ʻUmia ka hanu.

Hold the breath.

Be patient. Don’t give up too easily.

ʻŌlelo Noʻeau, compiled by Mary Kawena Pukui, #2875

Introduction

Figure 21.1: Free Diving in the Ocean with a hawksbill turtle

Why do we breathe? If you have ever choked on food, had the wind knocked out of you, or had dyspnea (shortness of breath) while visiting a mountainous area, you have undoubtedly experienced the fear of inability to take a breath. Yet, breathing is essential for life — we can go days without eating or drinking, but we cannot go more than a few minutes without breathing. We breathe to ensure that we have an adequate supply of oxygen to fuel cellular respiration and ensure the proper functioning of our tissues and organs. In this chapter, we delve into the anatomy and physiology of the respiratory system.

Figure 21.2: Haleakalā on Maui. Dyspnea can happen at a high altitude.  Haleakalā, Maui is 10,000 feet above sea level

21.1 Functions of the respiratory system

​​The major organs of the respiratory system have a broad range of functions:

1. Provide oxygen to body tissues for cellular respiration
2. Remove the waste product carbon dioxide
3. Collaborate with the cardiovascular system to transport oxygen and carbon dioxide
4. Maintain acid-base balance
5. Support olfactory processes and speech

The respiratory system’s primary function is to supply the body with oxygen for cellular respiration and to dispose of carbon dioxide. Every cell in the body needs to run the oxidative stages of cellular respiration which produces energy in the form of adenosine triphosphate (ATP). You may be surprised to learn that although oxygen is a critical need for cells, the accumulation of carbon dioxide primarily drives the need to breathe. In the respiratory system, oxygen is inhaled and delivered to the cells while carbon dioxide is exhaled as a waste product. The respiratory system also involves muscles to move air into and out of the lungs, passageways through which air moves, and microscopic gas exchange surfaces covered by capillaries. To complete the functions of the respiratory system, at least four processes must happen. Collectively, these processes are termed respiration.

Processes of respiration

Steps involved in respiration:

• Pulmonary ventilation
• External respiration
• Transport of respiratory gasses
• Internal respiration

Inspiration and Expiration Inspiration and expiration occur due to the expansion and contraction of the thoracic cavity, respectively. Pulmonary Ventilation – the act of breathing.	External Respiration In external respiration, oxygen diffuses across the respiratory membrane from the alveolus to the capillary, whereas carbon dioxide diffuses out of the capillary into the alveolus.
Carbon Dioxide Transport Carbon dioxide is transported by three different methods: (a) in erythrocytes; (b) after forming carbonic acid (H2CO3 ), which is dissolved in plasma; (c) and in plasma.	Internal Respiration Oxygen diffuses out of the capillary and into cells, whereas carbon dioxide diffuses out of cells and into the capillary.

Figure 21.3: The Four Processes of Respiration

21.2 Divisions of the respiratory system

The respiratory system includes the nose, nasal cavity, paranasal sinuses, the pharynx, the trachea, the bronchi and the smaller bronchi branches, and the lungs (including the alveoli) [Figure 21.4].

Figure 21.4: Major Respiratory Structures The major respiratory structures span the nasal cavity to the diaphragm. From OpenStax 

Structural classification of the respiratory system separates the organs into groups based on the relative location and consists of the upper respiratory system and the lower respiratory system. The organs of the upper respiratory system include the nose, nasal cavity, and pharynx, which are located in either head or neck. The organs of the lower respiratory system include the larynx, trachea, bronchioles, and lungs.

When categorizing the respiratory system functionally, we organize the respiratory organs based on their functions. Thus, the organs of the respiratory system can also be classified into a conducting zone or a respiratory zone. The conducting zone of the respiratory system includes the organs and structures not directly involved in the gas exchange: the nose, nasal cavity, pharynx, trachea, bronchi, and terminal bronchioles [Figure]. ​​The major functions of the conducting zone are to provide a route for incoming and outgoing air, remove debris and pathogens from the incoming air, and warm and humidify the incoming air. The lining of the conducting zone is composed mostly of pseudostratified ciliated columnar epithelium with goblet cells.

Figure 21.5: Conducting Zone Structures of the conducting zone include the nasal cavity, pharynx, trachea, bronchi, and terminal bronchioles. Air enters the respiratory system through the nasal cavity and pharynx, and then passes through the trachea and into the bronchi, which bring air into the lungs. (credit: modification of work by NCI)

The respiratory zone consists of the organs where gas exchange occurs. It begins where the terminal bronchioles join a respiratory bronchiole, the smallest type of bronchiole, and continues into the alveolar ducts, alveoli, and all the microscopic structures within the lungs [Figure 21.6].

Respiratory Zone

Structures of the Respiratory Zone (a) The alveolus is responsible for gas exchange. (b) A micrograph shows the alveolar structures within lung tissue. LM × 178. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Figure 21.6: Respiratory Zone Respiratory Zone Bronchioles lead to alveolar sacs in the respiratory zone, where gas exchange occurs. From OpenStax

Pathway of air through the respiratory system

Air must travel through the organs of the upper and lower respiratory tracts to reach the lungs for gas exchange to occur. Air enters the respiratory system through the nose (and sometimes the mouth) and travels a continuous pathway to end in the alveoli (where gas exchange occurs) [Figure 21.7].

Figure A shows the location of the lungs and airways in the body. Figure B is a detailed view of lung structures such as the bronchioles, neuroendocrine cells, alveoli, capillary network, surfactant, and interstitial space.

Gaseous exchange in the lung.

Figure 21.7 Path of Oxygen through the Respiratory System: Pulmonary ventilation provides air to the alveoli for this gas exchange process. At the respiratory membrane, where the alveolar and capillary walls meet, gases move across the membranes, with oxygen entering the bloodstream and carbon dioxide exiting. It is through this mechanism that blood is oxygenated and carbon dioxide, the waste product of cellular respiration, is removed from the body.

21.3 Gross and microscopic anatomy of the respiratory tract and related organs

The Upper Respiratory System

In the upper respiratory system, the air is conducted through the nose, nasal cavity, and pharynx on its way to the lungs. In this section, we will discuss those structures, as well as the structures in and near them to get a better understanding of the respiratory system.

External Nose

The main entrance and exit for the respiratory system are through the nose. In general, humans prefer nasal breathing, as the structure of the nose aids in the effective and efficient filtering and humidifying of air. Therefore, when discussing the nose, it is helpful to divide it into two major sections: the external nose and the nasal cavity or internal nose.

The external nose consists of surface and skeletal structures that result in the outward appearance and contribute to its numerous functions. The skeletal framework of the external nose includes the root and bridge of the nose which consists of the nasal and frontal bones. The protruding portion of the nose is composed of cartilage. As a result, when looking at a skull, it appears that the nose is missing because, unlike bone, cartilage decomposes upon death. The nasal bone is one of a pair of bones that lies under the root and bridge of the nose. The nasal bone articulates superiorly with the frontal bone and laterally with the maxillary bones. Septal cartilage is flexible hyaline cartilage connected to the nasal bone, forming the dorsum nasi. The alar cartilage consists of the apex of the nose; it surrounds the naris.

Figure 21.8 Nose This illustration shows features of the external nose (top) and skeletal features of the nose (bottom).

Nasal Cavity

​​Air, and oxygen, enter the body through the external nares (see Figure XX above) and then travel into the nasal cavity, which is separated into left and right sections by the nasal septum. The nasal septum is formed anteriorly by a portion of the septal cartilage (the flexible portion you can touch with your fingers) and posteriorly by the perpendicular plate of the ethmoid bone (a cranial bone located just posterior to the nasal bones) and the thin vomer bones (whose name refers to its plow shape).

Figure 21.9: Upper Airway.

Each lateral wall of the nasal cavity has three bony projections, called the superior, middle, and inferior nasal conchae. The inferior conchae are separate bones, whereas the superior and middle conchae are portions of the ethmoid bone. Due to the many twists and turns of these structures, the conchae serve to increase the surface area of the nasal cavity and disrupt the flow of air as it enters the nose, causing air to bounce along the epithelium, where it is filtered, humidified, and warmed. The conchae and meatuses also conserve water and prevent dehydration of the nasal epithelium by trapping water during exhalation. This is an important function, especially for individuals that reside in dry and cold climates. Finally, it is the shape of our nasal cavity that provides the uniqueness of our voice, as the sound resonates in the structures, creating an individual voice for each person.

The floor of the nasal cavity is composed of the palate. The hard palate at the anterior region of the nasal cavity is composed of bone. The soft palate at the posterior portion of the nasal cavity consists of muscle tissue. Air exits the nasal cavities via the internal nares and moves into the pharynx.

Paranasal Sinuses

Figure 21.10: Paranasal Sinuses

Several bones that help form the walls of the nasal cavity have air-containing spaces called the paranasal sinuses, which serve to warm and humidify incoming air. Sinuses are lined with mucosa. Each paranasal sinus is named for its associated bone: frontal sinus, maxillary sinus, sphenoidal sinus, and ethmoidal sinus. The sinuses produce mucus and lighten the weight of the skull.

Histologically, the conchae, meatuses, and paranasal sinuses are lined by pseudostratified ciliated columnar epithelium with olfactory mucosa and respiratory mucosa. Recall from Chapter 4 that mucosa is a type of epithelium that lines cavities in the body or covers the surface of organs. The two types of mucosa in the nasal cavity have different functions. The olfactory mucosa contains the smell receptors in the olfactory epithelium and are associated with the special sense of smell. Olfaction was discussed in detail in Chapter 4, so we will not go into details here. The respiratory mucosa lines the majority of the nasal cavity and consists of pseudostratified ciliated columnar epithelium that is scattered with goblet cells. Goblet cells are specialized columnar epithelial cells that produce mucus to trap and rid debris. The pseudostratified ciliated columnar epithelium is supported by lamina propria, a type of connective tissue that has an abundant plexus of superficial capillaries that are located just beneath the nasal epithelium and warm the air by convection.

Scattered throughout the lamina propria are also nasal glands that contain these goblet cells and serous cells (secrete antibacterial enzymes and defensins). Thus, the respiratory mucosa traps inspire dust and debris with mucus, but also act as the first line of defense, attacking bacteria and other invading microbes. Immune cells that patrol the connective tissue deep to the respiratory epithelium provide additional protection.

The constantly beating cilia on the cells of the nasal mucosa act as a type of escalator, gently and consistently sweeping mucus and debris towards the throat to be swallowed. Cold air slows the movement of the cilia, resulting in the accumulation of mucus that may in turn lead to a runny nose during cold weather.

Pseudostratified Ciliated Columnar Epithelium Respiratory epithelium is pseudostratified ciliated columnar epithelium. Seromucous glands provide lubricating mucus. LM × 680. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Pseudostratified columnar epithelium, animated image highlights the epithelial cells, goblet cells, then underlying connective tissue (see here for animated version)

Figure 21.11: Pseudostratified ciliated columnar epithelium

The Pharynx

The pharynx is a tube formed by skeletal muscle and lined by a mucous membrane that is continuous with that of the nasal cavities. The pharynx is divided into three major regions: the nasopharynx, the oropharynx, and the laryngopharynx [Figure 21.12].

Locations and Histology of the Tonsils (a) The pharyngeal tonsil is located on the roof of the posterior superior wall of the nasopharynx. The palatine tonsils lay on each side of the pharynx. (b) A micrograph shows the palatine tonsil tissue. LM × 40. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)

Divisions of the Pharynx The pharynx is divided into three regions: the nasopharynx, the oropharynx, and the laryngopharynx.

Figure 21.12: Pharynx and Tonsils

The nasopharynx is flanked by the conchae of the nasal cavity, and it serves only as an airway. Because it is superior to the soft palate, food normally does not pass through the nasopharynx. The uvula is a small bulbous, teardrop-shaped structure located at the apex of the soft palate. When you swallow, the soft palate and the uvula move superiorly, effectively closing off the nasopharynx and preventing ingested materials from entering the nasal cavity. At the top of the nasopharynx are the pharyngeal tonsils. A pharyngeal tonsil, also called an adenoid, is an aggregate of lymphoid reticular tissue similar to a lymph node that lies at the superior portion of the nasopharynx. The function of the pharyngeal tonsil is not well understood, but it contains a rich supply of lymphocytes and is covered, like the rest of the nasopharynx, with ciliated epithelium that traps and destroys invading pathogens that enter during inhalation. The pharyngeal tonsils are large in children, but interestingly, tend to regress with age and may even disappear. In addition, auditory (Eustachian) tubes that connect to each middle ear cavity open into the nasopharynx. This connection is why colds often lead to ear infections.

The oropharynx is a passageway for both air and food. The oropharynx is bordered superiorly by the nasopharynx and anteriorly by the oral cavity. As the nasopharynx becomes the oropharynx, the epithelium changes from pseudostratified ciliated columnar epithelium to stratified squamous epithelium. The oropharynx contains two distinct sets of tonsils, the palatine and lingual tonsils. A palatine tonsil is one of a pair of structures located laterally in the oropharynx. The lingual tonsil is located at the base of the tongue. Similar to the pharyngeal tonsil, the palatine and lingual tonsils are composed of lymphoid tissue and trap and destroy pathogens entering the body through the oral or nasal cavities.

The laryngopharynx is inferior to the oropharynx and posterior to the larynx. It continues the route for ingested material and air until its inferior end, where the digestive and respiratory systems diverge. The stratified squamous epithelium of the oropharynx is continuous with the laryngopharynx. Anteriorly, the laryngopharynx opens into the larynx, whereas posteriorly, it enters the esophagus — the esophagus directs food and fluids to the stomach while air enters the larynx.

The Lower Respiratory System

As air continues to travel through the conducting zone, it enters structures of the lower respiratory system including the larynx, trachea, bronchi, and bronchioles.

Larynx

The larynx is a cartilaginous structure inferior to the laryngopharynx that connects the pharynx to the trachea and helps regulate the volume of air that enters and leaves the lungs [Figure]. The structure of the larynx is formed by several pieces of cartilage. Three large cartilage pieces — the thyroid cartilage (anterior), epiglottis (superior), and cricoid cartilage (inferior) — form the major structure of the larynx. The thyroid cartilage, the main structure felt beneath the skin, is the largest piece of cartilage that makes up the larynx. The thyroid cartilage consists of the laryngeal prominence, or “Adam’s apple,” which tends to be more prominent in males. The thick cricoid cartilage forms a ring, with a wide posterior region and a thinner anterior region. Three smaller, paired cartilages — the arytenoids, corniculates, and cuneiforms — attach to the epiglottis and the vocal cords and muscles that help move the vocal cords to produce speech. All the cartilages associated with the larynx are hyaline cartilage, except for the epiglottis, which depends upon the flexibility of its elastic cartilage to cover the opening trachea. The act of swallowing causes the pharynx and larynx to lift upward, allowing the pharynx to expand and the epiglottis of the larynx to swing downward, closing the opening to the trachea. These movements produce a larger area for food to pass through while preventing food and beverages from entering the trachea.

Insert Figure 21.13 Larynx: The larynx extends from the laryngopharynx and the hyoid bone to the trachea. From Openstax Anatomy & Physiology

When in the “closed” position, the unattached end of the epiglottis rests on the glottis. The glottis is composed of the vestibular folds, the true vocal cords, and the space between these folds (Figure 21.14). A vestibular fold, or false vocal cord, is one of a pair of folded sections of the mucous membrane. A true vocal cord is one of the white, membranous folds attached by muscle to the thyroid and arytenoid cartilages of the larynx on their outer edges. The inner edges of the true vocal cords are free, allowing oscillation to produce sound. Sound production occurs when air moves past the vocal cords. The air causes the vocal cords to vibrate and the result is sound! Speech is made possible by the coordinated effort of the vocal cords and the contraction of facial muscles. The size of the membranous folds of the true vocal cords differs between individuals, and this size difference is what produces voices with different pitch ranges. Folds in males tend to be larger than those in females, which creates a deeper voice.

Figure 21.14: Vocal Cords The true vocal cords and vestibular folds of the larynx are viewed inferiorly from the laryngopharynx.

Continuous with the laryngopharynx, the superior portion of the larynx is lined with stratified squamous epithelium, transitioning into pseudostratified ciliated columnar epithelium that contains goblet cells. Similar to the nasal cavity and nasopharynx, this specialized epithelium produces mucus to trap debris and pathogens as they enter the trachea. Like an escalator moving upward, the cilia beat the mucus upward, away from the lungs, towards the laryngopharynx, where it can be swallowed down the esophagus.

Trachea

The trachea (also known as the windpipe) extends from the larynx toward the lungs. The trachea is formed by 16 to 20 stacked, C-shaped pieces of hyaline cartilage that are connected by dense connective tissue [Figure]. The tracheal wall consists of several layers which function in frictionless air movement. The mucosa layer is lined with pseudostratified ciliated columnar epithelium, which is continuous with the larynx, and thus has the same mucus-producing goblet cells that occur throughout most of the respiratory tract. The mucous membrane traps debris and pathogens and the cilia on these epithelial cells, as explained previously, move debris-laden mucus up toward the pharynx.

The trachealis muscle and elastic connective tissue, of the submucosa layer, together form the fibroelastic membrane, a flexible membrane that closes the posterior surface of the trachea, connecting the C-shaped cartilages. The rings, made of hyaline cartilage, form yet another layer, are open posteriorly, where they meet with the smooth muscle of the trachealis, and so the fibroelastic membrane allows the trachea to stretch and expand slightly during inhalation and exhalation and allows the esophagus to expand when filled with food, whereas the rings of cartilage provide structural support and prevent the trachea from collapsing. In addition, the trachealis muscle can be contracted to force air through the trachea during exhalation. The esophagus borders the trachea posteriorly. The outermost layer of the tracheal wall is the adventitia, and this layer surrounds the hyaline cartilage and is continuous with adventitia surrounding the esophagus.

Figure 21.16: Trachea (a) The tracheal tube is formed by stacked, C-shaped pieces of hyaline cartilage. (b) The layer visible in this cross-section of tracheal wall tissue between the hyaline cartilage and the lumen of the trachea is the mucosa, which is composed of pseudostratified ciliated columnar epithelium that contains goblet cells. LM × 1220. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

The Bronchi and Subdivisions

The trachea branches into the right and left primary bronchi at a structure called the carina [Figure 21.16]. These bronchi are also lined by pseudostratified ciliated columnar epithelium containing mucus-producing goblet cells. The carina is a raised structure that contains specialized nervous tissue that induces violent coughing if a foreign body, such as food, is present. Rings of cartilage, similar to those of the trachea, support the structure of the bronchi and prevent their collapse.

The primary bronchi extends into both lungs at the hilum, a concave region where blood vessels, lymphatic vessels, and nerves also enter the lungs. The bronchi continue to branch into a bronchial tree. A bronchial tree (or respiratory tree) is the collective term used for these multiple-branched bronchi, which become narrower and contain less cartilaginous rings as they branch. The walls of the bronchioles are lined with smooth muscle that can change the size of the tubing to increase or decrease airflow through the tube. The main function of the bronchial tree, like other conducting zone structures, is to provide a passageway for air to move into and out of each lung. Mucus-producing cells and cells with cilia are not commonly found in the bronchioles. If the functional anatomy of the previous organs failed to remove debris and pathogens, the last line of defense in the respiratory system are the macrophages in the alveoli. It is at the tips of the bronchial tree where the conduction zone structures merge into the respiratory zone.

Alveolar Ducts, Alveolar Sacs, Alveoli and the Respiratory Membrane

An alveolar duct is a tube composed of smooth muscle and connective tissue, which opens into a cluster of alveoli [Figure 21.17]. An alveolus is one of the many small, grape-like sacs that are attached to the alveolar ducts.

Respiratory Zone

Structures of the Respiratory Zone (a) The alveolus is responsible for gas exchange. (b) A micrograph shows the alveolar structures within lung tissue. LM × 178. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Figure 21.17: Respiratory Zone Structures Respiratory Zone Bronchioles lead to alveolar sacs in the respiratory zone, where gas exchange occurs. From OpenStax

An alveolar sac is a cluster of many individual alveoli that are responsible for gas exchange. An alveolus is approximately 200 μm (micrometer) in diameter with elastic walls that allow the alveolus to stretch during air intake, which greatly increases the surface area available for gas exchange. Alveoli are connected to their neighbors by alveolar pores, which help maintain equal air pressure throughout the alveoli and lungs.

The alveolar wall consists of three major cell types: type I alveolar cells, type II alveolar cells, and alveolar macrophages. A type I alveolar cell is a squamous epithelial cell of the alveoli, which constitutes up to 97 percent of the alveolar surface area. These cells are about 25 nm (nanometer) thick and are highly permeable to gasses. Squamous epithelial cells exist in areas of the body in which we want to facilitate the diffusion of small molecules and gasses. A type II alveolar cell is interspersed among the type I cells and secretes pulmonary surfactant, a substance composed of phospholipids and proteins that reduces the surface tension of the alveoli. Roaming around the alveolar wall is the alveolar macrophage, a phagocytic cell of the immune system that removes debris and pathogens that have reached the alveoli.

The simple squamous epithelium formed by type I alveolar cells is attached to a thin, elastic basement membrane. This epithelium is extremely thin and borders the endothelial membrane of capillaries. Taken together, the alveoli and capillary membranes form a respiratory membrane that is approximately 0.5 μm thick. The respiratory membrane allows gasses to cross by simple diffusion, allowing oxygen to be picked up by the blood for transport and CO2 to be released into the air of the alveoli.

Figure 21.18: Respiratory Membrane (Membrane respiratoire)

Lungs

A major organ of the respiratory system, each lung houses structures of both the conducting and respiratory zones. The lungs are a paired set of organs, located on either side of the heart, each in its own pleural cavity. The main function of the lungs is to perform the exchange of oxygen and carbon dioxide with air from the atmosphere. To this end, the lungs exchange respiratory gasses across a very large epithelial surface area — about 70 square meters — that is highly permeable to gasses.

The lungs are pyramid-shaped, paired organs that are connected to the trachea by the right and left bronchi; on the inferior surface, the lungs are bordered by the diaphragm. The diaphragm is a dome-shaped muscle located at the base of the lungs and thoracic cavity. The lungs are enclosed by the pleurae, which are attached to the mediastinum. The right lung is shorter and wider than the left lung, and the left lung occupies a smaller volume than the right. The cardiac notch is an indentation on the surface of the left lung, and it allows space for the heart, which is positioned on the left side of the body. The apex of the lung is the superior region, whereas the base is the opposite region near the diaphragm. The costal surface of the lung borders the ribs. The mediastinal surface faces the midline. The hilum, the region where the bronchi, pulmonary blood vessels, lymphatic vessels, and nerves pass through, is located in the middle of each lung

Thoracic Cavity	Pleura
Lungs, Chest Wall, and Diaphragm	Dorsal and Ventral Body Cavities, including thoracic cavity

Figure 21.20: Thoracic Cavity and Pleura: Anatomical relationships of organs in the thoracic cavity, with pleura labeled.

Each lung is composed of smaller units called lobes. Fissures separate these lobes from each other. The right lung has two fissures — the horizontal fissure and the oblique fissure — which consist of three lobes: the superior, middle, and inferior lobes [Refer to Lung Figure]. The left lung only has one fissure — the oblique fissure — and consists of two lobes: the superior and inferior lobes. A bronchopulmonary segment is a division of a lobe, and each lobe houses multiple bronchopulmonary segments. Each segment receives air from its tertiary bronchus and is supplied with blood by its artery. Some diseases of the lungs typically affect one or more bronchopulmonary segments, and in some cases, the diseased segments can be surgically removed with little influence on neighboring segments. A pulmonary lobule is a subdivision formed as the bronchi branch into bronchioles. Each lobule receives its own large bronchiole that has multiple branches. The interlobular septum, a wall composed of connective tissue, separates lobules from one another.

The Pleura

Each lung is enclosed within a cavity that is surrounded by the pleura. The pleura (plural = pleurae) is a serous membrane that surrounds the lung. The right and left pleurae, which enclose the right and left lungs, respectively, are separated by the mediastinum. The pleurae consist of two layers. The visceral pleura is the layer that is superficial to the lungs and extends into and lines the lung fissures. In contrast, the parietal pleura is the outer layer that connects to the thoracic wall, the mediastinum, and the diaphragm. The visceral and parietal pleurae connect at the hilum. In between the visceral and parietal layers is the pleural cavity, a space filled with fluid that aids in lung function.

The pleurae perform two major functions: They produce pleural fluid and create cavities that separate the major organs. Pleural fluid is secreted by mesothelial cells from both pleural layers and acts to lubricate their surfaces. This lubrication reduces friction between the two layers to prevent trauma during breathing and creates surface tension that helps maintain the position of the lungs against the thoracic wall. This adhesive characteristic of the pleural fluid causes the lungs to enlarge when the thoracic wall expands during ventilation, allowing the lungs to fill with air. The pleurae also create a division between major organs that prevents interference due to the movement of the organs, while preventing the spread of infection.

Blood Supply and Nervous Innervation of the Lungs

The blood supply of the lungs plays an important role in gas exchange and serves as a transport system for gasses throughout the body. In addition, innervation by both the parasympathetic and sympathetic nervous systems provides an important level of control through dilation and constriction of the airway.

The primary function of the lungs is to perform gas exchange, which requires blood from the pulmonary circulation [Figure 21.21]. This blood supply contains deoxygenated blood and travels to the lungs, where erythrocytes, also known as red blood cells, pick up oxygen to be transported to tissues throughout the body. The pulmonary artery is an artery that arises from the pulmonary trunk and carries deoxygenated, arterial blood to the alveoli. The pulmonary artery branches multiple times as it follows the bronchi, and each branch becomes progressively smaller in diameter. One arteriole and an accompanying venule supply and drain one pulmonary lobule. As they near the alveoli, the pulmonary arteries become the pulmonary capillary network. The pulmonary capillary network consists of tiny vessels with very thin walls that lack smooth muscle fibers. The capillaries branch and follow the bronchioles and structure of the alveoli. It is at this point that the capillary wall meets the alveolar wall, creating the respiratory membrane, with the capillaries forming a mesh-like network around the alveoli. Once gas exchange occurs and the blood is oxygenated, it drains from the alveoli through multiple pulmonary veins, which exit the lungs through the hilum to return to the heart.

The blood within the pulmonary circulation does not feed the lung tissue itself. The bronchioles and other lung tissue require their own blood supply. The bronchial circulation supplies blood to the tissues and airways of the lungs [Figure 21.21]. The bronchial arteries carry oxygenated blood to the lungs and the bronchial veins return the majority of the deoxygenated blood to the heart. A small portion of the deoxygenated blood in the bronchial veins is diverted from the systemic circulation to join the pulmonary circulation. This unique anatomical setup creates a physiological pulmonary shunt. This shunt is best illustrated via the change in partial pressure of respiratory gasses discussed later in this chapter.

Veins of the Thoracic and Abdominal Regions Veins of the thoracic and abdominal regions drain blood from the area above the diaphragm, returning it to the right atrium via the superior vena cava.	Cardiovascular Circulation The pulmonary circuit moves blood from the right side of the heart to the lungs and back to the heart. The systemic circuit moves blood from the left side of the heart to the head and body and returns it to the right side of the heart to repeat the cycle. The arrows indicate the direction of blood flow, and the colors show the relative levels of oxygen concentration.
Bronchial anatomy detail of alveoli and lung circulation A – Alveoli AS – Septum alveolare BR – Bronchus respiratorius BT – Bronchus terminalis D – Mucous gland DA – Ductus alveolaris M – Musculus N – Nervus PA – Branch of Arteria pulm. PV – Branch of Vena pulm.	Arteries of the Thoracic and Abdominal Regions The thoracic aorta gives rise to the arteries of the visceral and parietal branches.

Figure 21.21: Pulmonary and Bronchial Circulation

Dilation and constriction of the airway are achieved through nervous control by the parasympathetic and sympathetic nervous systems. The parasympathetic system causes bronchoconstriction, whereas the sympathetic nervous system stimulates bronchodilation. Reflexes such as coughing, and the ability of the lungs to regulate oxygen and carbon dioxide levels, also result from this autonomic nervous system control. Sensory nerve fibers arise from the vagus nerve, and from the second to fifth thoracic ganglia. The pulmonary plexus is a region on the lung root formed by the entrance of the nerves at the hilum. The nerves then follow the bronchi in the lungs and branch to innervate muscle fibers, glands, and blood vessels.

Effects of SNS and PNS Stimulation – Parasympathetic nervous system constricts bronchi, sympathetic nervous system dilates bronchi	Bronchodilators – image shows bronchoconstriction and bronchodilation
	Detailed illustration of the Vagus Nerve, including A.P.P, Anterior, and P.P.P, Posterior pulmonary plexuses

Figure 21.22: Bronchoconstriction, bronchodilation, vagus nerve, and nervous innervation

21.4 Processes of Respiration

Pulmonary ventilation

Pulmonary ventilation is the act of breathing or the movement of air into and out of the lungs. The primary mechanisms that drive pulmonary ventilation are atmospheric pressure, intra-alveolar pressure (the air pressure within the alveoli), and intrapleural pressure (the pressure within the pleural cavity).

Mechanisms of Breathing

The ability to have air enter the lungs during inspiration and leave the lungs during expiration is dependent on the difference in air pressure of the atmosphere and the air pressure within the lungs. Boyle’s Law describes the relationship between volume and pressure in a gas at a constant temperature. Boyle discovered that the pressure of a gas is inversely proportional to its volume:

• If the volume increases, the pressure decreases
• If the volume decreases, the pressure increases

Figure 21.23: Boyle’s Law: In a gas, pressure increases as volume decreases. OpenStax [link]

Pressure and volume are inversely related (P = k/V). Therefore, the pressure in the one-liter container (one-half the volume of the two-liter container) would be twice the pressure in the two-liter container. Boyle’s law is expressed by the following formula:

𝑃1𝑉1=𝑃2𝑉2

In this formula, P1 represents the initial pressure, and V1 represents the initial volume, whereas P2 and V2, respectively, represent the final pressure and volume. If the two- and one-liter containers were connected by a tube and the volume of one of the containers were changed, then the gasses would move from higher pressure (lower volume) to lower pressure (higher volume). The concept of how gasses move from higher pressure to lower pressure also describes how gas moves into and out of our body during pulmonary ventilation.

Atmospheric pressure is the amount of force exerted by gasses in the air surrounding any given surface, such as the body. Atmospheric pressure can be expressed in terms of the unit atmosphere (atm) or millimeters of mercury (mmHg). One atm is equal to 760mmHg, the atmospheric pressure at sea level. Typically, other pressure values are discussed for respiration in relation to atmospheric pressure. Therefore, negative pressure is a pressure lower than atmospheric pressure, and positive pressure is a pressure greater than atmospheric pressure. A pressure that is equal to the atmospheric pressure is expressed as zero. Intra-alveolar pressure (or intrapulmonary pressure) is the pressure of air within the alveoli. This pressure changes during the different phases of breathing. The intra-alveolar pressure always equals the atmospheric pressure.

Figure 21.24: Intrapulmonary and Intrapleural Pressure Relationships Intra-alveolar pressure changes during the different phases of the cycle. It equalizes at 760 mm Hg but does not remain at 760 mm Hg. [OpenStax [link] Figure 22.16 AA]

Intrapleural pressure is the air pressure within the pleural cavity between the visceral and parietal pleurae, and this pressure is less than atmospheric pressure, and thus considered a negative pressure. Intrapleural pressure also changes with the different phases of breathing. The majority of pulmonary ventilation is driven by the difference in atmospheric pressure and intrapleural pressure.

Manipulating the size and thus the pressures in the thoracic cavity drive pulmonary ventilation because air flows down a pressure gradient. The difference in pressures causes pulmonary ventilation because air flows from an area of higher pressure to an area of lower pressure. The respiratory cycle is one sequence of inspiration and expiration.

Figure 21.25: Inspiration and expiration [OpenStax [link] Figure 22.17 (AA)]

Two muscle groups are used during normal inspiration: The diaphragm and external intercostal muscles. Additional muscles can be used if a larger breath is required. When the dome-shaped diaphragm contracts, it flattens out and moves inferiorly toward the abdominal cavity. This creates a larger thoracic cavity and more space for the lungs. Contraction of the external intercostal muscles moves the ribs upward and outward, causing the rib cage to expand, increasing the volume of the thoracic cavity. The adhesive force of pleural fluid causes the lungs to stretch and expand with the expanding thoracic cavity. As the volume of the thoracic cavity increases, the pressure within the cavity (intra-alveolar pressure) decreases (Boyle’s Law). This creates a pressure lower than atmospheric pressure within the thoracic cavity. This pressure gradient drives air into the lungs (air moves from higher pressure to lower pressure). Thus, inspiration is considered an active process because muscles must actively engage in moving the thoracic cavity.

The process of normal expiration is passive, occurring not because of muscle contraction, but due to volume and pressure changes. Energy is not required to push air out of the lungs. Instead, the elasticity of the lung tissue causes it to recoil. As the diaphragm and intercostal muscles relax following inspiration, the thoracic cavity and lungs decrease in volume. As a result, the intrapulmonary pressure rises above the atmospheric pressure, creating a pressure gradient that causes air to leave the lungs.

There are different types of breathing that require a slightly different process to allow inspiration and expiration. Quiet breathing, also known as eupnea, is a mode of breathing that occurs at rest and does not require the cognitive thought process. During quiet breathing, the diaphragm and external intercostals must contract for inspiration to occur. In contrast, forced breathing, also known as hyperpnea, can occur during exercise or actions that require active manipulation of breathing, such as singing. During forced breathing, inspiration and expiration both occur due to muscle contractions and the contraction of the diaphragm and intercostals. During forced inspiration, muscles of the neck (scalene muscles) must contract and lift the thoracic wall. During forced expiration, muscles of the abdomen (obliques) must contract to force the abdominal organs upward against the diaphragm to help push more air out.

Other factors that affect pulmonary ventilation include surface tension of the alveolar fluid, airway resistance, and thoracic wall compliance. There is surface tension within the alveoli caused by water present in the lining of the alveoli. This surface tension tends to inhibit the expansion of the alveoli and make the lungs less compliant. However, pulmonary surfactant secreted by type II alveolar cells mixes with that water and helps reduce this surface tension. Without pulmonary surfactant, the alveoli would collapse during expiration. Resistance is a force that slows motion, in this case, the flow of gasses. The size of the airway is the primary factor affecting resistance. A small tubular diameter forces air through a smaller space, causing more collisions of air molecules with the walls of the airways. Thoracic wall compliance is the ability of the thoracic wall to stretch while under pressure. This can also affect the effort expended in the process of breathing. For inspiration to occur, the thoracic cavity must expand. Normal healthy lungs have high compliance and stretch easily. The expansion of the thoracic cavity directly influences the capacity of the lungs to expand. If the tissues of the thoracic wall are not very compliant, it will be difficult to expand the thorax to increase the size of the lungs. Low compliance is associated with some respiratory disorders.

Respiratory Volumes and Capacities

Respiratory Volume describes the various volumes of air moved by or associated with the lungs at a given point in the respiratory cycle. There are four major types of respiratory volumes:

• Tidal volume (TV) is the amount of air that enters and exits the lungs during quiet breathing

• Expiratory Reserve Volume (ERV) is the amount of air you can forcefully exhale after an average tidal volume expiration

• Inspiratory Reserve Volume (IRV) is the amount of air that can be forcibly inspired after a tidal inspiration

• Residual Volume (RV) is the air left in the lungs if you forcibly exhale as much air as possible. Residual volume can make breathing easier because air left in the lungs can prevent the alveoli from collapsing

Figure 21.26: Respiratory Volumes and Capacities [link] OpenStax Figure 22.18

Respiratory volume depends on various factors, and measuring different types of respiratory volumes can provide vital information about a person’s respiratory health.

Respiratory capacity is the combination of two or more selected volumes, which further describes the amount of air in the lungs at a given time.

• Total Lung Capacity (TLC) is the sum of all lung volumes (TV, ERV, IRV, and RV). This is the total air a person can hold in the lungs after a forceful inhalation.
• Vital Capacity (VC) is the amount of air a person can move into or out of the lungs. This is the sum of TV, ERV, and IRV.
• Inspiratory Capacity (IC) is the maximum amount of air that can be inhaled past a normal tidal expiration. This is the sum of the TC and IRV.
• Functional Residual Capacity (FRC) is the amount of air that remains in the lungs after a normal tidal expiration. This is the sum of the ERV and RV.

Spirometry is the most common type of test used to measure pulmonary function. A spirometer is used to measure lung volumes and capacities. Generally, lung volumes are larger in males, taller individuals, and younger adults.

Figure 21.27: Spirometers and people taking spirometry tests

Figure 21.28: Spirometer Values: Typical output from a spirometer of a normal person taking 4 tidal breaths, followed by maximal inspiration and expiration. Corresponding volumes and capacities are noted in the right-hand boxes

Respiratory Rate and Control of Ventilation

Breathing usually occurs without thought, although you can control it when swimming underwater, singing a song, or blowing bubbles. The respiratory rate is the total number of breaths, or respiratory cycles, per minute. Our pattern of inhaling and exhaling constantly repeats itself. At rest, we take an average of 12-16 breaths per minute. This process is more complex than it may seem, as control of ventilation is regulated by the nervous system. The control of ventilation is a complex interplay of multiple regions in the brain that signal the muscles used in pulmonary ventilation to contract. The result is typically a rhythmic, consistent ventilation rate that provides the body with sufficient amounts of oxygen, while adequately removing carbon dioxide. The respiratory center in the medulla oblongata in the central nervous system responds to changes in carbon dioxide concentration, oxygen concentration, and pH levels in the blood. In response to these factors, the dorsal respiratory group (DRG) and ventral respiratory center (VRG) in the medulla oblongata sets the rate and rhythm of normal breathing. The pneumotaxic center and apneustic centers in the pons help to regulate the rate and depth of breathing. Chemoreceptors in the aortic arch and the common carotid arteries respond to shifts in the concentration of CO2, H+, and O2 in the blood. CO2 levels are the primary stimulus for changes in respiratory rate.

Because the hypothalamus regulates body temperature, it can affect breathing rate — an increase in body temperature results in an increased breathing rate and a decrease in body temperature triggers a decreased breathing rate. Irritant receptors and stretch receptors in the lungs, located in the bronchioles, assert control over bronchiole diameter and lung compliance, resulting in decreased breathing rate and prevention of overinflation of the lungs (inflation reflex). Finally, we have voluntary control over our body’s activities and thus we may consciously choose to hold our breath (like when swimming underwater). Other factors such as pain and blood pressure can affect the respiratory rate. Respiratory rate can be an indicator of disease.

Table 21.1: Summary of Ventilation Regulation [link] openstax table 22.1

Internal and External Respiration

As mentioned previously, the purpose of the respiratory system is to perform gas exchange. Pulmonary ventilation provides air to the alveoli for this gas exchange process.

At the respiratory membrane (where the alveolar and capillary walls meet), oxygen diffuses into the bloodstream, and carbon dioxide diffuses out of the bloodstream. Through this mechanism, blood is oxygenated, and carbon dioxide, the waste product of cellular respiration, is removed from the body. This is known as External respiration and occurs at the level of the lungs. Internal respiration occurs at the level of the tissues and the gas exchange is exactly the opposite- oxygen diffuses out of the bloodstream into the tissues and carbon dioxide diffuses from the tissues into the blood. The rate and amount of gasses diffusing into and out of the blood is depending upon several factors that we will discuss in detail below.

Gas Laws and Air Composition

We previously discussed Boyle’s Law, but several other gas laws help describe the behavior of gases. Gas molecules exert a force on the surface on which they are in contact. This force is called pressure. The atmosphere consists of oxygen, nitrogen, carbon dioxide, and other gaseous molecules. This gaseous mixture exerts a pressure called atmospheric pressure. Partial pressure is the pressure of a single type of gas in a mixture of gasses. In the atmosphere, oxygen exerts a partial pressure and nitrogen exerts a different partial pressure independent of oxygen. Dalton’s Law states that the total pressure is the sum of all the partial pressures. Partial pressure is important for predicting the movement of gasses. Gasses tend to equalize their pressure in two regions that are connected. A gas will move from an area where its partial pressure is higher to an area where its partial pressure is lower. The greater the partial pressure difference between two areas, the faster the gas will move. Thus, Dalton’s Law and the principles behind it help us answer the question of how gasses move into and out of the blood.

Table 21.2: Partial Pressures of Atmospheric Gases

Figure 21.29: Partial and Total Pressures of a Gas Partial pressure is the force exerted by a gas. The sum of the partial pressures of all the gases in a mixture equals the total pressure.
OpenStax Table 22.21 and Figure 22.21

Solubility of Gasses in Liquids

Henry’s Law describes the behavior of gasses when they come into contact with liquid such as blood. Henry’s Law states that the concentration of gas in a liquid is directly proportional to the solubility and partial pressure of that gas. The greater the partial pressure of the gas, the greater number of gas molecules that will dissolve in the liquid. Therefore, higher partial pressure of oxygen in the blood means that there is more oxygen present in the blood. The concentration of the gas in a liquid is also dependent on the solubility of the gas in a liquid. For example, although nitrogen is present in the atmosphere, very little nitrogen dissolves in blood because the solubility of nitrogen in blood is very low.

The composition of the air in the atmosphere and the alveoli differs. Alveolar air contains a greater amount of carbon dioxide and less oxygen than atmospheric air. Both deep and forced breathing causes the alveolar air composition to change more rapidly during quiet breathing. As a result, the partial pressures of oxygen and carbon dioxide change, affecting the diffusion process that moves materials across the membrane. This will cause oxygen to enter and carbon dioxide to leave the blood more quickly.

Ventilation and Perfusion

There are two important aspects of gas exchange in the lungs: ventilation and perfusion. Ventilation is the movement of air into and out of the lungs and perfusion is the flow of blood in the pulmonary capillaries. For gas exchange to be efficient, the volumes in ventilation and perfusion should be compatible. However, factors such as blocked alveolar ducts or disease can cause ventilation and perfusion to be imbalanced. The partial pressure of oxygen in alveolar air is about 104 mm Hg, whereas the partial pressure of oxygenated blood in pulmonary veins is about 100 mm Hg.

When ventilation is sufficient, oxygen enters the alveoli at a high rate, and the partial pressure of oxygen in the alveoli remains high. In contrast, when ventilation is insufficient, the partial pressure of oxygen in the alveoli drops. Without the large difference in partial pressure between the alveoli and the blood, oxygen does not diffuse efficiently across the respiratory membrane. The body has mechanisms that counteract this problem. In cases when ventilation is not sufficient for an alveolus, the body redirects blood flow to alveoli that are receiving sufficient ventilation. This is achieved by constricting the pulmonary arterioles that serve the dysfunctional alveolus, which redirects blood to other alveoli that have sufficient ventilation. At the same time, the pulmonary arterioles that serve alveoli receive sufficient ventilation vasodilate, which brings in greater blood flow. Factors such as carbon dioxide, oxygen, and pH levels can all serve as stimuli for adjusting blood flow in the capillary networks associated with the alveoli.

Gas Exchange

Gas exchange occurs at two sites in the body (lungs and tissues). In the lungs, oxygen is picked up and carbon dioxide is released at the respiratory membrane. In the tissues, oxygen is released and carbon dioxide is picked up. External respiration is the exchange of gasses with the external environment and occurs in the alveoli of the lungs. Internal respiration is the exchange of gasses within the internal environment and occurs in the tissues. The actual exchange of gasses is due to simple diffusion driven by pressure gradients that allow them to diffuse. Energy is not required to move oxygen or carbon dioxide across membranes. Instead, these gasses follow pressure gradients that allow them to diffuse.

External Respiration

The pulmonary artery carries deoxygenated blood into the lungs from the heart, where it branches and eventually becomes the capillary network composed of pulmonary capillaries. These pulmonary capillaries create the respiratory membrane with the alveoli. As blood is pumped through this capillary network, gas exchange occurs. Although a small amount of oxygen can dissolve directly into the plasma from the alveoli, most of the oxygen is picked up by red blood cells and binds to a protein called hemoglobin. Carbon dioxide is released in the opposite direction of oxygen, from the blood to the alveoli. Some of the carbon dioxide is returned via hemoglobin, but it can also be dissolved in plasma or present in a converted form, which will be described later in the chapter.

Figure 21.30: Respiratory membrane (membrane respiratoire)

External Respiration occurs as a function of partial pressure differences in oxygen and carbon dioxide between the alveoli and the blood in the pulmonary capillaries. There is a drastic difference in the partial pressure of oxygen in the alveoli versus in the blood of the pulmonary capillaries. This large difference in partial pressure creates a strong pressure gradient that causes oxygen to rapidly cross the respiratory membrane from the alveoli into the blood.

The relative concentrations of oxygen and carbon dioxide that diffuse across the respiratory membrane are similar.

Figure 21.31: External Respiration OpenStax Figure 22.22 (AA)

Internal Respiration

Internal Respiration is a gas exchange that occurs at the level of body tissue. Similar to external respiration, internal respiration also occurs as simple diffusion due to a partial pressure gradient. However, the partial pressure gradients are the opposite of those present in the respiratory membrane. The partial pressure of oxygen in tissues is low because oxygen is continuously used for cellular respiration. In contrast, the partial pressure of oxygen in the blood is higher creating a pressure gradient that causes oxygen to dissociate from hemoglobin and diffuse out of the blood into the tissues.

During cellular respiration, carbon dioxide is continuously produced as a waste product. The partial pressure of carbon dioxide is lower in the blood than in the tissue, causing carbon dioxide to diffuse out of the tissue and enter the blood.

Figure 21.32: Internal Respiration OpenStax Figure 22.23 (AA)

Gas Transport

The major function of respiration is to provide oxygen to the cells for ATP production (cellular respiration) and eliminate carbon dioxide (a waste product) from the body. Here, we will discuss how oxygen and carbon dioxide are transported throughout the body and delivered to the appropriate sites for gas exchange.

Oxygen Transport in Blood

Oxygen is not very soluble in liquids. Therefore, the majority of oxygen transport relies on the red blood cell. Red blood cells contain a protein called hemoglobin that serves to bind oxygen and carry it throughout the body [Figure]. Heme is the portion of hemoglobin that contains iron, and it is heme that binds oxygen. Each hemoglobin molecule is capable of carrying up to four molecules of oxygen. Appreciate that a person has roughly 25 trillion red blood cells (depending on the amount of blood they have), and each of those red blood cells contains roughly 280 million hemoglobin molecules, and each of these hemoglobin molecules can bind as many as 4 O2 molecules. That is a tremendous amount of oxygen-carrying capacity!

Figure 21.33: Erythrocyte and Hemoglobin Hemoglobin consists of four subunits, each of which contains one molecule of iron. OpenStax Figure 22.25 (AA)

As oxygen diffuses across the respiratory membrane from the alveolus to the capillary, it also diffuses into the red blood cell and is picked up by hemoglobin.

The following reversible chemical reaction describes the production of the final product, oxyhemoglobin (Hb–O2), which is formed when oxygen binds to hemoglobin. Oxyhemoglobin is a bright, red-colored molecule that contributes to the bright red color of oxygenated blood.

Hb + O₂ ↔ Hb−O₂

Hemoglobin is composed of four subunits arranged in a ring-link fashion with an iron atom bound to the heme in the center of each subunit. The binding of the first oxygen molecule causes a conformational change in the hemoglobin that allows the second molecule of oxygen to bind more readily. As each molecule of oxygen is bound, it further facilitates the binding of the next molecule until four sites are occupied. Thus, the binding of oxygen to hemoglobin helps hemoglobin bind to more oxygen. When all four sites are occupied, the hemoglobin is said to be “saturated”. The opposite occurs as well, once one molecule of oxygen is “dropped off” at the tissues, the next oxygen molecule comes off (dissociates) more readily. When oxygen is unloaded from red blood cells in the tissues, the result is deoxyhemoglobin, which is a state in which few or no oxygen is bound to hemoglobin.

An oxygen-hemoglobin dissociation curve is a graph that describes the relationship of partial pressure to the binding of oxygen to heme and its subsequent dissociation from heme [Figure 21.34]. Remember that gasses travel from an area of higher partial pressure to an area of lower partial pressure. In addition, the affinity of an oxygen molecule for heme increases as more oxygen molecules are bound. Therefore, in the oxygen–hemoglobin saturation curve, as the partial pressure of oxygen increases, a proportionately greater number of oxygen molecules are bound by heme.

The mechanisms behind the oxygen-hemoglobin saturation/dissociation also serve as autonomic control mechanisms that regulate how much oxygen is delivered to different tissues throughout the body. This is important because some tissues have a higher metabolic rate than others. For example, muscle tissue is highly active and requires more oxygen to produce ATP compared to other tissues. As muscle tissue uses more oxygen, it lowers the partial pressure of oxygen in the tissue creating a large partial pressure gradient between the tissue and blood. This pressure gradient causes oxygen to diffuse into the tissue, therefore providing more oxygen to support ATP production.

Figure 21.34: Oxygen-Hemoglobin Dissociation and Effects of pH and Temperature These three graphs show (a) the relationship between the partial pressure of oxygen and hemoglobin saturation, (b) the effect of pH on the oxygen–hemoglobin dissociation curve, and (c) the effect of temperature on the oxygen–hemoglobin dissociation curve. OpenStax Figure 22.26 (AA)

Other factors that can affect the oxygen-hemoglobin saturation/dissociation curve are temperature and pH. Higher temperatures promote hemoglobin and oxygen to dissociate faster, whereas a lower temperature inhibits dissociation. The Bohr effect is a phenomenon that arises from the relationship between pH and oxygen’s affinity for hemoglobin: a lower, more acidic pH promotes oxygen dissociation from hemoglobin. In contrast, a higher, or more basic, pH inhibits oxygen dissociation from hemoglobin. The greater the amount of carbon dioxide in the blood, the more molecules that must be converted, which in turn generates hydrogen ions and thus lowers blood pH. Furthermore, blood pH may become more acidic when certain byproducts of cell metabolism, such as lactic acid, carbonic acid, and carbon dioxide, are released into the bloodstream.

Carbon Dioxide Transport in the Blood

Carbon dioxide is transported by three major mechanisms [Figure]. The first mechanism of carbon dioxide transport is by blood plasma, as some carbon dioxide molecules dissolve in the blood. The second mechanism is transport in the form of bicarbonate ion (HCO3–), which also dissolves in plasma. The third mechanism of carbon dioxide transport is similar to the transport of oxygen by red blood cells.

Figure 21.35: Carbon Dioxide Transport OpenStax Figure 22.28 (AA)

Dissolved in plasma

A small fraction (~7-10%) of carbon dioxide diffuses into the blood from the tissue and is dissolved in plasma. The dissolved carbon dioxide travels in the bloodstream, when the blood reaches the pulmonary capillaries, the dissolved carbon dioxide diffuses across the respiratory membrane into the alveoli and is exhaled during pulmonary ventilation.

Bicarbonate Buffer

Approximately 70 percent of the carbon dioxide that diffuses into the blood is transported to the lungs as HCO3–. Most of the HCO3– is produced in red blood cells after carbon dioxide diffuses into the capillaries and the red blood cells. Carbonic anhydrase (CA) causes carbon dioxide and water to form carbonic acid (H2CO3), which dissociates into two ions: HCO3–) and hydrogen (H+). The following formula depicts this reaction:

CO₂ + H₂O ↔ H₂CO₃ ↔ H+ + HCO₃–

At the pulmonary capillaries, the chemical reaction that produced HCO₃– (depicted above) is reversed, and carbon dioxide and water are the products. The carbon dioxide is released through exhalation.

Carbaminohemoglobin

About 20 percent of carbon dioxide is bound by hemoglobin and transported to the lungs. Carbon dioxide does not bind to iron as oxygen does. Instead, carbon dioxide binds to amino acids on hemoglobin to form carbaminohemoglobin. When hemoglobin is not transporting oxygen, it tends to have a bluish-purple tone to it, creating the darker maroon color typical of deoxygenated blood. The following formula depicts this reversible reaction:

CO₂ + Hb ↔ HbCO₂

Similar to the transport of oxygen by heme, the binding and dissociation of carbon dioxide to and from hemoglobin is dependent on the partial pressure of carbon dioxide. Because carbon dioxide is released from the lungs, blood that leaves the lungs and reaches body tissues has a lower partial pressure of carbon dioxide than is found in the tissues. As a result, carbon dioxide leaves the tissues because of its higher partial pressure, enters the blood, and then moves into red blood cells, binding to hemoglobin. In contrast, in the pulmonary capillaries, the partial pressure of carbon dioxide is high compared to within the alveoli. As a result, carbon dioxide dissociates readily from hemoglobin and diffuses across the respiratory membrane into the air.

21.5 Modifications in Respiratory Functions

Hyperpnea

Hyperpnea is an increased depth and rate of ventilation to meet an increase in oxygen demand. This might be seen in exercise or disease. This does not significantly alter blood oxygen or carbon dioxide levels but increases the rate and depth of ventilation to meet the demand of the cells. What’s the difference between hyperpnea and hyperventilation? Hyperventilation is an increased ventilation rate that is independent of the cellular oxygen needs and leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH.

High Altitude Effects

An increase in altitude results in a decrease in atmospheric pressure. Although the proportion of oxygen relative to gasses in the atmosphere remains the same, its partial pressure decreases. This makes it more difficult for the body to achieve the same level of oxygen saturation at high altitudes compared to low altitudes, due to lower atmospheric pressure.

Partial pressure is very important in determining how much gas can cross the respiratory membrane and enter the pulmonary capillaries. A lower partial pressure of oxygen means that there is a smaller difference in partial pressures between the alveoli and the blood, therefore less oxygen can cross the respiratory membrane. As a result, fewer oxygen molecules are bound by hemoglobin. Despite this, the tissues of the body can still receive a sufficient amount of oxygen during rest at high altitudes. This is due to two major mechanisms. First, the number of oxygen molecules that enter the tissue from the blood is nearly equal between sea level and high altitudes. Secondly, at high altitudes, a greater amount of 2,3-Bisphosphoglycerate (BPG), a byproduct of glycolysis, is produced by red blood cells, which enhances the dissociation of oxygen from hemoglobin.

Physical exertion, such as skiing or hiking, can lead to altitude sickness due to the low amount of oxygen reserves in the blood at high altitudes. At sea level, there is a large amount of oxygen reserve in venous blood (even though venous blood is thought of as “deoxygenated”) from which the muscles can draw during physical exertion. Because the oxygen saturation is much lower at higher altitudes, this venous reserve is small, resulting in pathological symptoms of low blood oxygen levels. You may have heard that it is important to drink more water when traveling at higher altitudes than you are accustomed to. This is because your body will increase micturition (urination) at high altitudes to counteract the effects of lower oxygen levels. By removing fluids, blood plasma levels drop but not the total number of erythrocytes. In this way, the overall concentration of erythrocytes in the blood increases, which helps tissues obtain the oxygen they need.

Chapter Summary

Key Terms

acclimatization

process of adjustment that the respiratory system makes due to chronic exposure to high altitudes

acute mountain sickness (AMS)

condition that occurs a result of acute exposure to high altitude due to a low partial pressure of oxygen

ala

(plural = alae) small, flaring structure of a nostril that forms the lateral side of the nares

alveolar duct

small tube that leads from the terminal bronchiole to the respiratory bronchiole and is the 

point of attachment for alveoli

alveolar macrophage

immune system cell of the alveolus that removes debris and pathogens

alveolar pore

opening that allows airflow between neighboring alveoli

alveolar sac

cluster of alveoli

alveolus

small, grape-like sac that performs gas exchange in the lungs

apex

tip of the external nose

apneustic center

network of neurons within the pons that stimulate the neurons in the dorsal respiratory group; controls the depth of inspiration

atmospheric pressure

amount of force that is exerted by gases in the air surrounding any given surface

Bohr effect

relationship between blood pH and oxygen dissociation from hemoglobin

Boyle’s law

relationship between volume and pressure as described by the formula: P1V1 = P2V2

bridge

portion of the external nose that lies in the area of the nasal bones

bronchial tree

collective name for the multiple branches of the bronchi and bronchioles of the respiratory system

bronchiole

branch of bronchi that are 1 mm or less in diameter and terminate at alveolar sacs

bronchoconstriction

decrease in the size of the bronchiole due to relaxation of the muscular wall

bronchodilation

increase in the size of the bronchiole due to contraction of the muscular wall

bronchus

tube connected to the trachea that branches into many subsidiaries and provides a passageway for air to enter and leave the lungs

carbaminohemoglobin

bound form of hemoglobin and carbon dioxide

carbonic anhydrase (CA)

enzyme that catalyzes the reaction that causes carbon dioxide and water to form carbonic acid

cardiac notch

indentation on the surface of the left lung that allows space for the heart

cellular respiration

production of ATP from glucose oxidation via glycolysis, the Krebs cycle, and oxidative phosphorylation

conducting zone

region of the respiratory system that includes the organs and structures that provide passageways for air and are not directly involved in gas exchange

cricoid cartilage

portion of the larynx composed of a ring of cartilage with a wide posterior region and a thinner anterior region; attached to the esophagus

Dalton’s law

statement of the principle that a specific gas type in a mixture exerts its own pressure, as if that specific gas type was not part of a mixture of gasses

dorsal respiratory group (DRG)

region of the medulla oblongata that stimulates the contraction of the diaphragm and intercostal muscles to induce inspiration

dorsum nasi

intermediate portion of the external nose that connects the bridge to the apex and is supported by the nasal bone

epiglottis

leaf-shaped piece of elastic cartilage that is a portion of the larynx that swings to close the trachea during swallowing

expiration

(also, exhalation) process that causes the air to leave the lungs

expiratory reserve volume (ERV)

amount of air that can be forcefully exhaled after a normal tidal exhalation

external nose

region of the nose that is easily visible to others

external respiration

gas exchange that occurs in the alveoli

fibroelastic membrane

specialized membrane that connects the ends of the C-shape cartilage in the trachea; contains smooth muscle fibers

forced breathing

(also, hyperpnea) mode of breathing that occurs during exercise or by active thought that requires muscle contraction for both inspiration and expiration

functional residual capacity (FRC)

sum of ERV and RV, which is the amount of air that remains in the lungs after a tidal expiration

glottis

opening between the vocal folds through which air passes when producing speech

Henry’s law

statement of the principle that the concentration of gas in a liquid is directly proportional to the solubility and partial pressure of that gas

hilum

concave structure on the mediastinal surface of the lungs where blood vessels, lymphatic vessels, nerves, and a bronchus enter the lung

hyperpnea

increased rate and depth of ventilation due to an increase in oxygen demand that does not significantly alter blood oxygen or carbon dioxide levels

hyperventilation

increased ventilation rate that leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH

inspiration

(also, inhalation) process that causes air to enter the lungs

inspiratory capacity (IC)

sum of the TV and IRV, which is the amount of air that can maximally be inhaled past a tidal expiration

inspiratory reserve volume (IRV)

amount of air that enters the lungs due to deep inhalation past the tidal volume

internal respiration

gas exchange that occurs at the level of body tissues

intra-alveolar pressure

(intrapulmonary pressure) pressure of the air within the alveoli

intrapleural pressure

pressure of the air within the pleural cavity

laryngeal prominence

region where the two lamine of the thyroid cartilage join, forming a protrusion known as “Adam’s apple”

laryngopharynx

portion of the pharynx bordered by the oropharynx superiorly and esophagus and trachea inferiorly; serves as a route for both air and food

larynx

cartilaginous structure that produces the voice, prevents food and beverages from entering the trachea, and regulates the volume of air that enters and leaves the lungs

lingual tonsil

lymphoid tissue located at the base of the tongue

Lower respiratory system

include the larynx, trachea, bronchioles, and lungs  

lung

organ of the respiratory system that performs gas exchange

meatus

one of three recesses (superior, middle, and inferior) in the nasal cavity attached to the conchae that increase the surface area of the nasal cavity

naris

(plural = nares) opening of the nostrils

nasal bone

bone of the skull that lies under the root and bridge of the nose and is connected to the frontal and maxillary bones

nasal septum

wall composed of bone and cartilage that separates the left and right nasal cavities

nasopharynx

portion of the pharynx flanked by the conchae and oropharynx that serves as an airway

oropharynx

portion of the pharynx flanked by the nasopharynx, oral cavity, and laryngopharynx that is a passageway for both air and food

oxygen–hemoglobin dissociation curve

graph that describes the relationship of partial pressure to the binding and disassociation of oxygen to and from heme

oxyhemoglobin

(Hb–O2) bound form of hemoglobin and oxygen

palatine tonsil

one of the paired structures composed of lymphoid tissue located anterior to the uvula at the roof of isthmus of the fauces

paranasal sinus

one of the cavities within the skull that is connected to the conchae that serve to warm and humidify incoming air, produce mucus, and lighten the weight of the skull; consists of frontal, maxillary, sphenoidal, and ethmoidal sinuses

parietal pleura

outermost layer of the pleura that connects to the thoracic wall, mediastinum, and diaphragm

partial pressure

force exerted by each gas in a mixture of gases

pharyngeal tonsil

structure composed of lymphoid tissue located in the nasopharynx

pharynx

region of the conducting zone that forms a tube of skeletal muscle lined with respiratory epithelium; located between the nasal conchae and the esophagus and trachea

pleural cavity

space between the visceral and parietal pleurae

pleural fluid

substance that acts as a lubricant for the visceral and parietal layers of the pleura during the movement of breathing

pneumotaxic center

network of neurons within the pons that inhibit the activity of the neurons in the dorsal respiratory group; controls rate of breathing

pulmonary artery

artery that arises from the pulmonary trunk and carries deoxygenated, arterial blood to the 

alveoli

pulmonary plexus

network of autonomic nervous system fibers found near the hilum of the lung

pulmonary surfactant

substance composed of phospholipids and proteins that reduces the surface tension of the alveoli; made by type II alveolar cells

pulmonary ventilation

exchange of gases between the lungs and the atmosphere; breathing

quiet breathing

(also, eupnea) mode of breathing that occurs at rest and does not require the cognitive thought of the individual

residual volume (RV)

amount of air that remains in the lungs after maximum exhalation

respiration

A combination of four processes including pulmonary ventilation (movement of air into and out of lungs), external respiration (gas exchange at the lung tissue), transportation of respiratory gases (in the blood), and internal respiration (gas exchange at the body tissues)

respiratory bronchiole

specific type of bronchiole that leads to alveolar sacs

respiratory cycle

one sequence of inspiration and expiration

respiratory epithelium

ciliated lining of much of the conducting zone that is specialized to remove debris and pathogens, and produce mucus

respiratory membrane

alveolar and capillary wall together, which form an air-blood barrier that facilitates the simple diffusion of gases

respiratory rate

total number of breaths taken each minute

respiratory volume

varying amounts of air within the lung at a given time

respiratory zone

includes structures of the respiratory system that are directly involved in gas exchange

root

region of the external nose between the eyebrows

thoracic wall compliance

ability of the thoracic wall to stretch while under pressure

thyroid cartilage

largest piece of cartilage that makes up the larynx and consists of two lamine

tidal volume (TV)

amount of air that normally enters the lungs during quiet breathing

total lung capacity (TLC)

total amount of air that can be held in the lungs; sum of TV, ERV, IRV, and RV

total pressure

sum of all the partial pressures of a gaseous mixture

trachea

tube composed of cartilaginous rings and supporting tissue that connects the lung bronchi and the larynx; provides a route for air to enter and exit the lung

trachealis muscle

smooth muscle located in the fibroelastic membrane of the trachea

true vocal cord

one of the pair of folded, white membranes that have a free inner edge that oscillates as air passes through to produce sound

type I alveolar cell

squamous epithelial cells that are the major cell type in the alveolar wall; highly permeable to gases

type II alveolar cell

cuboidal epithelial cells that are the minor cell type in the alveolar wall; secrete pulmonary surfactant

ventilation

movement of air into and out of the lungs; consists of inspiration and expiration

ventral respiratory group (VRG)

region of the medulla oblongata that stimulates the contraction of the accessory muscles involved in respiration to induce forced inspiration and expiration

vestibular fold

part of the folded region of the glottis composed of mucous membrane; supports the epiglottis during swallowing

visceral pleura

innermost layer of the pleura that is superficial to the lungs and extends into the lung fissures

vital capacity (VC)

sum of TV, ERV, and IRV, which is all the volumes that participate in gas exchange