RESPIRATORY SYSTEM

The respiratory system consists of the lungs and the passages that carry air to and from the lungs. The system is composed of three functional parts: conducting, respiratory, and ventilating portions. The conducting portion consists of the nasal cavities and associated sinuses, nasopharynx, oropharynx (which conducts both air and food), larynx, trachea, bronchi, bronchioles, and terminal bronchioles. The olfactory mucosa is associated with the conducting portion, being found in the superior part of each nasal cavity. The respiratory portion is specialized for the rapid exchange of gases between blood and air. It includes the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli. Components of the ventilating portion include the thoracic cage, intercostal muscles along with certain other muscles, muscular diaphragm, and elastic tissue of the lungs. These components assist the conducting and respiratory portions of the respiratory system in performing their functions.

Larynx

The larynx, interposed between the nasopharynx and trachea, is the part of the air passage specialized for vocalization. The larynx is studied to best advantage in gross anatomy, and only its main histological features will be mentioned here, namely the epithelia, glands, and cartilages.

Study slide B8, vocal cord, human, (H&E). This section shows the vocal cord and its overlying stratified squamous epithelium. Locate the invagination of the larynx. This is the laryngeal ventricle. The large fold on one side of the ventricle is the false vocal cord (ventricular fold). The fold in the opposite direction is the true vocal cord (vocal fold). Skeletal muscle can be found in the vocal fold; glands are present in the ventricular fold. This is the thyroarytenoid muscle; the vocal ligament is not evident.

Epithelia

1. Stratified squamous (moist). This type, as in other sites in the body, is found where there is considerable friction, such as from air, food or contact with other surfaces. It lines most of the epiglottis (except part of the lower, posterior surface), the aryepiglottic folds, and the true vocal folds.

2. Ciliated pseudostratified columnar. This type of epithelium, which contains goblet cells begins near the base of the posterior surface of the epiglottis and lines most of the remainder of the larynx. It lines the false vocal folds, but not the true vocal folds. The cilia are 3.5-5 mm long and beat toward the mouth, moving foreign particles and mucus from the air passages toward the exterior of the body.

3. Ciliated stratified columnar. This type of epithelium frequently occupies the transitional area between typical stratified squamous and typical ciliated pseudostratified columnar.

Glands

Mixed glands of the tubuloalveolar type, containing mucous and serous cell types arranged as alveoli, are present in the connective tissue throughout most of the larynx. The exception is the true vocal folds where glands are absent. The laryngeal glands contain more mucous cells than serous cells.

Cartilages

There are nine cartilages in the larynx, three paired (arytenoid, cuneiform, and

corniculate) and three unpaired (epiglottis, thyroid, and cricoid). The cartilages provide the framework of the larynx and are either hyaline or elastic in the adult.

1. Hyaline cartilages. These include the thyroid, cricoid, and arytenoid (except

vocal processes of arytenoid).

2. Elastic cartilages. These include the epiglottic, corniculate, cuneiform, and vocal process of arytenoid. They change early in life from hyaline to elastic cartilage.

Study slide #BB , elastic cartilage, epiglottis, (aldehyde fuchsin).

Trachea and extrapulmonary bronchi

The trachea, part of the conducting portion of the respiratory tree, begins in the neck (C-6) at the lower border of the larynx (cricoid cartilage) and ends in the thorax (upper border of T-5) by dividing into two main stem bronchi (primary bronchi). It is a hollow, flexible tube whose patency is maintained by 16-20 C-shaped rings of hyaline cartilage. In the adult male, the trachea is about 11 cm long and 2.5 cm in diameter.

Study slide B9, trachea, human, (H&E). An incomplete cross section, but demonstrates the “C” shaped cartilage ring. The respiratory epithelium, covered in places by mucus, overlies the lamina propria. Mixed glands are present in the submucosa below an incomplete layer of elastic tissue. Note specifically the thick basement membrane of the epithelium. Smooth muscle is present where the cartilage ends would be if they were present.

Study slide B10, trachea, esophagus and thyroid, monkey, (H&E). This is a cross section from the upper trachea. Many sections will include portions of laryngeal cartilages instead of the typical tracheal cartilage. The mucosa contains relatively few glands, and the elastic layer is not prominent. Cilia and basal bodies are well shown in the epithelium. What type of muscle is present around the esophagus at this level?

Compare and contrast the slides B9 and B10, and continue to examine the three concentric layers comprise the wall: mucosa, submucosa, and fibrosa (external layer), using the descriptions below.

Identify the mucosa (epithelium and lamina propria) as the innermost layer, which borders the lumen. The tracheal epithelium is normally ciliated pseudostratified columnar, but it is highly metaplastic and may change to another type in response to an irritation, such as chronic cough. The basement membrane on which the epithelium rests is the thickest in the body and should be located in slide B9. Identify three types of epithelial cells: ciliated columnar, goblet, and basal. Compare with Figure 64 below. Small lymphocytes can be seen migrating between the epithelial cells to reach the lumen.

Figure 64: Micrograph depicting the main components of the respiratory epithelium, ciliated and goblet cells. The nuclei of basal cells are present also. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 350, Figure 17-2.

Ciliated columnar cells outnumber the other cell types. They contain typical cilia (200-300 per cell) at the apical surface. The cilia are part of the mucociliary system, which extends through the tracheobronchial tree and into the respiratory bronchioles. This system protects the respiratory surface from dirt and airborne infection and represents the principal mechanism of defense in the respiratory tract. The cilia beat in unison (about 1,000 strokes per minute) and in a wave-like fashion, thereby propelling mucus and entrapped foreign material toward the oropharynx for expectoration or swallowing. Some substances, such as cigarette smoke, are ciliotoxic.

Goblet cells are quite numerous. They are usually filled with mucous secretory droplets. The droplets are discharged into the lumen of the trachea where they form a mucous blanket on the epithelial surface. It has been shown in experimental animals that goblet cell mucus is necessary for ciliary action. In the absence of enough mucus, the cilia fail to have a beat-like motion. Their action can be restored by the addition of mucus.

Basal cells are also called short cells because they do not extend to the free surface. They are undifferentiated epithelial cells, which have the potential to become ciliated cells and goblet cells.

Figure 65: Micrograph of the tracheal wall. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 354, Figure 17-6.

Study the four layers that comprise the wall of the trachea in Figure 65 above. The lamina propria is the connective tissue portion of the mucosa, which lies below the epithelium and the thick basement membrane of the trachea. It has a superficial portion of loose texture, which is infiltrated with lymphocytes, and a deeper portion of somewhat denser texture, which is rich in elastic fibers. The elastic fibers are not clearly shown in H&E preparations, but in special stains for elastic fibers they can be seen coursing mainly in a longitudinal direction and condensing near the submucosa to form an elastic membrane. The fibers are part of the elastic recoil mechanism, which stretch during inspiration and recoil during expiration. They extend into the successive branches of the bronchial tree and are continuous with the elastic components of the terminal air passages.

The submucosa is the middle stratum of the trachea. It is a layer of rather dense connective tissue in which the tracheal glands are embedded (slide B9). Blood vessels, nerves, and lymphatics are also present in this layer. The tracheal glands are mixed glands of the compound tubuloalveolar type. They contain mostly mucous cells. Demilunes of serous cells often cap the mucous cells. Ducts of the glands pass through the lamina propria to empty onto the epithelial surface.

The fibrosa is the external layer of the trachea, which contains, as its chief constituent, C-shaped rings of hyaline cartiIlage. The open end of each ring is directed posteriorly and is closed by a transverse band of smooth muscle, the trachealis muscle (slides B9 and B10). Each cartilaginous ring is covered on both sides by perichondrium. It is not unusual for the cartilaginous rings to branch and fuse with adjoining cartilages or for their ends to bifurcate. Dense fibroelastic connective tissue lies outside the cartilage and extends between the tracheal rings to connect adjacent cartilages to each other. It contains nerves, blood vessels, fat cells, and the paratracheal lymph nodes. Note in slides B9 and B10 that the tracheal glands extend into the fibrosa at the open ends of the c-shaped rings of cartilage. Longitudinal sections of the trachea show that the glands also extend into the fibrosa at the interspaces between the cartilaginous rings.

The structure of extrapulmonary bronchi is like that of the trachea. The three layers contain the same constituents, including C-shaped rings of hyaline cartilage.

Study slide B11, trachea, longitudinal section, monkey, (H&E). Most slides are characteristic of the trachea, but some are from very distal trachea or more likely, bronchus. These will have bundles of smooth muscle between the cartilage and the epithelium and possibly extra, irregular, plates of hyaline cartilage.

Study slide A29, hyaline cartilage, monkey, (H&E).

Drawing of trachea

Using slide B9 or B10 (H&E), draw in outline a strip of the tracheal wall to show the three layers of the trachea. Include the epithelium and lamina propria of the mucosa, the tracheal glands of the submucosa, and the cartilage of the fibrosa.

Intrapulmonary bronchi

The histology of intrapulmonary bronchi differs in several respects from that of the trachea and extrapulmonary bronchi.

Study slide B15, lung, (H & Trisosine). Identify the large intrapulmonary bronchus (2 sizes are present) and note the main features of its five layers (mucosa, muscularis, submucosa, cartilage-fibrous layer, and peribronchial layer). See Figure 66 below. The mucosa, as in the trachea and extrapulmonary bronchi, consists of an epithelium (ciliated pseudostratified columnar with goblet cells), a basement membrane, and a lamina propria. The latter is rich in elastic fibers of the recoil mechanism. Unlike the previous air passages, a muscularis is present and lies just external to the lamina propria. It may not appear as a complete layer because it is composed of two sets of smooth muscle fibers, which extend down the bronchial tree in a right and left spiral. The submucosa is a layer of loose connective tissue, which lies outside the muscularis. Bronchial glands are present in this layer and also extend into the intercartilaginous intervals. If possible, find a duct that is passing through the lamina propria to open onto the epithelial surface. The cartilage-fibrous layer lies outside the submucosa. It contains discontinuous plates of hyaline cartilage and fibrous connective tissue. The peribronchial layer is the thin outermost layer of connective tissue. It contains many elastic fibers and separates the wall of the bronchus from the pulmonary parenchyma. The peribronchial layer permits bronchi to move independent of other lung parenchyma. Note the relationship of the intrapulmonary bronchi to the pulmonary and bronchial vasculature.

Figure 66: Micrograph showing the layers in the wall of a large bronchus. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 355, Figure 17-8.

After examining the large bronchus on slide B15 observe some of the smaller bronchi on the same slide. Note that the amount of cartilage decreases and that the amount of smooth muscle increases as the bronchi become smaller. Due to the scarcity of cartilage and to the contraction of the muscle, the bronchial mucosa of smaller bronchi is folded. After a number of divisions, the cartilage disappears, the smooth muscle reaches its full development, and an air tube becomes known as a bronchiole.

Bronchioles

These arise from the bifurcation of terminal bronchi. Bronchioles lack cartilage and glands and generally have a diameter less than 1 mm. They are comparable to intralobular ducts of glands. One bronchiole serves a unit of the lung called a lobule. Three layers can be distinguished: mucosa, muscularis, and an outer layer. The mucosa is highly folded, due to the absence of cartilage and to contraction of the smooth muscle, and is usually lined by ciliated pseudostratified columnar (low) epithelium. Goblet cells are rare. The lamina propria is thin but rich in elastic fibers. The muscularis is the thickest layer. It has thick bands of smooth muscle, which completely encircle the bronchiole. The outer layer is thin. As in the remainder of the airways, the connective tissue of this layer is continuous with the parenchyma of the lung so that these passages move with the lungs. Identify bronchioles in slide B15.

Terminal bronchioles

These arise from the final bifurcations of bronchioles. They have a diameter of 0.5 mm or less and are called "terminal" because they are the final link in the air conducting passage before respiratory tissue is reached. Since bronchioles and terminal bronchioles lack cartilage (and bronchial glands), they are sometimes referred to as membranous airways to distinguish them from the cartilaginous airways (trachea and bronchi) and from the gas exchange airways (respiratory bronchioles and alveolar ducts). Structurally, terminal bronchioles resemble bronchioles except for the following:

1. The diameter is smaller than that of a bronchiole.

2. The epithelium varies from ciliated simple columnar to ciliated simple cuboidal. The cilia, however, are sometimes lost during tissue processing.

3. Goblet cells are absent.

4. The mucosa is less folded and the lamina propria is even thinner than that of

bronchioles.

Study slide B14, lung, human, (H&E). Try to identify the terminal bronchioles in this section. The wall, like that of bronchioles, is composed mainly of smooth muscle. Compare slide with Figure 67 below.

Figure 67: Micrograph of a terminal bronchiole. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 358, Figure 17-13.

Study slide B16 (orcein & H). This is a very nice stain for elastic fibers. Note the large number of elastic fibers in these structures and their close association with the smooth muscle. They stain red-brown in color. Also study their distribution in the alveolar septa and in the prominent elastic laminae of the arteries.

Respiratory bronchioles

These arise from terminal bronchioles (see Figure 68 below). They are the first structures, which belong to the respiratory portion of the lung. Structures mentioned previously belong to the conducting portion. They are called "respiratory" because they actually participate in the respiratory process by having several, small, sac-like outpocketings called alveoli which usually arise from only one side of their wall. Respiratory bronchioles are difficult to identify at first but with practice they become easier to locate.

Study slide B14, lung, human, (H&E). This is a typical section of lung containing a few respiratory bronchioles and many alveoli. Areas of “collapse” could be normal or due to tissue preparation. A portion of the pleural surface is present as are a moderate number of macrophages stained in vivo.

Figure 68: Micrograph of a terminal bronchiole, a respiratory bronchiole and surrounding alveoli. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 359, Figure 17-14.

1. Epithelium. Three types can be recognized.

a. Simple squamous. Found at outpocketings. It is drawn into a thin squamous

sheet which lines the alveolus.

b. Ciliated simple columnar or ciliated simple cuboidal. Found at the

proximal part (beginning) of the respiratory bronchiole.

c. Non-ciliated simple cuboidal (low). Found at the distal (terminal) part of the

respiratory bronchiole.

2. Lamina propria, muscularis, and outer layer. These layers cannot be visualized as separate entities but appear as a network of elastic fibers and smooth muscle.

Alveolar ducts

A respiratory bronchiole gives rise to several alveolar ducts, each characterized in sections by having many alveoli, which arise from both sides of its wall. See Figure 69 below.

Figure 69: Micrograph of a terminal bronchiole and an alveolar duct. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 361, Figure 17-18.

Study slide B17, lung, plastic, human, (H&E). Locate the alveolar ducts in and note their histological features.

1. Epithelium. The vast majority of cells are simple squamous but a few are simple

cuboidal (low).

2. Lamina propria. This is composed of a network of fine elastic fibers, reticular fibers,

and a few collagenous fibers. Smooth muscle is present only around the openings (mouths) of alveoli. Consequently, the lamina propria is thickened into little knobs at points where alveoli arise. The presence of these knobs helps to distinguish an alveolar duct from an alveolar sac. Elastic fibers in the knobs are shown in slide B16 (orcein & H).

3. Atria. Each of these is nothing more than a vestibule, which connects an alveolar

duct with an alveolar sac. They are sometimes considered as part of alveolar ducts.

4. Alveolar sacs. Each is a collection or cluster of alveoli. Alveoli of sacs do not have

knob-like thickenings.

5.Alveoli. Each alveolus is a cup-shaped, polyhedral thin-walled sac, which lacks one

wall and opens into a respiratory bronchiole, an alveolar duct, or an alveolar sac. There are about 300 million alveoli per lung. Each has a diameter of about 250 mm. Components of the alveolar wall and the blood-air barrier are described below and shown in Figure 70.

Figure 70: Micrograph showing the components of the blood-air barrier. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 363, Figure 17-23.

a. Alveolar wall (interalveolar septum). In slide B17 note the thin wall of the

alveolus, a feature which favors the interchange of gas between blood and air.

b. Small alveolar cells (Type I cells or respiratory alveolar cells) are squamous

cells. Nuclei are darkly stained, flattened, and usually far apart. Cytoplasmic processes extending from these cells are very thin. They appear with the light microscope as fine lines extending along the surface of the alveolar lumen.

c. Great alveolar cells (Type II cells) are cuboidal to round cells, which occupy

grooves in the alveolar wall or bulge into the alveolar lumen. With the light microscope, their cytoplasm is pale or lightly basophilic and usually vacuolated. The electron microscope shows that these cells are secretory cells (have an extensive Golgi apparatus, granular endoplasmic reticulum, etc.). They contain small membrane-bound bodies (0.2-1.0 pm in diameter) called cytosomes or lamellar bodies, which correspond to the cytoplasmic vacuoles seen with the light microscope. Cytosomes contain surfactant, a phospholipid wetting agent, which upon release from the cell spreads along the alveolar epithelium thereby reducing surface tension and preventing collapse of the alveoli. Some infants do not secrete adequate quantities of surfactant and die of respiratory distress during the first few days of life. This condition is called hyaline membrane disease.

Dust cells (alveolar macrophages or alveolar phagocytes)

Macrophages of the lung are commonly called dust cells. They are part of the reticuloendothelial system and are identical to macrophages elsewhere in the body. Dust cells are mobile and may occur anywhere in the lung.

Study slide B18, lung, human, normal and carbon, (H&E). This slide compares two sections taken from lungs exposed to either high levels of coal dust or to a “normal” environment. Two features are immediately apparent, the reduced number of alveoli and the massive number of carbon-filled macrophages. Identify dust cells in the interalveolar septa, lumina of alveoli, pleura, etc. Their cytoplasm contains large brown to black deposits, which is the carbon material. Dust cells can digest blood cells, which escape into the alveoli and they may contain iron pigment (hemosiderin). In certain cardiac diseases where the lungs become congested with blood, the macrophages engulf blood and are coughed up. Such cells contain iron and are referred to as heart-failure cells.

Alveolar pores (pores of Kohn)

These are small apertures (5-15 mm in diameter), which occur in the alveolar wall and usually vary in number from 1-6 per septum. They permit air to pass between alveoli and thus prevent collapse (atelectasis) of the alveoli in case of airway obstruction. They also permit the spread of bacteria and exudate to adjacent alveoli.

Canals of Lambert (Lambert's sinuses)

These are openings in the walls of terminal bronchioles or respiratory bronchioles, which communicate with alveoli. They provide an alternative route for entry or escape of air and probably play an important role when parts of the lungs become fibrotic. They also provide an avenue through which macrophages can pass from the alveolus to respiratory and terminal bronchioles where ciliated cells can remove or clear them from the lungs.

Pleura

The serous membrane lining the thoracic wall is called parietal pleura. At the hilus of each lung, the parietal pleura is reflected over the lung and becomes the visceral pleura. The potential space between the two serous membranes is called the pleural cavity and contains a thin film of fluid, which permits the two layers of pleura to slide easily against each other during respiration.

The free surface of the pleura (parietal and visceral) is lined with mesothelium. Fibroblasts, macrophages, and many capillaries and lymphatics are present between the connective tissue fibers. The parietal pleura contains sensory nerve fibers (from the phrenic and intercostal nerves) and is very sensitive to pain. Visceral pleura contains nerve fibers of vagal and sympathetic origin and is insensitive to pain. The visceral pleura covering the surface of the lung can be seen in slides B14 and B15.

Blood vessels of the lungs (pulmonary and bronchial circulation)

Examine slide B15 and B16 and study the blood vessels and their general distribution.

1. Pulmonary arteries and their branches. These vessels carry venous blood from

the right ventricle to the lungs for oxygenation. They accompany bronchi and their branches through the respiratory bronchioles, and finally end in capillary networks, which lie in the alveolar septa. The larger branches of pulmonary arteries are elastic arteries, but the smaller branches, which accompany terminal and respiratory bronchioles are muscular arteries. The smooth muscle of both arterial types is richly innervated by sympathetic fibers of the autonomic nervous system.

2. Pulmonary veins and their tributaries. These vessels collect oxygenated blood

from the alveolar capillaries and from the visceral pleura and return it to the left atrium. The smaller tributaries of the pulmonary veins are located away from the airways in the interlobular septa of connective tissue. When the veins become larger, they course with bronchi, but arteries alone accompany bronchioles, terminal bronchioles, and respiratory bronchioles.

3. Bronchial arteries and their branches. These small vessels usually arise from the

aorta. They carry oxygenated blood for nourishment of the air tubes, the walls of the pulmonary vessels, and part of the visceral pleura. They accompany bronchi and their branches as far as the respiratory bronchioles where they, too, break up into capillaries, which anastomose with capillaries from the pulmonary arteries. Thus, most of the blood carried by the bronchial arteries is returned to the heart by the pulmonary veins. In case the pulmonary arterial supply is shut off, as by emboli, the bronchial arteries can sustain the pulmonary parenchyma in the absence of significant cardiac failure.

4. Bronchial veins and their tributaries. These vessels drain blood from the bronchi

located near the hilus of the lung. Other blood is returned by the pulmonary veins.

Tabulation of differences between the various parts of the respiratory tree

Table 2 below is a summary of the histologic features of the divisions of the Bronchial tree. How does the nasal epithelium differ from the respiratory epithelium? Be able to use these characteristics to aide you in the identification of the various parts of the respiratory system.

Table 2: Divisions of the Bronchial Tree. Taken from Ross et al., Histology, a text and atlas, 10^th edition, p. 589, Table 18.1.