mechanics explain the different lung volumes that are used to clinically assess static and dynamic pulmonary function. Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Lung Compliance To repeat, the degree of lung expansion at any instant is proportional to the transpulmonary pressure, Palv − Pip. But just how much any given change in transpulmonary pressure expands the lungs depends upon the stretchability, or compliance, of the lungs. Lung compliance (CL ) is defined as the magnitude of the change in lung volume (ΔVL) produced by a given change in the transpulmonary pressure: Δ Δ (13-4) This equation indicates that the greater the lung compliance, the easier it is to expand the lungs at any given change in transpulmonary pressure (Figure 13.16). Compliance can be considered the inverse of stiffness. A low lung compliance means that a greater-than-normal transpulmonary pressure must be developed across the lung to produce a given amount of lung expansion. In other words, when lung compliance is abnormally low (increased stiffness), intrapleural pressure must be made more subatmospheric than usual during inspiration to achieve lung expansion. This requires more vigorous contractions of the diaphragm and inspiratory intercostal muscles. The less compliant the lung, the more energy is required to produce a given amount of expansion. Persons with low lung compliance due to disease tend to breathe shallowly and at a higher frequency to inspire an adequate volume of air. This reduces the work of breathing. Copyright © 2022. McGraw-Hill US Higher Ed ISE. All rights reserved. Figure 13.16 A graphic representation of lung compliance. Changes in lung volume and transpulmonary pressure are measured as a subject takes progressively larger breaths. When compliance is lower than normal (the lung is stiffer), there is a lesser increase in lung volume for any given increase in transpulmonary pressure. When compliance is increased, as in emphysema, small decreases in Ptp allow the lung to collapse. DIG DEEPER Widmaier, Eric, et al. Vander's Human Physiology, McGraw-Hill US Higher Ed ISE, 2022. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/twc-ebooks/detail.action?docID=6861910. Created from twc-ebooks on 2024-10-03 14:34:40.  Premature infants with inadequate surfactant have decreased lung compliance (respiratory distress syndrome of the newborn). If surfactant is not available to administer for therapy, what would you suggest could be done to inflate the lung? Answer found in Appendix A. Determinants of Lung Compliance There are two major determinants of lung compliance. One is the stretchability of the lung tissues, particularly their elastic connective tissues. Therefore, a thickening of the lung tissues decreases lung compliance. However, an equally if not more important determinant of lung compliance is the surface tension at the air–water interfaces within the alveoli. The inner surface of the alveolar cells is moist, so the alveoli can be pictured as air-filled sacs lined with a thin layer of liquid. At an air–water interface, the attractive forces between the water molecules, known as surface tension, make the water lining like a stretched balloon that constantly tends to shrink and resists further stretching. Therefore, expansion of the lung requires energy not only to stretch the connective tis