22.1 Organs and Structures of the Respiratory System
The respiratory system is responsible for obtaining oxygen and getting rid of carbon dioxide, and aiding in speech production and in sensing odors. From a functional perspective, the respiratory system can be divided into two major areas: the conducting zone and the respiratory zone. The conducting zone consists of all of the structures that provide passageways for air to travel into and out of the lungs: the nasal cavity, pharynx, trachea, bronchi, and most bronchioles. The nasal passages contain the conchae and meatuses that expand the surface area of the cavity, which helps to warm and humidify incoming air, while removing debris and pathogens. The pharynx is composed of three major sections: the nasopharynx, which is continuous with the nasal cavity; the oropharynx, which borders the nasopharynx and the oral cavity; and the laryngopharynx, which borders the oropharynx, trachea, and esophagus. The respiratory zone includes the structures of the lung that are directly involved in gas exchange: the terminal bronchioles and alveoli.
The lining of the conducting zone is composed mostly of pseudostratified ciliated columnar epithelium with goblet cells. The mucus traps pathogens and debris, whereas beating cilia move the mucus superiorly toward the throat, where it is swallowed. As the bronchioles become smaller and smaller, and nearer the alveoli, the epithelium thins and is simple squamous epithelium in the alveoli. The endothelium of the surrounding capillaries, together with the alveolar epithelium, forms the respiratory membrane. This is a blood-air barrier through which gas exchange occurs by simple diffusion.
22.2 The Lungs
The lungs are the major organs of the respiratory system and are responsible for performing gas exchange. The lungs are paired and separated into lobes; The left lung consists of two lobes, whereas the right lung consists of three lobes. Blood circulation is very important, as blood is required to transport oxygen from the lungs to other tissues throughout the body. The function of the pulmonary circulation is to aid in gas exchange. The pulmonary artery provides deoxygenated blood to the capillaries that form respiratory membranes with the alveoli, and the pulmonary veins return newly oxygenated blood to the heart for further transport throughout the body. The lungs are innervated by the parasympathetic and sympathetic nervous systems, which coordinate the bronchodilation and bronchoconstriction of the airways. The lungs are enclosed by the pleura, a membrane that is composed of visceral and parietal pleural layers. The space between these two layers is called the pleural cavity. The mesothelial cells of the pleural membrane create pleural fluid, which serves as both a lubricant (to reduce friction during breathing) and as an adhesive to adhere the lungs to the thoracic wall (to facilitate movement of the lungs during ventilation).
22.3 The Process of Breathing
Pulmonary ventilation is the process of breathing, which is driven by pressure differences between the lungs and the atmosphere. Atmospheric pressure is the force exerted by gases present in the atmosphere. The force exerted by gases within the alveoli is called intra-alveolar (intrapulmonary) pressure, whereas the force exerted by gases in the pleural cavity is called intrapleural pressure. Typically, intrapleural pressure is lower, or negative to, intra-alveolar pressure. The difference in pressure between intrapleural and intra-alveolar pressures is called transpulmonary pressure. In addition, intra-alveolar pressure will equalize with the atmospheric pressure. Pressure is determined by the volume of the space occupied by a gas and is influenced by resistance. Air flows when a pressure gradient is created, from a space of higher pressure to a space of lower pressure. Boyle’s law describes the relationship between volume and pressure. A gas is at lower pressure in a larger volume because the gas molecules have more space to in which to move. The same quantity of gas in a smaller volume results in gas molecules crowding together, producing increased pressure.
Resistance is created by inelastic surfaces, as well as the diameter of the airways. Resistance reduces the flow of gases. The surface tension of the alveoli also influences pressure, as it opposes the expansion of the alveoli. However, pulmonary surfactant helps to reduce the surface tension so that the alveoli do not collapse during expiration. The ability of the lungs to stretch, called lung compliance, also plays a role in gas flow. The more the lungs can stretch, the greater the potential volume of the lungs. The greater the volume of the lungs, the lower the air pressure within the lungs.
Pulmonary ventilation consists of the process of inspiration (or inhalation), where air enters the lungs, and expiration (or exhalation), where air leaves the lungs. During inspiration, the diaphragm and external intercostal muscles contract, causing the rib cage to expand and move outward, and expanding the thoracic cavity and lung volume. This creates a lower pressure within the lung than that of the atmosphere, causing air to be drawn into the lungs. During expiration, the diaphragm and intercostals relax, causing the thorax and lungs to recoil. The air pressure within the lungs increases to above the pressure of the atmosphere, causing air to be forced out of the lungs. However, during forced exhalation, the internal intercostals and abdominal muscles may be involved in forcing air out of the lungs.
Respiratory volume describes the amount of air in a given space within the lungs, or which can be moved by the lung, and is dependent on a variety of factors. Tidal volume refers to the amount of air that enters the lungs during quiet breathing, whereas inspiratory reserve volume is the amount of air that enters the lungs when a person inhales past the tidal volume. Expiratory reserve volume is the extra amount of air that can leave with forceful expiration, following tidal expiration. Residual volume is the amount of air that is left in the lungs after expelling the expiratory reserve volume. Respiratory capacity is the combination of two or more volumes. Anatomical dead space refers to the air within the respiratory structures that never participates in gas exchange, because it does not reach functional alveoli. Respiratory rate is the number of breaths taken per minute, which may change during certain diseases or conditions.
Both respiratory rate and depth are controlled by the respiratory centers of the brain, which are stimulated by factors such as chemical and pH changes in the blood. These changes are sensed by central chemoreceptors, which are located in the brain, and peripheral chemoreceptors, which are located in the aortic arch and carotid arteries. A rise in carbon dioxide or a decline in oxygen levels in the blood stimulates an increase in respiratory rate and depth.
22.4 Gas Exchange
The behavior of gases can be explained by the principles of Dalton’s law and Henry’s law, both of which describe aspects of gas exchange. Dalton’s law states that each specific gas in a mixture of gases exerts force (its partial pressure) independently of the other gases in the mixture. Henry’s law states that the amount of a specific gas that dissolves in a liquid is a function of its partial pressure. The greater the partial pressure of a gas, the more of that gas will dissolve in a liquid, as the gas moves toward equilibrium. Gas molecules move down a pressure gradient; in other words, gas moves from a region of high pressure to a region of low pressure. The partial pressure of oxygen is high in the alveoli and low in the blood of the pulmonary capillaries. As a result, oxygen diffuses across the respiratory membrane from the alveoli into the blood. In contrast, the partial pressure of carbon dioxide is high in the pulmonary capillaries and low in the alveoli. Therefore, carbon dioxide diffuses across the respiratory membrane from the blood into the alveoli. The amount of oxygen and carbon dioxide that diffuses across the respiratory membrane is similar.
Ventilation is the process that moves air into and out of the alveoli, and perfusion affects the flow of blood in the capillaries. Both are important in gas exchange, as ventilation must be sufficient to create a high partial pressure of oxygen in the alveoli. If ventilation is insufficient and the partial pressure of oxygen drops in the alveolar air, the capillary is constricted and blood flow is redirected to alveoli with sufficient ventilation. External respiration refers to gas exchange that occurs in the alveoli, whereas internal respiration refers to gas exchange that occurs in the tissue. Both are driven by partial pressure differences.
22.5 Transport of Gases
Oxygen is primarily transported through the blood by erythrocytes. These cells contain a metalloprotein called hemoglobin, which is composed of four subunits with a ring-like structure. Each subunit contains one atom of iron bound to a molecule of heme. Heme binds oxygen so that each hemoglobin molecule can bind up to four oxygen molecules. When all of the heme units in the blood are bound to oxygen, hemoglobin is considered to be saturated. Hemoglobin is partially saturated when only some heme units are bound to oxygen. An oxygen–hemoglobin saturation/dissociation curve is a common way to depict the relationship of how easily oxygen binds to or dissociates from hemoglobin as a function of the partial pressure of oxygen. As the partial pressure of oxygen increases, the more readily hemoglobin binds to oxygen. At the same time, once one molecule of oxygen is bound by hemoglobin, additional oxygen molecules more readily bind to hemoglobin. Other factors such as temperature, pH, the partial pressure of carbon dioxide, and the concentration of 2,3-bisphosphoglycerate can enhance or inhibit the binding of hemoglobin and oxygen as well. Fetal hemoglobin has a different structure than adult hemoglobin, which results in fetal hemoglobin having a greater affinity for oxygen than adult hemoglobin.
Carbon dioxide is transported in blood by three different mechanisms: as dissolved carbon dioxide, as bicarbonate, or as carbaminohemoglobin. A small portion of carbon dioxide remains. The largest amount of transported carbon dioxide is as bicarbonate, formed in erythrocytes. For this conversion, carbon dioxide is combined with water with the aid of an enzyme called carbonic anhydrase. This combination forms carbonic acid, which spontaneously dissociates into bicarbonate and hydrogen ions. As bicarbonate builds up in erythrocytes, it is moved across the membrane into the plasma in exchange for chloride ions by a mechanism called the chloride shift. At the pulmonary capillaries, bicarbonate re-enters erythrocytes in exchange for chloride ions, and the reaction with carbonic anhydrase is reversed, recreating carbon dioxide and water. Carbon dioxide then diffuses out of the erythrocyte and across the respiratory membrane into the air. An intermediate amount of carbon dioxide binds directly to hemoglobin to form carbaminohemoglobin. The partial pressures of carbon dioxide and oxygen, as well as the oxygen saturation of hemoglobin, influence how readily hemoglobin binds carbon dioxide. The less saturated hemoglobin is and the lower the partial pressure of oxygen in the blood is, the more readily hemoglobin binds to carbon dioxide. This is an example of the Haldane effect.
22.6 Modifications in Respiratory Functions
Normally, the respiratory centers of the brain maintain a consistent, rhythmic breathing cycle. However, in certain cases, the respiratory system must adjust to situational changes in order to supply the body with sufficient oxygen. For example, exercise results in increased ventilation, and chronic exposure to a high altitude results in a greater number of circulating erythrocytes. Hyperpnea, an increase in the rate and depth of ventilation, appears to be a function of three neural mechanisms that include a psychological stimulus, motor neuron activation of skeletal muscles, and the activation of proprioceptors in the muscles, joints, and tendons. As a result, hyperpnea related to exercise is initiated when exercise begins, as opposed to when tissue oxygen demand actually increases.
In contrast, acute exposure to a high altitude, particularly during times of physical exertion, does result in low blood and tissue levels of oxygen. This change is caused by a low partial pressure of oxygen in the air, because the atmospheric pressure at high altitudes is lower than the atmospheric pressure at sea level. This can lead to a condition called acute mountain sickness (AMS) with symptoms that include headaches, disorientation, fatigue, nausea, and lightheadedness. Over a long period of time, a person’s body will adjust to the high altitude, a process called acclimatization. During acclimatization, the low tissue levels of oxygen will cause the kidneys to produce greater amounts of the hormone erythropoietin, which stimulates the production of erythrocytes. Increased levels of circulating erythrocytes provide an increased amount of hemoglobin that helps supply an individual with more oxygen, preventing the symptoms of AMS.
22.7 Embryonic Development of the Respiratory System
The development of the respiratory system in the fetus begins at about 4 weeks and continues into childhood. Ectodermal tissue in the anterior portion of the head region invaginates posteriorly, forming olfactory pits, which ultimately fuse with endodermal tissue of the early pharynx. At about this same time, an protrusion of endodermal tissue extends anteriorly from the foregut, producing a lung bud, which continues to elongate until it forms the laryngotracheal bud. The proximal portion of this structure will mature into the trachea, whereas the bulbous end will branch to form two bronchial buds. These buds then branch repeatedly, so that at about week 16, all major airway structures are present. Development progresses after week 16 as respiratory bronchioles and alveolar ducts form, and extensive vascularization occurs. Alveolar type I cells also begin to take shape. Type II pulmonary cells develop and begin to produce small amounts of surfactant. As the fetus grows, the respiratory system continues to expand as more alveoli develop and more surfactant is produced. Beginning at about week 36 and lasting into childhood, alveolar precursors mature to become fully functional alveoli. At birth, compression of the thoracic cavity forces much of the fluid in the lungs to be expelled. The first inhalation inflates the lungs. Fetal breathing movements begin around week 20 or 21, and occur when contractions of the respiratory muscles cause the fetus to inhale and exhale amniotic fluid. These movements continue until birth and may help to tone the muscles in preparation for breathing after birth and are a sign of good health.