General Human Histology. The Respiratory System

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2 General Human Histology Lecture 5 Assist. Prof. Ahmed Anwar Albir The Respiratory System The respiratory system includes the lungs and a system of tubes that link the sites of gas exchange with the external environment. The respiratory system is divided into 2 principal regions (Figure 1): 1. The Conducting Portion: Consisting of the nasal cavity, nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles. 2. The Respiratory Portion: Consisting of respiratory bronchioles, alveolar ducts, and alveoli. Alveoli: Are specialized saclike structures that make up the greater part of the lungs. They are the main sites for the principal function of the lungs-the exchange of O 2 and CO 2 between inspired air and blood. 1

3 Figure 1. The main divisions of the respiratory tract. 1- The Conducting Portion of the Respiratory System Most of the conducting portion is lined with ciliated pseudostratified columnar epithelium that contains a rich population of goblet cells and is known as respiratory epithelium (Figure 2). 2

4 Figure 2. Photomicrograph illustrating the main components of the respiratory epithelium. Typical respiratory epithelium consists of 5 cell types (as seen in the electron microscope): A. Ciliated Columnar Cells: Constitute the most abundant type. Each cell has about 300 cilia on its apical surface (Figures 2 and 3); beneath the cilia, in addition to basal bodies, are numerous small mitochondria which supply ATP for ciliary beating. B. Mucous Goblet Cells: The next most abundant cells in the respiratory epithelium (Figure 2). The apical portion of these cells contains the mucous droplets composed of glycoproteins. 3

5 C. Brush Cells: The remaining columnar cells (Figure 4) because of the numerous microvilli on their apical surface. Brush cells have afferent nerve endings on their basal surfaces and are considered to be sensory receptors. D. Basal (Short) Cells: Are small rounded cells that lie on the basal lamina but do not extend to the luminal surface of the epithelium. These cells are believed to be generative stem cells that undergo mitosis and subsequently differentiate into the other cell types. E. Small Granule Cell: Resembles a basal cell except that it possesses numerous granules nm in diameter with dense cores. All cells of the ciliated pseudostratified columnar epithelium touch the basement membrane (Figure 2). 4

6 Figure 3. Electron micrograph of ciliated columnar cells of the respiratory epithelium, showing the ciliary microtubules in transverse and oblique section. In the cell apex are the U-shaped basal bodies that serve as the source of, and anchoring sites for, the ciliary axonemes. The local accumulation of mitochondria is related to energy production for ciliary movement. Note the junctional complex. 5

7 Figure 4. Scanning electron micrographs of the surface of respiratory mucosa. Top: Most of the surface is covered with cilia. G, goblet cells. Bottom: Subsurface accumulations of mucus are evident in the goblet cells (thin arrows). Thick arrowheads indicate brush cells. 6

8 Nasal Cavity The nasal cavity consists of 2 structures: the external vestibule and the internal nasal fossae. Vestibule The vestibule is the most anterior and dilated portion of the nasal cavity. The outer integument of the nose enters the nares (nostrils) and continues partway up the vestibule. Around the inner surface of the nares are numerous sebaceous and sweat glands, in addition to the thick short hairs, or vibrissae, that filter out large particles from the inspired air. Within the vestibule, the epithelium loses its keratinized nature and undergoes a transition into typical respiratory epithelium before entering the nasal fossae. Nasal Fossae Within the skull lie 2 cavernous chambers separated by the osseous nasal septum. Extending from each lateral wall are 3 bony shelflike projections known as conchae. Of the superior, middle, and inferior conchae, only the middle and inferior projections are covered with respiratory epithelium. The superior conchae are covered with a specialized olfactory epithelium. The narrow, ribbonlike passages created by the conchae improve the conditioning of the inspired air by increasing the surface area of respiratory epithelium and by creating turbulence in the airflow. The result is increased contact between air streams and the mucous layer. Within the lamina propria of the conchae 7

9 are large venous plexuses known as swell bodies. Every minutes, the swell bodies on one side of the nasal fossae become engorged with blood, resulting in distention of the conchal mucosa and a concomitant decrease in the flow of air. During this time, most of the air is directed through the other nasal fossa. These periodic intervals of occlusion reduce airflow, allowing the respiratory epithelium to recover from desiccation. Smell (Olfaction) The olfactory chemoreceptors are located in the olfactory epithelium, a specialized area of the mucous membrane in the superior conchae, located in the roof of the nasal cavity. In humans, it is about 10cm 2 in area and up to 100µm in thickness. It is a pseudostratified columnar epithelium composed of 3 types of cells (Figure 5): 1. The Supporting Cells: Have broad, cylindrical apexes and narrower bases. On their free surface are microvilli submerged in a fluid layer. Well-developed junctional complexes bind the supporting cells to the adjacent olfactory cells. The cells contain a light yellow pigment that is responsible for the color of the olfactory mucosa. 2. The Basal Cells: Are small; they are spherical or cone-shaped and form a single layer at the base of the epithelium. 3. The Olfactory Cells: Are located between the basal cells and the supporting cells, bipolar neurons distinguished from the supporting cells by the position of their nuclei, which lie 8

10 below the nuclei of the supporting cells. The nucleus of the cell is spherical. Their apexes (dendrites) possess elevated and dilated areas from which arise 6-8 cilia. These cilia are very long, nonmotile (Figure 5), and respond to odoriferous substances by generating a receptor potential. They increase the receptor surface considerably. The afferent axons of these bipolar neurons unite in small bundles directed toward the central nervous system, where they synapse with neurons of the brain olfactory lobe. The lamina propria of the olfactory epithelium possesses the glands of Bowman. Their secretion produces a fluid environment around the olfactory cilia that may clear the cilia, facilitating the access of new odoriferous substances. Figure 5. Olfactory mucosa showing the 3 cell types (supporting, olfactory, and basal) and a Bowman's gland. 9

11 Conditioning of Air A major function of the conducting portion is to condition the inspired air. Before it enters the lungs, inspired air is cleansed, moistened, and warmed. To carry out these functions, the mucosa of the conducting portion is lined with a specialized respiratory epithelium, and there are numerous mucous and serous glands as well as a rich superficial vascular network in the lamina propria. As the air enters the nose, large vibrissae (specialized hairs) remove coarse particles of dust. Once the air reaches the nasal fossae, particulate and gaseous impurities are trapped in a layer of mucus. This mucus, in conjunction with serous secretions, also serves to moisten the incoming air, protecting the delicate alveolar lining from desiccation. A rich superficial vascular network also warms the incoming air. Paranasal Sinuses The paranasal sinuses are closed cavities in the frontal, maxillary, ethmoid, and sphenoid bones. They are lined with a thinner respiratory epithelium that contains few goblet cells. The lamina propria contains only a few small glands and is continuous with the underlying periosteum. The paranasal sinuses communicate with the nasal cavity through small openings. The mucus produced in these cavities drains into the nasal passages as a result of the activity of its ciliated epithelial cells. 10

12 Medical Application Sinusitis is an inflammatory process of the sinuses that may persist for long periods of time, mainly because of obstruction of drainage orifices. Chronic sinusitis and bronchitis are components of immotile cilia syndrome, which is characterized by defective ciliary action. Nasopharynx The nasopharynx is the first part of the pharynx. It is lined by a respiratory epithelium, whereas the oral and laryngeal regions are lined by a stratified squamous epithelium. The lamina propria is composed of a loose to dense, irregular type of vascularized connective tissue housing seromucous glands and lymphoid elements. Larynx The larynx, or voice box, is responsible for phonation and for preventing the entry of food and fluids into the respiratory system during swallowing. It connects the pharynx to the trachea. It is cylindrical tube 4 cm in length and approximately 4 cm in diameter (Figure 6). Within the lamina propria lie a number of laryngeal cartilages. The larger cartilages (thyroid, cricoid, and most of the arytenoids) are hyaline. The smaller cartilages (epiglottis, cuneiform, corniculate, and the tips of the arytenoids) are elastic cartilages. These cartilages are connected to one another by ligaments. In addition to their supporting role (maintenance of an open airway), these cartilages serve as a valve to prevent swallowed food or fluid from entering the trachea. They also participate in producing sounds for phonation. 11

13 The epiglottis, which projects from the rim of the larynx, extends into the pharynx and has both a lingual and a laryngeal surface. The entire lingual surface and the apical portion of the laryngeal surface are covered with stratified squamous epithelium. Toward the base of the epiglottis on the laryngeal surface, the epithelium undergoes a transition into ciliated pseudostratified columnar epithelium. Mixed mucous and serous glands are found beneath the epithelium. Below the epiglottis, the mucosa forms 2 paris of folds that extend into the lumen of the larynx. The upper pair (superior) constitutes the false vocal cords (vestibular folds), covered with typical respiratory epithelium. Their lamina propria below the epithelium composed of loose connective tissue, houses seromucous glands, their sections of excretory ducts are seen among the alveoli; these ducts open onto the epithelial surface, adipose cells, and lymphoid elements (lymphatic nodules) occur in the lamina propria on the ventricular side of the fold. The ventricle is deep indentation and recess separating the false vocal fold from the true vocal fold. The mucosa of its lateral wall is similar in structure to that of the false vocal fold. Lymphatic nodules are more numerous, however, and are sometimes called the laryngeal tonsils. The lamina propria blends with the perichondrium of the thyroid cartilage; there is no distinct submucosa. The lower wall of the ventricle makes a transition to the true vocal fold. The lower pair (inferior) of folds constitutes the true vocal cords, covered with a stratified squamous epithelium (nonkeratinized) and thin, dense lamina propria. No glands are present. At the apex of the true vocal fold is the vocal ligament which consists of a mass of dense elastic fibers. Attached to the vocal ligament are bundles of skeletal muscle, the 12

14 vocalis muscle which regulate the tension of the fold and its ligaments. As air is forced between the folds, these muscles provide the means for sounds, of different frequencies to be produced. Figure 6. Larynx (frontal section). 13

15 Clinical Correlations Laryngitis: Inflammation of the laryngeal tissues including the vocal folds, prevents the vocal folds from vibrating freely. Persons suffering from laryngitis sound hoarse or can only whisper. Trachea The trachea has three layers: mucosa, submucosa, adventitia, and hyaline cartilage rings (C-rings) are located in the adventitia (Figure 7). The trachea is a tube, 12 cm long and 2 cm in diameter, 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. Because of this arrangement of the C-rings, the trachea is rounded anteriorly but flattened posteriorly. The perichondrium of each C-ring is connected to the perichondria lying directly above and below it by fibroelastic connective tissue, which provides flexibility to the trachea and permits its elongation during inspiration. Contraction of the trachealis muscle decreases the diameter of the tracheal lumen, resulting in faster air flow, which assists in the dislodging of foreign material (or mucus or other irritants) from the larynx by coughing. 14

16 Mucosa The mucosal lining of the trachea is composed of pseudostratified ciliated columnar (respiratory epithelium), the subepithelial connective tissue (lamina propia), and a relatively thick bundle of elastic fibers separating the mucosa from the submucosa. Lamina Propria 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. Submucosa The tracheal submucosa is composed of a dense, irregular fibroelastic connective tissue housing numerous mucous and seromucous glands (produce a more fluid mucus). The short ducts of these glands pierce the elastic lamina and the lamina propria to open onto the epithelial surface. Lymphoid elements are also present in the submucosa. Moreover, this region has a rich blood and lymph supply, the smaller branches of which reach the lamina propria. 15

17 Figure 7. Trachea (panoramic view, transverse section). Adventitia The adventitia of the trachea is composed of a fibroelastic connective tissue. The most prominent features of the adventitia are the hyaline cartilage C-rings and the intervening fibrous connective tissue. The adventitia also is responsible for anchoring the trachea to the adjacent structures (i.e., esophagus and connective tissues of the neck). 16

18 Bronchial Tree The trachea divides into 2 primary bronchi (Figure 1) that enter the lungs at the hilum. At each hilum, arteries enter, and veins and lymphatic vessels leave. These structures are surrounded by dense connective tissue and form a unit called the pulmonary root. After entering the lungs, the primary bronchi course downward and outward, giving rise to 3 bronchi in the right lung and 2 in the left lung (Figure 1), each of which supplies a pulmonary lobe. These lobar bronchi divide repeatedly, giving rise to smaller bronchi, whose terminal branches are called bronchioles. Each bronchiole enters a pulmonary lobule, where it branches to form 5-7 terminal bronchioles. Each terminal bronchiole subdivides into 2 or more respiratory bronchioles that serve as regions of transition between the conducting and respiratory portions of the respiratory system. Bronchi Each primary bronchus branches dichotomously 9-12 times, with each branch becoming progressively smaller until it reaches a diameter of about 5mm. Except for the organization of cartilage and smooth muscle, the mucosa of the bronchi is structurally similar to the mucosa of the trachea (Figure 7). The bronchial cartilages are more irregular in shape than those found in the trachea; in the larger portions of the bronchi, the cartilage rings completely encircle the lumen. As bronchial diameter decreases, the cartilage rings are replaced with isolated plates, or islands, of hyaline cartilage. Beneath the epithelium, in the bronchial lamina propria, is a smooth muscle layer consisting of crisscrossing bundles of spirally arranged smooth muscle (Figures 8 through 9). 17

19 Figure 8. Structure of a bronchus. Smooth muscle is present in the entire bronchiolar tree, including the respiratory bronchiole. Contraction of this muscle induces folding of the mucosa. The elastic fibers in the bronchus continue into the bronchiole. The lower portion of the drawing represents a region with its connective tissue removed to show the presence of elastic fibers and smooth muscle. The adventitia is not shown. Figure 9. Large bronchus. Note the distinct layer of smooth muscle that influences the flux of air in the respiratory system. 18

20 Bundles of smooth muscle become more prominent near the respiratory zone. Contraction of this muscle layer after death is responsible for the folded appearance of the bronchial mucosa observed in histologic section. The lamina propria is rich in elastic fibers and contains an abundance of mucous and serous glands (Figure 9) whose ducts open into the bronchial lumen. Numerous lymphocytes (Figures 10 and 11) are found both within the lamina propria and among the epithelial cells. Lymphatic nodules are present and are particularly numerous at the branching points of the bronchial tree. Figure 10. Section of a bronchus wall with bronchus-associated lymphoid tissue (BALT), a component of the diffuse mucosa-associated lymphoid tissue (MALT). Medium magnification. 19

21 Figure 11. The same section as in Figure 10 but at higher magnification. The respiratory epithelium and its cilia are more evident. The lower part of the figure shows an activated region (germinal center) with light-stained areas, most with antigenpresenting macrophages. Bronchioles Bronchioles, intralobular airways (supply air to a pulmonary lobule) with diameters of 5 mm or less, have neither cartilage nor glands in their mucosa (Figure 12). 20

22 Figure 12. Light photomicrograph of a bronchiole. Note the presence of smooth muscle and the absence of cartilage in its wall. The epithelial lining of bronchioles 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. Clara cells, which are devoid of cilia, have secretory granules in their apex and are known to secrete proteins that protect bronchiolar lining against oxidative pollutants and inflammation. Bronchioles also exhibit specialized regions called neuroepithelial bodies. These are formed by groups of cells that contain secretory granules and receive cholinergic nerve endings. Their function is poorly understood, but they are probably chemoreceptors that react to changes in gas composition within the airway. They also seem involved in the reparative process of airway epithelial cell renewal after injury. 21

23 Bronchiolar lamina propria is composed largely of smooth muscle and elastic fibers. The musculature of both the bronchi and the bronchioles is under the control of the vagus nerve and the sympathetic nervous system. Stimulation of the vagus nerve decreases the diameter of these structures; sympathetic stimulation produces the opposite effect. Terminal Bronchioles Each bronchiole subdivides to form several smaller terminal bronchioles, which are less than 0.5 mm in diameter and constitute the terminus of the conducting portion of the respiratory system. These structures supply air to lung acini, subdivisions of the lung lobule. The epithelium of terminal bronchioles is composed of Clara cells and cuboidal cells (Figure 13), some with cilia. Figure 13. Transition of a terminal bronchiole into an alveolar duct (arrow). Note the Clara cells (arrowheads). 22

24 The narrow lamina propria consists of fibroelastic connective tissue and is surrounded by one or two layers of smooth muscle cells (Figure 14). Elastic fibers radiate from the adventitia and, as with the bronchioles, bind to elastic fibers radiating from other members of the bronchial tree. Terminal bronchioles branch to give rise to respiratory bronchioles. Figure 14: Photomicrograph of a section from the wall of a terminal bronchiole. Note that no cartilage is present, but there is an incomplete ring of smooth muscle. 23