1. Copyright 2007 by Saunders/Elsevier. All rights reserved. Chapter 15: Respiratory System Color Textbook of Histology, 3rd ed. Gartner & Hiatt Copyright 2007 by Saunders/Elsevier. All rights reserved.

2. Olfactory Epithelium The respiratory system has two major portions, the conducting portion, situated both outside and within the lungs, conveys air from the external milieu to the lungs and the respiratory portion, located strictly within the lungs, functions in the actual exchange of oxygen for carbon dioxide (external respiration). The roof of the nasal cavity, the superior aspect of the nasal septum, and the superior concha are covered by an olfactory epithelium. The underlying lamina propria houses serous fluid–secreting Bowman’s glands, a rich vascular plexus, and collections of axons that arise from the olfactory cells of the olfactory epithelium. The olfactory epithelium is composed of three types of cells: olfactory, sustentacular, and basal cells. Olfactory cells are bipolar neurons whose apical aspect, the distal terminus of its slender dendrite, is modified to form a bulb, the olfactory vesicle, which projects above the surface of the sustentacular cells. Six to eight long, nonmotile olfactory cilia extend from the olfactory vesicle and lie on the free surface of the epithelium. The basal region of the olfactory cell is its axon, which penetrates the basal lamina and joins similar axons to form bundles of nerve fibers that synapse with secondary neurons in the olfactory bulb. The tall, columnar sustentacular cells have secretory granules housing a yellow pigment characteristic of the color of the olfactory mucosa. These cells are believed to provide physical support, nourishment, and electrical insulation for the olfactory cells. Basal cells have considerable proliferative capacity and can replace both sustentacular and olfactory cells. In a healthy person, the olfactory and sustentacular cells have a life span of less than a year. For more information see Olfactory Epithelium in Chapter 14 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 15–2 The olfactory epithelium, displaying basal, olfactory, and sustentacular cells.

3. Copyright 2007 by Saunders/Elsevier. All rights reserved. Trachea The trachea is a tube that begins at the cricoid cartilage of the larynx and ends when it bifurcates to form the primary bronchi. The wall of the trachea is reinforced by 10 to 12 horseshoe-shaped hyaline cartilage rings (C-rings). The open ends of these rings face posteriorly and are connected to each other by smooth muscle, the trachealis muscle. The trachea has three layers: mucosa, submucosa, and adventitia. The mucosal lining of the trachea is composed of pseudostratified ciliated columnar epithelium, the subepithelial connective tissue (lamina propria), and a relatively thick bundle of elastic fibers separating the mucosa from the submucosa. The lamina propria of the trachea is composed of a loose, fibroelastic connective tissue. It contains lymphoid elements (e.g., lymphoid nodules, lymphocytes, and neutrophils) as well as mucous and seromucous glands, whose ducts open onto the epithelial surface. A dense layer of elastic fibers, the elastic lamina, separates the lamina propria from the underlying submucosa. The tracheal submucosa is composed of a dense, irregular fibroelastic connective tissue housing numerous mucous and seromucous glands. The short ducts of these glands pierce the elastic lamina and the lamina propria to open onto the epithelial surface. The adventitia of the trachea is composed of a fibroelastic connective tissue that anchors the trachea to adjoining structures. The most prominent features of the adventitia are the hyaline cartilage C-rings and the intervening fibrous connective tissue. For more information see Trachea in Chapter 14 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 15–4 Light photomicrograph of the trachea in a monkey (´270). There are numerous cilia (Ci) as well as goblet cells (GC) in the epithelium. Also observe the mucous glands (MG) in the subepithelial connective tissue and the hyaline C-ring (HC) in the adventitia. L, lumen; PC, perichondrium.

4. Copyright 2007 by Saunders/Elsevier. All rights reserved. Bronchi and Bronchioles The bronchial tree (conducting portion) begins at the bifurcation of the trachea, as the right and left primary bronchi, which arborize. The bronchial tree is composed of airways located outside the lungs, the primary bronchi, and airways located inside the lungs, the intrapulmonary bronchi, bronchioles, and terminal bronchioles. Primary bronchi are identical to the trachea, except that bronchi are smaller in diameter and their walls are thinner. Intrapulmonary bronchi are similar to primary bronchi, except that the cartilage C-rings are replaced by irregular plates of hyaline cartilage that completely surround the lumina of the intrapulmonary bronchi. The smooth muscle is located at the interface of the fibroelastic lamina propria and submucosa as two distinct smooth muscle layers spiraling in opposite directions. Elastic fibers, radiate from the adventitia to connect with elastic fibers arising from other parts of the bronchial tree. Each bronchiole supplies air to a pulmonary lobule. Their epithelial lining ranges from ciliated simple columnar with occasional goblet cells in larger bronchioles to simple cuboidal (many with cilia) with occasional Clara cells and no goblet cells in smaller bronchioles. Terminal bronchioles are lined by Clara cells and cuboidal cells. The thin lamina propria consists of fibroelastic connective tissue and is surrounded by one or two layers of smooth muscle cells. Elastic fibers radiate from the adventitia and bind to elastic fibers radiating from other members of the bronchial tree. For more information see Bronchial Tree in Chapter 14 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 15–7 The respiratory system, displaying bronchioles, terminal bronchioles, respiratory bronchioles, alveolar ducts, alveolar pores, and alveoli.

5. Copyright 2007 by Saunders/Elsevier. All rights reserved. Respiratory Portion The respiratory portion of the respiratory system is composed of respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli. Respiratory bronchioles are similar to terminal bronchioles, but their wall is interrupted by alveoli, where gaseous exchange (O 2 for CO 2 ) can occur. Subsequent to several branchings, each respiratory bronchiole terminates in an alveolar duct Alveolar ducts do not have walls of their own. Each alveolar duct usually ends as a blind outpouching composed of two or more small clusters of alveoli, in which each cluster is known as an alveolar sac. These alveolar sacs thus open into a common space, which some investigators call the atrium. Alveoli are small air sacs composed of highly attenuated type I pneumocytes and larger type II pneumocytes. The region between adjacent alveoli is known as the interalveolar septum. It is occupied by an extensive capillary bed composed of continuous capillaries. The thinnest regions of the interalveolar septum where gases can be exchanged are called the blood-gas barriers The narrowest blood-gas barrier, where the type I pneumocyte is in intimate contact with the endothelial lining of the capillary and the basal laminae of the two epithelia become fused, is most efficient for the exchange of O 2 (in the alveolar lumen) for CO 2 (in the blood). These regions are composed of surfactant (manufactured by type II pneumocytes), type I pneumocytes, basal lamina, endothelial cells. For more information see Respiratory Portion of the Respiratory System in Chapter 14 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 15–11 A, A respiratory bronchiole, alveolar sac, alveolar pore, and alveoli. B, Interalveolar septum. C, Carbon dioxide uptake from body tissues by erythrocytes and plasma. D, Carbon dioxide release by erythrocytes and plasma in the lung. (Compare A with the alveolar duct shown in Fig. 15-10.)

6. Copyright 2007 by Saunders/Elsevier. All rights reserved. Respiration Approximately 200 ml of CO 2 is formed by the cells of the body per minute. CO 2 enters the blood stream and is transported in three forms: as a dissolved gas in plasma (20 ml), bound to hemoglobin (40 ml), and as plasma bicarbonate ion (140 ml). The following sequence of events occurs : 1. Most of the CO 2 dissolved in the plasma diffuses into the cytosol of the erythrocytes. 2. Some of the CO 2 binds to the globin moiety of hemoglobin. Although CO 2 is carried in a different region of the hemoglobin molecule, its binding capacity is greater in the absence than in the presence of O 2 in the heme portion. 3. Within the cytosol of the erythrocyte, most of the CO 2 combines with water, a reaction catalyzed by the enzyme carbonic anhydrase, to form carbonic acid, which dissociates into hydrogen ion (H + ) and bicarbonate ion (HCO 3 – ). The hydrogen ion binds to hemoglobin, and the bicarbonate ion leaves the erythrocyte to enter the plasma. To maintain ionic equilibrium, chloride ion (Cl – ) enters the erythrocyte from the plasma; this exchange of bicarbonate for chloride ions is known as the chloride shift. Figure 15–11 A, A respiratory bronchiole, alveolar sac, alveolar pore, and alveoli. B, Interalveolar septum. C, Carbon dioxide uptake from body tissues by erythrocytes and plasma. D, Carbon dioxide release by erythrocytes and plasma in the lung. (Compare A with the alveolar duct shown in Fig. 15-10.)

7. Copyright 2007 by Saunders/Elsevier. All rights reserved. Respiration (cont.) The bicarbonate-rich blood is delivered to the lungs by the pulmonary arteries. Because the level of CO2 is greater in the blood than in the lumina of the alveoli, CO2 is released (following the concentration gradient). The mechanism of release is the reverse of the previous reactions. The following sequence of events occurs: Bicarbonate ions enter the erythrocytes (with a consequent release of Cl– from the red blood cells into the plasma, known as the chloride shift). Bicarbonate ions and hydrogen ions within the erythrocyte cytosol combine to form carbonic acid. In the lung, the combining of O2 with hemoglobin makes the hemoglobin more acidic and reduces its ability to bind CO2. Additionally, the excess hydrogen ions released because of the greater acidity of hemoglobin become bound to bicarbonate ions, forming carbonic acid. Carbonic anhydrase catalyzes the cleavage of carbonic acid to form water and CO2. CO2 dissolved in the plasma, bound to hemoglobin, and cleaved from carbonic acid follows the concentration gradient to diffuse across the blood-gas barrier to enter the lumina of the alveoli. Hemoglobin also has two types of binding sites for nitric oxide (NO), a neurotransmitter substance that, when released by endothelial cells of blood vessels, causes relaxation of the vascular smooth muscle cells with a resultant dilation of the blood vessels. Hemoglobin, S- nitrosylated (binding site 1) by nitric oxide manufactured by blood vessels of the lung, ferries bound nitric oxide to arterioles and metarterioles of the tissues, where NO is released and causes vasodilation. In this fashion, hemoglobin not only contributes to the modulation of blood pressure but also facilitates the more efficient exchange of O2 for CO2. Moreover, once O2 leaves the heme portion of hemoglobin to oxygenate the tissues, NO takes its place on the iron atoms (binding site 2) and is transported into the lungs, where it is released into the alveoli to be exhaled along with CO 2. For more information see section on Respiration in Chapter 15 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 15–11 A, A respiratory bronchiole, alveolar sac, alveolar pore, and alveoli. B, Interalveolar septum. C, Carbon dioxide uptake from body tissues by erythrocytes and plasma. D, Carbon dioxide release by erythrocytes and plasma in the lung. (Compare A with the alveolar duct shown in Fig. 15-10.)