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Structure of the Lower Respiratory Tract
Structure of the Lower Respiratory Tract Amir Hakim and OS Usmani, National Heart and Lung Institute, Royal Brompton Hospital, Imperial College London, London, UK Ó 2014 Elsevier Inc. All rights reserved.
The Respiratory System The respiratory system is vital for supplying the body with oxygen and removing carbon dioxide. This essential function allows trillions of cells making up the body to carry out their cellular functions. Four major processes collectively facilitate respiration: they are pulmonary ventilation, external respiration, transport of respiratory gases, and internal respiration. The respiratory system consists of the chest wall structures responsible for moving air in and out of the lungs and the airways that carry inhaled air to the alveoli, which are the gas exchanging region of the lung. The airways are subdivided into two major regions, the upper and lower respiratory tracts. The upper respiratory tract consists of the external nares to the larynx, whereas the lower respiratory tract continues from the larynx to the alveoli (Figure 1). Nutrients and gas exchange are delivered to the lungs via the richly perfused neighboring blood vessels. The lower respiratory tract branches into many bronchioles to maximize delivery of air to all parts of the lung as well as providing the maximal surface area for gas exchange. The structural design of the respiratory system ensures that the process of breathing meets the oxygen demands of the body. The initial increase in the intrathoracic volume orchestrated by the diaphragm and thoracic muscles and subsequent decrease in intra-alveolar pressure ensure effective movement of inhaled air through the upper respiratory tract into the lower respiratory tract for gaseous exchange to take place at the alveoli.
Embryology The development of the respiratory system in the fetus can first be observed at approximately 26 days of gestation. During this time there is a rapid increase in epithelial proliferation at regions of the endoderm tube. The remaining structures of the airways originate from the mesenchyme. The structural
Figure 1
development and maturation of the respiratory tract passes through four main stages during gestation: the embryonic, pseudoglandular, canalicular, and saccular phases (Figure 2) (Burri, 1984; Agrons et al., 2005). The embryonic phase occurs in 4–5 weeks of gestation. A respiratory diverticulum (bud) forms from the laryngotracheal groove on the ventral aspect of the caudal segment of the foregut. This respiratory diverticulum enlarges at its distal end to form a tracheal bud which then divides to form bronchial buds. It is during the fifth week of embryological development that the tracheoesophageal ridges have fused to make the tracheoesophageal septum separating the trachea and foregut and the bronchial buds have developed into the right and left main bronchi. The pseudoglandular phase occurs between weeks 6 and 16 of gestation. The main bronchi undergo further development and tubular branching continues with the formation of secondary and tertiary bronchi. By 2 months, all the segmental bronchi have been formed. The conducting airways are lined with tall columnar epithelium and distal structures are lined with cuboidal epithelium. The canalicular phase occurs between weeks 17 and 24 of gestation. Distal airways such as the terminal bronchioles develop and the lumina of the bronchi enlarge. The development of the pulmonary and arterial systems causes the lung tissues to become highly vascularized. Epithelial cells subdivide into type I pneumocytes for gas exchange and type II pneumocytes for surfactant synthesis and secretion at 23 weeks of gestation. Finally, the saccular phase occurs from 24 weeks of gestation to the time of delivery. In this phase the terminal saccules, alveolar ducts, and finally alveoli start forming resulting in increased surface area for future gas exchange. It is important to note that further lung maturation occurs after birth. This is often referred to as the ‘alveolar phase.’ The newborn has only one-fifth of the number of alveoli of an adult and further alveolar multiplication and maturation occurs during early childhood until approximately 8 years of age.
Upper and lower respiratory tracts. http://www.hivandhepatitis.com/0_images2009/pulm_lung_test.jpg.
Reference Module in Biomedical Research, 3rd edition
http://dx.doi.org/10.1016/B978-0-12-801238-3.00215-4
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Structure of the Lower Respiratory Tract
Figure 2
Stages of the developing lung. http://usmle-az.com/lungs-development/.
The Lower Respiratory Tract The lower respiratory tract includes the larynx, trachea, bronchi, bronchioles, and the lungs. The lungs contain the alveoli, the main site of gaseous exchange. These structural features of the lower respiratory tract are essential components of the airways that facilitate maximum delivery of air to all parts of the lungs as well as providing maximal surface area for gaseous exchange. In humans, the trachea divides into two main bronchi that descend into the lungs. The two bronchi continue to divide into multiple divisions within the lung giving rise to bronchioles. At each division point (or generation), an airway branch may divide into two or more smaller airways. There are approximately 23 airway generations in the adult lower respiratory tract (Weibel and Gomez, 1962). Bronchoscopic examinations reveal that these generations are asymmetric and give rise to a number of anatomical variants in the structure of the tracheobronchial tree. Clusters of alveoli form at the terminal ends of bronchioles and are supplied by a rich source of blood vessels. Figure 3 The anatomical regions of the larynx. http://www.yorku.ca/ earmstro/journey/larynx.html.
Larynx The larynx connects the pharynx to the trachea and is made up of nine cartilages and dense connective tissue (Figure 3) (Armstrong and Netterville, 1995; Friedrich and Lichtenegger, 1997). The majority of the cartilage making up the larynx is hyaline cartilage with the exception of the epiglottis (Cohen et al., 1992). The larynx has the vital role of preventing food from entering into the lower respiratory tract and resides between the third and sixth cervical vertebrae. The function of the larynx can be categorized into three major areas: voice production, maintaining the pathway of the air passages, and preventing food from entering the lower respiratory tract (Sasaki et al., 2001; Jafari et al., 2003; Muller, 2005; Vilkman
et al., 1996). Two cartilage plates fuse together to form the shield-shaped thyroid cartilage of the larynx. Externally, the midpoint of the fusion, the midline laryngeal prominence is colloquially known as the ‘Adam’s apple.’ The third cartilage, the ring-shaped cricoid cartilage lies directly below the thyroid cartilage and attaches onto the trachea. A further three smaller cartilages, the arytenoids, cuneiform, and corniculate cartilages, fuse together to form the lateral and posterior walls of the larynx. Finally, the ninth cartilage has a different impression made up of elastic cartilage and forms the epiglottis. In the absence of swallowing, the free side of the epiglottis protrudes
Structure of the Lower Respiratory Tract
upward allowing air into the lower respiratory tract. During swallowing, the epiglottis covers the laryngeal inlet to prevent food entering into the lower respiratory tract.
Conducting Zone Structures The conducting zone of the airways includes the trachea, bronchi, and nonalveolated bronchioles and relates to airway generations 1–7 (Figure 4). The conducting zone allows for the movement of air in and out of the lungs to ensure it reaches the alveolar site of gaseous exchange. The length, number, and cross-sectional area of the conducting airways vary considerably between people and are determined by the development of the airways during various fetal stages. Forces generated by the contractile airway smooth muscle and pleural pressure in the intrapulmonary conducting airways impact on the crosssectional area of the airways, which subsequently affects airway resistance. The conducting airways of the lower respiratory tract are composed of a mucosal layer, made up of epithelial cells, and a connective tissue–rich layer known as the submucosal layer. Airway smooth muscle cells, blood vessels, cartilage plates, lymphoid tissue, mast cells, nerves, and seromucous glands can be found within the connective tissue–rich submucosal layer. This layer is surrounded by hyaline cartilage from the trachea to the bronchi. There are approximately six different types of epithelial cells located throughout the conducting airways. They are ciliated columnar, goblet, Clara, basal, brush, and neuroendocrine epithelial cells. The pseudostratified epithelium is mainly ciliated and resides upon a thick lamina propria. As one descends into the conducting airways, finds less and less ciliated epithelial cells, with reduced height. Alongside the pseudostratified epithelial cells in the larger conducting airways lie basal cells which are mitotic stem cells (Liu et al., 2006). Clara and brush cells are nonciliated epithelial cells. Clara cells are cuboidal, whereas brush cells are slender in shape (Nakajima et al., 1998). Clara cells contain many secretory granules and
Figure 4 Airway dimensions and physiological compartments of the tracheobronchial tree.
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lysozymes, and produce the lipoprotein, pulmonary surfactant (Reynolds and Malkinson, 2010). Finally, round-shaped neuroendocrine cells are situated predominantly in the basal part of the epithelium and are part of the dispersed neuroendocrine system of amine precursor uptake and decarboxylation cells. They are either found as a single cell or in clusters of cells known as neuroepithelial bodies. Neuroepithelial bodies are usually found within the intrapulmonary airways, whereas isolates of pulmonary neuroendocrine cells are found throughout the tracheobronchial tree (Cutz, 1982, 1997). External to the mucosal layer is the submucosal layer which is made up of a rich source of connective tissue. This contains many networks of longitudinal bands of elastin that are essential for the elastic recoil during expiration. Embedded within the submucosal layer are tubuloacinar seromucus glands. These glands are predominantly found in the upper regions of the conducting airways and, to a lesser extent, in the larger bronchioles. They contain both mucous and serous cells that secrete mucins, the bacteriostatic substances lysozyme and lactoferrin, secretory immunoglobulin A antibodies, and protease inhibitors, which are essential for neutralizing leukocyte-derived proteases. The submucosal layer is also embedded with smooth muscle cells. The tone of these muscle cells is regulated by the vagal nervous system, where contraction of these cells leads to airway narrowing and relaxation leads to airway dilatation. Smooth muscles found in the intrapulmonary bronchial tree form two helical tracts, which disappear at the level of the alveoli.
Trachea The trachea descends from the larynx and is a flexible 10 to 12cm-long tube, with a typical diameter of 1.5–2 cm in adults (Figure 5) (Minnich and Mathisen, 2007). It contains 16–20 C-shaped rings of cartilage. Each cartilage forms an incomplete ring, which is completed by the fibroelastic tissue and smooth muscle to prevent collapsing of the trachea. Each cartilage ring measures approximately 4 mm in depth and 1 mm in width. The first and last cartilages differ in size from the rest. The first cartilage is the broadest, whereas the last cartilage is centrally thick due to its lower border being prolonged into a triangular hook-shaped process. During deep inspiration the trachea can swiftly alter its length due to its structural components. The trachea wall is made up of several layers that include the mucosa, submucosa, hyaline cartilage, and the adventitia. The mucosal layer is made up of goblet cell-containing pseudostratified epithelium that are ubiquitously located throughout most of the respiratory tract, with only variations in the number of different cell types between the trachea, bronchi, and bronchioles. The submucosal layer of the respiratory tract contains seromucous glands that are vital for the production of mucus. External to the submucosal layer lies the hyaline cartilage which is encased by the outermost layer of connective tissue, the adventitia. The cervical and thoracic parts of the trachea cross many important anatomical regions within the neck and thorax. The anterior aspect of the cervical part of the trachea crosses several anatomical structures such as the aortic arch, the sternothyroid and sternohyoid, as well as the thyroid gland between the second and fourth tracheal cartridges. Meanwhile, the thoracic
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Similar to the epithelial cells found in the trachea, the epithelial cells in the mucosal layer of the bronchi and nonalveolated bronchioles are generally pseudostratified and ciliated. The epithelium is mostly longitudinal ridge folds that have the added advantage of changing the luminal diameter.
Bronchioles The bronchioles are further divisions of the trachea and are also essential for cleaning, warming, and moistening the incoming inhaled air (Berend et al., 1991; Horsfield et al., 1987). The left and right bronchi further divide into lobar and segmental bronchi and bronchioles within the lungs. Bronchioles are made up of smooth muscle layers to facilitate bronchodilatation and bronchoconstriction. The epithelial cells mainly lining the bronchial tree are ciliated columnar cells that are tightly packed and coupled by gap junctions. Each columnar cell has up to 300 cilia projecting from its apical surface that facilitate mucociliary clearance from the lower respiratory tract. The cilia project through a watery fluid into a layer of thick mucus secreted by the goblet cells in the submucosal glands.
Respiratory Zone Structures Figure 5 The tracheobronchial tree. http://open.jorum.ac.uk/xmlui/ bitstream/handle/123456789/2521/content/tracheobronchial.htm.
part of the trachea lies behind the manubrium sterni, as well as the thymic remnants and the inferior thyroid vein, as it descends through the superior mediastinum. The cervical and thoracic parts of the trachea rest in front of the esophagus, which separates them from the vertebrate column.
The respiratory zones of the airways include the respiratory bronchioles and alveoli (Figure 4) (Berend et al., 1991; Horsfield et al., 1987). The airway wall in the respiratory zones of the airways is much thinner, therefore maximizing gaseous exchange between the oxygenated inspired air and the gas dissolved in the pulmonary capillaries. Unlike the epithelial cells lining the conducting zones of the airways, the epithelial cells in the respiratory zones of the airways have reduced height and, as one descends into the respiratory zones, the epithelial cells are mostly composed of cuboidal and nonciliated cells.
Bronchi At the level of the fifth thoracic vertebrate, the trachea bifurcates into the right and left principal bronchi. The right and left principal bronchi are 2.5 and 5 cm long, respectively, with the right bronchus being more vertical and wider than the left. The right principal bronchus branches into the superior lobar bronchus, which runs superolaterally to enter the hilum and approximately 1 cm from its origin it divides into three segmental bronchi, the apical, posterior, and anterior. The apical, posterior, and anterior segmental bronchi serve the apex of the lung, posteroinferior aspect of the superior lobe, and the remaining segments of the superior lobe, respectively. As the right principal bronchus continues descending passed the pulmonary hilum it further divides into the right middle and inferior lobar bronchi. The right middle lobar bronchi and the right inferior lobar bronchi also further divide into segmental bronchi that serve the middle and inferior lobes respectively. The narrower and longer left principal bronchus is anterior to the descending aorta, esophagus, and thoracic duct, and branches into the superior and inferior lobar bronchi. The left superior bronchus supplies the left superior lobe. Unlike the right principal bronchi, the left principal bronchus only splits into two segmental bronchi due to the absence of a middle lobe in the left lung. The distribution of the left inferior lobar bronchi to the left inferior lobe is similar to the right inferior lobe.
Alveoli The alveoli are small air sacs within the lung parenchyma that originate from the terminal ends of alveolar sacs and ducts (Figure 6). There are approximately 300 million alveoli in the adult respiratory system, which have a total mean surface area of 143 m2 (Ochs et al., 2004). Each alveolus has an average diameter of 200 mm and is composed of a single epithelial layer of cells and extracellular matrix surrounded by capillaries. This is to ensure minimum diffusion distance (as little as 0.2 mm) between the atmosphere and the blood capillaries for gaseous exchange (Ochs et al., 2004). The alveolar wall is composed of mainly type I and type II alveolar cells (pneumocytes) (Ward and Nicholas, 1984). The former are simple squamous alveolar cells, with a thin cytoplasm between 0.05 and 0.2 mM. They make up 97% of the alveolar surface and are attached to the basal laminae of the capillary endothelium to form the interalveolar septa. Type II alveolar cells are believed to be progenitor cells, as they give rise to type I alveolar cells following replication (Mason et al., 1997). The smaller type II alveolar cells are associated with the interalveolar pores of Kohn and synthesize surfactant, which is a phospholipid that lines the alveoli and reduces surface tension (Cordingley, 1972; Fehrenbach, 2001; Ward and Nicholas, 1984). The interalveolar pores of Kohn link adjacent alveolar airspaces and
Structure of the Lower Respiratory Tract
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Figure 7 The right and left lungs. http://www.metrohealth.org/body. cfm?id¼1551&oTopID¼1551.
Figure 6 Alveoli and surrounding blood vessels. http://www.memrise. com/item/920186/alveoli-1-microscopic-sac-like-endings-of-the-bron/.
typically each human alveolus may have up to seven pores. These pores are also essential as passageway for the migration of alveolar macrophages, which are vital for phagocytosing inhaled particles that may reach the alveoli (Gordon and Read, 2002).
The Lungs The lungs, the epicenter of respiration, are located on either side of the heart. They are attached to the heart and the trachea at the hilum and pulmonary ligament, respectively. The right lung of an adult usually weighs greater than the left lung. The lungs are highly elastic with a smooth and shiny surface. They have numerous fine and dark lines that outline the many small polyhedral domains. The polyhedral domains further subdivide into sections of the lung that are in contact with the pleural surface. Each lung is composed of surface features that include an apex, base, costal and medial surfaces, and the pulmonary borders. Furthermore, each lung is divided by pulmonary fissures into several lobes (Figure 7). The lung parenchyma refers to the alveolar tissue with respiratory bronchioles, alveolar ducts, and terminal bronchioles.
The Apex and Base Anatomically, the apex of the lung extends to the root of the neck (between 2.5 and 4 cm above the sternal end of the first rib), it also lies posterior to the first rib and is covered in suprapleural membrane. Major components of the nervous system, the cervicothoracic (stellate) sympathetic ganglion and the ventral ramus of the first thoracic spinal nerve are located posterior to the apex. Several major blood vessels are located adjacent to the left medial surface of the apex such as the left subclavian artery and brachiocephalic vein. At the other
extreme end of the lung is the basal surface which sits upon the superior surface of the diaphragm. It is semilunar and concave in shape, with greater concavity in the right lung. The basal surfaces of the right and left lung separate it from the right and left lobes of the liver respectively.
Costal and Medial Surfaces The smooth and convex costal surface of the lung, which is in contact with the costal pleura, corresponds to the shape of the thoracic wall, whereas the deeply concave anterior mediastinal segment of the medial surface of the lung corresponds to the shape of the heart. The triangular hilum is the anatomical site where many structures enter and leave the lung, and it resides posterosuperior to the deep concave anterior mediastinal segment. The posterior vertebral segment forms the second structure of the medial surface of the lung that is in contact with the thoracic vertebrae and intervertebral discs.
Pulmonary Fissures and Lobes The two interlobular fissures, oblique and horizontal, divide the right lung into the superior, middle, and inferior lobes. The oblique fissure, which crosses the inferior border of the lung approximately 7.5 cm behind its anterior end, divides the inferior from the middle and superior lobes. While the horizontal fissure divides the middle from the superior lobe, running horizontally from the oblique fissure, near the midaxillary line toward the anterior border of the lung, which is anatomically at the same level as the sternal end of the fourth costal cartilage. These fissures are usually visible on frontal and lateral chest radiographs, as well as high-resolution computed tomography scans of patients. Unlike the right lung, the left lung is only divided into two lobes by the oblique fissure, the superior and inferior lobes. The oblique fissure begins from the medial surface of the posterosuperior segment of the hilum and it ascends to the posterior border of the lung, 6 cm below the apex, before descending toward the costal surface of its lower border. From its lower border it ascends on the medial surface to the hilum.
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Vascular Supply The lungs are perfused by two functionally different circulatory pathways: the pulmonary and the bronchial circulations. The pulmonary vessels include the pulmonary arteries, capillaries, and veins (Figure 8). The pulmonary arteries which divide into the pulmonary capillary networks carry deoxygenated blood to the alveolar walls and lie anterior to the main bronchi. The pulmonary artery divides into the right and left pulmonary arteries, which further divide into pulmonary vessels that lie dorsolateral to the segmental and subsegmental bronchi of the lower respiratory tract. The right pulmonary artery bifurcates into the superior and inferior branches which supply the lobes of the lungs. Unlike the superior branch of the right pulmonary artery which only serves the superior lobe of the lung, the inferior branch serves the middle lobe and the inferior lobar segments of the lung, as well as branching into a smaller pulmonary vessel to serve the superior lobe. The inferior branch of the right pulmonary artery descends anterior to the superior lobe and branches anatomically into the vessels that supply the middle and inferior lobes at the site where the horizontal fissure crosses the oblique fissure.
The left pulmonary artery descends toward the oblique fissure anterior to the ascending aorta and splits into a branch that serves the anterior segment of the left superior lobe. As the left pulmonary artery descends and enters the oblique fissure, it divides further into a blood vessel that supplies the superior segment of the inferior lobe. Further blood vessels arise at the oblique fissure site and further branching of the pulmonary artery supply the remaining parts of the lower lobe. The pulmonary capillary networks surround the alveoli and form single layer plexuses that reside in the interalveolar septa. The pulmonary veins, usually four in total (two in each lung), originate from the pulmonary capillary network in the respiratory zones and carry oxygenated blood to the left atrium of the heart for systemic distribution through the left ventricle. The pulmonary capillaries traverse the lungs until they drain into the pulmonary veins. The pulmonary vessels accompany the main bronchial divisions at the hilum. In contrast to the pulmonary arteries, the much smaller bronchial vessels provide oxygenated systemic blood to regions of the lung tissue that are not in close contact with atmospheric oxygen such as bronchi and large bronchioles of the conducting airways. The right bronchial artery may stem from the third
Figure 8 Vascular supply to the tracheobronchial tree. Reproduced from Minnich, D.J., Mathisen, D.J., 2007. Anatomy of the trachea, carina, and bronchi. Thorac. Surg. Clin. 17, 571–585.
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posterior intercostal artery, the upper left bronchial artery or any number of the right intercostal arteries. Whereas the left superior and inferior bronchial arteries stem directly from the thoracic aorta. The bronchial arteries descend and divide alongside the bronchi, until they end at the level of the respiratory bronchioles, where they may anastomose with pulmonary arteries in the walls of the smaller bronchi and in the visceral pleura.
The Lymphatic System The lymph glands of the thorax are divided into parietal and visceral. The visceral lymph glands consist of three groups, anterior mediastinal, posterior mediastinal, and tracheobronchial. The tracheobronchial glands are located in four major regions: either side of the trachea, between the trachea and bronchi, in the hilus of each lung, and at the larger branches of the bronchi within the lung substance. The pulmonary lymphatic vessels originate in two plexuses, a superficial subpleural plexus and a deep plexus. The deep plexus runs alongside the pulmonary bronchi and vessels. In the upper regions of the conducting zone, the deep plexus is made up of two networks, one which lies beneath the mucus membrane and a second which resides on the outside of the walls of the bronchi. In the lower regions of the conducting airways, there is only a single plexus which descends as far as the bronchioles. In the peripheral regions of the lungs, superficial and deep plexuses are connected by small channels, which may divert flow of lymph from the deep to the superficial plexus.
Innervation Parasympathetic and sympathetic motor nerve fibers and visceral sensory fibers innervate the lung through the pulmonary plexus. These nerve bundles descend in parallel to the bronchial tubes and blood vessels as far as the acinar region. Parasympathetic motor nerve fibers are responsible for regulating bronchoconstriction of the airways, whereas sympathetic motor nerve fibers regulate bronchodilatation of the airways. Autonomic excitatory cholinergic nerves secrete acetycholine into the bronchial smooth muscle cells and submucosal glands to cause airway bronchoconstriction and mucus production. Inhibitory nonadrenergic and noncholinergic nerves lead to airway bronchodilatation via vasoactive intestinal peptide and neural nitric oxide (Belvisi et al., 1992; Morice et al., 1983).
Pleura The pleura, a thin double-layered serosa, surrounds the lungs and allows the lungs to move smoothly over the thorax wall during inspiration and expiration. The pleura also compartmentalizes the organs of the thoracic cavity so they do not become tangled. The pleura splits the thoracic cavity into the central mediastinum and the two lateral pleural compartments, which each hold a lung. The visceral pleural fluid layer, which extends from the pleura, covers the external lung surface and lines the fissures of the lungs.
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Acknowledgment Dr O.S. Usmani is a recipient of an NIHR Career Development Fellowship. This article was supported by the National Institute for Health Research (NIHR) Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.
See also: Cardiovascular Anatomy; Chronic Obstructive Pulmonary Disease; Human Embryonic Stem Cells; Pulmonary Circulation; Respiratory Physiology; The Esophagus: From Pathophysiology to Treatment; Vascular Function in Health and Disease.
References Agrons, G.A., Courtney, S.E., Stocker, J.T., Markowitz, R.I., 2005. From the archives of the AFIP: lung disease in premature neonates: radiologic-pathologic correlation. Radiographics 25, 1047–1073. Armstrong, W.B., Netterville, J.L., 1995. Anatomy of the larynx, trachea, and bronchi. Otolaryngol. Clin. North Am. 28, 685–699. Belvisi, M.G., Stretton, C.D., Miura, M., Verleden, G.M., Tadjkarimi, S., Yacoub, M.H., Barnes, P.J., 1992. Inhibitory NANC nerves in human tracheal smooth muscle: a quest for the neurotransmitter. J. Appl. Physiol. 73, 2505–2510. Berend, N., Rynell, A.C., Ward, H.E., 1991. Structure of a human pulmonary acinus. Thorax 46, 117–121. Burri, P.H., 1984. Fetal and postnatal development of the lung. Annu. Rev. Physiol. 46, 617–628. Cohen, S.R., Cheung, D.T., Nimni, M.E., Mahnovski, V., Lian, G., Perelman, N., Carranza, A.P., 1992. Collagen in the developing larynx. Preliminary study. Ann. Otol. Rhinol. Laryngol. 101, 328–332. Cordingley, J.L., 1972. Pores of Kohn. Thorax 27, 433–441. Cutz, E., 1982. Neuroendocrine cells of the lung. An overview of morphologic characteristics and development. Exp. Lung Res. 3, 185–208. Cutz, E., 1997. Introduction to pulmonary neuroendocrine cell system, structurefunction correlations. Microsc. Res. Tech. 37, 1–3. Fehrenbach, H., 2001. Alveolar epithelial type II cell: defender of the alveolus revisited. Respir. Res. 2, 33–46. Friedrich, G., Lichtenegger, R., 1997. Surgical anatomy of the larynx. J. Voice 11, 345–355. Gordon, S.B., Read, R.C., 2002. Macrophage defences against respiratory tract infections. Br. Med. Bull. 61, 45–61. Horsfield, K., Gordon, W.I., Kemp, W., Phillips, S., 1987. Growth of the bronchial tree in man. Thorax 42, 383–388. Jafari, S., Prince, R.A., Kim, D.Y., Paydarfar, D., 2003. Sensory regulation of swallowing and airway protection: a role for the internal superior laryngeal nerve in humans. J. Physiol. 550, 287–304. Liu, X., Driskell, R.R., Engelhardt, J.F., 2006. Stem cells in the lung. Methods Enzymol. 419, 285–321. Mason, R.J., Williams, M.C., Moses, H.L., Mohla, S., Berberich, M.A., 1997. Stem cells in lung development, disease, and therapy. Am. J. Respir. Cell Mol. Biol. 16, 355–363. Minnich, D.J., Mathisen, D.J., 2007. Anatomy of the trachea, carina, and bronchi. Thorac. Surg. Clin. 17, 571–585. Morice, A., Unwin, R.J., Sever, P.S., 1983. Vasoactive intestinal peptide causes bronchodilatation and protects against histamine-induced bronchoconstriction in asthmatic subjects. Lancet 2, 1225–1227. Muller, A., 2005. Reconstructive procedures for impaired upper airway function: laryngeal respiration. GMS Curr. Top Otorhinolaryngol. Head Neck Surg. 4. Doc09. Nakajima, M., Kawanami, O., Jin, E., Ghazizadeh, M., Honda, M., Asano, G., Horiba, K., Ferrans, V.J., 1998. Immunohistochemical and ultrastructural studies of basal cells, Clara cells and bronchiolar cuboidal cells in normal human airways. Pathol. Int. 48, 944–953. Ochs, M., Nyengaard, J.R., Jung, A., Knudsen, L., Voigt, M., Wahlers, T., Richter, J., Gundersen, H.J., 2004. The number of alveoli in the human lung. Am. J. Respir. Crit. Care Med. 169, 120–124.
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Reynolds, S.D., Malkinson, A.M., 2010. Clara cell: progenitor for the bronchiolar epithelium. Int. J. Biochem. Cell Biol. 42, 1–4. Sasaki, C.T., Ho, S., Kim, Y.H., 2001. Critical role of central facilitation in the glottic closure reflex. Ann. Otol. Rhinol. Laryngol. 110, 401–405. Vilkman, E., Sonninen, A., Hurme, P., Korkko, P., 1996. External laryngeal frame function in voice production revisited: a review. J. Voice 10, 78–92. Ward, H.E., Nicholas, T.E., 1984. Alveolar type I and type II cells. Aust. N. Z. J. Med. 14, 731–734. Weibel, E.R., Gomez, D.M., 1962. Architecture of the human lung. Use of quantitative methods establishes fundamental relations between size and number of lung structures. Science 137, 577–585.
Further Reading Armstrong, P., Wilson, A.G., Dee, P., Hansell, D.M., 2000. Imaging of Diseases of the Chest. Mosby, London, pp. 21–62. Marieb, E.N., Hoehn, K., 2007. Human Anatomy & Physiology, eighth ed. Pearson, San Francisco, pp. 804–819. Standring, S., 2000. Gray’s Anatomy: The Anatomical Basis of Clinical Practice, fortieth ed. Elsevier. pp. 989–1006.
The Respiratory System The respiratory system is vital for supplying the body with oxygen and removing carbon dioxide. This essential function allows trillions of cells making up the body to carry out their cellular functions. Four major processes collectively facilitate respiration: they are pulmonary ventilation, external respiration, transport of respiratory gases, and internal respiration. The respiratory system consists of the chest wall structures responsible for moving air in and out of the lungs and the airways that carry inhaled air to the alveoli, which are the gas exchanging region of the lung. The airways are subdivided into two major regions, the upper and lower respiratory tracts. The upper respiratory tract consists of the external nares to the larynx, whereas the lower respiratory tract continues from the larynx to the alveoli (Figure 1). Nutrients and gas exchange are delivered to the lungs via the richly perfused neighboring blood vessels. The lower respiratory tract branches into many bronchioles to maximize delivery of air to all parts of the lung as well as providing the maximal surface area for gas exchange. The structural design of the respiratory system ensures that the process of breathing meets the oxygen demands of the body. The initial increase in the intrathoracic volume orchestrated by the diaphragm and thoracic muscles and subsequent decrease in intra-alveolar pressure ensure effective movement of inhaled air through the upper respiratory tract into the lower respiratory tract for gaseous exchange to take place at the alveoli.
Embryology The development of the respiratory system in the fetus can first be observed at approximately 26 days of gestation. During this time there is a rapid increase in epithelial proliferation at regions of the endoderm tube. The remaining structures of the airways originate from the mesenchyme. The structural
Figure 1
development and maturation of the respiratory tract passes through four main stages during gestation: the embryonic, pseudoglandular, canalicular, and saccular phases (Figure 2) (Burri, 1984; Agrons et al., 2005). The embryonic phase occurs in 4–5 weeks of gestation. A respiratory diverticulum (bud) forms from the laryngotracheal groove on the ventral aspect of the caudal segment of the foregut. This respiratory diverticulum enlarges at its distal end to form a tracheal bud which then divides to form bronchial buds. It is during the fifth week of embryological development that the tracheoesophageal ridges have fused to make the tracheoesophageal septum separating the trachea and foregut and the bronchial buds have developed into the right and left main bronchi. The pseudoglandular phase occurs between weeks 6 and 16 of gestation. The main bronchi undergo further development and tubular branching continues with the formation of secondary and tertiary bronchi. By 2 months, all the segmental bronchi have been formed. The conducting airways are lined with tall columnar epithelium and distal structures are lined with cuboidal epithelium. The canalicular phase occurs between weeks 17 and 24 of gestation. Distal airways such as the terminal bronchioles develop and the lumina of the bronchi enlarge. The development of the pulmonary and arterial systems causes the lung tissues to become highly vascularized. Epithelial cells subdivide into type I pneumocytes for gas exchange and type II pneumocytes for surfactant synthesis and secretion at 23 weeks of gestation. Finally, the saccular phase occurs from 24 weeks of gestation to the time of delivery. In this phase the terminal saccules, alveolar ducts, and finally alveoli start forming resulting in increased surface area for future gas exchange. It is important to note that further lung maturation occurs after birth. This is often referred to as the ‘alveolar phase.’ The newborn has only one-fifth of the number of alveoli of an adult and further alveolar multiplication and maturation occurs during early childhood until approximately 8 years of age.
Upper and lower respiratory tracts. http://www.hivandhepatitis.com/0_images2009/pulm_lung_test.jpg.
Reference Module in Biomedical Research, 3rd edition
http://dx.doi.org/10.1016/B978-0-12-801238-3.00215-4
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Structure of the Lower Respiratory Tract
Figure 2
Stages of the developing lung. http://usmle-az.com/lungs-development/.
The Lower Respiratory Tract The lower respiratory tract includes the larynx, trachea, bronchi, bronchioles, and the lungs. The lungs contain the alveoli, the main site of gaseous exchange. These structural features of the lower respiratory tract are essential components of the airways that facilitate maximum delivery of air to all parts of the lungs as well as providing maximal surface area for gaseous exchange. In humans, the trachea divides into two main bronchi that descend into the lungs. The two bronchi continue to divide into multiple divisions within the lung giving rise to bronchioles. At each division point (or generation), an airway branch may divide into two or more smaller airways. There are approximately 23 airway generations in the adult lower respiratory tract (Weibel and Gomez, 1962). Bronchoscopic examinations reveal that these generations are asymmetric and give rise to a number of anatomical variants in the structure of the tracheobronchial tree. Clusters of alveoli form at the terminal ends of bronchioles and are supplied by a rich source of blood vessels. Figure 3 The anatomical regions of the larynx. http://www.yorku.ca/ earmstro/journey/larynx.html.
Larynx The larynx connects the pharynx to the trachea and is made up of nine cartilages and dense connective tissue (Figure 3) (Armstrong and Netterville, 1995; Friedrich and Lichtenegger, 1997). The majority of the cartilage making up the larynx is hyaline cartilage with the exception of the epiglottis (Cohen et al., 1992). The larynx has the vital role of preventing food from entering into the lower respiratory tract and resides between the third and sixth cervical vertebrae. The function of the larynx can be categorized into three major areas: voice production, maintaining the pathway of the air passages, and preventing food from entering the lower respiratory tract (Sasaki et al., 2001; Jafari et al., 2003; Muller, 2005; Vilkman
et al., 1996). Two cartilage plates fuse together to form the shield-shaped thyroid cartilage of the larynx. Externally, the midpoint of the fusion, the midline laryngeal prominence is colloquially known as the ‘Adam’s apple.’ The third cartilage, the ring-shaped cricoid cartilage lies directly below the thyroid cartilage and attaches onto the trachea. A further three smaller cartilages, the arytenoids, cuneiform, and corniculate cartilages, fuse together to form the lateral and posterior walls of the larynx. Finally, the ninth cartilage has a different impression made up of elastic cartilage and forms the epiglottis. In the absence of swallowing, the free side of the epiglottis protrudes
Structure of the Lower Respiratory Tract
upward allowing air into the lower respiratory tract. During swallowing, the epiglottis covers the laryngeal inlet to prevent food entering into the lower respiratory tract.
Conducting Zone Structures The conducting zone of the airways includes the trachea, bronchi, and nonalveolated bronchioles and relates to airway generations 1–7 (Figure 4). The conducting zone allows for the movement of air in and out of the lungs to ensure it reaches the alveolar site of gaseous exchange. The length, number, and cross-sectional area of the conducting airways vary considerably between people and are determined by the development of the airways during various fetal stages. Forces generated by the contractile airway smooth muscle and pleural pressure in the intrapulmonary conducting airways impact on the crosssectional area of the airways, which subsequently affects airway resistance. The conducting airways of the lower respiratory tract are composed of a mucosal layer, made up of epithelial cells, and a connective tissue–rich layer known as the submucosal layer. Airway smooth muscle cells, blood vessels, cartilage plates, lymphoid tissue, mast cells, nerves, and seromucous glands can be found within the connective tissue–rich submucosal layer. This layer is surrounded by hyaline cartilage from the trachea to the bronchi. There are approximately six different types of epithelial cells located throughout the conducting airways. They are ciliated columnar, goblet, Clara, basal, brush, and neuroendocrine epithelial cells. The pseudostratified epithelium is mainly ciliated and resides upon a thick lamina propria. As one descends into the conducting airways, finds less and less ciliated epithelial cells, with reduced height. Alongside the pseudostratified epithelial cells in the larger conducting airways lie basal cells which are mitotic stem cells (Liu et al., 2006). Clara and brush cells are nonciliated epithelial cells. Clara cells are cuboidal, whereas brush cells are slender in shape (Nakajima et al., 1998). Clara cells contain many secretory granules and
Figure 4 Airway dimensions and physiological compartments of the tracheobronchial tree.
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lysozymes, and produce the lipoprotein, pulmonary surfactant (Reynolds and Malkinson, 2010). Finally, round-shaped neuroendocrine cells are situated predominantly in the basal part of the epithelium and are part of the dispersed neuroendocrine system of amine precursor uptake and decarboxylation cells. They are either found as a single cell or in clusters of cells known as neuroepithelial bodies. Neuroepithelial bodies are usually found within the intrapulmonary airways, whereas isolates of pulmonary neuroendocrine cells are found throughout the tracheobronchial tree (Cutz, 1982, 1997). External to the mucosal layer is the submucosal layer which is made up of a rich source of connective tissue. This contains many networks of longitudinal bands of elastin that are essential for the elastic recoil during expiration. Embedded within the submucosal layer are tubuloacinar seromucus glands. These glands are predominantly found in the upper regions of the conducting airways and, to a lesser extent, in the larger bronchioles. They contain both mucous and serous cells that secrete mucins, the bacteriostatic substances lysozyme and lactoferrin, secretory immunoglobulin A antibodies, and protease inhibitors, which are essential for neutralizing leukocyte-derived proteases. The submucosal layer is also embedded with smooth muscle cells. The tone of these muscle cells is regulated by the vagal nervous system, where contraction of these cells leads to airway narrowing and relaxation leads to airway dilatation. Smooth muscles found in the intrapulmonary bronchial tree form two helical tracts, which disappear at the level of the alveoli.
Trachea The trachea descends from the larynx and is a flexible 10 to 12cm-long tube, with a typical diameter of 1.5–2 cm in adults (Figure 5) (Minnich and Mathisen, 2007). It contains 16–20 C-shaped rings of cartilage. Each cartilage forms an incomplete ring, which is completed by the fibroelastic tissue and smooth muscle to prevent collapsing of the trachea. Each cartilage ring measures approximately 4 mm in depth and 1 mm in width. The first and last cartilages differ in size from the rest. The first cartilage is the broadest, whereas the last cartilage is centrally thick due to its lower border being prolonged into a triangular hook-shaped process. During deep inspiration the trachea can swiftly alter its length due to its structural components. The trachea wall is made up of several layers that include the mucosa, submucosa, hyaline cartilage, and the adventitia. The mucosal layer is made up of goblet cell-containing pseudostratified epithelium that are ubiquitously located throughout most of the respiratory tract, with only variations in the number of different cell types between the trachea, bronchi, and bronchioles. The submucosal layer of the respiratory tract contains seromucous glands that are vital for the production of mucus. External to the submucosal layer lies the hyaline cartilage which is encased by the outermost layer of connective tissue, the adventitia. The cervical and thoracic parts of the trachea cross many important anatomical regions within the neck and thorax. The anterior aspect of the cervical part of the trachea crosses several anatomical structures such as the aortic arch, the sternothyroid and sternohyoid, as well as the thyroid gland between the second and fourth tracheal cartridges. Meanwhile, the thoracic
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Structure of the Lower Respiratory Tract
Similar to the epithelial cells found in the trachea, the epithelial cells in the mucosal layer of the bronchi and nonalveolated bronchioles are generally pseudostratified and ciliated. The epithelium is mostly longitudinal ridge folds that have the added advantage of changing the luminal diameter.
Bronchioles The bronchioles are further divisions of the trachea and are also essential for cleaning, warming, and moistening the incoming inhaled air (Berend et al., 1991; Horsfield et al., 1987). The left and right bronchi further divide into lobar and segmental bronchi and bronchioles within the lungs. Bronchioles are made up of smooth muscle layers to facilitate bronchodilatation and bronchoconstriction. The epithelial cells mainly lining the bronchial tree are ciliated columnar cells that are tightly packed and coupled by gap junctions. Each columnar cell has up to 300 cilia projecting from its apical surface that facilitate mucociliary clearance from the lower respiratory tract. The cilia project through a watery fluid into a layer of thick mucus secreted by the goblet cells in the submucosal glands.
Respiratory Zone Structures Figure 5 The tracheobronchial tree. http://open.jorum.ac.uk/xmlui/ bitstream/handle/123456789/2521/content/tracheobronchial.htm.
part of the trachea lies behind the manubrium sterni, as well as the thymic remnants and the inferior thyroid vein, as it descends through the superior mediastinum. The cervical and thoracic parts of the trachea rest in front of the esophagus, which separates them from the vertebrate column.
The respiratory zones of the airways include the respiratory bronchioles and alveoli (Figure 4) (Berend et al., 1991; Horsfield et al., 1987). The airway wall in the respiratory zones of the airways is much thinner, therefore maximizing gaseous exchange between the oxygenated inspired air and the gas dissolved in the pulmonary capillaries. Unlike the epithelial cells lining the conducting zones of the airways, the epithelial cells in the respiratory zones of the airways have reduced height and, as one descends into the respiratory zones, the epithelial cells are mostly composed of cuboidal and nonciliated cells.
Bronchi At the level of the fifth thoracic vertebrate, the trachea bifurcates into the right and left principal bronchi. The right and left principal bronchi are 2.5 and 5 cm long, respectively, with the right bronchus being more vertical and wider than the left. The right principal bronchus branches into the superior lobar bronchus, which runs superolaterally to enter the hilum and approximately 1 cm from its origin it divides into three segmental bronchi, the apical, posterior, and anterior. The apical, posterior, and anterior segmental bronchi serve the apex of the lung, posteroinferior aspect of the superior lobe, and the remaining segments of the superior lobe, respectively. As the right principal bronchus continues descending passed the pulmonary hilum it further divides into the right middle and inferior lobar bronchi. The right middle lobar bronchi and the right inferior lobar bronchi also further divide into segmental bronchi that serve the middle and inferior lobes respectively. The narrower and longer left principal bronchus is anterior to the descending aorta, esophagus, and thoracic duct, and branches into the superior and inferior lobar bronchi. The left superior bronchus supplies the left superior lobe. Unlike the right principal bronchi, the left principal bronchus only splits into two segmental bronchi due to the absence of a middle lobe in the left lung. The distribution of the left inferior lobar bronchi to the left inferior lobe is similar to the right inferior lobe.
Alveoli The alveoli are small air sacs within the lung parenchyma that originate from the terminal ends of alveolar sacs and ducts (Figure 6). There are approximately 300 million alveoli in the adult respiratory system, which have a total mean surface area of 143 m2 (Ochs et al., 2004). Each alveolus has an average diameter of 200 mm and is composed of a single epithelial layer of cells and extracellular matrix surrounded by capillaries. This is to ensure minimum diffusion distance (as little as 0.2 mm) between the atmosphere and the blood capillaries for gaseous exchange (Ochs et al., 2004). The alveolar wall is composed of mainly type I and type II alveolar cells (pneumocytes) (Ward and Nicholas, 1984). The former are simple squamous alveolar cells, with a thin cytoplasm between 0.05 and 0.2 mM. They make up 97% of the alveolar surface and are attached to the basal laminae of the capillary endothelium to form the interalveolar septa. Type II alveolar cells are believed to be progenitor cells, as they give rise to type I alveolar cells following replication (Mason et al., 1997). The smaller type II alveolar cells are associated with the interalveolar pores of Kohn and synthesize surfactant, which is a phospholipid that lines the alveoli and reduces surface tension (Cordingley, 1972; Fehrenbach, 2001; Ward and Nicholas, 1984). The interalveolar pores of Kohn link adjacent alveolar airspaces and
Structure of the Lower Respiratory Tract
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Figure 7 The right and left lungs. http://www.metrohealth.org/body. cfm?id¼1551&oTopID¼1551.
Figure 6 Alveoli and surrounding blood vessels. http://www.memrise. com/item/920186/alveoli-1-microscopic-sac-like-endings-of-the-bron/.
typically each human alveolus may have up to seven pores. These pores are also essential as passageway for the migration of alveolar macrophages, which are vital for phagocytosing inhaled particles that may reach the alveoli (Gordon and Read, 2002).
The Lungs The lungs, the epicenter of respiration, are located on either side of the heart. They are attached to the heart and the trachea at the hilum and pulmonary ligament, respectively. The right lung of an adult usually weighs greater than the left lung. The lungs are highly elastic with a smooth and shiny surface. They have numerous fine and dark lines that outline the many small polyhedral domains. The polyhedral domains further subdivide into sections of the lung that are in contact with the pleural surface. Each lung is composed of surface features that include an apex, base, costal and medial surfaces, and the pulmonary borders. Furthermore, each lung is divided by pulmonary fissures into several lobes (Figure 7). The lung parenchyma refers to the alveolar tissue with respiratory bronchioles, alveolar ducts, and terminal bronchioles.
The Apex and Base Anatomically, the apex of the lung extends to the root of the neck (between 2.5 and 4 cm above the sternal end of the first rib), it also lies posterior to the first rib and is covered in suprapleural membrane. Major components of the nervous system, the cervicothoracic (stellate) sympathetic ganglion and the ventral ramus of the first thoracic spinal nerve are located posterior to the apex. Several major blood vessels are located adjacent to the left medial surface of the apex such as the left subclavian artery and brachiocephalic vein. At the other
extreme end of the lung is the basal surface which sits upon the superior surface of the diaphragm. It is semilunar and concave in shape, with greater concavity in the right lung. The basal surfaces of the right and left lung separate it from the right and left lobes of the liver respectively.
Costal and Medial Surfaces The smooth and convex costal surface of the lung, which is in contact with the costal pleura, corresponds to the shape of the thoracic wall, whereas the deeply concave anterior mediastinal segment of the medial surface of the lung corresponds to the shape of the heart. The triangular hilum is the anatomical site where many structures enter and leave the lung, and it resides posterosuperior to the deep concave anterior mediastinal segment. The posterior vertebral segment forms the second structure of the medial surface of the lung that is in contact with the thoracic vertebrae and intervertebral discs.
Pulmonary Fissures and Lobes The two interlobular fissures, oblique and horizontal, divide the right lung into the superior, middle, and inferior lobes. The oblique fissure, which crosses the inferior border of the lung approximately 7.5 cm behind its anterior end, divides the inferior from the middle and superior lobes. While the horizontal fissure divides the middle from the superior lobe, running horizontally from the oblique fissure, near the midaxillary line toward the anterior border of the lung, which is anatomically at the same level as the sternal end of the fourth costal cartilage. These fissures are usually visible on frontal and lateral chest radiographs, as well as high-resolution computed tomography scans of patients. Unlike the right lung, the left lung is only divided into two lobes by the oblique fissure, the superior and inferior lobes. The oblique fissure begins from the medial surface of the posterosuperior segment of the hilum and it ascends to the posterior border of the lung, 6 cm below the apex, before descending toward the costal surface of its lower border. From its lower border it ascends on the medial surface to the hilum.
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Structure of the Lower Respiratory Tract
Vascular Supply The lungs are perfused by two functionally different circulatory pathways: the pulmonary and the bronchial circulations. The pulmonary vessels include the pulmonary arteries, capillaries, and veins (Figure 8). The pulmonary arteries which divide into the pulmonary capillary networks carry deoxygenated blood to the alveolar walls and lie anterior to the main bronchi. The pulmonary artery divides into the right and left pulmonary arteries, which further divide into pulmonary vessels that lie dorsolateral to the segmental and subsegmental bronchi of the lower respiratory tract. The right pulmonary artery bifurcates into the superior and inferior branches which supply the lobes of the lungs. Unlike the superior branch of the right pulmonary artery which only serves the superior lobe of the lung, the inferior branch serves the middle lobe and the inferior lobar segments of the lung, as well as branching into a smaller pulmonary vessel to serve the superior lobe. The inferior branch of the right pulmonary artery descends anterior to the superior lobe and branches anatomically into the vessels that supply the middle and inferior lobes at the site where the horizontal fissure crosses the oblique fissure.
The left pulmonary artery descends toward the oblique fissure anterior to the ascending aorta and splits into a branch that serves the anterior segment of the left superior lobe. As the left pulmonary artery descends and enters the oblique fissure, it divides further into a blood vessel that supplies the superior segment of the inferior lobe. Further blood vessels arise at the oblique fissure site and further branching of the pulmonary artery supply the remaining parts of the lower lobe. The pulmonary capillary networks surround the alveoli and form single layer plexuses that reside in the interalveolar septa. The pulmonary veins, usually four in total (two in each lung), originate from the pulmonary capillary network in the respiratory zones and carry oxygenated blood to the left atrium of the heart for systemic distribution through the left ventricle. The pulmonary capillaries traverse the lungs until they drain into the pulmonary veins. The pulmonary vessels accompany the main bronchial divisions at the hilum. In contrast to the pulmonary arteries, the much smaller bronchial vessels provide oxygenated systemic blood to regions of the lung tissue that are not in close contact with atmospheric oxygen such as bronchi and large bronchioles of the conducting airways. The right bronchial artery may stem from the third
Figure 8 Vascular supply to the tracheobronchial tree. Reproduced from Minnich, D.J., Mathisen, D.J., 2007. Anatomy of the trachea, carina, and bronchi. Thorac. Surg. Clin. 17, 571–585.
Structure of the Lower Respiratory Tract
posterior intercostal artery, the upper left bronchial artery or any number of the right intercostal arteries. Whereas the left superior and inferior bronchial arteries stem directly from the thoracic aorta. The bronchial arteries descend and divide alongside the bronchi, until they end at the level of the respiratory bronchioles, where they may anastomose with pulmonary arteries in the walls of the smaller bronchi and in the visceral pleura.
The Lymphatic System The lymph glands of the thorax are divided into parietal and visceral. The visceral lymph glands consist of three groups, anterior mediastinal, posterior mediastinal, and tracheobronchial. The tracheobronchial glands are located in four major regions: either side of the trachea, between the trachea and bronchi, in the hilus of each lung, and at the larger branches of the bronchi within the lung substance. The pulmonary lymphatic vessels originate in two plexuses, a superficial subpleural plexus and a deep plexus. The deep plexus runs alongside the pulmonary bronchi and vessels. In the upper regions of the conducting zone, the deep plexus is made up of two networks, one which lies beneath the mucus membrane and a second which resides on the outside of the walls of the bronchi. In the lower regions of the conducting airways, there is only a single plexus which descends as far as the bronchioles. In the peripheral regions of the lungs, superficial and deep plexuses are connected by small channels, which may divert flow of lymph from the deep to the superficial plexus.
Innervation Parasympathetic and sympathetic motor nerve fibers and visceral sensory fibers innervate the lung through the pulmonary plexus. These nerve bundles descend in parallel to the bronchial tubes and blood vessels as far as the acinar region. Parasympathetic motor nerve fibers are responsible for regulating bronchoconstriction of the airways, whereas sympathetic motor nerve fibers regulate bronchodilatation of the airways. Autonomic excitatory cholinergic nerves secrete acetycholine into the bronchial smooth muscle cells and submucosal glands to cause airway bronchoconstriction and mucus production. Inhibitory nonadrenergic and noncholinergic nerves lead to airway bronchodilatation via vasoactive intestinal peptide and neural nitric oxide (Belvisi et al., 1992; Morice et al., 1983).
Pleura The pleura, a thin double-layered serosa, surrounds the lungs and allows the lungs to move smoothly over the thorax wall during inspiration and expiration. The pleura also compartmentalizes the organs of the thoracic cavity so they do not become tangled. The pleura splits the thoracic cavity into the central mediastinum and the two lateral pleural compartments, which each hold a lung. The visceral pleural fluid layer, which extends from the pleura, covers the external lung surface and lines the fissures of the lungs.
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Acknowledgment Dr O.S. Usmani is a recipient of an NIHR Career Development Fellowship. This article was supported by the National Institute for Health Research (NIHR) Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.
See also: Cardiovascular Anatomy; Chronic Obstructive Pulmonary Disease; Human Embryonic Stem Cells; Pulmonary Circulation; Respiratory Physiology; The Esophagus: From Pathophysiology to Treatment; Vascular Function in Health and Disease.
References Agrons, G.A., Courtney, S.E., Stocker, J.T., Markowitz, R.I., 2005. From the archives of the AFIP: lung disease in premature neonates: radiologic-pathologic correlation. Radiographics 25, 1047–1073. Armstrong, W.B., Netterville, J.L., 1995. Anatomy of the larynx, trachea, and bronchi. Otolaryngol. Clin. North Am. 28, 685–699. Belvisi, M.G., Stretton, C.D., Miura, M., Verleden, G.M., Tadjkarimi, S., Yacoub, M.H., Barnes, P.J., 1992. Inhibitory NANC nerves in human tracheal smooth muscle: a quest for the neurotransmitter. J. Appl. Physiol. 73, 2505–2510. Berend, N., Rynell, A.C., Ward, H.E., 1991. Structure of a human pulmonary acinus. Thorax 46, 117–121. Burri, P.H., 1984. Fetal and postnatal development of the lung. Annu. Rev. Physiol. 46, 617–628. Cohen, S.R., Cheung, D.T., Nimni, M.E., Mahnovski, V., Lian, G., Perelman, N., Carranza, A.P., 1992. Collagen in the developing larynx. Preliminary study. Ann. Otol. Rhinol. Laryngol. 101, 328–332. Cordingley, J.L., 1972. Pores of Kohn. Thorax 27, 433–441. Cutz, E., 1982. Neuroendocrine cells of the lung. An overview of morphologic characteristics and development. Exp. Lung Res. 3, 185–208. Cutz, E., 1997. Introduction to pulmonary neuroendocrine cell system, structurefunction correlations. Microsc. Res. Tech. 37, 1–3. Fehrenbach, H., 2001. Alveolar epithelial type II cell: defender of the alveolus revisited. Respir. Res. 2, 33–46. Friedrich, G., Lichtenegger, R., 1997. Surgical anatomy of the larynx. J. Voice 11, 345–355. Gordon, S.B., Read, R.C., 2002. Macrophage defences against respiratory tract infections. Br. Med. Bull. 61, 45–61. Horsfield, K., Gordon, W.I., Kemp, W., Phillips, S., 1987. Growth of the bronchial tree in man. Thorax 42, 383–388. Jafari, S., Prince, R.A., Kim, D.Y., Paydarfar, D., 2003. Sensory regulation of swallowing and airway protection: a role for the internal superior laryngeal nerve in humans. J. Physiol. 550, 287–304. Liu, X., Driskell, R.R., Engelhardt, J.F., 2006. Stem cells in the lung. Methods Enzymol. 419, 285–321. Mason, R.J., Williams, M.C., Moses, H.L., Mohla, S., Berberich, M.A., 1997. Stem cells in lung development, disease, and therapy. Am. J. Respir. Cell Mol. Biol. 16, 355–363. Minnich, D.J., Mathisen, D.J., 2007. Anatomy of the trachea, carina, and bronchi. Thorac. Surg. Clin. 17, 571–585. Morice, A., Unwin, R.J., Sever, P.S., 1983. Vasoactive intestinal peptide causes bronchodilatation and protects against histamine-induced bronchoconstriction in asthmatic subjects. Lancet 2, 1225–1227. Muller, A., 2005. Reconstructive procedures for impaired upper airway function: laryngeal respiration. GMS Curr. Top Otorhinolaryngol. Head Neck Surg. 4. Doc09. Nakajima, M., Kawanami, O., Jin, E., Ghazizadeh, M., Honda, M., Asano, G., Horiba, K., Ferrans, V.J., 1998. Immunohistochemical and ultrastructural studies of basal cells, Clara cells and bronchiolar cuboidal cells in normal human airways. Pathol. Int. 48, 944–953. Ochs, M., Nyengaard, J.R., Jung, A., Knudsen, L., Voigt, M., Wahlers, T., Richter, J., Gundersen, H.J., 2004. The number of alveoli in the human lung. Am. J. Respir. Crit. Care Med. 169, 120–124.
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Reynolds, S.D., Malkinson, A.M., 2010. Clara cell: progenitor for the bronchiolar epithelium. Int. J. Biochem. Cell Biol. 42, 1–4. Sasaki, C.T., Ho, S., Kim, Y.H., 2001. Critical role of central facilitation in the glottic closure reflex. Ann. Otol. Rhinol. Laryngol. 110, 401–405. Vilkman, E., Sonninen, A., Hurme, P., Korkko, P., 1996. External laryngeal frame function in voice production revisited: a review. J. Voice 10, 78–92. Ward, H.E., Nicholas, T.E., 1984. Alveolar type I and type II cells. Aust. N. Z. J. Med. 14, 731–734. Weibel, E.R., Gomez, D.M., 1962. Architecture of the human lung. Use of quantitative methods establishes fundamental relations between size and number of lung structures. Science 137, 577–585.
Further Reading Armstrong, P., Wilson, A.G., Dee, P., Hansell, D.M., 2000. Imaging of Diseases of the Chest. Mosby, London, pp. 21–62. Marieb, E.N., Hoehn, K., 2007. Human Anatomy & Physiology, eighth ed. Pearson, San Francisco, pp. 804–819. Standring, S., 2000. Gray’s Anatomy: The Anatomical Basis of Clinical Practice, fortieth ed. Elsevier. pp. 989–1006.