Image summary: This is a portrait photograph. The image depicts a woman with voluminous curly hair wearing a striped collared shirt, holding a cigarette to her lips. The subject is captured in a side profile view, gazing away from the camera. The composition suggests a candid or contemplative moment, evoking a sense of introspection or relaxation.

The Respiratory System

The Respiratory System and Homeostasis

The respiratory system contributes to homeostasis by providing for the exchange of gases—oxygen and carbon dioxide—among the atmospheric air, blood, and tissue cells. It also helps adjust the pH of body fluids.

Your body's cells continually use oxygen ( O 2 ) for the metabolic reactions that generate A.T.P from the breakdown of nutrient molecules. At the same time, these reactions release carbon dioxide ( C O 2 ) as a waste product. Because an excessive amount of C O 2 produces acidity that can be toxic to cells, excess C O 2 must be eliminated quickly and efficiently. The cardiovascular and respiratory systems cooperate to supply O 2 and eliminate C O 2 . The respiratory system provides for gas exchange—intake of O 2 and elimination of C O 2 —and the cardiovascular system transports blood containing the gases between the lungs and body cells. Failure of either system disrupts homeostasis by causing rapid death of cells from oxygen starvation and buildup of waste products. In addition to functioning in gas exchange, the respiratory system also participates in regulating blood pH, contains receptors for the sense of smell, filters inspired air, produces sounds, and rids the body of some water and heat in exhaled air. As in the digestive and urinary systems, which will be covered in subsequent chapters, in the respiratory system there is an extensive area of contact between the external environment and capillary blood vessels.

23.1 Overview of the Respiratory System

Objectives

• Discuss the steps that occur during respiration.

• Define the respiratory system.

• Explain how the respiratory organs are classified structurally and functionally.

The Steps Involved in Respiration

The process of supplying the body with O₂ and removing C-O₂ is known as respiration, which has three basic steps (Figure 23.1):

① Pulmonary ventilation (pulmon-= lung), or breathing, is the inhalation (inflow) and exhalation (outflow) of air and involves the exchange of air between the atmosphere and the pulmonary alveoli of the lungs. Inhalation permits O₂ to enter the lungs and exhalation permits C-O₂ to leave the lungs.

Figure 23.1 summary: This figure is a biological diagram. It illustrates the integrated process of respiration, showing the flow of oxygen and carbon dioxide between the atmosphere, the lungs, the heart, and the systemic tissue cells. The diagram maps out the pathways of pulmonary circulation and systemic circulation, highlighting the exchange of gases at the pulmonary alveoli and the systemic capillaries, as well as the process of cellular respiration within tissue cells. It can be inferred that breathing serves as the initial step to bring oxygen into the body and remove carbon dioxide. The heart acts as a central pump that facilitates the transport of these gases via the blood. Oxygen is absorbed from the lungs into the blood and delivered to the tissues, where it is used for cellular respiration to produce energy, while carbon dioxide is collected from the tissues and transported back to the lungs for exhalation.

2 External (pulmonary) respiration is the exchange of gases between the pulmonary alveoli of the lungs and the blood in pulmonary capillaries across the respiratory membrane. In this process, pulmonary capillary blood gains O₂ and loses C-O₂.

③ Internal (tissue) respiration is the exchange of gases between blood in systemic capillaries and tissue cells. In this step the blood loses O₂ and gains C-O₂. Within cells, the metabolic reactions that consume O₂ and give off C-O₂ during the production of A.T.P are termed cellular respiration (discussed in Chapter 25).

Components of the Respiratory System

The respiratory system respiratore consists of the nose, pharynx (throat), larynx (voice box), trachea (windpipe), bronchi, and lungs (Figure 23.2). Its parts can be classified according to either structure or function. Structurally, the respiratory system consists of two parts: (1) The upper respiratory system includes the nose, nasal cavity, pharynx, and associated structures; (2) the lower respiratory system includes the larynx, trachea, bronchi, and lungs. Functionally, the respiratory system also consists of two parts. (1) The conducting zone consists of a series of interconnecting cavities and tubes both outside and within the lungs. These include the nose, nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles; their function is to filter, warm, and moisten air and conduct it into the lungs. (2) The respiratory zone consists of tubes and tissues within the lungs where gas exchange occurs. These include the respiratory bronchioles, alveolar ducts, alveolar saccules (sacs),

Figure 23.2 summary: This figure consists of two anatomical diagrams. The first image provides a general anterior view of the respiratory system within a human body, labeling the nose, nasal cavity, pharynx, larynx, trachea, right main bronchus, and lungs. The second image shows a detailed anterior dissection of the thoracic cavity with the chest wall and pleura removed, revealing the lungs, heart in its pericardial sac, diaphragm, liver, and various associated blood vessels and nerves such as the aorta and carotid arteries. Together, these diagrams illustrate the structural organization of the respiratory tract and its spatial relationship with the cardiovascular system and other thoracic organs, demonstrating how air travels from the external environment through the upper respiratory tract into the lungs for gas exchange.

Figure 23.1 The Three Basic Steps Involved in Respiration.

During respiration, the body is supplied with O₂ and C-O₂ is removed.

Q How does external respiration differ from internal respiration? and pulmonary alveoli and are the main sites of gas exchange between air and blood.

The branch of medicine that deals with the diagnosis and treatment of diseases of the ears, nose, and throat E.N.T is called otorhinolaryngology (o' -to-ri' nolaringology; oto-= ear; -rhino-= nose; -laryngo-= voice box; -logy = study of).

Checkpoint

1. What are the three basic steps involved in respiration?

2. What are the components of the respiratory system?

3. Why is the respiratory zone important?

Figure 23.2 Structures of the Respiratory System.

The upper respiratory system includes the nose, nasal cavity, pharynx, and associated structures; the lower respiratory system includes the larynx, trachea, bronchi, and lungs.

Functions of the respiratory system

1. Provides for gas exchange: intake of O 2 for delivery to body cells and removal of C O 2 produced by body cells.

2. Helps regulate blood pH.

3. Contains receptors for sense of smell, filters inspired air, produces vocal sounds (phonation), and excretes small amounts of water and heat.

23.2 The Upper Respiratory System

• Describe the anatomy and histology of the nose, pharynx and associated structures.

• Identify the functions of these respiratory structures.

Nose

The nose is a specialized organ at the entrance of the respiratory system that consists of a visible external portion (external nose) and an internal portion inside the skull called the nasal cavity (internal nose). The external nose is the portion of the nose visible on the face and consists of a supporting framework of bone and hyaline cartilage covered with muscle and skin and lined by a mucous membrane. The frontal bone, nasal bones, and maxillae form the bony framework of the external nose (Figure 23.3a). The cartilaginous framework of the external nose consists of several pieces of hyaline cartilage connected to each other and certain skull bones by fibrous connective tissue. The components of the cartilaginous framework are the nasal septal cartilage, which forms the anterior portion of the nasal septum; the lateral nasal cartilages inferior to the nasal bones; and the alar cartilages (A-lar), which form a portion of the walls of the nostrils. Because it consists of pliable hyaline cartilage, the cartilaginous framework of the external nose is somewhat flexible. On the undersurface of the external nose are two openings called the nostrils (external nares) which lead into cavities called the nasal vestibules. Figure 23.4 shows the surface anatomy of the nose.

Figure 23.4 summary: This figure is an annotated photograph. The image shows a woman's face with several numbered lines pointing to specific anatomical regions, including the eye, the bridge of the nose, the side of the nose, and the cheek area. These markers are used to identify key facial landmarks for anatomical or clinical reference.

Figure 23.3 Respiratory Structures in the Head and Neck.

The interior structures of the external nose have three functions: (1) warming, moistening, and filtering incoming air; (2) detecting olfactory stimuli; and (3) modifying speech vibrations as they pass through the large, hollow resonating chambers. Resonance refers to prolonging, amplifying, or modifying a sound by vibration.

Clinical Connection

Rhinoplasty

Rhinoplasty (Rᵇ-no-plas'-te; rhin = nose; -plasty = to mold or to shape), or "nose job," is a surgical procedure in which the shape of the external nose is altered. Although rhinoplasty is often done for cosmetic reasons, it is sometimes performed to repair a fractured nose or a deviated nasal septum. In the procedure, both local and general anesthetics are given. Instruments are then inserted through the nostrils, the nasal cartilage is reshaped, and the nasal bones are fractured and repositioned to achieve the desired shape. An internal packing and splint are inserted to keep the nose in the desired position as it heals.

The nasal cavity (internal nose) is a large space in the anterior aspect of the skull that lies inferior to the nasal bone and superior to the oral cavity; it is lined with muscle and mucous membrane. A vertical partition, the nasal septum, divides the nasal cavity into right and left sides. The anterior portion of the nasal septum consists primarily of hyaline cartilage; the remainder is formed by the vomer and the perpendicular plate of the ethmoid, maxillae, and palatine bones (see Figure 7.11).

Anteriorly, the nasal cavity merges with the external nose, and posteriorly the nasal cavity communicates with the pharynx through two openings called the choanae (ko-A-ne) or internal nares (see Figure 23.3b). Ducts from the paranasal sinuses (which drain mucus) and the nasolacrimal ducts (which drain As air passes through the nose, it is warmed, filtered, and moistened, and olfaction occurs.

Figure 23.3 summary: This figure is an anatomical diagram. It provides an anterolateral view of the human nose, identifying the structural components that form its shape. The diagram distinguishes between the bony framework, which includes the frontal bone, nasal bones, and maxilla, and the cartilaginous framework, which consists of the lateral nasal cartilages, nasal septal cartilage, and both major and minor alar cartilages. Additionally, it identifies the presence of dense fibrous connective and adipose tissue. The figure demonstrates that the nose is supported by a combination of rigid bone at the upper bridge and flexible cartilage at the lower tip and nostrils, providing both structural stability and flexibility.

Figure 23.3 Continued

What is the path taken by air molecules into and through the nose?

Figure 23.4 Surface Anatomy of the Nose.

The external nose has a cartilaginous framework and a bony framework.

1. Root: Superior attachment of the nose to the frontal bone 2. Apex: Tip of nose 3. Bridge: Bony framework of nose formed by nasal bones 4. Nostril: External opening into nasal cavity Which part of the nose is attached to the frontal bone? tears) also open into the nasal cavity. Recall from Chapter 7 that the paranasal sinuses are cavities in certain cranial cavity and facial bones lined with mucous membrane that are continuous with the lining of the nasal cavity. Skull bones containing the paranasal sinuses are the frontal, sphenoid, ethmoid, and maxillae.

Besides producing mucus, the paranasal sinuses serve as resonating chambers for sound as we speak or sing. The lateral walls of the internal nose are formed by the ethmoid, maxillae, lacrimal, palatine, and inferior nasal conchae bones (see Figure 7.9); the ethmoid bone also forms the roof. The palatine bones and palatine processes of the maxillae, which together constitute the hard palate, form the floor of the internal nose.

The bony and cartilaginous framework of the nose help to keep the nasal vestibule and nasal cavity patent, that is, open or unobstructed. The nasal cavity is divided into a larger, inferior respiratory region and a smaller, superior olfactory region. The respiratory region is lined with ciliated pseudostratified columnar epithelium with numerous goblet cells, which is frequently called the respiratory epithelium (see Table 4.1). The anterior portion of the nasal cavity just inside the nostrils, called the nasal vestibule, is surrounded by cartilage; the superior part of the nasal cavity is surrounded by bone.

When air enters the nostrils, it passes first through the nasal vestibule, which is lined by skin containing coarse hairs that filter out large dust particles. Three shelves formed by projections of the superior nasal conchae, middle nasal conchae, and inferior nasal conchae bones konke extend out of each lateral wall of the nasal cavity. The conchae, almost reaching the nasal septum, subdivide each side of the nasal cavity into a series of groovelike air passageways—the superior, middle, and inferior nasal meatuses (me-A-tus-ez = openings or passages; singular is meatus). Mucous membrane lines the nasal cavity and its shelves. The arrangement of conchae and meatuses increases surface area in the internal nose and prevents dehydration by trapping water droplets during exhalation.

Clinical Connection

Tonsillectomy

Tonsillectomy tonsillectome; -ektome = excision or to cut out) is surgical removal of the tonsils. The procedure is usually performed under general anesthesia on an outpatient basis. Tonsillectomies are performed in individuals who have frequent tonsillitis (ton'-si-Li-tis), that is, inflammation of the tonsils; tonsils that develop an abscess or tumor; or tonsils that obstruct breathing during sleep.

As inhaled air whirls around the conchae and meatuses, it is warmed by blood in the capillaries. Mucus secreted by the goblet cells moistens the air and traps dust particles. Drainage from the nasolacrimal ducts also helps moisten the air, and is sometimes assisted by secretions from the paranasal sinuses. The cilia move the mucus and trapped dust particles toward the pharynx, at which point they can be swallowed or spit out, thus removing the particles from the respiratory tract.

The olfactory sensory neurons, supporting epithelial cells, and basal epithelial cells lie in the respiratory region, which is near the superior nasal conchae and adjacent septum. These cells make up the olfactory epithelium. It contains cilia but no goblet cells.

Pharynx

The pharynx farinks, or throat, is a funnel-shaped tube about 13 centimeters (5 in.) long that starts at the choanae and extends to the level of the cricoid cartilage, the most inferior cartilage of the larynx (voice box) (see Figure 23.3b). The pharynx lies just posterior to the nasal and oral cavities, superior to the larynx, and just anterior to the cervical vertebrae. Its wall is composed of skeletal muscles and is lined with a mucous membrane. Relaxed skeletal muscles help keep the pharynx patent.

Contraction of the skeletal muscles assists in deglutition (swallowing). The pharynx functions as a passageway for air and food, provides a resonating chamber for speech sounds, and houses the tonsils, which participate in immunological reactions against foreign invaders.

The pharynx can be divided into three anatomical regions: (1) nasopharynx, (2) oropharynx, and (3) laryngopharynx. (See the lower orientation diagram in Figure 23.3b.) The muscles of the entire pharynx are arranged in two layers, an outer circular layer and an inner longitudinal layer.

The superior portion of the pharynx, called the nasopharynx, lies posterior to the nasal cavity and extends to the soft palate. The soft palate, which forms the posterior portion of the roof of the mouth, is an arch-shaped muscular partition between the nasopharynx and oropharynx that is lined by mucous membrane. There are five openings in its wall: two choanae, two openings that lead into the auditory (pharyngotympanic) tubes (commonly known as the eustachian tubes), and the opening into the oropharynx. The posterior wall also contains the pharyngeal tonsil faringeal, or adenoid. Through the choanae, the nasopharynx receives air from the nasal cavity along with packages of dust-laden mucus.

The nasopharynx is lined with ciliated pseudostratified columnar epithelium, and the cilia move the mucus down toward the most inferior part of the nasopharynx. The nasopharynx also exchanges small amounts of air with the auditory tubes to equalize air pressure between the tympanic cavity and the atmosphere.

The intermediate portion of the pharynx, the oropharynx, lies posterior to the oral cavity and extends from the soft palate inferiorly to the level of the upper border of the epiglottis. It has only one opening into it, the fauces fawsez = throat), the opening from the mouth. This portion of the pharynx has both respiratory and digestive functions, serving as a common passageway for air, food, and drink.

Because the oropharynx is subject to abrasion by food particles, it is lined with nonkeratinized stratified squamous epithelium. Two pairs of tonsils, the palatine and lingual tonsils, are found in the oropharynx.

The inferior portion of the pharynx, the laryngopharynx laringofarings begins at the level of the hyoid bone. At its inferior end it opens into the esophagus (food tube) posteriorly and the larynx (voice box) anteriorly. Like the oropharynx, the laryngopharynx is both a respiratory and a digestive pathway and is lined by nonkeratinized stratified squamous epithelium.

Checkpoint

23.3 The Lower Respiratory System

Objectives

• Identity the features and purpose of the larynx.

• List the structures of voice production.

• Describe the anatomy and histology of the trachea.

• Identify the functions of each bronchial structure.

Larynx

The larynx laringks, or voice box, is a short passageway that connects the laryngopharynx with the trachea. It lies in the midline of the neck anterior to the esophagus and the fourth through sixth cervical vertebrae C.4-C.6.

The wall of the larynx is composed of nine pieces of cartilage (Figure 23.5). Three occur singly (thyroid cartilage, epiglottic cartilage, and cricoid cartilage), and three occur in pairs (arytenoid, cuneiform, and corniculate cartilages). Of the paired cartilages, the arytenoid cartilages are the most important because they influence changes in position and tension of

Figure 23.5 summary: This figure consists of a series of anatomical diagrams and cross-sectional views. The content illustrates the human larynx and associated structures from multiple perspectives, including anterior and posterior views, as well as sagittal and coronal sections. Key anatomical features labeled across the views include various cartilages such as the epiglottic, thyroid, cricoid, and arytenoid cartilages, along with the hyoid bone, thyroid gland, parathyroid glands, and tracheal cartilage. The internal structures of the larynx, such as the vocal folds, vestibular folds, and the laryngeal vestibule and cavity, are also detailed. These views collectively demonstrate the complex three-dimensional arrangement of the respiratory and endocrine structures in the neck, showing how the cartilaginous framework supports the airway and protects the lower respiratory tract while providing the structural basis for phonation.

Figure 23.5 The Larynx.

The larynx is composed of nine pieces of cartilage. the vocal folds (true vocal cords for speech). The extrinsic muscles of the larynx connect the cartilages to other structures in the throat; the intrinsic muscles connect the cartilages to one another. The laryngeal cavity is the space that extends from the entrance into the larynx down to the inferior border of the cricoid cartilage (described shortly).

The portion of the laryngeal cavity above the vestibular folds (false vocal cords) is called the laryngeal vestibule. The portion of the cavity of the larynx below the vocal folds is called the infraglottic cavity (infra-= below) (Figure 23.5d).

The thyroid cartilage (laryngeal prominence or Adam's apple) consists of two fused plates of hyaline cartilage that form the anterior wall of the larynx and give it a triangular shape. It is present in both males and females but is usually larger in males due to the influence of male sex hormones on its growth during puberty. The ligament that connects the thyroid cartilage to the hyoid bone is called the thyrohyoid membrane.

The epiglottic cartilage (epi-= over; -glottic = tongue) is a large, leaf-shaped piece of elastic cartilage. The term epiglottis refers to the epiglottic cartilage and its mucous membrane covering (see also Figure 23.3b). The "stem" of the epiglottis is the tapered inferior portion that is attached to the internal surface of the thyroid cartilage. The broad superior "leaf" portion of the epiglottis is unattached and is free to move up and down like a trap door.

During swallowing, the pharynx and larynx rise. Elevation of the pharynx widens it to receive food or drink; elevation of the larynx causes the epiglottis to move down and form a lid over the glottis, closing it off. The glottis consists of a pair of folds of mucous membrane, the vocal folds (true vocal cords) in the larynx, and the space between them called the rima glottidis (Ri-ma glottidis. The closing of the larynx in this way during swallowing routes liquids and foods into the esophagus and keeps them out of the larynx and airways. When small particles of dust, smoke, food, or liquids pass into the larynx, a cough reflex occurs, usually expelling the material.

The cricoid cartilage krlkoyd = ringlike) is a ring of hyaline cartilage that forms the inferior wall of the larynx. It is attached to the first ring of cartilage of the trachea by the cricotracheal ligament krlkotrakeal. The thyroid cartilage is connected to the cricoid cartilage by the cricothyroid ligament. The cricoid cartilage is the landmark for making an emergency airway called a tracheotomy (see Clinical Connection: Tracheostomy and Endotracheal Intubation).

The paired arytenoid cartilages aritenoyd = ladlelike) are triangular pieces of mostly hyaline cartilage located at the posterior, superior border of the cricoid cartilage. They form synovial joints with the cricoid cartilage and have a wide range of mobility.

The paired corniculate cartilages kornikulat = shaped like a small horn), horn-shaped pieces of elastic cartilage, are located at the apex of each arytenoid cartilage. The paired cuneiform cartilages (KÜ-ne-i-form = wedge-shaped), club-shaped elastic cartilages anterior to the corniculate cartilages, support the vocal folds and lateral aspects of the epiglottis.

The lining of the larynx superior to the vocal folds is nonkeratinized stratified squamous epithelium. The lining of the larynx inferior to the vocal folds is ciliated pseudostratified columnar epithelium consisting of ciliated columnar cells, goblet cells, and basal cells. The mucus produced by the goblet cells helps trap dust not removed in the upper passages. The cilia in the upper respiratory tract move mucus and trapped particles down toward the oropharynx; the cilia in the lower respiratory tract move them up toward the laryngopharynx.

The Structures of Voice Production

The mucous membrane of the larynx forms two pairs of folds (Figure 23.5c): a superior pair called the vestibular folds (false vocal cords) and an inferior pair called the vocal folds (true vocal cords). The space between the vestibular folds is known as the rima vestibuli. The laryngeal ventricle is a lateral expansion of the middle portion of the laryngeal cavity inferior to the vestibular folds and superior to the vocal folds (see Figure 23.3b). While the vestibular folds do not function in voice production, they do have other important functional roles. When the vestibular folds are brought together, they function in holding the breath against pressure in the thoracic cavity, such as might occur when a person strains to lift a heavy object.

The vocal folds are the principal structures of voice production. Deep to the mucous membrane of the vocal folds, which is nonkeratinized stratified squamous epithelium, are

Figure 23.6 Movement of the Vocal Folds.

bands of elastic ligaments stretched between the rigid cartilages of the larynx like the strings on a guitar. Intrinsic laryngeal muscles attach to both the rigid cartilages and the vocal folds. When the muscles contract they move the cartilages, which pulls the elastic ligaments tight, and this stretches the vocal folds out into the airways so that the rima glottidis is narrowed. Contracting and relaxing the muscles varies the tension in the vocal folds, much like loosening or tightening a guitar string. Air passing through the larynx vibrates the folds and produces sound (phonation) by setting up sound waves in the column of air in the pharynx, nose, and mouth.

The variation in the pitch of the sound is related to the tension in the vocal folds. The greater the pressure of air, the louder the sound produced by the vibrating vocal folds.

When the intrinsic muscles of the larynx contract, they pull on the arytenoid cartilages, which causes the cartilages to pivot and slide. Contraction of the posterior cricoarytenoid muscles, for example, moves the vocal folds apart (abduction), thereby opening the rima glottidis (Figure 23.6a). By contrast, contraction of the lateral cricoarytenoid muscles moves the vocal folds together (adduction), thereby closing the rima glottidis.

The glottis consists of a pair of folds of mucous membrane in the larynx (the vocal folds) and the space between them (the rima glottidis).

(Figure 23.6b). Other intrinsic muscles can elongate (and place tension on) or shorten (and relax) the vocal folds.

Pitch is controlled by the tension on the vocal folds. If they are pulled taut by the muscles, they vibrate more rapidly, and a higher pitch results. Decreasing the muscular tension on the vocal folds causes them to vibrate more slowly and produce lower-pitched sounds.

Due to the influence of androgens (male sex hormones), vocal folds are usually thicker and longer in males than in females, and therefore they vibrate more slowly. This is why a man's voice generally has a lower range of pitch than that of a woman.

Sound originates from the vibration of the vocal folds, but other structures are necessary for converting the sound into recognizable speech. The pharynx, mouth, nasal cavity, and paranasal sinuses all act as resonating chambers that give the voice its human and individual quality. We produce the vowel sounds by constricting and relaxing the muscles in the wall of the pharynx. Muscles of the face, tongue, and lips help us enunciate words.

Whispering is accomplished by closing all but the posterior portion of the rima glottidis. Because the vocal folds do not vibrate during whispering, there is no pitch to this form of speech. However, we can still produce intelligible speech while whispering by changing the shape of the oral cavity as we enunciate. As the size of the oral cavity changes, its resonance qualities change, which imparts a vowel-like pitch to the air as it rushes toward the lips.

Figure 23.6 summary: This figure consists of a series of anatomical diagrams and medical illustrations. The images provide a comparative view of the larynx from a superior perspective of the cartilages and through a laryngoscope, showing the internal structures including the thyroid cartilage, cricoid cartilage, vocal folds, and various muscles. The illustrations contrast two different states of the glottis: one where the vocal folds are moved apart and another where they are brought together. It can be inferred that the posterior cricoarytenoid muscles facilitate the abduction of the vocal folds to open the airway, while the lateral cricoarytenoid muscles facilitate adduction to close the glottis, which is essential for functions such as phonation and protecting the airway.

Figure 23.7 Location of the Trachea in Relation to the Esophagus.

Laryngitis and Cancer of the Larynx

Laryngitis is an inflammation of the larynx that is most often caused by a respiratory infection or irritants such as cigarette smoke. Inflammation of the vocal folds causes hoarseness or loss of voice by interfering with the contraction of the folds or by causing them to swell to the point where they cannot vibrate freely. Many long-term smokers acquire a permanent hoarseness from the damage done by chronic inflammation.

Cancer of the larynx is found almost exclusively in individuals who smoke. The condition is characterized by hoarseness, pain on swallowing, or pain radiating to an ear. Treatment consists of radiation therapy and/or surgery.

Trachea

The trachea trakea = sturdy), or windpipe, is a tubular passageway for air that is about 12 centimeters (5 in.) long and 2.5 centimeters (1 in.) in diameter. It is located anterior to the esophagus (Figure 23.7) and extends from the larynx to the superior border of the fifth thoracic vertebra T.5, where it divides into right and left primary bronchi (see Figure 23.8).

Figure 23.7 summary: This figure consists of a diagrammatic representation, a transverse anatomical cross-section, and a high-magnification micrograph. The content illustrates the anatomical relationship between the trachea and the esophagus, highlighting the presence of tracheal cartilage, the trachealis muscle, and the lobes of the thyroid gland. The micrograph provides a detailed view of the ciliated epithelial lining of the respiratory tract. From the figure, it can be inferred that the trachea is positioned anterior to the esophagus. The absence of cartilage in the posterior wall of the trachea, where the trachealis muscle is located, allows for the expansion of the esophagus during the passage of food.

Figure 23.8 summary: This is an anatomical diagram. It illustrates the anterior view of the human respiratory system, specifically detailing the bronchial tree. The image labels key structures including the larynx, trachea, and the branching network of the right and left lungs, ranging from the main bronchi down to the terminal bronchioles, as well as the surrounding pleura and the diaphragm. The figure demonstrates the hierarchical branching pattern of the airway, showing how the trachea divides into main bronchi, which further split into lobar and segmental bronchi, eventually narrowing into bronchioles. This structure indicates a system designed for the efficient distribution of air from a single primary conduit into increasingly smaller pathways to reach the deep tissues of both lungs.

Figure 23.8 Branching of Airways from the Trachea.

The bronchial tree consists of macroscopic airways that begin at the trachea and continue through the terminal bronchioles.

Table summary: The table outlines the hierarchical progression of airway branching, dividing the system into the conducting zone and the respiratory zone, with the generation number increasing as the branches move from the trachea toward the alveolar saccules.

The layers of the tracheal wall, from deep to superficial, are the (1) respiratory mucosa, (2) submucosa, (3) hyaline cartilage, and (4) adventitial layer (composed of areolar connective tissue). The respiratory mucosa of the trachea consists of an epithelial layer of ciliated pseudostratified columnar epithelium and an underlying layer of lamina propria that contains elastic and reticular fibers. It provides the same protection against dust as the membrane lining the nasal cavity and larynx. The submucosa consists of areolar connective tissue that contains seromucous glands and their ducts.

The 16 to 20 incomplete, horizontal rings of hyaline cartilage resemble the letter C, are stacked one above another, and are connected by dense connective tissue. They may be felt

Clinical Connection

Tracheostomy and Endotracheal Intubation

Several conditions may block airflow by obstructing the trachea. Two methods are used to reestablish airflow when this happens.

One of these methods is called a tracheostomy trakeostome, also referred to as a tracheotomy. It is usually done in an operating room under general anesthesia. In this surgical procedure, a skin incision is followed by a short longitudinal incision into the trachea below the cricoid cartilage. Then, an endotracheal (within the trachea) tube endotrakeal is placed through the opening to provide an airway when the usual route for breathing is obstructed or impaired and to remove secretions from the lungs. Indications for a tracheostomy include medical conditions that require use of a mechanical ventilator (breathing machine), vocal cord paralysis, throat cancer, severe neck or mouth injuries, airway burns, foreign body obstructions, and conditions that make it difficult for a person to cough up secretions.

An alternative procedure to maintain a patent (open) airway is called endotracheal intubation, or simply intubation. In this procedure, also done in a hospital setting under anesthesia, an endotracheal tube is advanced through the mouth (or sometimes the nose), pharynx, and larynx into the trachea. During the procedure, a laryngoscope, a lighted instrument that permits visualization of the larynx, is employed. Once the vocal folds are located, the tube is placed in the inferior portion of the trachea. The laryngoscope also holds through the skin inferior to the larynx. The open part of each C-shaped cartilage ring faces posteriorly toward the esophagus (Figure 23.7) and is spanned by the membranous wall of the trachea. Within this membranous wall are transverse smooth muscle fibers, called the trachealis muscle (tra-ke-A-lis), and elastic connective tissue that allow the diameter of the trachea to change subtly during inhalation and exhalation, which is important in maintaining efficient airflow.

Image summary: This is an anatomical diagram. The figure illustrates the placement of an endotracheal tube within the human upper respiratory tract, showing the path from the mouth, past the tongue and epiglottis, and down into the trachea. It also indicates the location for a tracheostomy. The diagram demonstrates that an endotracheal tube provides a direct airway to the lungs by bypassing the upper pharyngeal structures, while a tracheostomy provides an alternative surgical access point directly into the trachea.

The solid C-shaped cartilage rings provide a semirigid support to maintain patency so that the tracheal wall does not collapse inward (especially during inhalation) and obstruct the air passageway. The adventitial layer of the trachea consists of areolar connective tissue that joins the trachea to surrounding tissues. the tongue aside while the tube is inserted into the trachea. Endotrachial intubation is used to permit air to freely pass into and out of the lungs. The tube can also be connected to a ventilator. In some cases, the tube can be used to introduce anesthesia, medications, and oxygen or to suction respiratory secretions.

A mechanical ventilator or simply a ventilator, is a machine that is used to support ventilation (breathing). It is a form of life support. It does so by oxygenating the lungs, removing carbon dioxide, helping people breathe more easily and ventilating for individuals who have lost the ability to breathe on their own.

The mechanical ventilator blows humidified and warmed air and oxygen through a tube into the airways and then into the lungs. The rate at which this is done can be adjusted to deliver a certain amount of air per minute. The tube is then placed into the trachea via the tracheostomy or endotracheal intubation procedure just described. Mechanical ventilation is an invasive procedure.

A noninvasive type of ventilation is Continuous Positive Airway Pressure or C.P.A.P. This consists of a machine that contains a motorized fan that draws air in from a room, humidifies it, and gently pressurizes it. The air is then delivered through a hose that connects to a mask placed over the nose and/or mouth. The mildly pressurized air helps to keep the airways open. C.P.A.P is indicated for sleep-related disorders, such as sleep apnea.

Image summary: This is an anatomical diagram. The figure illustrates the process of endotracheal intubation, showing a cross-section of the human head and neck. It depicts a laryngoscope being used to displace the tongue and expose the airway, allowing an endotracheal tube to pass through the epiglottis and into the trachea. The illustration demonstrates how the medical instruments are positioned to bypass the upper airway obstructions and establish a direct path to the lungs.

Figure 4 summary: This figure consists of two clinical photographs. The images depict a medical procedure for percutaneous tracheostomy, showing a healthcare provider utilizing a specialized tool to create an opening in the neck and another image showing the patient receiving respiratory support via a mask and tubing during the process. The figure demonstrates the practical application of a technical modification intended to facilitate the percutaneous tracheostomy procedure, suggesting a method for establishing an airway in a clinical setting.

Bronchi

Image summary: This is a photograph. The image depicts a medical professional wearing surgical scrubs, a cap, and a mask performing a procedure on a patient. The practitioner is using a specialized medical tool and a tube near the patient's airway. The scene indicates a clinical or surgical setting where an invasive medical intervention is being carried out to manage a patient's breathing or airway access.

At the superior border of the fifth thoracic vertebra, the trachea divides into a right main (primary) bronchus brongkus = windpipe), which goes into the right lung, and a left main (primary) bronchus, which goes into the left lung (Figure 23.8). The right main bronchus is more vertical, shorter, and wider than the left. As a result, an aspirated object is more likely to enter and lodge in the right main bronchus than the left. Like the trachea, the main bronchi brongki contain incomplete rings of cartilage and are lined by ciliated pseudostratified columnar epithelium.

At the point where the trachea divides into right and left main bronchi an internal ridge called the carina (ka-Rî-na = keel of a boat) is formed by a posterior and somewhat inferior projection of the last tracheal cartilage. The mucous membrane of the carina is one of the most sensitive areas of the entire larynx and trachea for triggering a cough reflex. Widening and distortion of the carina is a serious sign because it usually indicates a carcinoma of the lymph nodes around the region where the trachea divides.

On entering the lungs, the main bronchi divide to form smaller bronchi—the lobar (secondary) bronchi, one for each lobe of the lung. (The right lung has three lobes; the left lung has two.) The lobar bronchi continue to branch, forming still smaller bronchi, called segmental (tertiary) bronchi tersheere, that supply the specific bronchopulmonary segments within the lobes. There are 13 segmental bronchi in the right lung and eight segmental bronchi in the left lung. The segmental bronchi then divide into bronchioles.

Bronchioles in turn branch repeatedly, and the smallest ones branch into even smaller tubes called terminal bronchioles. These bronchioles contain exocrine bronchiolar (Clara) cells, which are nonciliated columnar cells, interspersed among ciliated simple columnar cells. The exocrine bronchiolar cells may protect against harmful effects of inhaled toxins and carcinogens, produce surfactant (discussed shortly), and function as stem cells, which give rise to various cells of the epithelium.

The terminal bronchioles represent the end of the conducting zone of the respiratory system. This extensive branching from the trachea through the terminal bronchioles resembles an inverted tree and is commonly referred to as the bronchial tree. Beyond the terminal bronchioles of the bronchial tree, the branches become microscopic. These branches are called the respiratory bronchioles and alveolar ducts, which will be described shortly (see Figure 23.11).

Figure 23.11 summary: This figure consists of a composite illustration including a schematic diagram, a light microscopy image, and a scanning electron microscopy image. The figure illustrates the structural organization of a lung lobule, detailing the hierarchy of microscopic airways from terminal bronchioles to respiratory bronchioles, alveolar ducts, alveolar saccules, and finally pulmonary alveoli. It also identifies associated vascular structures, such as pulmonary arterioles, venules, and capillaries, as well as the visceral pleura and lymphatic vessels. Based on the provided images, it can be inferred that the respiratory system branches progressively into smaller units to maximize surface area for gas exchange. The transition from conducting airways to respiratory zones is characterized by a shift toward thin-walled alveolar structures, which are closely integrated with a dense network of pulmonary blood vessels to facilitate efficient diffusion.

The respiratory passages from the trachea to the alveolar ducts contain about 23 generations of branching; branching from the trachea into main bronchi is called first-generation branching, that from main bronchi into lobar bronchi is called second-generation branching, and so on down to the alveolar ducts (Figure 23.8b).

As the branching becomes more extensive in the bronchial tree, several structural changes may be noted.

1. The mucous membrane in the bronchial tree changes from ciliated pseudostratified columnar epithelium in the main bronchi, lobar bronchi, and segmental bronchi to ciliated simple columnar epithelium with some goblet cells in larger bronchioles, to mostly ciliated simple cuboidal epithelium with no goblet cells in smaller bronchioles, to mostly non-ciliated simple cuboidal epithelium in terminal bronchioles. Recall that ciliated epithelium of the respiratory membrane removes inhaled particles in two ways: mucus produced by goblet cells traps the particles, and the cilia move the mucus and trapped particles toward the pharynx for removal. In regions where non-ciliated simple cuboidal epithelium is present, inhaled particles are removed by macrophages.

2. Plates of cartilage gradually replace the incomplete rings of cartilage in main bronchi and finally disappear in the distal bronchioles.

3. As the amount of cartilage decreases, the amount of smooth muscle increases. Smooth muscle encircles the epithelial-lined lumen in spiral bands and helps maintain

Figure 23.9 Relationship of the pleural membranes to the lungs. patency. However, because there is no supporting cartilage, muscle spasms can close off the airways. This is what happens during an asthma attack, which can be a life-threatening situation.

Figure 23.9 summary: This figure is an anatomical cross-section diagram. It displays a transverse plane view of the human thoracic cavity, labeling key structures including the sternum, lungs, heart-related vessels such as the aorta and vena cava, the esophagus, and the spinal column. The image illustrates the spatial relationship between the pleural membranes and the pleural cavity surrounding the lungs. Based on the anatomical positioning, it can be inferred that the lungs occupy the majority of the lateral thoracic space, while the heart and major vessels are centrally located between the lungs. The spinal cord and the body of the vertebra provide posterior structural support and protection for the central nervous system.

During exercise, activity in the sympathetic part of the autonomic nervous system (A.N.S) increases and the suprarenal medulla releases the hormones epinephrine and norepinephrine; both of these events cause relaxation of smooth muscle in the bronchioles, which dilates the airways. Because air reaches the pulmonary alveoli more quickly, lung ventilation improves. The parasympathetic part of the A.N.S and mediators of allergic reactions such as histamine have the opposite effect, causing contraction of bronchiolar smooth muscle, which results in constriction of distal bronchioles.

Checkpoint

6. How does the larynx function in respiration and voice production?

7. Describe the location, structure, and function of the trachea.

8. Describe the structure of the bronchial tree.

Lungs

A pulmonologist pulmonologist; pulmo-= lung) is a specialist in the diagnosis and treatment of lung diseases. The lungs (= lightweights, because they float) are paired conespared organs in the thoracic cavity (Figure 23.9). They are separated from each other by the heart and other structures of the mediastinum, which divides the thoracic cavity into two anatomically distinct chambers. As a result, if trauma causes one lung to collapse, the other may remain expanded. Each lung is enclosed and protected by a double-layered serous membrane called the pleural membrane plooral; pleur-= side) or pleura. The superficial layer, called the parietal pleura, lines the wall of the thoracic cavity; the deep layer, the visceral pleura, covers the lungs themselves (Figure 23.9). Between the visceral and parietal pleurae is a small space, the pleural cavity, which contains a small amount of lubricating fluid secreted by the membranes.

This pleural fluid reduces friction between the membranes, allowing them to slide easily over one another during breathing. Pleural fluid also causes the two membranes to adhere to one another just as a film of water causes two glass microscope slides to stick together, a phenomenon called surface tension. Separate pleural cavities surround the left and right lungs.

Inflammation of the pleural membrane, called pleurisy or pleuritis, may in its early stages cause pain due to friction between the parietal and visceral layers of the pleura. If the inflammation persists, excess fluid accumulates in the pleural space, a condition known as pleural effusion.

Figure 23.10 Surface Anatomy of the Lungs.

Clinical Connection

Pneumothorax and Hemothorax

In certain conditions, the pleural cavities may fill with air (pneumothorax; numothoraks; pneumo-= air or breath), blood (hemothorax), or pus. Air in the pleural cavities, most commonly introduced in a surgical opening of the chest or as a result of a stab or gunshot wound, may cause the lungs to collapse. This collapse of a part of a lung, or rarely an entire lung, is called atelectasis atelektasis; ateles-= incomplete; -ectasis = expansion). The goal of treatment is the evacuation of air (or blood) from the pleural cavity, which allows the lung to reinflate. A small pneumothorax may resolve on its own, but it is often necessary to insert a chest tube to assist in evacuation.

The lungs extend from the diaphragm to just slightly superior to the clavicles and lie against the ribs anteriorly and posteriorly (Figure 23.10a). The broad inferior portion of the lung, the base, is concave and fits over the convex area of the diaphragm. The narrow superior portion of the lung is the apex. The surface of the lung lying against the ribs, the The oblique fissure divides the left lung into two lobes. The oblique and horizontal fissures divide the right lung into three lobes. costal surface, matches the rounded curvature of the ribs. The mediastinal (medial) surface of each lung contains a region, the hilum, through which bronchi, pulmonary blood vessels, lymphatic vessels, and nerves enter and exit (Figure 23.10e). These structures are held together by the pleura and connective tissue and constitute the root of the lung. Medially, the left lung also contains a concavity, the cardiac notch, in which the apex of the heart lies. Due to the space occupied by the heart, the left lung is about 10% smaller than the right lung is thicker and broader, it is also somewhat shorter than the left lung because the diaphragm is higher on the right side, accommodating the liver that lies inferior to it.

The lungs almost fill the thorax (Figure 23.10a). The apex of the lungs lies superior to the medial third of the clavicles, and this is the only area that can be palpated. The anterior, lateral, and posterior surfaces of the lungs lie against the ribs. The base of the lungs extends from the sixth costal cartilage anteriorly to the spinous process of the tenth thoracic vertebra posteriorly. The pleura extends about 5 centimeters (2 in.) below the base from the sixth costal cartilage anteriorly to the twelfth rib posteriorly.

Thus, the lungs do not completely fill the pleural cavity in this area. Removal of excessive fluid in the pleural cavity can be accomplished without injuring lung tissue by inserting a needle anteriorly through the seventh intercostal space, a procedure called thoracentesis (thor'a-sen-TÉ-sis; -centesis = puncture). The needle is passed along the superior border of the lower rib to avoid damage to the intercostal nerves and blood vessels. Inferior to the seventh intercostal space there is danger of penetrating the diaphragm.

Lobes, Fissures, and Lobules One or two fissures divide each lung into sections called lobes (Figure 23.10b-e). Both lungs have an oblique fissure, which extends inferiorly and anteriorly; the right lung also has a horizontal fissure. The oblique fissure in the left lung separates the superior lobe from the inferior lobe. In the right lung, the superior part of the oblique fissure separates the superior lobe from the inferior lobe; the inferior part of the oblique fissure separates the inferior lobe from the middle lobe, which is bordered superiorly by the horizontal fissure.

Each lobe receives its own lobar bronchus. Thus, the right main bronchus gives rise to three lobar bronchi called the superior, middle, and inferior lobar bronchi, and the left main bronchus gives rise to two lobar bronchi called the superior and inferior lobar bronchi. Within the lung, the lobar bronchi give rise to the segmental bronchi, which are constant in both origin and distribution—there are 10 segmental bronchi in each lung. The portion of lung tissue that each segmental bronchus supplies is called a bronchopulmonary segment brongkopulmonare. Bronchial and pulmonary disorders (such as tumors or abscesses) that are localized in a bronchopulmonary segment may be surgically removed without seriously disrupting the surrounding lung tissue.

Each bronchopulmonary segment of the lungs has many small compartments called lobules; each lobule is wrapped in elastic connective tissue and contains a lymphatic vessel, an arteriole, a venule, and a branch from a terminal bronchiole (Figure 23.11a). Terminal bronchioles in a lobule subdivide into microscopic branches called respiratory bronchioles (Figure 23.11b). They also have pulmonary alveoli (described shortly) budding from their walls. Pulmonary alveoli participate in gas exchange, and thus respiratory bronchioles begin the respiratory zone of the respiratory system. As the respiratory bronchioles penetrate more deeply into the lungs, the epithelial lining changes from simple cuboidal to simple squamous. Respiratory bronchioles in turn subdivide into several (2 to 11) alveolar ducts (al-vê-Ô-lar), which consist of simple squamous epithelium.

Alveolar Saccules and Pulmonary Alveoli The terminal dilation of an alveolar duct is called an alveolar saccule or alveolar sac and is analogous to a cluster of grapes. Each alveolar saccule is composed of outpouchings called pulmonary alveoli (al-ve-آ-li), analogous to individual grapes (Figure 23.11). There are about 100 alveolar saccules at the end of each alveolar duct and each alveolar saccule contains about 20 to 30 pulmonary alveoli, which are 200 to 300 μm (0.2 to 0.3 millimeters) in diameter. The wall of each pulmonary alveolus (singular) consists of two types of alveolar epithelial cells (Figure 23.12). The more numerous (about 95%) pneumocyte type I (type I alveolar cell) are simple squamous epithelial cells that form a nearly continuous lining of the pulmonary alveolar wall. Pneumocyte type 2 (type 2 alveolar cell), also called septal cells, are fewer in number and are found between pneumocytes type I. The thin wall of pneumocytes type I are the main sites of gas exchange. Pneumocytes type 2 are rounded or cuboidal epithelial cells with

Figure 23.12 summary: This figure consists of a series of anatomical diagrams and micrographs. The content includes a schematic illustration of a pulmonary alveolus showing the respiratory membrane and gas exchange process, a light micrograph of lung tissue, and a scanning electron micrograph of alveolar structures. The figure demonstrates that the thinness of the respiratory membrane, composed of pneumocytes and capillary endothelium, facilitates the efficient diffusion of oxygen into the blood and carbon dioxide into the alveoli. It further illustrates the presence of specialized cells such as alveolar macrophages and different types of pneumocytes within the lung architecture to maintain air space cleanliness and structural integrity.

Figure 23.10 summary: This figure consists of a series of anatomical diagrams. The images provide an anterior view of the lungs and pleurae within the thoracic cavity, as well as lateral and medial views of both the right and left lungs. The content illustrates the spatial relationship between the lungs, the ribs, and the pleural membranes. It identifies key anatomical landmarks including the apex and base of the lungs, the pleural cavity, and the pleura. The detailed views of the individual lungs highlight the division of the organs into lobes by horizontal and oblique fissures, the location of the cardiac notch on the left lung, and the position of the hilum where the root contents enter the lungs. From these diagrams, it can be inferred that the right and left lungs are asymmetrical in their structure. The right lung is divided into more lobes than the left lung due to the presence of an additional fissure. Furthermore, the left lung features a distinct indentation, the cardiac notch, to accommodate the heart's position within the thoracic cavity.

Figure 23.11 Microscopic Anatomy of a Lobule of the Lungs.

free surfaces containing microvilli, secrete pulmonary alveolar fluid, which keeps the surface between the cells and the air moist. Included in the pulmonary alveolar fluid is surfactant surfaktant, a complex mixture of phospholipids and lipoproteins. Surfactant lowers the surface tension of pulmonary alveolar fluid, which reduces the tendency of pulmonary alveoli to collapse and thus maintains their patency (described later).

Also present in the pulmonary alveolar wall are alveolar macrophages, phagocytes that remove fine dust particles and other debris from the pulmonary alveolar spaces, and fibroblasts that produce reticular and elastic fibers. Underlying the layer of pneumocytes type I is an elastic basement membrane. On the outer surface of the pulmonary alveoli, the lobule's arteriole and venule disperse into a network of blood capillaries (see Figure 23.11a) that consist of a single layer of endothelial cells and basement membrane.

The exchange of O 2 and C-O 2 between the air spaces in the lungs and the blood takes place by diffusion across the pulmonary alveolar and capillary walls, which together form the respiratory membrane. Extending from the pulmonary alveolar air space to blood plasma, the respiratory membrane consists of four layers (Figure 23.12b):

1. A layer of pneumocytes type I and type 2 and associated alveolar macrophages that constitutes the alveolar wall

2. An epithelial basement membrane underlying the pulmonary alveolar wall

3. A capillary basement membrane that is often fused to the epithelial basement membrane

4. The capillary endothelium

Despite having several layers, the respiratory membrane is very thin—only 0.5 mu m thick, about one-sixteenth the diameter of a red blood cell—to allow rapid diffusion of gases. It has been estimated that both lungs contain 300 to 500 million pulmonary alveoli, providing an immense surface area of about 75 m (807 ft ^2 ) —about the size of a racquetball court or slightly

Clinical Connection

Coryza and Seasonal Influenza

Hundreds of viruses can cause coryza (ko-Ri-za), which is the common cold, but a group of viruses called rhinoviruses (Ri-no-virus-es) is responsible for about 40 percent of all colds in adults.

Recent investigations suggest an association between emotional stress and the common cold. The higher the stress level, the greater the frequency and duration of colds.

Seasonal influenza (flu) is also caused by viruses, called influenza viruses. The influenza viruses responsible for seasonal influenza are designated as influenza type A virus and influenza type B virus. It is important to recognize that influenza is a respiratory disease, not a digestive canal disease. Many people mistakenly report having seasonal flu when they are suffering from a digestive canal illness.

Because the cold and flu have some overlapping signs and symptoms, it is not always easy to distinguish between the two. However, there are some guidelines as follows. The onset of the flu is generally abrupt and the signs and symptoms are more intense; the onset of a cold is more gradual and the signs and symptoms are typically milder. The flu is usually accompanied by chills and a fever higher than 101 degrees Fahrenheit 33 degrees Celsius that lasts for several days; this is rare with a cold. The flu can result in life-threatening complications, such as pneumonia, worsening of heart disease and bronchial asthma, neurological conditions that range from confusion to seizures, and respiratory failure.

A cold may be accompanied by less serious complications such as sinusitis, ear infections, laryngitis, and bronchitis. General body aches, headache, fatigue, and weakness are typical and often severe with the flu, but milder or rare with a cold. Sneezing, stuffy nose, and sore throat occur sometimes with the flu, but are more common with a cold. larger—for gas exchange. The hundreds of millions of pulmonary alveoli account for the spongy texture of the lungs.

Blood Supply to the Lungs The lungs receive blood via two sets of arteries: pulmonary arteries and bronchial arteries. Deoxygenated blood passes through the pulmonary trunk, which divides into a left pulmonary artery that enters the left lung and a right pulmonary artery that enters the right lung. (The pulmonary arteries are the only arteries in the body that carry deoxygenated blood.) Return of the oxygenated blood to the heart occurs by way of the four pulmonary veins, which drain into the left atrium (see Figure 21.30). A unique feature of pulmonary blood vessels is their constriction in response to localized hypoxia (low O 2 level). In all other body tissues, hypoxia causes dilation of blood vessels to increase blood flow. In the lungs, however, vasoconstriction in response to hypoxia diverts pulmonary blood from poorly ventilated areas of the lungs to well-ventilated regions for more efficient gas exchange. This phenomenon is known as ventilation-perfusion coupling perfyuzhun because the perfusion (blood flow) to each area of the lungs matches the extent of ventilation (airflow) to alveoli in that area.

Bronchial arteries, which branch from the ay-or-tuh, deliver oxygenated blood to the lungs. This blood mainly perfuses the muscular walls of the bronchi and bronchioles. Connections do exist between branches of the bronchial arteries and branches of the pulmonary arteries, however; most blood returns to the heart via pulmonary veins. Some blood drains into bronchial

The ultimate goal of vaccination against the flu is to make a vaccine that will protect against all strains (variations) of the flu and provide long-term immunity to the general population. Unfortunately, this goal has not been reached for several reasons. Using information from numerous countries in the northern hemisphere each year, usually in February, scientists use various data to decide which strains of the virus should be incorporated into the vaccine for use later that year. This is not easy to predict and the vaccine may not contain all of the strains responsible for the flu in a given year. Further, circulating strains of the virus can mutate (change rapidly), rendering the vaccine ineffective.

For those individuals who develop the flu, antiviral medications may be taken. These include Tamiflu ^{} and Relenza ^{} . These medications can ease the signs and symptoms and shorten the duration of the illness and are most effective when given within 24 hours of the first signs and symptoms. Other treatments for the flu depend on the signs and symptoms and may include bedrest, decongestants, antihistamines, cough medications, and medications to relieve fever and body aches.

In order to prevent infection: (1) wash your hands often with soap and water or use an alcohol-based sanitizer; (2) cover your mouth with a tissue when coughing or sneezing and disposing of the tissue or cough or sneeze into your elbow, not your hands; (3) avoid touching your mouth, nose, or eyes; (4) do not share personal items such as makeup, utensils, or sports or office equipment; (5) avoid close contact (within six feet) with people who have flu-like signs and symptoms; and (6) stay home for seven days after signs and symptoms begin or after being free of signs and symptoms for 24 hours, whichever is longer.

Figure 23.12 Structural components of a pulmonary alveolus. The respiratory membrane consists of a layer of pneumocytes type I and pneumocytes type 2, an epithelial basement membrane, a capillary basement membrane, and the capillary endothelium.

The exchange of respiratory gases occurs by diffusion across the respiratory membrane. veins, branches of the azygos system, and returns to the heart via the superior vena cava.

Patency of the Respiratory System

Throughout the discussion of the respiratory organs, several examples were given of structures or secretions that help to maintain patency of the system so that air passageways are kept free of obstruction. These included the bony and cartilaginous frameworks of the nose, skeletal muscles of the pharynx, cartilages of the larynx, C-shaped rings of cartilage in the trachea and bronchi, smooth muscle in the bronchioles, and surfactant in the pulmonary alveoli.

Unfortunately, there are also factors that can compromise patency. These include crushing injuries to bone and cartilage, a deviated nasal septum, nasal polyps, inflammation of mucous membranes, spasms of smooth muscle, and a deficiency of surfactant.

A summary of the epithelial linings and special features of the organs of the respiratory system is presented in Table 23.1.

Table 23.1 summary: This table outlines the histological characteristics of the respiratory system, showing a transition in epithelium from protective stratified squamous in the nasal vestibule and lower pharynx to ciliated pseudostratified columnar in the primary conducting pathways. As the airways narrow from the trachea through the bronchi and into the bronchioles, the epithelium becomes simpler and thinner, eventually becoming simple squamous in the alveolar ducts and alveoli to facilitate gas exchange. The presence of cilia and goblet cells is widespread in the upper and middle conducting regions but disappears in the most distal respiratory zones.

9. Where are the lungs located? Distinguish the parietal pleura from the visceral pleura.

10. Define each of the following parts of a lung: base, apex, costal surface, medial surface, hilum, root, cardiac notch, lobe, and lobule.

11. What is a bronchopulmonary segment?

12. Describe the histology and function of the respiratory membrane.

23.4 Pulmonary Ventilation

Objective

- Describe the events that cause inhalation and exhalation.

Pulmonary ventilation, or breathing, is the flow of air into and out of the lungs. In pulmonary ventilation, air flows between the atmosphere and the pulmonary alveoli of the lungs because of alternating pressure differences created by contraction and relaxation of respiratory muscles. The rate of airflow and the amount of effort needed for breathing are also influenced by alveolar surface tension, compliance of the lungs, and airway resistance.

Pressure Changes During Pulmonary Ventilation

Air moves into the pulmonary alveoli of the lungs when the air pressure inside the lungs is less than the air pressure in the atmosphere. Air moves out of the pulmonary alveoli of the lungs when the air pressure inside the lungs is greater than the air pressure in the atmosphere.

Inhalation Breathing in is called inhalation (inspiration). Just before each inhalation, the air pressure inside the lungs is equal to the air pressure of the atmosphere, which at sea level is about 760 millimeters of mercury (mmHg), or 1 atmosphere (atm). For air to flow into the lungs, the pressure inside the pulmonary alveoli must become lower than the atmospheric pressure. This condition is achieved by increasing the size of the lungs.

The pressure of a gas in a closed container is inversely proportional to the volume of the container. This means that if the size of a closed container is increased, the pressure of the gas inside the container decreases, and that if the size of the container is decreased, then the pressure inside it increases. This inverse relationship between volume and pressure, called Boyle's law, may be demonstrated as follows (Figure 23.13): Suppose we place a gas in a cylinder that has a movable piston

Figure 23.13 summary: This figure is a conceptual diagram. It illustrates a gas-filled cylinder equipped with a movable piston and a pressure gauge, showing two different states of the system. In the first state, the piston is high, resulting in a larger volume and a lower pressure reading. In the second state, the piston is pushed down, compressing the gas into a smaller volume and causing the pressure gauge to show a higher reading. The diagram demonstrates an inverse relationship between volume and pressure for a fixed amount of gas. As the volume of the container decreases, the pressure increases, indicating that compressing the gas leads to a higher frequency of collisions against the container walls.

Figure 23.13 Boyle's Law.

The volume of a gas varies inversely with its pressure. and a pressure gauge, and that the initial pressure created by the gas molecules striking the wall of the container is 1 atm. If the piston is pushed down, the gas is compressed into a smaller volume, so that the same number of gas molecules strikes less wall area. The gauge shows that the pressure doubles as the gas is compressed to half its original volume. In other words, the same number of molecules in half the volume produces twice the pressure.

Conversely, if the piston is raised to increase the volume, the pressure decreases. Thus, the pressure of a gas varies inversely with volume.

Differences in pressure caused by changes in lung volume force air into our lungs when we inhale and out when we exhale. For inhalation to occur, the lungs must expand, which increases lung volume and thus decreases the pressure in the lungs to below atmospheric pressure. The first step in expanding the lungs during normal quiet inhalation involves contraction of the main muscle of inhalation, the diaphragm, with resistance from external intercostals (Figure 23.14).

The most important muscle of inhalation is the diaphragm, the dome-shaped skeletal muscle that forms the floor of the thoracic cavity. It is innervated by fibers of the phrenic nerves, which emerge from the spinal cord at cervical levels 3, 4, and 5. Contraction of the diaphragm causes it to flatten, lowering its dome. This increases the vertical diameter of the thoracic cavity.

During normal quiet inhalation, the diaphragm descends about 1 centimeters (0.4 in.), producing a pressure difference of 1 to 3 mmHg and the inhalation of about 500 mL of air. In strenuous breathing, the diaphragm may descend 10 centimeters (4 in.), which produces a pressure difference of 100 mmHg and the inhalation of 2 to 3 liters of air. Contraction of the diaphragm is responsible for about 75% of the air that enters the lungs during quiet breathing. Advanced pregnancy, excessive obesity, or confining abdominal clothing can prevent complete descent of the diaphragm.

The next most important muscles of inhalation are the external intercostals. When these muscles contract, they elevate the ribs. As a result, there is an increase in the anteroposterior and lateral diameters of the chest cavity. Contraction of the external intercostals is responsible for about 25% of the air that enters the lungs during normal quiet breathing.

Figure 23.14 Muscles of inhalation and exhalation. The pectoralis minor muscle (not shown here) is illustrated in Figure 11.14a.

During normal, quiet inhalation, the diaphragm and external intercostals contract, the lungs expand, and air moves into the pulmonary alveoli of the lungs; during normal, quiet exhalation, the diaphragm and external intercostals relax and the lungs recoil, forcing air out of the pulmonary alveoli of the lungs.

Right now, what is the main muscle that is powering your breathing?

Intrapleural pressure is the pressure within the pleural cavity. Recall that the pleural cavity is the space between the parietal pleura and visceral pleura (see Figure 23.15). A small amount of lubricating fluid is present in this space. Intrapleural pressure is always a negative pressure (lower than atmospheric pressure), ranging from 754 to 756 mmHg during normal quiet breathing.

Figure 23.15 summary: This figure consists of a series of anatomical diagrams and a conceptual illustration. The content depicts the mechanical process of breathing, showing the thoracic cavity and diaphragm in different states, alongside an illustration of a bucket handle to serve as an analogy for rib movement. Based on the diagrams, it can be inferred that inhalation occurs when the diaphragm contracts and the lower ribs move upward and outward, increasing the volume of the thoracic cavity and lowering alveolar pressure relative to atmospheric pressure. Conversely, the process of exhalation involves the relaxation of these structures, which increases alveolar pressure and forces air out of the lungs.

Because the pleural cavity has a negative pressure, it essentially functions as a vacuum. The suction of this vacuum attaches the visceral pleura to the chest wall. Thus, if the thoracic cavity increases in size, the lungs also expand; if the thoracic cavity decreases in size, the lungs recoil (become smaller). Just before inhalation, intrapleural pressure is about 4 mmHg less than atmospheric pressure, or about 756 mmHg at an atmospheric pressure of 760 mmHg (Figure 23.15). As the diaphragm and external intercostals contract and the overall size of the thoracic cavity increases, the volume of the pleural cavity also increases, which causes intrapleural pressure to decrease to about 754 mmHg. As the thoracic cavity expands, the parietal pleura lining the cavity is pulled outward in all directions, and the visceral pleura and lungs and pulled along with it.

As the volume of the lungs increases in this way, the pressure of air within the pulmonary alveoli of the lungs, called the alveolar (intrapulmonic) pressure, drops from 760 to 758 mmHg. A pressure difference is thus established between the atmosphere and the pulmonary alveoli. Because air always flows from a region of higher pressure to a region of lower pressure, inhalation takes place. Air continues to flow into the lungs as long as a pressure difference exists. Although the lungs enlarge in all directions during inhalation, most of the increase in volume appears to be due to the lengthening and expansion of the Figure 23.15 Pressure changes in pulmonary ventilation. During inhalation, the diaphragm contracts, the chest expands, the lungs are pulled outward, and alveolar pressure decreases. During exhalation, the diaphragm relaxes, the lungs recoil inward, and alveolar pressure increases, forcing air out of the lungs.

Air moves into the lungs when alveolar pressure is less than atmospheric pressure, and out of the lungs when alveolar pressure is greater than atmospheric pressure.

1. At rest, when the diaphragm is relaxed, alveolar pressure is equal to atmospheric pressure, and there is no air flow.

Q How does the intrapleural pressure change during a normal, quiet breath? alveolar ducts and the increase in size of the openings into the alveoli. During deep, forceful inhalations, accessory muscles of inspiration also participate in increasing the size of the thoracic cavity (see Figure 23.14a). The muscles are so named because they make little, if any, contribution during normal quiet inhalation, but during exercise or forced breathing they may contract vigorously. The accessory muscles of inhalation include the sternocleidomastoid muscles, which elevate the sternum; the scalene muscles, which elevate the first two ribs; and the pectoralis minor muscles, which elevate the third through fifth ribs. Because both normal quiet inhalation and inhalation during exercise or forced breathing involve muscular contraction, the process of inhalation is said to be active.

2. During inhalation, the diaphragm contracts and the external intercostals contract. The chest cavity expands, and the alveolar pressure drops below atmospheric pressure. Air flows into the lungs in response to the pressure gradient and the lung volume expands. During deep inhalation, the scalene and sternocleidomastoid muscles expand the chest further, thereby creating a greater drop in alveolar pressure.

Exhalation Breathing out, called exhalation (expiration), is also due to a pressure gradient, but in this case the gradient is in the opposite direction: The pressure in the lungs is greater than the pressure of the atmosphere. Normal exhalation during quiet breathing, unlike inhalation, is a passive process because no muscular contractions are involved. Instead, exhalation results from elastic recoil of the chest wall and lungs, both of which have a natural tendency to spring back after they have been stretched. Two inwardly directed forces contribute to elastic recoil: (1) the recoil of elastic fibers that were stretched during inhalation and (2) the inward pull of surface tension due to the film of intrapleural fluid between the visceral and parietal pleura.

Exhalation starts when the inspiratory muscles relax. As the diaphragm relaxes, its dome moves superiorly owing to its elasticity. As the external intercostals relax, the ribs are depressed.

These movements decrease the vertical, lateral, and anteroposterior diameters of the thoracic cavity, which decreases lung volume. In turn, the alveolar pressure increases to about 762 mmHg. Air then flows from the area of higher pressure in the pulmonary alveoli to the area of lower pressure in the atmosphere (see Figure 23.15).

Exhalation becomes active only during forceful breathing, as occurs while playing a wind instrument or during exercise. During these times, muscles of exhalation—the abdominal and internal intercostals (see Figure 23.14a)—contract, which increases pressure in the abdominal region and thorax. Contraction of the abdominal muscles moves the inferior ribs downward and compresses the abdominal viscera, thereby forcing the diaphragm superiorly.

Contraction of the internal intercostals, which extend inferiorly and posteriorly between adjacent ribs, pulls the ribs inferiorly. Although intrapleural pressure is always less than alveolar pressure, it may briefly exceed atmospheric pressure during a forceful exhalation, such as during a cough.

Other Factors Affecting Pulmonary Ventilation

As you have just learned, air pressure differences drive airflow during inhalation and exhalation. However, three other factors affect the rate of airflow and the ease of pulmonary ventilation: surface tension of the alveolar fluid, compliance of the lungs, and airway resistance.

Surface Tension of Alveolar Fluid

As noted earlier, a thin layer of alveolar fluid coats the luminal surface of pulmonary alveoli and exerts a force known as surface tension. Surface tension arises at all air-water interfaces because the polar water molecules are more strongly attracted to each other than they are to gas molecules in the air. When liquid surrounds a sphere of air, as in a pulmonary alveolus or a soap bubble, surface tension produces an inwardly directed force.

Soap bubbles “burst” because they collapse inward due to surface tension. In the lungs, surface tension causes the pulmonary alveoli to assume the smallest possible diameter. During breathing, surface tension must be overcome to expand the lungs during each inhalation.

Surface tension also accounts for two-thirds of lung elastic recoil, which decreases the size of pulmonary alveoli during exhalation.

The surfactant (a mixture of phospholipids and lipoproteins) present in alveolar fluid reduces its surface tension below the surface tension of pure water. A deficiency of surfactant in premature infants causes respiratory distress syndrome, in which the surface tension of pulmonary alveolar fluid is greatly increased, so that many pulmonary alveoli collapse at the end of each exhalation. Great effort is then needed at the next inhalation to reopen the collapsed pulmonary alveoli.

Respiratory Distress Syndrome

Respiratory distress syndrome (R.D.S) is a breathing disorder of premature newborns in which the pulmonary alveoli do not remain open due to a lack of surfactant. Recall that surfactant reduces surface tension and is necessary to prevent the collapse of pulmonary alveoli during exhalation. The more premature the newborn, the greater the chance that R.D.S will develop. The condition is also more common in infants whose mothers have diabetes and in males; it also occurs more often in European Americans than African Americans. Symptoms of R.D.S include labored and irregular breathing, flaring of the nostrils during inhalation, grunting during exhalation, and perhaps a blue skin color.

Besides the symptoms, R.D.S is diagnosed on the basis of chest radiographs and a blood test. A newborn with mild R.D.S may require only supplemental oxygen administered through an oxygen hood or through a tube placed in the nose. In severe cases oxygen may be delivered by continuous positive airway pressure (C.P.A.P) through tubes in the nostrils or a mask on the face. In such cases surfactant may be administered directly into the lungs.

Compliance of the Lungs Compliance refers to how much effort is required to stretch the lungs and chest wall. High compliance means that the lungs and chest wall expand easily; low compliance means that they resist expansion. By analogy, a thin balloon that is easy to inflate has high compliance, and a heavy and stiff balloon that takes a lot of effort to inflate has low compliance.

In the lungs, compliance is related to two principal factors: elasticity and surface tension. The lungs normally have high compliance and expand easily because elastic fibers in lung tissue are easily stretched and surfactant in alveolar fluid reduces surface tension. Decreased compliance is a common feature in pulmonary conditions that (1) scar lung tissue (for example, tuberculosis), (2) cause lung tissue to become filled with fluid (pulmonary edema), (3) produce a deficiency in surfactant, or (4) impede lung expansion in any way (for example, paralysis of the intercostal muscles).

Increased lung compliance occurs in emphysema (see Disorders: Homeostatic Imbalances at the end of the chapter) due to destruction of elastic fibers in alveolar walls.

Airway Resistance Like the flow of blood through blood vessels, the rate of airflow through the airways depends on both the pressure difference and the resistance: Airflow equals the pressure difference between the pulmonary alveoli and the atmosphere divided by the resistance. The walls of the airways, especially the bronchioles, offer some resistance to the normal flow of air into and out of the lungs. As the lungs expand during inhalation, the bronchioles enlarge because their walls are pulled outward in all directions.

Larger-diameter airways have decreased resistance. Airway resistance then increases during exhalation as the diameter of bronchioles decreases. Airway diameter is also regulated by the degree of contraction or relaxation of smooth muscle in the walls of the airways. Signals from the sympathetic division of the autonomic nervous system (A.N.S) cause relaxation of bronchiolar smooth muscle (bronchodilation), which results in decreased resistance. Signals from the parasympathetic part of the A.N.S cause contraction of bronchiolar smooth muscle (bronchoconstriction) resulting in increased resistance.

Any condition that narrows or obstructs the airways increases resistance, so that more pressure is required to maintain the same airflow. The hallmark of asthma or chronic obstructive pulmonary disease (C.O.P.D)—emphysema or chronic bronchitis—is increased airway resistance due to obstruction or collapse of airways.

Breathing Patterns and Modified Breathing Movements

The term for the normal pattern of quiet breathing is eupnea (üp-NË-a; eu-= good, easy, or normal; -pnea = breath). Eupnea can consist of shallow, deep, or combined shallow and deep breathing. A pattern of shallow (chest) breathing, called costal breathing, consists of an upward and outward movement of the chest due to contraction of the external intercostal muscles. A pattern of deep (abdominal) breathing, called diaphragmatic breathing diafragmatik, consists of the outward movement of the abdomen due to the contraction and descent of the diaphragm.

Breathing also provides humans with methods for expressing emotions such as laughing, sighing, and sobbing and can be used to expel foreign matter from the lower air passages through actions such as sneezing and coughing. Breathing movements are also modified and controlled during talking and singing. Some of the modified breathing movements that express emotion or clear the airways are listed in Table 23.2. All of these movements are reflexes, but some of them also can be initiated voluntarily.

Table 23.2 summary: This table describes various modified breathing movements, detailing the specific physiological mechanisms of inhalation and exhalation, the role of the rima glottidis, and the typical stimuli or purposes associated with each action, ranging from reflexive responses like coughing and sneezing to emotional expressions such as crying and laughing.

Checkpoint

23.5 Lung Volumes and Capacities

- Explain the differences among tidal volume, inspiratory reserve volume, expiratory reserve volume, and residual volume.

• Differentiate among inspiratory capacity, functional residual capacity, vital capacity, and total lung capacity.

During inhalation and exhalation, varying amounts of air move into and out of the lungs. These amounts depend on many factors related to various characteristics of healthy individuals and pulmonary disorders. The different amounts of air can be classified into two types: (1) lung volumes, which can be measured directly by use of a spirometer (described shortly) and (2) lung capacities, which are combinations of different lung volumes. The apparatus used to measure volumes and capacities is called a spirometer spirometer; spiro-= breathe; -meter = measuring device) or respirometer respirometer. The record is called a spirogram. Inhalation is recorded as an upward deflection and exhalation is recorded as a downward deflection (Figure 23.16). In general, lung volumes and capacities are larger in males, taller individuals, younger adults, people who live at higher altitudes, and those who are not obese. Various disorders may be diagnosed by comparison of actual and predicted normal values for a person's gender, height, and age.

Figure 23.16 summary: This figure is a line graph representing a spirogram. It illustrates various lung volumes and capacities over time, depicting cycles of inhalation and exhalation including normal tidal breathing and maximal respiratory efforts. The data indicates that total lung capacity is the sum of all other volumes, while vital capacity represents the maximum amount of air a person can expel after a maximum inhalation. The graph demonstrates that the inspiratory reserve volume is the largest single volume, significantly exceeding the tidal volume and the expiratory reserve volume.

Lung Volumes

While at rest, a healthy adult averages 12 breaths a minute, with each inhalation and exhalation moving about 500 mL of air into and out of the lungs. The volume of one breath is called the tidal volume (5 T) .

Tidal volume varies considerably from one person to another and in the same person at different times. In a typical adult, about 70% of the tidal volume (350 mL) actually reaches the respiratory zone of the respiratory system—the respiratory bronchioles, alveolar ducts, alveolar saccules, and alveoli—and participates in external respiration. The other 30% (150 mL) remains in the conducting airways of the nose, pharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles. Collectively, the conducting airways with air that does not undergo respiratory exchange are known as the anatomic (respiratory) dead space. (An easy rule of thumb for determining the volume of your anatomic dead space is that it is about the same in milliliters as your ideal weight in pounds.) Not all of the inhaled air can be used in gas exchange because some of it remains in the anatomic dead space.

Figure 23.16 Spirogram of lung volumes and capacities. The average values for a healthy adult male and female are indicated, with the values for a female in parentheses. Note that the spirogram is read from right (start of record) to left (end of record).

Lung capacities are combinations of various lung volumes.

By taking a very deep breath, you can inhale a good deal more than 500 mL. This additional inhaled air, called the inspiratory reserve volume I.R.V, is about 3100 mL in an average adult male and 1900 mL in an average adult female (Figure 23.16). Even more air can be inhaled if inhalation follows forced exhalation. If you inhale normally and then exhale as forcibly as possible, you should be able to push out considerably more air in addition to the 500 mL of tidal volume. The extra 1200 mL in males and 700 mL in females is called the expiratory reserve volume E.R.V. The forced expiratory volume in 1 second (F.E.V.1) is the volume of air that can be exhaled from the lungs in 1 second with maximal effort following a maximal inhalation. Typically, chronic obstructive pulmonary disease (C.O.P.D) greatly reduces F.E.V.1 because C.O.P.D increases airway resistance.

Even after the expiratory reserve volume is exhaled, considerable air remains in the lungs because the subatmospheric intrapleural pressure keeps the alveoli slightly inflated, and some air remains in the noncollapsible airways. This volume, which cannot be measured by spirometry, is called the residual volume residual R.V and amounts to about 1200 mL in males and 1100 mL in females.

If the thoracic cavity is opened, the intrapleural pressure rises to equal the atmospheric pressure and forces out some of the residual volume. The air remaining is called the minimal volume. Minimal volume provides a medical and legal tool for determining whether a baby is born dead (stillborn) or died after birth. The presence of minimal volume can be demonstrated by placing a piece of lung in water and observing if it floats. Fetal lungs contain no air, so the lung of a stillborn baby will not float in water.

Lung Capacities

Lung capacities are combinations of specific lung volumes (Figure 23.16). Inspiratory capacity I.C is the sum of tidal volume and inspiratory reserve volume (500 mL + 3100 mL = 3600 mL in males and 500 mL + 1900 mL = 2400 mL in females). Functional residual capacity F.R.C is the sum of residual volume and expiratory reserve volume (1200 mL + 1200 mL = 2400 mL in males and 1100 mL + 700 mL = 1800 mL in females). Vital capacity V.C is the sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume (4800 mL in males and 3100 mL in females). Finally, total lung capacity T.L.C is the sum of vital capacity and residual volume (4800 mL + 1200 mL = 6000 mL in males and 3100 mL + 1100 mL = 4200 mL in females).

Another way to assess pulmonary function is to determine the amount of air that flows into and out of the lungs each minute. The minute ventilation (5)—the total volume of air inspired and expired each minute—is tidal volume multiplied by respiratory rate. In a typical adult at rest, minute ventilation is about 6000 milliliters per minute (V = 12 breaths per minute × 500 mL = 6000 milliliters per minute). A lower-than-normal minute ventilation usually is a sign of pulmonary malfunction.

As noted earlier, not all of inhaled air (500 mL) actually reaches the respiratory zone of the respiration system. The 150 mL in the conducting zone is the anatomic dead space.

Hence, not all of the minute ventilation can be used in gas exchange because some of it remains in the anatomic dead space. The alveolar ventilation ( {V}_{A} ) is the volume of air per minute that actually reaches the respiratory zone (350 mL). Alveolar ventilation is typically about 4200 milliliters per minute ( {V}_{A} = 12 breaths per minute × 350 mL = 4200 milliliters per minute).

17. What is a spirometer?

18. What is the difference between a lung volume and a lung capacity?

19. How is minute ventilation calculated?

20. Define alveolar ventilation rate and forced expiratory volume in 1 second.

23.6 Exchange of Oxygen and Carbon Dioxide

Objectives

• Explain Dalton's law and Henry's law.

• Describe the exchange of oxygen and carbon dioxide in external and internal respiration.

The exchange of oxygen and carbon dioxide between alveolar air and pulmonary blood occurs via passive diffusion, which is governed by the behavior of gases as described by two gas laws, Dalton's law and Henry's law. Dalton's law is important for understanding how gases move down their pressure gradients by diffusion, and Henry's law helps explain how the solubility of a gas relates to its diffusion.

Gas Laws: Dalton's Law and Henry's Law

According to Dalton's law, each gas in a mixture of gases exerts its own pressure as if no other gases were present. The pressure of a specific gas in a mixture is called its partial pressure (P 10) ; the subscript is the chemical formula of the gas. The total pressure of the mixture is calculated simply by adding all of the partial pressures.

Atmospheric air is a mixture of gases—nitrogen N 2, oxygen O 2, argon Ar, carbon dioxide C O 2, variable amounts of water vapor H 2 O, plus other gases present in small quantities. Atmospheric pressure is the sum of the pressures of all of these gases:

Math summary: This calculation determines the total atmospheric pressure by performing a summation. It adds together the individual pressure values of nitrogen, oxygen, argon, water vapor, carbon dioxide, and other trace gases to produce the final total pressure.

We can determine the partial pressure exerted by each component in the mixture by multiplying the percentage of the gas in the mixture by the total pressure of the mixture. Atmospheric air is 78.6% nitrogen, 20.9% oxygen, 0.093% argon, 0.04% carbon dioxide, and 0.06% other gases; a variable amount of water vapor is also present. The amount of water varies from practically 0% over a desert to 4% over the ocean, to about 0.3% on a cool, dry day. Thus, the partial pressures of the gases in inhaled air are as follows:

Math summary: This calculation determines the partial pressure of individual gases within a mixture. It multiplies the fractional concentration of each gas by the total atmospheric pressure to produce the specific pressure for each component.

These partial pressures determine the movement of O 2 and C-O 2 between the atmosphere and lungs, between the lungs and blood, and between the blood and body cells. Each gas diffuses across a permeable membrane from the area where its partial pressure is greater to the area where its partial pressure is less. The greater the difference in partial pressure, the faster the rate of diffusion.

Compared with inhaled air, alveolar air has less oxygen 2 (13.6% versus 20.9%) and more carbon dioxide 2 (5.2% versus 0.04%) for two reasons. First, gas exchange in the alveoli increases the carbon dioxide 2 content and decreases the oxygen 2 content of alveolar air. Second, when air is inhaled it becomes humidified as it passes along the moist mucosal linings.

As water vapor content of the air increases, the relative percentage that is O 2 decreases. In contrast, exhaled air contains more O 2 than alveolar air (16% versus 13.6%) and less C-O 2 (4.5% versus 5.2%) because some of the exhaled air was in the anatomic dead space and did not participate in gas exchange. Exhaled air is a mixture of alveolar air and inhaled air that was in the anatomic dead space.

Henry's law states that the quantity of a gas that will dissolve in a liquid is proportional to the partial pressure of the gas and its solubility. In body fluids, the ability of a gas to stay in solution is greater when its partial pressure is higher and when it has a high solubility in water. The higher the partial pressure of a gas over a liquid and the higher the solubility, the more gas will stay in solution. In comparison to oxygen, much more C-O 2 is dissolved in blood plasma because the solubility of C-O 2 is 24 times greater than that of O 2 . Even though the air we breathe contains mostly N 2 , this gas has no known effect on bodily functions, and at sea level pressure very little of it dissolves in blood plasma because its solubility is very low.

An everyday experience gives a demonstration of Henry's law. You have probably noticed that a soft drink makes a hissing sound when the top of the container is removed, and bubbles rise to the surface for some time afterward. The gas dissolved in carbonated beverages is C-O 2 . Because the soft drink is bottled or canned under high pressure and capped, the C-O 2 remains dissolved as long as the container is unopened. Once you remove the cap, the pressure decreases and the gas begins to bubble out of solution.

Hyperbaric Oxygenation

A major clinical application of Henry's law is hyperbaric oxygenation (hyper-= over; -baros = pressure), the use of pressure to cause more O 2 to dissolve in the blood. It is an effective technique in treating patients infected by anaerobic bacteria, such as those that cause tetanus and gangrene. (Anaerobic bacteria cannot live in the presence of free O 2 .) A person undergoing hyperbaric oxygenation is placed in a hyperbaric chamber, which contains O 2 at a pressure greater than 1 atmosphere (760 mmHg). As body tissues pick up the O 2 , the bacteria are killed. Hyperbaric chambers may also be used for treating certain heart disorders, carbon monoxide poisoning, gas embolisms, crush injuries, cerebral edema, certain hard-to-treat bone infections caused by anaerobic bacteria, smoke inhalation, near-drowning, asphyxia, vascular insufficiencies, and burns.

Henry's law explains two conditions resulting from changes in the solubility of nitrogen in body fluids. As the total air pressure increases, the partial pressures of all of its gases increase. When a scuba diver breathes air under high pressure, the nitrogen in the mixture can have serious negative effects.

Because the partial pressure of nitrogen is higher in a mixture of compressed air than in air at sea level pressure, a considerable amount of nitrogen dissolves in plasma and interstitial fluid. Excessive amounts of dissolved nitrogen may produce giddiness and other symptoms similar to alcohol intoxication. The condition is called nitrogen narcosis or “rapture of the deep.”

If a diver comes to the surface slowly, the dissolved nitrogen can be eliminated by exhaling it. However, if the ascent is too rapid, nitrogen comes out of solution too quickly and forms gas bubbles in the tissues, resulting in decompression sickness (the bends). The effects of decompression sickness typically result from bubbles in nervous tissue and can be mild or severe, depending on the number of bubbles formed. Symptoms include joint pain, especially in the arms and legs, dizziness, shortness of breath, extreme fatigue, paralysis, and unconsciousness.

External Respiration

External respiration or pulmonary gas exchange is the diffusion of O 2 from air in the pulmonary alveoli of the lungs to blood in pulmonary capillaries and the diffusion of C-O 2 in the opposite direction (Figure 23.17a). External respiration in the lungs converts deoxygenated blood (depleted of some O 2 ) coming from the right side of the heart into oxygenated blood (saturated with O 2 ) that returns to the left side of the heart (see Figure 21.30). As blood flows through the pulmonary capillaries, it picks up O 2 from pulmonary alveolar air and unloads C-O 2 into pulmonary alveolar air. Although this process is commonly called an “exchange” of gases, each gas diffuses independently from the area where its partial pressure is higher to the area where its partial pressure is lower.

Figure 23.17 Changes in partial pressures of oxygen and carbon dioxide (in mmHg) during external and internal respiration.

Figure 23.17 summary: This figure is a biological diagram illustrating the process of gas exchange in the human body. The diagram depicts the circulatory loop between the lungs and systemic tissue cells, showing the movement of oxygen and carbon dioxide through pulmonary ventilation, external respiration in the pulmonary capillaries, and internal respiration in the systemic capillaries. It can be inferred that oxygen moves from the atmospheric air into the blood at the alveoli and is subsequently delivered to the tissue cells, while carbon dioxide follows the opposite path, moving from the tissue cells into the blood to be exhaled by the lungs. The process demonstrates a continuous cycle of oxygenation and deoxygenation of blood to maintain homeostatic gas levels in the body.

Gases diffuse from areas of higher partial pressure to areas of lower partial pressure.

As Figure 23.17a shows, O 2 diffuses from pulmonary alveolar air, where its partial pressure is 105 mmHg, into the blood in pulmonary capillaries, where P O 2 is only 40 mmHg in a resting person. If you have been exercising, the P O 2 will be even lower because contracting muscle fibers are using more O 2 . Diffusion continues until the P O 2 of pulmonary capillary blood increases to match the P O 2 of alveolar air, 105 mmHg. Because blood leaving pulmonary capillaries near pulmonary alveolar air spaces mixes with a small volume of blood that has flowed through conducting portions of the respiratory system, where gas exchange does not occur, the P O 2 of blood in the pulmonary veins is slightly less than the P O 2 in pulmonary capillaries, about 100 mmHg.

While oxygen 2 is diffusing from pulmonary alveolar air into deoxygenated blood, carbon dioxide 2 is diffusing in the opposite direction. The partial pressure of carbon dioxide 2 of deoxygenated blood is 45 millimeters of mercury in a resting person, and the partial pressure of carbon dioxide 2 of pulmonary alveolar air is 40 millimeters of mercury. Because of this difference in partial pressure of carbon dioxide 2, carbon dioxide diffuses from deoxygenated blood into the pulmonary alveoli until the partial pressure of carbon dioxide 2 of the blood decreases to 40 millimeters of mercury. Exhalation keeps alveolar partial pressure of carbon dioxide 2 at 40 millimeters of mercury. Oxygenated blood returning to the left side of the heart in the pulmonary veins thus has a partial pressure of carbon dioxide 2 of 40 millimeters of mercury.

The number of capillaries near pulmonary alveoli in the lungs is very large, and blood flows slowly enough through these capillaries that it picks up a maximal amount of O 2 . During vigorous exercise, when cardiac output is increased, blood flows more rapidly through both the systemic and pulmonary circulations. As a result, blood's transit time in the pulmonary capillaries is shorter. Still, the P O 2 of blood in the pulmonary veins normally reaches 100 mmHg. In diseases that decrease the rate of gas diffusion, however, the blood may not come into full equilibrium with pulmonary alveolar air, especially during exercise. When this happens, the P O 2 declines and P C-O 2 rises in systemic arterial blood.

Internal Respiration

The left ventricle pumps oxygenated blood into the ay-or-tuh and through the systemic arteries to systemic capillaries. The exchange of O 2 and C-O 2 between systemic capillaries and tissue cells is called internal respiration or systemic gas exchange (Figure 23.17b). As O 2 leaves the bloodstream, oxygenated blood is converted into deoxygenated blood. Unlike external respiration, which occurs only in the lungs, internal respiration occurs in tissues throughout the body.

The P O 2 of blood pumped into systemic capillaries is higher (100 mmHg) than the P O 2 in tissue cells (40 mmHg at rest) because the cells constantly use O 2 to produce A.T.P. Due to this pressure difference, oxygen diffuses out of the capillaries into tissue cells and blood P O 2 drops to 40 mmHg by the time the blood exits systemic capillaries.

While oxygen 2 diffuses from the systemic capillaries into tissue cells, carbon dioxide 2 diffuses in the opposite direction. Because tissue cells are constantly producing carbon dioxide 2, the partial pressure of carbon dioxide 2 of cells (45 millimeters of mercury at rest) is higher than that of systemic capillary blood (40 millimeters of mercury). As a result, carbon dioxide 2 diffuses from tissue cells through interstitial fluid into systemic capillaries until the partial pressure of carbon dioxide 2 in the blood increases to 45 mmHg. The deoxygenated blood then returns to the heart and is pumped to the lungs for another cycle of external respiration.

In a person at rest, tissue cells, on average, need only 25% of the available oxygen 2 in oxygenated blood; despite its name, deoxygenated blood retains 75% of its oxygen 2 content. During exercise, more oxygen 2 diffuses from the blood into metabolically active cells, such as contracting skeletal muscle fibers. Active cells use more oxygen 2 for A.T.P production, causing the oxygen 2 content of deoxygenated blood to drop below 75%.

The rate of pulmonary and systemic gas exchange depends on several factors.

• Partial pressure difference of the gases. Alveolar P O 2 must be higher than blood P O 2 for oxygen to diffuse from pulmonary alveolar air into the blood. The rate of diffusion is faster when the difference between P O 2 in pulmonary alveolar air and pulmonary capillary blood is larger; diffusion is slower when the difference is smaller. The differences between P O 2 and P C O 2 in pulmonary alveolar air versus pulmonary blood increase during exercise.

The larger partial pressure differences accelerate the rates of gas diffusion. The partial pressures of O 2 and C-O 2 in pulmonary alveolar air also depend on the rate of airflow into and out of the lungs. Certain drugs (such as morphine) slow ventilation, thereby decreasing the amount of O 2 and C-O 2 that can be exchanged between pulmonary alveolar air and blood.

With increasing altitude, the total atmospheric pressure decreases, as does the partial pressure of O 2 —from 159 mmHg at sea level, to 110 mmHg at 10,000 ft, to 73 mmHg at 20,000 ft. Although O 2 still is 20.9% of the total, the P O2 of inhaled air decreases with increasing altitude. Pulmonary alveolar P O2 decreases correspondingly, and O 2 diffuses into the blood more slowly. The common signs and symptoms of high altitude sickness—shortness of breath, headache, fatigue, insomnia, nausea, and dizziness—are due to a lower level of oxygen in the blood.

• Surface area available for gas exchange. As you learned earlier in the chapter, the surface area of the pulmonary alveoli is huge (about 75 m² or 807 ft²). In addition, many capillaries surround each pulmonary alveolus, so many that as much as 900 mL of blood is able to participate in gas exchange at any instant. Any pulmonary disorder that decreases the functional surface area of the respiratory membranes decreases the rate of external respiration. In emphysema (see Disorders: Homeostatic Imbalances at the end of the chapter), for example, pulmonary alveolar walls disintegrate, so surface area is smaller than normal and pulmonary gas exchange is slowed.

• Diffusion distance. The respiratory membrane is very thin, so diffusion occurs quickly. Also, the capillaries are so narrow that the red blood cells must pass through them in single file, which minimizes the diffusion distance from a pulmonary alveolar air space to hemoglobin inside red blood cells. Buildup of interstitial fluid between pulmonary alveoli, as occurs in pulmonary edema (see Disorders: Homeostatic Imbalances at the end of the chapter), slows the rate of gas exchange because it increases diffusion distance.

• Molecular weight and solubility of the gases. Because O 2 has a lower molecular weight than C O 2, it could be expected to diffuse across the respiratory membrane about 1.2 times faster. However, the solubility of C O 2 in the fluid portions of the respiratory membrane is about 24 times greater than that of O 2. Taking both of these factors into account, net outward C O 2 diffusion occurs 20 times more rapidly than net inward O 2 diffusion. Consequently, when diffusion is slower than normal—for example, in emphysema or pulmonary edema—O 2 insufficiency (hypoxia) typically occurs before there is significant retention of C O 2 (hypercapnia).

Checkpoint

23.7 Transport of Oxygen and Carbon Dioxide

Objective

• Describe how the blood transports oxygen and carbon dioxide.

As you have already learned, the blood transports gases between the lungs and body tissues. When O 2 and C-O 2 enter the blood, certain chemical reactions occur that aid in gas transport and gas exchange.

Oxygen Transport

Oxygen does not dissolve easily in water, so only about 1.5% of inhaled O 2 is dissolved in blood plasma, which is mostly water. About 98.5% of blood O 2 is bound to hemoglobin in red blood cells (Figure 23.18). Each 100 mL of oxygenated blood contains the equivalent of 20 mL of gaseous O 2 . Using the percentages just given, the amount dissolved in the plasma is 0.3 mL and the amount bound to hemoglobin is 19.7 mL.

Figure 23.18 summary: This figure is a schematic diagram illustrating the physiological processes of gas transport in the human body. It depicts the circulatory pathway between the pulmonary alveoli and systemic tissue cells, focusing on how oxygen and carbon dioxide are transported by the blood via erythrocytes and plasma. The diagram shows that oxygen is primarily transported bound to hemoglobin, with a small fraction dissolved in plasma, while carbon dioxide is transported in multiple forms, predominantly as bicarbonate ions, followed by binding to hemoglobin and a small amount dissolved in plasma. It can be inferred that hemoglobin is the primary vehicle for oxygen transport, whereas carbon dioxide transport relies more heavily on chemical conversion to bicarbonate for efficient movement through the bloodstream.

Figure 23.18 Transport of Oxygen ( O 2 ) and Carbon Dioxide ( C-O 2 ) in the Blood.

Most O₂ is transported by hemoglobin as oxyhemoglobin (Hb-O₂) within red blood cells; most C-O₂ is transported in blood plasma as bicarbonate ions bicarbonate.

The heme portion of hemoglobin contains four atoms of iron, each capable of binding to a molecule of O 2 (see Figure 19.4b, c). Oxygen and hemoglobin bind in an easily reversible reaction to form oxyhemoglobin:

Math summary: This expression describes a reversible chemical reaction that calculates the binding of oxygen to reduced hemoglobin. The process combines reduced hemoglobin and oxygen as inputs to produce oxyhemoglobin as the output, while the reverse process results in the dissociation of oxygen.

The 98.5% of the O 2 that is bound to hemoglobin is trapped inside R.B.C's, so only the dissolved O 2 (1.5%) can diffuse out of tissue capillaries into tissue cells. Thus, it is important to understand the factors that promote O 2 binding to and dissociation (separation) from hemoglobin.

The Relationship Between Hemoglobin and Oxygen Partial Pressure The most important factor that determines how much O₂ binds to hemoglobin is the P₀₂; the higher the P₀₂, the more O₂ combines with Hb. When reduced hemoglobin (Hb) is completely converted to oxyhemoglobin (Hb−O₂), the hemoglobin is said to be fully saturated; when hemoglobin consists of a mixture of Hb and Hb−O₂, it is partially saturated. The percent saturation of hemoglobin expresses the average saturation of hemoglobin with oxygen. For instance, if each hemoglobin molecule has bound two O₂ molecules, then the hemoglobin is 50% saturated because each Hb can bind a maximum of four O₂.

The relationship between the percent saturation of hemoglobin and P O 2 is illustrated in the oxygen–hemoglobin dissociation curve in Figure 23.19. Note that when the P O 2 is high, hemoglobin binds with large amounts of O 2 and is almost 100 percent saturated. When P O 2 is low, hemoglobin is only partially saturated. In other words, the greater the P O 2, the more O 2 will bind to hemoglobin, until all the available hemoglobin molecules are saturated. Therefore, in pulmonary capillaries, where P O 2 is high, a lot of O 2 binds to hemoglobin. In tissue capillaries, where the P O 2 is lower, hemoglobin does not hold as much O 2, and the dissolved O 2 is unloaded via diffusion into tissue cells (see Figure 23.18b). Note that hemoglobin is still 75 percent saturated.

Figure 23.19 summary: This figure is a line graph. It illustrates the relationship between the partial pressure of oxygen and the percent saturation of hemoglobin, highlighting specific physiological states including deoxygenated blood in contracting skeletal muscle, deoxygenated blood in systemic veins at rest, and oxygenated blood in systemic arteries. The graph demonstrates that as the partial pressure of oxygen increases, the saturation of hemoglobin also increases, following a sigmoidal curve that eventually plateaus. It can be inferred that hemoglobin has a high affinity for oxygen at the pressures found in systemic arteries, ensuring maximum loading, while it releases oxygen more readily at the lower pressures found in systemic veins and even more so in active skeletal muscles where oxygen demand is highest.

Figure 23.19 Oxygen-hemoglobin dissociation curve showing the relationship between hemoglobin saturation and PO2 at normal body temperature. with oxygen at a partial pressure of oxygen of 40 millimeters of mercury, the average partial pressure of oxygen of tissue cells in a person at rest. This is the basis for the earlier statement that only 25 percent of the available oxygen unloads from hemoglobin and is used by tissue cells under resting conditions.

When the partial pressure of oxygen is between 60 and 100 millimeters of mercury, hemoglobin is 90 percent or more saturated with oxygen (Figure 23.19). Thus, blood picks up a nearly full load of oxygen from the lungs even when the partial pressure of oxygen of alveolar air is as low as 60 millimeters of mercury. The hemoglobin partial pressure of oxygen curve explains why people can still perform well at high altitudes or when they have certain cardiac and pulmonary diseases, even though partial pressure of oxygen may drop as low as 60 millimeters of mercury. Note also in the curve that at a considerably lower partial pressure of oxygen of 40 millimeters of mercury, hemoglobin is still 75 percent saturated with oxygen. However, oxygen saturation of hemoglobin drops to 35 percent at 20 millimeters of mercury. Between 40 and 20 millimeters of mercury, large amounts of oxygen are released from hemoglobin in response to only small decreases in partial pressure of oxygen. In active tissues such as contracting muscles, partial pressure of oxygen may drop well below 40 millimeters of mercury. Then, a large percentage of the oxygen is released from hemoglobin, providing more oxygen to metabolically active tissues.

Other Factors Affecting the Affinity of Hemoglobin for Oxygen Although P O 2 is the most important factor that determines the percent O 2 saturation of hemoglobin, several other factors influence the tightness or affinity with which hemoglobin binds O 2 . In effect, these factors shift the entire curve either to the left (higher affinity) or to the right (lower affinity). The changing affinity of hemoglobin for O 2 is another example of how homeostatic mechanisms adjust body activities to cellular needs. Each one makes sense if you keep in mind that metabolically active tissue cells need O 2 and produce acids, C-O 2 , and heat as wastes. The following four factors affect the affinity of hemoglobin for O 2 :

1. Acidity (pH). As acidity increases (pH decreases), the affinity of hemoglobin for O₂ decreases, and O₂ dissociates more readily from hemoglobin (Figure 23.20a). In other words, increasing acidity enhances the unloading of oxygen from hemoglobin. The main acids produced by metabolically active tissues are lactic acid and carbonic acid. When pH decreases, the entire oxygen-hemoglobin dissociation curve shifts to the right; at any given P₀₂, Hb is less saturated with O₂, a change termed the Bohr effect (BÖR). The Bohr effect works both ways: An increase in H⁺ in blood causes O₂ to unload from hemoglobin, and the binding of O₂ to hemoglobin causes unloading of H⁺ from hemoglobin. The explanation for the Bohr effect is that hemoglobin can act as a buffer for hydrogen ions (H⁺). But when H⁺ ions bind to amino acids in hemoglobin, they alter its structure slightly, decreasing its oxygen-carrying capacity. Thus, lowered pH drives O₂ off hemoglobin, making more O₂ available for tissue cells. By contrast, elevated pH increases the affinity of hemoglobin for O₂ and shifts the oxygen-hemoglobin dissociation curve to the left.

2. Partial pressure of carbon dioxide. Carbon dioxide also can bind to hemoglobin, and the effect is similar to that of hydrogen ions (shifting the curve to the right). As the partial pressure of carbon dioxide rises, hemoglobin releases oxygen more readily (Figure 23.20b). The partial pressure of carbon dioxide and pH are related factors because low blood pH (acidity) results from high partial pressure of carbon dioxide.

Figure 23.20 Oxygen-hemoglobin dissociation curves showing the relationship of (a) pH and (b) P CO2 to hemoglobin saturation at normal body temperature. As pH increases or P CO2 decreases, O 2 combines more tightly with hemoglobin, so that less is available to tissues. The broken lines emphasize these relationships.

Figure 23.20 summary: This figure consists of two line graphs illustrating oxygen dissociation curves. The graphs plot the percent saturation of hemoglobin against the partial pressure of oxygen, showing how changes in blood pH and the partial pressure of carbon dioxide influence the affinity of hemoglobin for oxygen. In the first graph, an increase in pH shifts the curve to the left, while a decrease in pH shifts it to the right. In the second graph, a decrease in the partial pressure of carbon dioxide shifts the curve to the left, and an increase shifts it to the right. These shifts indicate that higher pH levels and lower carbon dioxide concentrations increase hemoglobin's affinity for oxygen, whereas lower pH levels and higher carbon dioxide concentrations decrease this affinity, facilitating the release of oxygen to tissues.

As pH decreases or P C O 2 increases, the affinity of hemoglobin for O 2 declines, so less O 2 combines with hemoglobin and more is available to tissues.

As C-O₂ enters the blood, much of it is temporarily converted to carbonic acid (H₂C-O₃), a reaction catalyzed by an enzyme in red blood cells called carbonic anhydrase C.A:

Math summary: This process calculates the chemical conversion of carbon dioxide and water into carbonic acid using an enzyme as a catalyst. The resulting carbonic acid then splits into two separate outputs consisting of hydrogen ions and bicarbonate ions.

The carbonic acid thus formed in red blood cells dis- sociates into hydrogen ions and bicarbonate ions. As the hydrogen ion concentration increases, pH decreases. Thus, an increased partial pressure of carbon dioxide produces a more acidic environment, which helps release oxygen from hemoglobin. During exercise, lactic acid—a by-product of anaerobic metabolism within muscles—also decreases blood pH. Decreased partial pressure of carbon dioxide (and elevated pH) shift the saturation curve to the left.

3. Temperature. Within limits, as temperature increases, so does the amount of O 2 released from hemoglobin (Figure 23.21). Heat is a by-product of the metabolic reactions of all cells, and the heat released by contracting muscle fibers tends to raise body temperature. Metabolically active cells require more O 2 and liberate more acids and heat. The acids and heat in turn promote release of O 2 from oxyhemoglobin.

Figure 23.21 summary: This figure is a line graph showing oxygen dissociation curves. It plots the percent saturation of hemoglobin against the partial pressure of oxygen across three different temperature conditions: low, normal blood, and high temperature. The data indicates that as temperature increases, the curve shifts to the right, demonstrating that hemoglobin has a lower affinity for oxygen at higher temperatures. Conversely, lower temperatures increase the affinity of hemoglobin for oxygen, requiring a lower partial pressure to achieve the same level of saturation.

Fever produces a similar result. In contrast, during hypothermia (lowered body temperature) cellular metabolism slows, the need for O 2 is reduced, and more O 2 remains bound to hemoglobin (a shift to the left in the saturation curve).

4. B.P.G. A substance found in red blood cells called 2,3-bisphosphoglycerate B.P.G bisphosphoglycerate, formerly called diphosphoglycerate D.P.G, decreases the affinity of hemoglobin for O₂ and thus helps unload O₂ from hemoglobin. B.P.G is formed in red blood cells when they break down glucose to produce A.T.P in a process called glycolysis (described in Section 25.3). When B.P.G combines with hemoglobin by binding to the terminal amino groups of the two beta globin chains, the hemoglobin binds O₂ less tightly at the heme group sites. The greater the level of B.P.G, the more O₂ is unloaded from hemoglobin. Certain hormones, such as thyroxine, human growth hormone, epinephrine, norepinephrine, and testosterone, increase the formation of B.P.G. The level of B.P.G also is higher in people living at higher altitudes.

Figure 23.21 Oxygen-Hemoglobin Dissociation Curves Showing the Effect of Temperature Changes.

Oxygen Affinity of Fetal and Adult Hemoglobin

Fetal hemoglobin (Hb-F) differs from adult hemoglobin (Hb-A) in structure and in its affinity for O₂. Hb-F has a higher affinity for O₂ because it binds B.P.G less strongly. Thus, when P₀₂ is low, Hb-F can carry up to 30% more O₂ than maternal Hb-A (Figure 23.22). As the maternal blood enters the placenta, O₂ is readily transferred to fetal blood. This is very important because the O₂ saturation in maternal blood in the placenta is quite low, and the fetus might suffer hypoxia were it not for the greater affinity of fetal hemoglobin for O₂.

Figure 23.22 summary: This figure is a line graph. It displays the relationship between the partial pressure of oxygen and the percent saturation of hemoglobin for both fetal and maternal blood. The graph shows that fetal hemoglobin maintains a higher saturation level than maternal hemoglobin across a wide range of oxygen partial pressures. Consequently, fetal hemoglobin has a higher affinity for oxygen, which facilitates the transfer of oxygen from the maternal bloodstream to the fetus.

Clinical Connection

Carbon Monoxide Poisoning

Carbon monoxide (C-O) is a colorless and odorless gas found in exhaust fumes from automobiles, gas furnaces and space heaters, and in tobacco smoke. It is a by-product of the combustion of carbon-containing materials such as coal, gas, and wood. C-O binds to the heme group of hemoglobin, just as O₂ does, except that the binding of carbon monoxide to hemoglobin is over 200 times as strong as the binding of O₂ to hemoglobin. Thus, at a concentration as small as 0.1% (Pₒ = 0.5 mmHg), C-O will combine with half the available hemoglobin molecules and reduce the oxygen-carrying capacity of the blood by 50%. Elevated blood levels of C-O cause carbon monoxide poisoning, which can cause the lips and oral mucosa to appear bright cherry-red (the color of hemoglobin with carbon monoxide bound to it). Without prompt treatment, carbon monoxide poisoning is fatal. It is possible to rescue a victim of C-O poisoning by administering pure oxygen, which speeds up the separation of carbon monoxide from hemoglobin.

Figure 23.22 Oxygen-Hemoglobin Dissociation Curves Comparing Fetal and Maternal Hemoglobin.

Fetal hemoglobin has a higher affinity for O₂ than does adult hemoglobin.

Carbon Dioxide Transport

Under normal resting conditions, each 100 mL of deoxygenated blood contains the equivalent of 53 mL of gaseous C-O 2 , which is transported in the blood in three main forms (see Figure 23.18):

1. Dissolved C-O₂. The smallest percentage—about 7%—is dissolved in blood plasma. On reaching the lungs, it diffuses into alveolar air and is exhaled.

2. Carbamino compounds. A somewhat higher percentage, about 23%, combines with the amino groups of amino acids and proteins in blood to form carbamino compounds (karbAM-i-nô). Because the most prevalent protein in blood is hemoglobin (inside red blood cells), most of the C-O₂ transported in this manner is bound to hemoglobin. The main C-O₂ binding sites are the terminal amino acids in the two alpha and two beta globin chains. Hemoglobin that has bound C-O₂ is termed carbaminohemoglobin (Hb-C-O₂):

Math summary: This expression describes a reversible chemical reaction where hemoglobin and carbon dioxide combine. The process results in the formation of carbaminohemoglobin, which can later split back into the original components.

The formation of carbaminohemoglobin is greatly influenced by partial pressure of carbon dioxide. For example, in tissue capillaries partial pressure of carbon dioxide is relatively high, which promotes formation of carbaminohemoglobin. But in pulmonary capillaries, partial pressure of carbon dioxide is relatively low, and the carbon dioxide readily splits apart from globin and enters the alveoli by diffusion.

3. Bicarbonate ions. The greatest percentage of C-O₂—about 70%—is transported in blood plasma as bicarbonate ions bicarbonate bicarbonate. As C-O₂ diffuses into systemic capillaries and enters red blood cells, it reacts with water in the presence of the enzyme carbonic anhydrase C.A to form carbonic acid, which dissociates into H⁺ and bicarbonate.

Math summary: This process describes a chemical reaction sequence catalyzed by the enzyme carbonic anhydrase. Carbon dioxide and water combine to form carbonic acid, which then breaks down into hydrogen ions and bicarbonate ions.

Thus, as blood picks up carbon dioxide, bicarbonate accumulates inside R.B.C's. Some bicarbonate moves out into the blood plasma, down its concentration gradient. In exchange, chloride ions, chloride minus, move from blood plasma into the R.B.C's. This exchange of negative ions, which maintains the electrical balance between blood plasma and R.B.C cytosol, is known as the chloride shift (see Figure 23.23b). The net effect of these reactions is that carbon dioxide is removed from tissue cells and transported in blood plasma as bicarbonate. As blood passes through pulmonary capillaries in the lungs, all of these reactions reverse and carbon dioxide is exhaled.

The amount of carbon dioxide that can be transported in the blood is influenced by the percent saturation of hemoglobin with oxygen. The lower the amount of oxyhemoglobin (hemoglobin oxygen 2), the higher the carbon dioxide carrying capacity of the blood, a relationship known as the Haldane effect. Two characteristics of deoxyhemoglobin give rise to the Haldane effect: (1) Deoxyhemoglobin binds to and thus transports more carbon dioxide than does hemoglobin oxygen 2.

Deoxyhemoglobin also buffers more H⁺ than does Hb-O₂, thereby removing H⁺ from solution and promoting conversion of C-O₂ to bicarbonate via the reaction catalyzed by carbonic anhydrase.

Summary of Gas Exchange and Transport in Lungs and Tissues

Deoxygenated blood returning to the pulmonary capillaries in the lungs (Figure 23.23a) contains carbon dioxide dissolved in blood plasma, carbon dioxide combined with globin as carbaminohemoglobin (Hb–C-O₂), and C-O₂ incorporated into bicarbonate within R.B.C's. The R.B.C's have also picked up H⁺, some of which binds to and therefore is buffered by hemoglobin (Hb–H). As blood passes through the pulmonary capillaries, molecules of C-O₂ dissolved in blood plasma and C-O₂ that dissociates from the globin portion of hemoglobin diffuse into pulmonary alveolar air and are exhaled. At the same time, inhaled O₂ is diffusing from pulmonary alveolar air into R.B.C's and is binding to hemoglobin to form oxyhemoglobin (Hb–O₂). Carbon dioxide also is released from bicarbonate when H⁺ combines with bicarbonate inside R.B.C's. The H₂C-O₃ formed from this reaction then splits into C-O₂, which is exhaled, and H₂O. As the concentration of bicarbonate declines inside

Figure 23.23 Summary of Chemical Reactions That Occur During Gas Exchange. (a) As Carbon

Figure 23.2: exchange. (a) As carbon dioxide (C-O₂) is exhaled, hemoglobin (Hb) inside red blood cells in pulmonary capillaries unloads C-O₂ and picks up O₂ from pulmonary alveolar air. Binding of O₂ to Hb–H releases hydrogen ions (H⁺). Bicarbonate ions bicarbonate pass into the R.B.C and bind to released H⁺, forming carbonic acid (H₂C-O₃). The H₂C-O₃ dissociates into water (H₂O) and C-O₂, and the C-O₂ diffuses from blood plasma into pulmonary alveolar air. To maintain electrical balance, a chloride ion (Cl⁻) exits the R.B.C for each bicarbonate that enters (reverse chloride shift). (b) C-O₂ diffuses out of tissue cells that produce it and enters red blood cells, where some of it binds to hemoglobin, forming carbaminohemoglobin (Hb–C-O₂). This reaction causes O₂ to dissociate from oxyhemoglobin (Hb–O₂). Other molecules of C-O₂ combine with water to produce bicarbonate ions bicarbonate and hydrogen ions (H⁺). As Hb buffers H⁺, the Hb releases O₂ (Bohr effect). To maintain electrical balance, a chloride ion (Cl⁻) enters the R.B.C for each bicarbonate that exits (chloride shift).

Hemoglobin Inside Red Blood Cells Transports O 2 , C-O 2 , and H superscript plus .

R.B.C's in pulmonary capillaries, bicarbonate with a negative charge diffuses in from the blood plasma, in exchange for chloride with a negative charge. In sum, oxygenated blood leaving the lungs has increased oxygen content and decreased amounts of carbon dioxide and hydrogen ions with a positive charge. In systemic capillaries, as cells use oxygen and produce carbon dioxide, the chemical reactions reverse (Figure 23.23b).

Figure 23.23 summary: This figure consists of two schematic diagrams illustrating the biochemical processes of gas exchange. The top diagram depicts external respiration within the pulmonary capillaries, showing the movement of oxygen from the pulmonary alveolus into the red blood cell and the movement of carbon dioxide from the blood into the alveolus to be exhaled. The bottom diagram depicts internal respiration within systemic capillaries, showing oxygen moving from the red blood cell into tissue cells and carbon dioxide moving from tissue cells into the blood. Both diagrams detail the chemical reactions involving hemoglobin, carbonic anhydrase, and the chloride shift that facilitate the transport of these gases. It can be inferred that gas exchange is driven by concentration gradients and supported by enzymatic activity and ion shifts to maintain chemical equilibrium. The figure concludes that external respiration focuses on oxygenating blood and removing carbon dioxide, while internal respiration focuses on delivering oxygen to tissues and collecting carbon dioxide for transport.

Checkpoint

25. In a resting person, how many O 2 molecules are attached to each hemoglobin molecule, on average, in blood in the pulmonary arteries? In blood in the pulmonary veins?

26. What is the relationship between hemoglobin and partial pressure of oxygen? How do temperature, hydrogen ions, partial pressure of carbon dioxide, and B.P.G influence the affinity of hemoglobin for oxygen?

27. Why can hemoglobin unload more oxygen as blood flows through capillaries of metabolically active tissues, such as skeletal muscle during exercise, than is unloaded at rest?

23.8 Control of Breathing

Objective

• Explain how the nervous system controls breathing.

At rest, about 200 mL of O 2 is used each minute by body cells. During strenuous exercise, however, O 2 use typically increases 15-to 20-fold in normal healthy adults, and as much as 30-fold in elite endurance-trained athletes. Several mechanisms help match breathing effort to metabolic demand.

Respiratory Center

The size of the thorax is altered by the action of the breathing muscles, which contract as a result of nerve impulses transmitted from centers in the brain and relax in the absence of nerve impulses. These nerve impulses are sent from clusters of neurons located bilaterally in the brain stem. This widely dispersed group of neurons, collectively called the respiratory center, can be divided into two principal areas on the basis of location and function: (1) the medullary respiratory center in the medulla oblongata and (2) the pontine respiratory group in the pons (Figure 23.24).

Figure 23.24 summary: This figure is an anatomical diagram consisting of a sagittal section of the brainstem and a view of the thoracic musculature. The illustration maps the neural pathways from the respiratory centers in the brainstem, specifically the pontine and medullary groups, to the effector muscles of the chest. It identifies key neurological structures such as the midbrain, pons, and medulla oblongata, and shows how they connect via the phrenic and intercostal nerves to the diaphragm and external intercostal muscles. The diagram demonstrates that breathing is controlled by a hierarchical system where signals originate in the brainstem and are transmitted through specific nerves to trigger the contraction of respiratory muscles, thereby facilitating ventilation.

Medullary Respiratory Center The medullary respiratory center is made up of two collections of neurons called the dorsal respiratory group D.R.G, formerly called the inspiratory area, and the ventral respiratory group V.R.G, formerly called the expiratory area. During normal quiet breathing, neurons of the D.R.G generate impulses to the diaphragm via the phrenic nerves and the external intercostal muscles via the intercostal nerves (Figure 23.25a). These impulses are

Figure 23.24 Locations of Areas of the Respiratory Center.

The respiratory center is composed of neurons in the medullary respiratory center in the medulla plus the pontine respiratory group in the pons. released in bursts, which begin weakly, increase in strength for about two seconds, and then stop altogether. When the nerve impulses reach the diaphragm and external intercostals, the muscles contract and inhalation occurs. When the D.R.G becomes inactive after two seconds, the diaphragm and external intercostals relax for about three seconds, allowing the passive recoil of the lungs and thoracic wall. Then, the cycle repeats itself.

Located in the V.R.G is a cluster of neurons called the pre-Bötzinger complex Botzinger that is believed to be important in the generation of the rhythm of breathing (see Figure 23.24a). This rhythm generator, analogous to the one in the heart, is composed of pacemaker cells that set the basic rhythm of breathing. The exact mechanism of these pacemaker cells is unknown and is the topic of much ongoing research. However, it is thought that the pacemaker cells provide input to the D.R.G, driving the rate at which D.R.G neurons fire action potentials.

The remaining neurons of the V.R.G do not participate in normal quiet breathing. The V.R.G becomes activated when forceful breathing is required, such as during exercise, when playing a wind instrument, or at high altitudes. During forceful inhalation Figure 23.25 Roles of the medullary respiratory center in controlling (a) normal quiet breathing and (b) forceful breathing.

Figure 23.25 summary: This figure is a flow chart. It illustrates the neural pathways and muscular actions involved in both normal quiet breathing and forceful breathing. The diagram differentiates between the roles of the dorsal respiratory group and the ventral respiratory group in controlling the diaphragm, external intercostal muscles, and various accessory muscles during inhalation and exhalation. The content indicates that normal quiet breathing is primarily managed by the alternating activity and inactivity of the dorsal respiratory group, leading to the contraction and relaxation of the diaphragm and external intercostals. In contrast, forceful breathing requires the activation of the ventral respiratory group to engage additional accessory muscles for both inhalation and exhalation. It can be inferred that quiet breathing is a more simplified process relying on primary respiratory muscles, whereas forceful breathing is a more complex physiological response involving multiple muscle groups to increase air flow.

During normal quiet breathing, the ventral respiratory group is inactive; during forceful breathing, the dorsal respiratory group activates the ventral respiratory group.

(Figure 23.25b), nerve impulses from the D.R.G not only stimulate the diaphragm and external intercostal muscles to contract, they also activate neurons of the V.R.G involved in forceful inhalation to send impulses to the accessory muscles of inhalation (sternocleidomastoid, scalenes, and pectoralis minor). Contraction of these muscles results in forceful inhalation.

During forceful exhalation (Figure 23.25b), the D.R.G is inactive along with the neurons of the V.R.G that result in forceful inhalation. However, those neurons of the V.R.G involved in forceful exhalation send nerve impulses to the accessory muscles of exhalation (internal intercostals, external abdominal oblique, internal abdominal oblique, transversus abdominis, and rectus abdominis). Contraction of these muscles results in forceful exhalation.

Pontine Respiratory Group The pontine respiratory group P.R.G pontine, formerly called the pneumotaxic area, is a collection of neurons in the pons (see Figure 23.24a). The neurons in the P.R.G are active during inhalation and exhalation. The P.R.G transmits nerve impulses to the D.R.G in the medulla. The P.R.G may play a role in both inhalation and exhalation by modifying the basic rhythm of breathing generated by the V.R.G, as when exercising, speaking, or sleeping.

Regulation of the Respiratory Center

Activity of the respiratory center can be modified in response to inputs from other brain regions, receptors in the peripheral nervous system, and other factors in order to maintain the homeostasis of breathing.

Cortical Influences on Breathing Because the cerebral cortex has connections with the respiratory center, we can voluntarily alter our pattern of breathing. We can even refuse to breathe at all for a short time. Voluntary control is protective because it enables us to prevent water or irritating gases from entering the lungs. The ability to not breathe, however, is limited by the buildup of C-O₂ and H⁺ in the body.

When PCO2 and H⁺ concentrations increase to a certain level, the D.R.G neurons of the medullary respiratory center are strongly stimulated, nerve impulses are sent along the phrenic and intercostal nerves to inspiratory muscles, and breathing resumes, whether the person wants it to or not. It is impossible for small children to kill themselves by voluntarily holding their breath, even though many have tried in order to get their way. If breath is held long enough to cause fainting, breathing resumes when consciousness is lost. Nerve impulses from the hypothalamus and limbic system also stimulate the respiratory center, allowing emotional stimuli to alter breathing as, for example, in laughing and crying.

Chemoreceptor Regulation of Breathing Cer-

tain chemical stimuli modulate how quickly and how deeply we breathe. The respiratory system functions to maintain proper levels of C-O 2 and O 2 and is very responsive to changes in the levels of these gases in body fluids. We introduced sensory neurons that are responsive to chemicals, called chemoreceptors chemoreceptors, in Chapter 21. Chemoreceptors in two locations of the respiratory system monitor levels of C-O₂, H⁺, and O₂ and provide input to the respiratory center (Figure 23.26). Central chemoreceptors are located in or near the medulla oblongata in the central nervous system. They respond to changes in H⁺ concentration or PCO2, or both, in cerebrospinal fluid. Peripheral chemoreceptors are located in the aortic bodies, clusters of chemoreceptors located in the wall of the aortic arch, and in the carotid bodies, which are oval nodules in the wall of the left and right common carotid arteries where they divide into the internal and external carotid arteries. (The chemoreceptors of the aortic bodies are located close to the aortic baroreceptors, and the carotid bodies are located close to the carotid sinus baroreceptors.

Figure 23.26 summary: This is an anatomical diagram. The figure illustrates the anatomical positioning of peripheral chemoreceptors, specifically highlighting the carotid bodies located at the bifurcation of the common carotid arteries into internal and external carotid arteries, and the aortic bodies situated within the aortic arch. It traces the neural pathways from these receptors, showing sensory axons traveling through the glossopharyngeal and vagus nerves to reach the medulla oblongata in the brain. The diagram demonstrates that peripheral chemoreceptors are strategically placed in major arterial pathways to monitor blood chemistry, with the resulting sensory information being transmitted to the brainstem for respiratory and cardiovascular regulation.

Recall from Chapter 21 that baroreceptors are sensory receptors that monitor blood pressure.) These chemoreceptors are part of the peripheral nervous system and are sensitive to changes in PCO2, H⁺, and PCO2 in the blood. Axons of sensory neurons from the aortic bodies are part of the vagus (10) nerves, and those from the carotid bodies are part of the right and left glossopharyngeal (9) nerves. Recall from Chapter 17 that olfactory nerve cells for the sense of smell and gustatory epithelial cells for the sense of taste are also chemoreceptors. Both respond to external stimuli.

Because C-O₂ is lipid-soluble, it easily diffuses into cells where, in the presence of carbonic anhydrase, it combines with water (H₂O) to form carbonic acid (H₂C-O₃). Carbonic acid quickly breaks down into H⁺ and bicarbonate. Thus, an increase in C-O₂ in the blood causes an increase in H⁺ inside cells, and a decrease in C-O₂ causes a decrease in H⁺.

Normally, the partial pressure of carbon dioxide in arterial blood is 40 mmHg. If even a slight increase in partial pressure of carbon dioxide occurs—a condition called hypercapnia (h i perkapnia or hypercarbia—the central chemoreceptors are stimulated and respond vigorously to the resulting increase in hydrogen ion level. The peripheral chemoreceptors also are stimulated by both the high partial pressure of carbon dioxide and the rise in hydrogen ion. In addition, the peripheral chemoreceptors (but not the central chemoreceptors) respond to a deficiency of oxygen. When partial pressure of oxygen in arterial blood falls from a normal level of 100 mmHg but is still above 50 mmHg, the peripheral chemoreceptors are stimulated. Severe deficiency of oxygen depresses activity of the central chemoreceptors and D.R.G, which then do not respond well to any inputs and send fewer impulses to the muscles of inhalation. As the breathing rate decreases or breathing ceases altogether, partial pressure of oxygen falls lower and lower, establishing a positive feedback cycle with a possibly fatal result.

The chemoreceptors participate in a negative feedback system that regulates the levels of carbon dioxide, oxygen, and hydrogen ions in the blood (Figure 23.27). As a result of increased partial pressure of carbon dioxide, decreased pH (increased hydrogen ions), or decreased partial pressure of oxygen, input from the central and peripheral chemoreceptors causes the D.R.G to become highly active, and the rate and depth of breathing increase. Rapid and deep breathing, called hyperventilation, allows the inhalation of more oxygen and exhalation of more carbon dioxide until the partial pressure of carbon dioxide and hydrogen ions are lowered to normal.

Figure 23.27 summary: This figure is a flow chart depicting a biological feedback loop. It illustrates the process by which the body responds to a stimulus that disrupts homeostasis, specifically an increase in arterial blood carbon dioxide or a decrease in pH and oxygen levels. The process follows a sequence from the stimulus to receptors, including central chemoreceptors in the medulla and peripheral chemoreceptors in the aortic and carotid bodies, which send nerve impulses to the control center in the dorsal respiratory group of the medulla oblongata. This center then sends output impulses to effectors, specifically the muscles of inhalation and exhalation, leading to hyperventilation. The resulting response is a decrease in arterial blood carbon dioxide and an increase in pH and oxygen levels. The figure demonstrates a negative feedback mechanism where the response counteracts the initial stimulus to return the body to a state of homeostasis.

If arterial P CO2 is lower than 40 mmHg—a condition called hypocapnia or hypocarbia—the central and peripheral Chemoreceptors are sensory neurons that respond to changes in the levels of certain chemicals in the body. chemoreceptors are not stimulated, and stimulatory impulses are not sent to the D.R.G. As a result, D.R.G neurons set their own moderate pace until C-O₂ accumulates and the PCO2 rises to 40 mmHg. D.R.G neurons are more strongly stimulated when PCO2 is rising above normal than when PCO2 is falling below normal. As a result, people who hyperventilate voluntarily and cause hypocapnia can hold their breath for an unusually long period. Swimmers were once encouraged to hyperventilate just before diving in to compete. However, this practice is risky.

Figure 23.27 Regulation of breathing in response to changes in blood P C O 2, P O 2, and pH (H plus) via negative feedback control. because the O 2 level may fall dangerously low and cause fainting before the P CO2 rises high enough to stimulate inhalation. If you faint on land you may suffer bumps and bruises, but if you faint in the water you could drown.

Proprioceptor Stimulation of Breathing soon as you start exercising, your rate and depth of breathing increase, even before changes in P O 2 , P C-O 2 , or H^+ level occur. The main stimulus for these quick changes in respiratory effort is input from proprioceptors, which monitor movement of joints and muscles. Nerve impulses from the proprioceptors stimulate the D.R.G of the medulla. At the same time, axon collaterals (branches) of upper motor neurons that originate in the primary motor cortex (precentral gyrus) also feed excitatory impulses into the D.R.G.

Clinical Connection

Hypoxia

Hypoxia hypoxia; hypo-= under) is a deficiency of O₂ at the tissue level. Based on the cause, we can classify hypoxia into four types, as follows:

1. Hypoxic hypoxia is caused by a low P O2 in arterial blood as a result of high altitude, airway obstruction, or fluid in the lungs.

2. In anemic hypoxia, too little functioning hemoglobin is present in the blood, which reduces O 2 transport to tissue cells. Among the causes are hemorrhage, anemia, and failure of hemoglobin to carry its normal complement of O 2 , as in carbon monoxide poisoning.

3. In ischemic hypoxia (is-K E bar -mik), blood flow to a tissue is so reduced that too little O 2 is delivered to it, even though P O 2 and oxyhemoglobin levels are normal.

4. In histotoxic hypoxia histotoxic, the blood delivers adequate O 2 to tissues, but the tissues are unable to use it properly because of the action of some toxic agent. One cause is cyanide poisoning, in which cyanide blocks an enzyme required for the use of O 2 during A.T.P synthesis.

The Inflation Reflex Similar to those in the blood vessels, stretch-sensitive receptors called baroreceptors or stretch receptors are located in the walls of bronchi and bronchioles. When these receptors become stretched during overinflation of the lungs, nerve impulses are sent along the vagus (10) nerves to the dorsal respiratory group D.R.G in the medullary respiratory center. In response, the D.R.G is inhibited and the diaphragm and external intercostals relax.

As a result, further inhalation is stopped and exhalation begins. As air leaves the lungs during exhalation, the lungs deflate and the stretch receptors are no longer stimulated. Thus, the D.R.G is no longer inhibited, and a new inhalation begins.

This reflex is referred to as the inflation reflex or Hering-Breuer reflex Hering Breuer. In infants, the reflex appears to function in normal breathing. In adults, however, the reflex is not activated until tidal volume (normally 500 mL) reaches more than 1500 mL. Therefore, the reflex in adults is a protective mechanism that prevents excessive inflation of the lungs, for example, during severe exercise, rather than a key component in the normal control of breathing.

Other Influences on Breathing Other factors that contribute to regulation of breathing include the following:

• Limbic system stimulation. Anticipation of activity or emotional anxiety may stimulate the limbic system, which then sends excitatory input to the D.R.G, increasing the rate and depth of breathing.

• Temperature. An increase in body temperature, as occurs during a fever or vigorous muscular exercise, increases the rate of breathing. A decrease in body temperature decreases breathing rate. A sudden cold stimulus (such as plunging into cold water) causes temporary apnea apnea; a-= without; -pnea = breath), an absence of breathing.

• Pain. A sudden, severe pain brings about brief apnea, but a prolonged somatic pain increases breathing rate. Visceral pain may slow the rate of breathing.

• Stretching the anal sphincter muscle. This action increases the breathing rate and is sometimes used to stimulate respiration in a newborn baby or a person who has stopped breathing.

• Irritation of airways. Physical or chemical irritation of the pharynx or larynx brings about an immediate cessation of breathing followed by coughing or sneezing.

• Blood pressure. The carotid and aortic baroreceptors that detect changes in blood pressure have a small effect on breathing. A sudden rise in blood pressure decreases the rate of breathing, and a drop in blood pressure increases the breathing rate.

Table 23.3 summarizes the stimuli that affect the rate and depth of breathing.

Table 23.3 summary: This table contrasts the various physiological and psychological stimuli that either enhance or reduce the rate and depth of respiration. Factors that increase breathing include voluntary hyperventilation, elevated arterial carbon dioxide and acidity, moderate drops in oxygen levels, increased proprioceptor activity, higher body temperature, prolonged pain, and lower blood pressure. Conversely, breathing is decreased by voluntary hypoventilation, low arterial carbon dioxide, extreme oxygen deficiency, reduced proprioceptor activity, lower body temperatures, severe pain, higher blood pressure, and irritation of the upper respiratory tract.

30. How do the cerebral cortex, levels of carbon dioxide and oxygen, proprioceptors, inflation reflex, temperature changes, pain, and irritation of the airways modify breathing?

23.9 Exercise and the Respiratory System

Objective

- Describe the effects of exercise on the respiratory system.

The respiratory and cardiovascular systems make adjustments in response to both the intensity and duration of exercise. The effects of exercise on the heart are discussed in Chapter 20. Here we focus on how exercise affects the respiratory system.

Recall that the heart pumps the same amount of blood to the lungs as to all the rest of the body. Thus, as cardiac output rises, the blood flow to the lungs, termed pulmonary perfusion, increases as well. In addition, the O 2 diffusing capacity, a measure of the rate at which O 2 can diffuse from alveolar air into the blood, may increase threefold during maximal exercise because more pulmonary capillaries become maximally perfused. As a result, there is a greater surface area available for diffusion of O 2 into pulmonary blood capillaries.

When muscles contract during exercise, they consume large amounts of O 2 and produce large amounts of C-O 2 . During vigorous exercise, O 2 consumption and breathing both increase dramatically. At the onset of exercise, an abrupt increase in breathing is followed by a more gradual increase. With moderate exercise, the increase is due mostly to an increase in the depth of breathing rather than to increased breathing rate. When exercise is more strenuous, the frequency of breathing also increases.

The abrupt increase in breathing at the start of exercise is due to neural changes that send excitatory impulses to the dorsal respiratory group D.R.G of the medullary respiratory center in the medulla. These changes include (1) anticipation of the activity, which stimulates the limbic system; (2) sensory impulses from proprioceptors in muscles, tendons, and joints; and motor impulses from the primary motor cortex (precentral gyrus). The more gradual increase in breathing during moderate exercise is due to chemical and physical changes in the bloodstream, including (1) slightly decreased partial pressure of oxygen, due to increased oxygen consumption; (2) slightly increased partial pressure of carbon dioxide, due to increased carbon dioxide production by contracting muscle fibers; and (3) increased temperature, due to liberation of more heat as more oxygen is utilized. During strenuous exercise, bicarbonate buffers hydrogen ions released by lactic acid in a reaction that liberates carbon dioxide, which further increases partial pressure of carbon dioxide.

At the end of an exercise session, an abrupt decrease in breathing is followed by a more gradual decline to the resting

Clinical Connection

Effects of Cigarette Smoking on the Respiratory System

Cigarette smoking accounts for nearly 500,000 deaths annually in the United States, making it responsible for twenty percent of all deaths. There are over 4000 chemicals in cigarette smoke and about 70 of them are carcinogenic (cancer-causing). Cigarette smoking affects virtually every system on the body and can result in conditions such as cancer, coronary artery disease, stroke, blood clots, hypertension, type 2 diabetes, rheumatoid arthritis, fetal disorders, cataracts, accelerated skin aging, reduced fertility, erectile dysfunction, preterm (early) delivery, low birth weight, ectopic pregnancy, slow wound healing, diseases of the gums and teeth, and decreased immune functions.

With regard to the respiratory system, cigarette smoking results in lung cancer and chronic obstructive pulmonary diseases (C.O.P.D) such as emphysema and chronic bronchitis. These are discussed in detail at the end of this chapter. In addition to these conditions, cigarette smoking may cause a person to become easily “winded” during even moderate exercise because several factors decrease respiratory efficiency in smokers. Following are some of the effects of smoking on the respiratory system:

1. Nicotine constricts terminal bronchioles, which decreases airflow into and out of the lungs.

2. Carbon monoxide in smoke binds to hemoglobin and reduces its oxygen-carrying capability.

3. Irritants in smoke cause increased mucus secretion by the mucosa of the bronchial tree and swelling of the mucosal lining, both of which impede airflow into and out of the lungs.

4. Irritants in smoke also inhibit the movement of cilia and destroy cilia in the lining of the respiratory system. Thus, excess mucus and foreign debris are not easily removed, which further adds to the difficulty in breathing. This leads to a smoker's cough and contributes to the tendency for smokers to be sick more often than non-smokers. The irritants can also convert the normal respiratory epithelium into stratified squamous epithelium, which lacks cilia and goblet cells.

5. With time, smoking leads to destruction of elastic fibers in the lungs and is the prime cause of emphysema. These changes cause collapse of small bronchioles and trapping of air in alveoli at the end of exhalation. The result is less efficient gas exchange.

level. The initial decrease is due mainly to changes in neural factors when movement stops or slows; the more gradual phase reflects the slower return of blood chemistry levels and temperature to the resting state.

31. How does exercise affect the D.R.G?

Objective

23.10 Development of the Respiratory System

• Describe the development of the respiratory system.

The development of the mouth and pharynx is discussed in Chapter 24. Here we consider the development of the other structures of the respiratory system that you learned about in this chapter.

At about 4 weeks of development, the respiratory system begins as an outgrowth of the foregut (precursor of some digestive organs) just inferior to the pharynx. This outgrowth is called the respiratory bud (Figure 23.28). The endoderm lining the respiratory bud gives rise to the epithelium and glands of the trachea, bronchi, and pulmonary alveoli. Mesoderm surrounding the respiratory bud gives rise to the connective tissue, cartilage, and smooth muscle of these structures.

Figure 23.28 summary: This figure is a series of anatomical diagrams. The content illustrates the embryonic development of the respiratory system over several stages, starting from the appearance of the respiratory bud and progressing through the formation of the laryngotracheal diverticulum, primary bronchial buds, main bronchi, lobar bronchi, and segmental bronchi, culminating in the development of the lungs with distinct lobes and pleura. The sequence shows that the respiratory system undergoes significant branching and complexity as it develops from a simple bud into a structured system of airways and lobes over the course of several weeks, indicating a pattern of progressive specialization and growth from the endoderm and mesoderm.

The epithelial lining of the larynx develops from the endoderm of the respiratory bud; the cartilages and muscles originate from the fourth and sixth pharyngeal arches, swellings on the surface of the embryo (see Figure 29.13).

As the respiratory bud elongates, its distal end enlarges to form a globular laryngotracheal diverticulum, which gives rise to the trachea. Soon after, the tracheal bud divides into primary bronchial buds, which branch repeatedly and develop into the bronchi. By 24 weeks, 17 orders of branches have formed and respiratory bronchioles have developed.

During weeks 6 to 16, all major elements of the lungs have formed, except for those involved in gaseous exchange (respiratory bronchioles, alveolar ducts, and pulmonary alveoli). Since breathing is not possible at this stage, fetuses born during this time cannot survive.

During weeks 16 to 26, lung tissue becomes highly vascular and respiratory bronchioles, alveolar ducts, and some primitive alveoli develop. Although it is possible for a fetus born near the end of this period to survive if given intensive care, death frequently occurs due to the immaturity of the respiratory and other systems.

From 26 weeks to birth, many more primitive pulmonary alveoli develop; they consist of pneumocytes type I (main sites of gaseous exchange) and pneumocytes type 2 that produce surfactant. Blood capillaries also establish close contact with the primitive pulmonary alveoli. Recall that surfactant is necessary to lower surface tension of alveolar fluid and thus reduce the tendency of pulmonary alveoli to collapse on exhalation. Although surfactant production begins by 20 weeks, it is present in only small quantities.

Amounts sufficient to permit survival of a premature (preterm) infant are not produced until 26 to 28 weeks' gestation. Infants born before 26 to 28 weeks are at high risk of respiratory distress syndrome (R.D.S), in which the pulmonary alveoli collapse during exhalation and must be reinflated during inhalation (see Clinical Connection: Respiratory Distress Syndrome in Section 23.2).

At about 30 weeks, mature pulmonary alveoli develop. However, it is estimated that only about one-sixth of the full complement of pulmonary alveoli develop before birth; the remainder develop after birth during the first 8 years.

As the lungs develop, they acquire their pleural sacs. The visceral pleura and the parietal pleura develop from mesoderm. The space between the pleural layers is the pleural cavity.

During development, breathing movements of the fetus cause the aspiration of fluid into the lungs. This fluid is a mixture of amniotic fluid, mucus from bronchial glands, and surfactant. At birth, the lungs are about half-filled with fluid. When breathing begins at birth, most of the fluid is rapidly reabsorbed by blood and lymph capillaries and a small amount is expelled through the nose and mouth during delivery.

Checkpoint

32. What structure develops from the laryngotracheal diverticulum?

23.11 Aging and the Respiratory System

Objective

• Describe the effects of aging on the respiratory system.

With advancing age, the airways and tissues of the respiratory tract, including the pulmonary alveoli, become less elastic and more rigid; the chest wall becomes more rigid as well. The result is a decrease in lung capacity. In fact, vital capacity (the maximum amount of air that can be exhaled after maximal inhalation) can decrease as much as 35% by age 70. A decrease in blood level of O 2 , decreased activity of alveolar macrophages, and diminished ciliary action of the epithelium lining the respiratory tract occur. Because of these age-related factors, elderly people are more susceptible to pneumonia, bronchitis, emphysema, and other pulmonary disorders. Age-related changes in the structure and functions of the lung can also contribute to an older person's reduced ability to perform vigorous exercises, such as running.

33. What accounts for the decrease in lung capacity with aging?

To appreciate the many ways that the respiratory system contributes to homeostasis of other body systems, examine Focus on Homeostasis: Contributions of the Respiratory System. Next, in Chapter 24, we will see how the digestive system makes nutrients available to body cells so that oxygen provided by the respiratory system can be used for A.T.P production.

Disorders: Homeostatic Imbalances

Coronavirus Disease 2019 covid 19

Coronavirus disease 2019, is also known as COVID-19 (CoronaVirus Disease 19, first recognized in 2019). The term corona, meaning crown, refers to the crown-like spikes (see illustration below) on the surface of the virus. The disease is caused by a new coronavirus called severe acute respiratory syndrome coronavirus 2 S.A.R.S CoV 2. Coronaviruses are a family of viruses that can cause illnesses such as coryza, severe acute respiratory syndrome S.A.R.S, and Middle East respiratory syndrome M.E.R.S. Signs and symptoms of coronavirus infection range from mild to moderate upper respiratory illnesses or even lower respiratory illnesses that include pneumonia and bronchitis. The COVID-19 outbreak was declared a pandemic in March 2020.

Image summary: This is a medical illustration. The image depicts a spherical viral particle featuring a dense array of protruding spike proteins across its entire surface. The structure suggests a complex envelope designed for host cell attachment, indicating a highly infectious biological agent typical of a coronavirus.

Since COVID-19 is a newly emerging disease, there are still many questions about the virus itself, all possible signs and symptoms, transmission, effects on the body, susceptibility, immunity, and treatment modalities. However, there is data that relates to known signs or symptoms as of now. They may appear from 2 to 14 days following exposure to the virus and can range from very mild to severe. In fact, some individuals present with no signs or symptoms. The signs or symptoms include fever, cough, shortness of breath or difficulty breathing, wheezing, chest pain, purple swollen toes, chills, muscle pains, fatigue, headache, congestion or runny nose, sore throat, diarrhea, nausea, vomiting, new loss of taste or smell, and blood clots. Elderly individuals or those with underlying chronic medical conditions such as diabetes, heart disease, or pulmonary disease appear to be at higher risk of serious illness.

It is unclear how contagious the new virus is, but it has been shown that it is transmitted from person-to-person in people who are in close contact. The virus spreads by respiratory droplets released when a person coughs, sneezes, or even talks.

There are several steps that can be taken to reduce the risk of infection with the virus. Among these are the following: (1) avoid travel to or take up residence in areas known to have large numbers of COVID-19 cases, (2) avoid close contact (within 6 feet) with someone who has COVID-19, (3) avoid large mass gatherings, (4) maintain social distance of 6 feet or more, (5) wash your hands frequently with soap and water for at least 20 seconds or use an alcohol-based hand sanitizer that contains at least 60% alcohol, (6) cover your mouth and nose with your elbow or a tissue when you cough or sneeze, (7) don't touch your mouth, nose, or mouth unless you have just washed or sanitized your hands, (8) avoid sharing glasses, dishes, bedding, and other household items if you are sick, (9) clean and disinfect high-contact surfaces, and (10) stay home and quarantined if you are sick.

Lung Cancer

In the United States, lung cancer is the leading cause of cancer death in both males and females, accounting for 160,000 deaths annually. At the time of diagnosis, lung cancer is usually well advanced, with distant metastases present in about 55% of patients, and regional lymph node involvement in an additional 25%. Most people with lung cancer die within a year of the initial diagnosis; the overall survival rate is only 10 to 15%. Cigarette smoke is the most common cause of lung cancer. Roughly 85% of lung cancer cases are related to smoking, and the disease is 10 to 30 times more common in smokers than nonsmokers.

Exposure to secondhand smoke is also associated with lung cancer and heart disease. In the United States, secondhand smoke causes an estimated 4000 deaths a year from lung cancer, and nearly 40,000 deaths a year from heart disease. Other causes of lung cancer are ionizing radiation and inhaled irritants, such as asbestos and radon gas. Emphysema is a common precursor to the development of lung cancer.

The most common type of lung cancer, bronchogenic carcinoma bronchogenic, starts in the epithelium of the bronchial tubes. Bronchogenic tumors are named based on where they arise. For example, adenocarcinomas (ad-en-okar-si-No-mas; adeno-= gland) develop in peripheral areas of the lungs from bronchial glands and pulmonary alveolar cells, squamous cell carcinomas develop from the squamous cells in the epithelium of larger bronchial tubes, and small (oat) cell carcinomas develop from epithelial cells in primary bronchi near the hilum of the lungs that get their name due to their flat cell shape with little cytoplasm.

They tend to involve the mediastinum early on. Depending on the type, bronchogenic tumors may be aggressive, locally invasive, and undergo widespread metastasis. The tumors begin as epithelial lesions that grow to form masses that obstruct the bronchial tubes or invade adjacent lung tissue. Bronchogenic carcinomas metastasize to lymph nodes, the brain, bones, liver, and other organs.

Symptoms of lung cancer are related to the location of the tumor. These may include a chronic cough, spitting blood from the respiratory tract, wheezing, shortness of breath, chest pain, hoarseness, difficulty swallowing, weight loss, anorexia, fatigue, bone pain, confusion, problems with balance, headache, anemia, thrombocytopenia, and jaundice.

Treatment consists of partial or complete surgical removal of a diseased lung (pulmonectomy), radiation therapy, and chemotherapy.

Focus on Homeostasis

Contributions of the Respiratory System for All Body Systems

• Provides oxygen and removes carbon dioxide

• Helps adjust pH of body fluids through exhalation of carbon dioxide

Image summary: This is an anatomical illustration. The figure depicts a human male body with the respiratory system visible through the chest and throat. It shows the nasal cavity, pharynx, larynx, trachea, and the lungs. The illustration demonstrates the connection between the upper respiratory tract and the lungs, indicating how air travels from the external environment into the pulmonary system for gas exchange.

Image summary: This figure is an anatomical illustration. It depicts the human muscular system, showing the distribution of muscles across the entire body from the head down to the feet. The illustration indicates that skeletal muscles are distributed extensively throughout the body, covering the torso, arms, and legs to facilitate movement and structural support.

Image summary: This figure is a medical illustration. It depicts a posterior view of a human body, showcasing the distribution of a specific system or condition across the back, arms, and legs. The illustration indicates a widespread and symmetrical pattern of involvement throughout the entire body.

Image summary: This is an anatomical diagram. The figure depicts a human body with specific internal organs highlighted within the torso. Based on the highlighted areas, the figure illustrates the location and relative size of organs such as the liver and gallbladder within the abdominal cavity.

Image summary: This figure is an anatomical diagram. It depicts the human circulatory system, showing the network of blood vessels distributed throughout the entire body, including the head, torso, arms, and legs. The illustration demonstrates that the vascular network is extensive and reaches all extremities, indicating a comprehensive system for transporting blood to every part of the human anatomy.

Image summary: This figure is an anatomical illustration. It depicts a female human figure with internal organs visible through a translucent body, overlaid with a series of horizontal parallel lines. The illustration shows the positioning of major organs within the torso and the overall alignment of the body. It can be inferred that the figure is intended to demonstrate a mapping or a scanning process across different anatomical levels of the human body.

Image summary: This figure is an anatomical illustration. It depicts a human figure with a cross-sectional view of the torso, revealing internal organs and the skeletal structure of the body. The illustration suggests a study of human anatomy, highlighting the spatial relationship between the internal organs and the overall bodily frame.

Image summary: This figure is an anatomical diagram. It depicts a human silhouette with specific internal organs highlighted in the abdominal and pelvic regions, specifically showing the kidneys and the reproductive or urinary system. The illustration indicates the anatomical positioning and distribution of these organs within the human body.

Image summary: This is a diagrammatic illustration. The figure depicts a human silhouette with horizontal lines across the body and specific markings in the pelvic region. The illustration suggests a mapping of anatomical areas or a representation of systemic distribution across the human form.

Muscular System

• Increased rate and depth of breathing support increased activity of skeletal muscles during exercise

Nervous System

• Nose contains receptors for sense of smell

• Vibrations of air flowing across vocal folds produce sounds for speech

Endocrine System

• Angiotensin-converting enzyme in lungs catalyzes formation of the hormone angiotensin two from angiotensin I

Cardiovascular System

• During inhalations, respiratory pump aids return of venous blood to the heart

Lymphoid (Lymphatic) System and Immunity

• Hairs in nose, cilia and mucus in trachea, bronchi, and smaller airways, and alveolar macrophages contribute to nonspecific resistance to disease

• Pharynx contains lymphatic tissue (tonsils)

• Respiratory pump (during inhalation)

Digestive System

• Forceful contraction of respiratory muscles can assist in defecation

Urinary System

• Together, respiratory and urinary systems regulate pH of body fluids

Genital (Reproductive) Systems

• Increased rate and depth of breathing support activity during sexual intercourse

• Internal respiration provides oxygen to developing fetus

Image summary: This figure is an anatomical diagram. It depicts a full-body female silhouette with horizontal striping and a highlighted region in the pelvic area. The diagram indicates a localized area of focus or abnormality within the lower abdomen and reproductive region compared to the rest of the body.

Pneumonia

Pneumonia (noo-MÖ-ne-a) is an acute infection or inflammation of the pulmonary alveoli. It is the most common infectious cause of death in the United States, where an estimated 4 million cases occur annually. When certain microbes enter the lungs of susceptible individuals, they release damaging toxins, stimulating inflammation and immune responses that have damaging side effects. The toxins and immune response damage pulmonary alveoli and bronchial mucous membranes; inflammation and edema cause the pulmonary alveoli to fill with fluid, interfering with ventilation and gas exchange.

The most common cause of pneumonia is the pneumococcal bacterium Streptococcus pneumoniae streptococcus noo-Mö-në-ï), but other microbes may also cause pneumonia. Those who are most susceptible to pneumonia are the elderly, infants, immunocompromised individuals A.I.D.S or cancer patients, or those taking immunosuppressive drugs), cigarette smokers, and individuals with an obstructive lung disease. Most cases of pneumonia are preceded by an upper respiratory infection that often is viral. Individuals then develop fever, chills, productive or dry cough, malaise, chest pain, and sometimes dyspnea (difficult breathing) and hemoptysis (spitting blood).

Treatment may involve antibiotics, bronchodilators, oxygen therapy, increased fluid intake, and chest physiotherapy (percussion, vibration, and postural drainage).

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (C.O.P.D) is a type of respiratory disorder characterized by chronic and recurrent obstruction of airflow, which increases airway resistance. C.O.P.D affects about 30 million Americans and is the fourth leading cause of death behind heart disease, cancer, and cerebrovascular disease. The principal types of C.O.P.D are emphysema and chronic bronchitis.

In most cases, C.O.P.D is preventable because its most common cause is cigarette smoking or breathing secondhand smoke. Other causes include air pollution, pulmonary infection, occupational exposure to dusts and gases, and genetic factors. Because men, on average, have more years of exposure to cigarette smoke than women, they are twice as likely as women to suffer from C.O.P.D; still, the incidence of C.O.P.D in women has risen sixfold in the past 50 years, a reflection of increased smoking among women.

Emphysema Emphysema (em-fi-SÊ-ma = blown up or full of air) is a disorder characterized by destruction of the walls of the pulmonary alveoli, producing abnormally large air spaces that remain filled with air during exhalation. With less surface area for gas exchange, O₂ diffusion across the damaged respiratory membrane is reduced. Blood O₂ level is somewhat lowered, and any mild exercise that raises the O₂ requirements of the cells leaves the patient breathless. As increasing numbers of pulmonary alveolar walls are damaged, lung elastic recoil decreases due to loss of elastic fibers, and an increasing amount of air becomes trapped in the lungs at the end of exhalation.

Over several years, added exertion during inhalation increases the size of the chest cage, resulting in a “barrel chest.”

Emphysema is generally caused by a long-term irritation; cigarette smoke, air pollution, and occupational exposure to industrial dust are the most common irritants. Some destruction of alveolar saccules may be caused by an enzyme imbalance. Treatment consists of cessation of smoking, removal of other environmental irritants, exercise training under careful medical supervision, breathing exercises, use of bronchodilators, and oxygen therapy.

Chronic Bronchitis Chronic bronchitis is a disorder characterized by excessive secretion of bronchial mucus accompanied by a productive cough (sputum is raised) that lasts for at least 3 months of the year for two successive years. Cigarette smoking is the leading cause of chronic bronchitis. Inhaled irritants lead to chronic inflammation with an increase in the size and number of mucous glands and goblet cells in the airway epithelium.

The thickened and excessive mucus produced narrows the airway and impairs ciliary function. Thus, inhaled pathogens become embedded in airway secretions and multiply rapidly. Besides a productive cough, symptoms of chronic bronchitis are shortness of breath, wheezing, cyanosis, and pulmonary hypertension. Treatment for chronic bronchitis is similar to that for emphysema.

Asthma

Asthma asthma = panting) or bronchial asthma is a disorder characterized by chronic airway inflammation, airway hypersensitivity to a variety of stimuli, and airway obstruction. It is at least partially reversible, either spontaneously or with treatment. Asthma affects 3 to 5% of the U.S. population and is more common in children than in adults. Airway obstruction may be due to smooth muscle spasms in the walls of smaller bronchi and bronchioles, edema of the mucosa of the airways, increased mucus secretion, and/or damage to the epithelium of the airway.

Individuals with asthma typically react to concentrations of agents too low to cause symptoms in people without asthma. Sometimes the trigger is an allergen such as pollen, house dust mites, molds, or a particular food. Other common triggers of asthma attacks are emotional upset, aspirin, sulfiting agents (used in wine and beer and to keep greens fresh in salad bars), exercise, and breathing cold air or cigarette smoke.

In the early phase (acute) response, smooth muscle spasm is accompanied by excessive secretion of mucus that may clog the bronchi and bronchioles and worsen the attack. The late phase (chronic) response is characterized by inflammation, fibrosis, edema, and necrosis (death) of bronchial epithelial cells. A host of mediator chemicals, including leukotrienes, prostaglandins, thromboxane, platelet-activating factor, and histamine, take part.

Symptoms include difficult breathing, coughing, wheezing, chest tightness, tachycardia, fatigue, moist skin, and anxiety. An acute attack is treated by giving an inhaled beta₂-adrenergic agonist (albuterol) to help relax smooth muscle in the bronchioles and open up the airways. This drug mimics the effect of sympathetic stimulation, that is, it causes bronchodilation.

However, long-term therapy of asthma strives to suppress the underlying inflammation. The anti-inflammatory drugs that are used most often are inhaled corticosteroids (glucocorticoids), cromolyn sodium (Intal®), and leukotriene blockers (Accolate®).

Tuberculosis

The bacterium Mycobacterium tuberculosis (mi'–ko–bak-Tle–um) produces an infectious, communicable disease called tuberculosis T.B that most often affects the lungs and the pleurae but may involve other parts of the body. Once the bacteria are inside the lungs, they multiply and cause inflammation, which stimulates neutrophils and macrophages to migrate to the area and engulf the bacteria to prevent their spread. If the immune system is not impaired, the bacteria remain dormant for life, but impaired immunity may enable the bacteria to escape into blood and lymph to infect other organs. In many people, symptoms—fatigue, weight loss, lethargy, anorexia, a low-grade fever, night sweats, cough, dyspnea, chest pain, and hemoptysis—do not develop until the disease is advanced.

During the past several years, the incidence of T.B in the United States has risen dramatically. Perhaps the single most important factor related to this increase is the spread of the human immunodeficiency virus H.I.V. People infected with H.I.V are much more likely to develop tuberculosis because their immune systems are impaired. Among the other factors that have contributed to the increased number of cases are homelessness, increased drug abuse, increased immigration from countries with a high prevalence of tuberculosis, increased crowding in housing among the poor, and airborne transmission of tuberculosis in prisons and shelters.

In addition, recent outbreaks of tuberculosis involving multi-drug-resistant strains of Mycobacterium tuberculosis have occurred because patients fail to complete their antibiotic and other treatment regimens. T.B is treated with the medication isoniazid.

Pulmonary Edema

Pulmonary edema is an abnormal accumulation of fluid in the interstitial spaces and pulmonary alveoli. The edema may arise from increased permeability of the pulmonary capillaries (pulmonary origin) or increased pressure in the pulmonary capillaries (cardiac origin); the latter cause may coincide with congestive heart failure. The most common symptom is dyspnea. Others include wheezing, tachypnea (rapid breathing rate), restlessness, a feeling of suffocation, cyanosis, pallor (paleness), diaphoresis (excessive perspiration), and pulmonary hypertension.

Treatment consists of administering oxygen, drugs that dilate the bronchioles and lower blood pressure, diuretics to rid the body of excess fluid, and drugs that correct acid-base imbalance; suctioning of airways; and mechanical ventilation. One of the recent culprits in the development of pulmonary edema was found to be "phen-fen" diet pills.

Sudden Infant Death Syndrome

Sudden infant death syndrome S.I.D.S is the sudden, unexpected death of an apparently healthy infant during sleep. It rarely occurs before 2 weeks or after 6 months of age, with the peak incidence between the second and fourth months. S.I.D.S is more common in premature infants, male babies, low-birth-weight babies, babies of drug users or smokers, babies who have stopped breathing and have had to be resuscitated, babies with upper respiratory tract infections, and babies who have had a sibling die of S.I.D.S. African-American and Native American babies are at higher risk. The exact cause of S.I.D.S is unknown. However, it may be due to an abnormality in the mechanisms that control respiration or low levels of oxygen in the blood. S.I.D.S may also be linked to hypoxia while sleeping in a prone position (on the stomach) and the rebreathing of exhaled air trapped in a depression of a mattress. It is recommended that for the first 6 months infants be placed on their backs for sleeping ("back to sleep").

Severe Acute Respiratory Syndrome

Severe acute respiratory syndrome S.A.R.S is an example of an emerging infectious disease, that is, a disease that is new or changing. Other examples of emerging infectious diseases are West Nile encephalitis, mad cow disease, and AIDS. sars first appeared in southern China in late 2002 and has subsequently spread worldwide. It is a respiratory illness caused by a new variety of coronavirus. Symptoms of sars include fever, malaise, muscle aches, nonproductive (dry) cough, difficulty in breathing, chills, headache, and diarrhea. About 10 to 20% of patients require mechanical ventilation and in some cases death may result.

The disease is primarily spread through person-to-person contact. There is no effective treatment for sars and the death rate is 5 to 10%, usually among the elderly and in persons with other medical problems.

Malignant Mesothelioma

Malignant mesothelioma mesothelioma is a rare form of cancer that affects the mesothelium (simple squamous epithelium) of a serous membrane. The most common form of the disease, about 75% of all cases, affects the pleura of the lungs (pleural mesothelioma). The second most common form of the disease affects the peritoneum (peritoneal mesothelioma).

Other forms of the disease develop in the pericardium (pericardial mesothelioma) and the testes (testicular mesothelioma). About 2000 to 3000 cases of malignant mesothelioma are diagnosed each year in the United States, accounting for about 3% of all cancers. The disease is almost entirely caused by asbestos, which has been widely used in insulation, textiles, cement, brake linings, gaskets, roof shingles, and floor products.

The signs and symptoms of malignant mesothelioma may not appear until 20 to 50 years or more after exposure to asbestos. With respect to pleural mesothelioma, signs and symptoms include chest pain, shortness of breath, pleural effusion, fatigue, anemia, blood in the sputum (fluid) coughed up, wheezing, hoarseness, and unexplained weight loss. Diagnosis is based on a medical history, physical examination, radiographs, C.T scans, and biopsy.

There is usually no cure for malignant mesothelioma unless the tumor is found very early and can be completely removed by surgery. However, the prognosis (chance of recovery) is poor since it is typically diagnosed in its later stages after symptoms have appeared. Chemotherapy, radiation therapy, and/or immunotherapy (using the body's immune system) may be used to help decrease symptoms. Sometimes multimodality therapy (combination of therapies) is used.

Medical Terminology

Abdominal thrust maneuver First-aid procedure designed to clear the airways of obstructing objects. It is performed by applying a quick upward thrust between the navel and costal margin that causes sudden elevation of the diaphragm and forceful, rapid expulsion of air in the lungs; this action forces air out the trachea to eject the obstructing object. The abdominal thrust maneuver is also used to expel water from the lungs of near-drowning victims before resuscitation is begun.

Asphyxia asphyxia; sphyxia = pulse) Oxygen starvation due to low atmospheric oxygen or interference with ventilation, external respiration, or internal respiration.

Aspiration (as'-pi-RÃ-shun) Inhalation of a foreign substance such as water, food, or a foreign body into the bronchial tree; also, the drawing of a substance in or out by suction.

Black lung disease A condition in which the lungs appear black instead of pink due to inhalation of coal dust over a period of many years. Most often it affects people who work in the coal industry.

Bronchiectasis (brong-ke-Ek-ta-sis; -ektasis = stretching) A chronic dilation of the bronchi or bronchioles resulting from damage to the bronchial wall, for example, from respiratory infections.

Bronchoscopy bronchoscopy Visual examination of the bronchi through a bronchoscope, an illuminated, flexible tubular instrument that is passed through the mouth (or nose), larynx, and trachea into the bronchi. The examiner can view the interior of the trachea and bronchi to biopsy a tumor, clear an obstructing object or secretions from an airway, take cultures or smears for microscopic examination, stop bleeding, or deliver drugs.

Cheyne-Stokes respiration Chan Stokes res'-pi-RÃ-shun) A repeated cycle of irregular breathing that begins with shallow breaths that increase in depth and rapidity and then decrease and cease altogether for 15 to 20 seconds. Cheyne-Stokes is normal in infants; it is also often seen just before death from pulmonary, cerebral, cardiac, and kidney disease.

Chapter Review

Review

23.1 Overview of the Respiratory System

1. Three basic steps are involved in respiration: (1) pulmonary ventilation, (2) external respiration, and (3) internal respiration.

2. The respiratory system consists of the nose, pharynx, larynx, trachea, bronchi, and lungs. They act with the cardiovascular system to supply oxygen ( O 2 ) and remove carbon dioxide ( C-O 2 ) from the blood.

3. It is divided into an upper and lower respiratory system.

23.2 The Upper Respiratory System

1. The external portion of the nose is made of cartilage and skin and is lined with a mucous membrane. Openings to the exterior are the nostrils. The internal portion of the nose communicates with the paranasal sinuses and nasopharynx through the choanae. The nasal cavity is

Dyspnea dyspnea; dys-= painful, difficult) Painful or labored breathing.

Epistaxis epistaxis Loss of blood from the nose due to trauma, infection, allergy, malignant growths, or bleeding disorders. It can be arrested by cautery with silver nitrate, electrocautery, or firm packing. Also called nosebleed.

Hypoventilation (hypo-= below) Slow and shallow breathing.

Rales Ralls Sounds sometimes heard in the lungs that resemble bubbling or rattling. Rales are to the lungs what murmurs are to the heart. Different types are due to the presence of an abnormal type or amount of fluid or mucus within the bronchi or pulmonary alveoli, or to bronchoconstriction that causes turbulent airflow.

Respiratory failure A condition in which the respiratory system either cannot supply sufficient O 2 to maintain metabolism or cannot eliminate enough C-O 2 to prevent respiratory acidosis (a lower-than-normal pH in interstitial fluid).

Rhinitis (ri-Ni-tis; rhin-= nose) Chronic or acute inflammation of the mucous membrane of the nose due to viruses, bacteria, or irritants. Excessive mucus production produces a runny nose, nasal congestion, and postnasal drip.

Sleep apnea apnea; a-= without; -pnea = breath) A disorder in which a person repeatedly stops breathing for 10 or more seconds while sleeping. Most often, it occurs because loss of muscle tone in pharyngeal muscles allows the airway to collapse.

Sputum sputum = to spit) Mucus and other fluids from the air passages that is expectorated (expelled by coughing).

Strep throat Inflammation of the pharynx caused by the bacterium Streptococcus pyogenes. It may also involve the tonsils and middle ear. Tachypnea tachypnea; tachy-= rapid; -pnea = breath) Rapid breathing rate.

Wheeze wheeze A whistling, squeaking, or musical high-pitched sound during breathing resulting from a partially obstructed airway. divided by a nasal septum. The anterior portion of the cavity is called the nasal vestibule. The nose warms, moistens, and filters air and functions in olfaction and speech.

2. The pharynx is a muscular tube lined by a mucous membrane. The anatomical regions are the nasopharynx, oropharynx, and laryngopharynx. The nasopharynx functions in respiration. The oropharynx and laryngopharynx function in both breathing and digestion.

23.3 The Lower Respiratory System

1. The larynx is a passageway that connects the pharynx with the trachea. It contains the thyroid cartilage; the epiglottic cartilage, which prevents food from entering the larynx; the cricoid cartilage, which connects the larynx and trachea; and the paired arytenoid, corniculate, and cuneiform cartilages. The larynx contains vocal folds, which produce sound as they vibrate. Taut folds produce high pitches, and relaxed ones produce low pitches.

2. The trachea extends from the larynx to the main bronchi. It is composed of C-shaped rings of cartilage and smooth muscle and is lined with ciliated pseudostratified columnar epithelium.

3. The bronchial tree consists of the trachea, main bronchi, lobar bronchi, segmental bronchi, bronchioles, and terminal bronchioles. Walls of bronchi contain rings of cartilage; walls of bronchioles contain increasingly smaller plates of cartilage and increasing amounts of smooth muscle.

4. Lungs are paired organs in the thoracic cavity enclosed by the pleural membrane. The parietal pleura is the superficial layer that lines the thoracic cavity; the visceral pleura is the deep layer that covers the lungs. The right lung has three lobes separated by two fissures; the left lung has two lobes separated by one fissure and a depression, the cardiac notch.

5. Lobar bronchi give rise to branches called segmental bronchi, which supply segments of lung tissue called bronchopulmonary segments. Each bronchopulmonary segment consists of lobules, which contain lymphatics, arterioles, venules, terminal bronchioles, respiratory bronchioles, alveolar ducts, alveolar saccules, and pulmonary alveoli.

6. Pulmonary alveolar walls consist of pneumocytes type I and pneumocytes type 2, and associated alveolar macrophages.

7. Gas exchange occurs across the respiratory membranes.

23.4 Pulmonary Ventilation

1. Pulmonary ventilation, or breathing, consists of inhalation and exhalation.

2. The movement of air into and out of the lungs depends on pressure changes governed in part by Boyle's law, which states that the volume of a gas varies inversely with pressure, assuming that temperature remains constant.

3. Inhalation occurs when alveolar pressure falls below atmospheric pressure. Contraction of the diaphragm and external intercostals increases the size of the thorax, thereby decreasing the intrapleural pressure so that the lungs expand. Expansion of the lungs decreases alveolar pressure so that air moves down a pressure gradient from the atmosphere into the lungs.

4. During forceful inhalation, accessory muscles of inhalation (sternocleidomastoids, scalenes, and pectoralis minors) are also used.

5. Exhalation occurs when alveolar pressure is higher than atmospheric pressure. Relaxation of the diaphragm and external intercostals results in elastic recoil of the chest wall and lungs, which increases intrapleural pressure; lung volume decreases and alveolar pressure increases, so air moves from the lungs to the atmosphere.

6. Forceful exhalation involves contraction of the internal intercostal and abdominal muscles.

7. The surface tension exerted by pulmonary alveolar fluid is decreased by the presence of surfactant.

8. Compliance is the ease with which the lungs and thoracic wall can expand.

9. The walls of the airways offer some resistance to breathing.

10. Normal quiet breathing is termed eupnea; other patterns are costal breathing and diaphragmatic breathing. Modified respiratory movements, such as coughing, sneezing, sighing, yawning, sobbing, crying, laughing, and hiccupping, are used to express emotions and to clear the airways. (See Table 23.2.)

23.5 Lung Volumes and Capacities

1. Lung volumes exchanged during breathing and the rate of respiration are measured with a spirometer.

2. Lung volumes measured by spirometry include tidal volume, minute ventilation, alveolar ventilation rate, inspiratory reserve volume,

expiratory reserve volume, and F.E.V 1.0 . Other lung volumes include anatomic dead space, residual volume, and minimal volume.

3. Lung capacities, the sum of two or more lung volumes, include inspiratory, functional, residual, vital, and total lung capacities.

23.6 Exchange of Oxygen and Carbon Dioxide

1. The partial pressure of a gas is the pressure exerted by that gas in a mixture of gases. It is symbolized by P 10 , where the subscript is the chemical formula of the gas.

2. According to Dalton's law, each gas in a mixture of gases exerts its own pressure as if all the other gases were not present.

3. Henry's law states that the quantity of a gas that will dissolve in a liquid is proportional to the partial pressure of the gas and its solubility (given constant temperature).

4. In internal and external respiration, oxygen 2 and carbon dioxide 2 diffuse from areas of higher partial pressures to areas of lower partial pressures.

5. External respiration or pulmonary gas exchange is the exchange of gases between pulmonary alveoli and pulmonary blood capillaries. It depends on partial pressure differences, a large surface area for gas exchange, a small diffusion distance across the respiratory membrane, and the rate of airflow into and out of the lungs.

6. Internal respiration or systemic gas exchange is the exchange of gases between systemic blood capillaries and tissue cells.

23.7 Transport of Oxygen and Carbon Dioxide

1. In each 100 mL of oxygenated blood, 1.5% of the O₂ is dissolved in blood plasma and 98.5% is bound to hemoglobin as oxyhemoglobin (Hb−O₂).

2. The binding of O₂ to hemoglobin is affected by P₀₂, acidity (pH), Pₐ₀₂, temperature, and 2,3-bisphosphoglycerate B.P.G.

3. Fetal hemoglobin differs from adult hemoglobin in structure and has a higher affinity for O₂.

4. In each 100 mL of deoxygenated blood, 7% of C-O₂ is dissolved in blood plasma, 23% combines with hemoglobin as carbaminohemoglobin (Hb-C-O₂), and 70% is converted to bicarbonate ions bicarbonate.

5. In an acidic environment, hemoglobin's affinity for O₂ is lower, and O₂ dissociates more readily from it (Bohr effect).

6. In the presence of O 2, less C O 2 binds to hemoglobin (Haldane effect).

23.8 Control of Breathing

1. The respiratory center consists of a medullary respiratory center in the medulla and a pontine respiratory group in the pons.

2. The medullary respiratory center in the medulla is made up of a dorsal respiratory group D.R.G, which controls normal quiet breathing, and a ventral respiratory group V.R.G, which is used during forceful breathing and controls the rhythm of breathing.

3. The pontine respiratory group in the pons may modify the rhythm of breathing during exercise, speaking, and sleep.

4. The activity of the respiratory center can be modified in response to inputs from various parts of the body in order to maintain the homeostasis of breathing.

5. These include cortical influences; the inflation reflex; chemical stimuli, such as oxygen 2 and carbon dioxide 2 and hydrogen plus levels; proprioceptor input; blood pressure changes; limbic system stimulation; temperature; pain; and irritation to the airways. (See Table 23.3.)

23.9 Exercise and the Respiratory System

1. The rate and depth of breathing change in response to both the intensity and duration of exercise.

2. An increase in pulmonary perfusion and oxygen 2 diffusing capacity occurs during exercise.

3. The abrupt increase in breathing at the start of exercise is due to neural changes that send excitatory impulses to the dorsal respiratory group of the medullary respiratory center in the medulla oblongata. The more gradual increase in breathing during moderate exercise is due to chemical and physical changes in the bloodstream.

23.10 Development of the Respiratory System

1. The respiratory system begins as an outgrowth of endoderm called the respiratory bud.

Critical Thinking Questions

1. Aretha loves to sing. Right now she has a cold, a severely runny nose, and a sore throat that is affecting her ability to sing and talk. What structures are involved and how are they affected by her cold?

2. Ms. Brown has smoked cigarettes for years and is having breathing difficulties. She has been diagnosed with emphysema. Describe specific kinds of structural changes you would expect to observe in

Answers to Figure Questions

23.1 External respiration involves the exchange of oxygen 2 and carbon dioxide 2 between the pulmonary alveoli of the lungs and the blood in pulmonary capillaries; internal respiration involves the exchange of oxygen 2 and carbon dioxide 2 between the blood in systemic capillaries and tissue cells of the body.

23.2 The conducting zone of the respiratory system includes the nose, pharynx, larynx, trachea, bronchi, and bronchioles (except the respiratory bronchioles).

23.3 The path of air is nostrils goes to vestibule goes to nasal cavity goes to choanae.

23.4 The root of the nose attaches it to the frontal bone.

23.5 During swallowing, the epiglottis closes over the rima glottidis, the entrance to the trachea, to prevent aspiration of food and liquids into the lungs.

23.6 The main function of the vocal folds is voice production.

23.7 Because the tissues between the esophagus and trachea are soft, the esophagus can bulge and press against the trachea during swallowing.

23.8 The left lung has two lobes and two lobar bronchi; the right lung has three of each.

23.9 The pleural membrane is a serous membrane.

23.10 Because two-thirds of the heart lies to the left of the midline, the left lung contains a cardiac notch to accommodate the presence of the heart. The right lung is shorter than the left because the diaphragm is higher on the right side to accommodate the liver.

23.11 The wall of a pulmonary alveolus is made up of pneumocytes type I and type 2, and associated alveolar macrophages.

23.12 The respiratory membrane averages zero point five micrometers in thickness.

23.13 The pressure would increase fourfold, to 4 atm.

23.14 If you are at rest while reading, your diaphragm is responsible for about 75% of each inhalation.

23.15 At the start of inhalation, intrapleural pressure is about 756 mmHg. With contraction of the diaphragm, it decreases to about 754 mmHg as 2. Smooth muscle, cartilage, and connective tissue of the bronchial tubes and pleural sacs develop from mesoderm.

23.11 Aging and the Respiratory System

1. Aging r 0.

2. Elderly people are more susceptible to pneumonia, emphysema, bronchitis, and other pulmonary disorders.

Ms. Brown's respiratory system. How are air flow and gas exchange affected by these structural changes?

3. The Robinson family went to bed one frigid winter night and were found deceased the next day. A squirrel's nest was found in their chimney. What happened to the Robinsons? the volume of the space between the two pleural layers expands. With relaxation of the diaphragm, it increases back to 756 mmHg.

23.16 Breathing in and then exhaling as much air as possible demonstrates vital capacity.

23.17 A difference in P O 2 promotes oxygen diffusion into pulmonary capillaries from pulmonary alveoli and into tissue cells from systemic capillaries.

23.18 The most important factor that determines how much O₂ binds to hemoglobin is the P₀₂.

23.19 Both during exercise and at rest, hemoglobin in your pulmonary veins would be fully saturated with O 2 , a point that is at the upper right of the curve.

23.20 Because lactic acid and C-O₂ are produced by active skeletal muscles, blood pH decreases slightly and PCO2 increases when you are actively exercising. The result is lowered affinity of hemoglobin for O₂, so more O₂ is available to the working muscles.

23.21 Oxygen 2 is more available to your tissue cells when you have a fever because the affinity of hemoglobin for oxygen 2 decreases with increasing temperature.

23.22 At a partial pressure of oxygen of 40 millimeters of mercury, fetal hemoglobin is 80 percent saturated with oxygen and maternal hemoglobin is about 75 percent saturated.

23.23 Blood in a systemic vein would have a higher concentration of bicarbonate ion.

23.24 The medullary respiratory center in the medulla contains neurons that are active and then inactive in a repeating cycle.

23.25 The phrenic nerves innervate the diaphragm.

23.26 Peripheral chemoreceptors are responsive to changes in blood levels of oxygen, carbon dioxide, and H superscript plus .

23.27 Normal arterial blood P C O 2 is 40 millimeters of mercury.

23.28 The respiratory system begins to develop about 4 weeks after fertilization.

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