The respiratory system consists of organs-such as the nose, pharynx, larynx, trachea, bronchi-that transport respiratory gases into and out of the lungs and the lungs themselves. It is in the lungs that the gas exchange takes place between the atmosphere and blood. The major function of the respiratory system is to maintain the arterial blood levels for oxygen sufficiently high and the blood levels for carbon dioxide sufficiently low so that it allows the diffusion of oxygen from the blood into body cells and the simultaneous diffusion of carbon dioxide from the cells into the blood. The system also can assist in the control of blood acidity: a hyperventilation reduces acidity whereas hypoventilation elevates it.
In addition to simply transporting air, the conducting organs also prepare the air for entry into the lungs. The air must be cleaned, warmed, and moistened before it enters the alveoli. Therefore the inner walls of the nose, larynx, trachea, and bronchial tubes have special epithelia that perform this function. In addition, the larynx performs the special role of serving as the "voice box" of the body-functioning as the basic sound generator for the human vocal apparatus.
In this system you will study all of the major transport organs and concentrate on these important epithelial liners. The lungs will also be investigated in detail, with special emphasis on the structure of the alveoli. Since these alveolar structures are at the heart of respiratory function, you will learn the detailed nature of the respiratory membrane and the cell types which comprise it.
Air enters the respiratory system through the external nares (nostrils), which lead into the vestibule of the nose and then into the main body of the nasal cavity. Image 9.2a is a saggital section through the head of a human cadaver. The nasal cavity can be seen in the upper middle portion of the picture. Above the nasal cavity is seen the frontal sinus (marker/star in image 9.2a), an air-filled bony chamber which connects to the nasal cavity. The nostrils of the nose (upper right) allow air into the cavity and the air then passes over the concha (seen sliced in the cavity attached to the nasal septum) and into the pharynx (seen as a vertical dark tube). Note also the large oral cavity with the massive tongue inside located just below the nasal cavity. They are separated by the horizontal hard and soft palate. Image 9.2b is a closer view of the nasal cavity, showing the scroll-like concha bones in greater detail. There are numerous ethmoid sinuses (marker/star in image 9.2b) located immediately above the nasal cavity.
The upper picture in image 9.2c is a scanning micrograph of the nasal septum cut in a transverse section. This septum, which divides the nasal cavity into left and right chambers, consists of a central plate of cartilage (labeled "Ca" in image 9.2c) sandwiched in between two layers of mucus membrane (labeled "MM" in image 9.2c). Notice the respiratory epithelium (labeled "Ep" in image 9.2c) supported underneath by a connective tissue lamina propria (labeled "LP" in image 9.2c) laced with numerous blood vessels (labeled "BV" in image 9.2c). This blood vessel network provides the function of warming and moistening air before it passes into the lungs. The lower picture in image 9.2c is a scanning micrograph of cast of the blood vessels that underlie the epithelium. Note how extensive the blood vessel network (labeled "BV" in image 9.2c) is as it overlies the scrolled bone (labeled "Bo" in image 9.2c) of the concha. It is this extensive blood vessel network that contributes to the frequency of "nosebleeds" when the nasal epithelium becomes dry or damaged.
Image 9.2a: Frontal sinus (marker/star)
Image 9.2b: Ethmoid sinuses (marker/star)
Image 9.2c: Scanning micrograph of nasal septum (upper image) and blood vessels that unerlie the epithelium (lower image).
Image 9.3a is a scanning electron micrograph of the pseudostratified ciliated columnar epithelium (labeled "CE" in image 9.3a) that lines the nasal cavity. These cells, which are seen as clearly columnar in shape, carry numerous cilia (labeled "Ci" in image 9.3a) on their top surface. Note also that these cells produce mucus (labeled "Mu" in image 9.3a) by secretion. This sheet of mucus covering the mucous membrane further protects the respiratory system by trapping small particles that get past the nasal hairs guarding the entry to the nose. The mucus also has the ability to inactivate certain bacteria and act as a trapping filter for toxic macromolecules. The cilia of the membrane move in such a manner as to carry the particle-filled mucus toward the pharynx, where it can be removed by coughing or swallowing. Image 9.3b is a light microscopic view of another area of the nasal epithelium. Here the meaning of "pseudostratified" can be observed. Note that the nuclei of these columnar cells can be seen at different levels within the epithelium, giving the observer the misimpression that this is a truly stratified layer which it is not.
Image 9.3a: Pseudostratified ciliated columnar epithelium (CE) lining the nasal cavity with cilia (Ci) and the produced mucus (Mu).
Image 9.3b: Light microscope view of nasal epithelium.
The diagram in image 9.4a shows the structure of the larynx located below the hyoid bone and attached underneath to the trachea. The larynx is composed of two separate cartilages: the upper thyroid cartilage and the lower cricoid cartilage. The thyroid cartilage is shaped like a shield with its forward protuberance, the laryngeal prominence which is called the "Adam's apple" in common terminology. The cricoid cartilage is a smaller, ringed-shaped structure located below the thyroid cartilage and connected to it by a tough ligament.
The diagram in image 9.4b is of the larynx cut in a longitudinal section. Note the position of the rounded epiglottis on top, the positions of the thyroid and cricoid cartilages which make up the walls of the larynx, and the position of the false and true vocal cords inside the larynx. Image 9.4c is a longitudinal cut made through the larynx. The false vocal cord (labeled "a" in image 9.4c), the true vocal cord (labeled "b" in image 9.4c), and the cartilage in the wall of the larynx (labeled "c" in image 9.4c) can be identified.
Image 9.4a: Larynx structures illustrated.
Image 9.4b: Larynx cut in longitudinal section.
Image 9.4c: False vocal cord (labeled "a"), true vocal cord (labeled "b", and carilage (labeled "c").
The trachea, or windpipe, is a tube about 1 inch in diameter and 5 inches long, extending down from the base of the larynx to the lungs, where it forks into two branches, the right and left bronchi. The trachea is kept open by 16 to 20 C-shaped cartilaginous rings that are open on the dorsal side next to the esophagus. The rings are connected by fibroelastic connective tissue and longitudinal smooth muscle, making the trachea both flexible and extensible.
Image 9.5a shows a cut section of the trachea showing its outer epithelium (labeled "Ep" in image 9.5a) with its underlying basement membrane (labeled "BM" in image 9.5a) just above the lamina propria (labeled "Lp" in image 9.5a) that is also underlied with numerous blood vessels (labeled "BV" in image 9.5a). In the submucosa (labeled "Su"in image 9.5a) is located the hyaline cartilage (labeled "HC" in image 9.5a) tracheal ring. The ring is just above the outer connective tissue adventitia (labeled "Ad" in image 9.5a).
Image 9.5b is a similar view of the trachea as seen in a light microscope slide. Note the darker, wavy epithelium at the top, the lighter loose connective tissue submucosa underneath, and the elongate, pinkish, cartilaginous ring at the bottom.
Image 9.5a: Trachea epithelium (Ep), basement membrane (BM), lamina propria (Lp), blood vessels (BV), submucosa (Su), hyaline carltilage (HC), and adventitia (Ad).
image 9.5b: Light microscope image of the trachea.
The inside surface of the trachea is lined with pseudostratified ciliated columnar epithelium, which produces moist mucus. It contains upward-beating cilia. Those dust particles that are not caught in the nose and pharynx may be trapped in the trachea and carried up to the larynx and throat. In image 9.6a, you can see an internal surface view of the tracheal epithelium (folded). Note that the epithelial cells are covered with cilia (labeled "Ci" in image 9.6a), each cell containing about 200 cilia on average. The intermingled goblet cells (labeled "GC" in image 9.6a) secrete mucus and these cells are covered with microvilli (too small to be seen here). Image 9.6b is a light microscope slide of the tracheal epithelium. Note that it is similar to the epithelium that is found in the nasal cavity-it is a ciliated pseudostratified columnar epithelium. Observe that the arrow in image 9.6b points to the cilia on the surface of the epithelium.
Image 9.6a: Internal surface of tracheal epithelium
Image 9.6b: Light microscope slide of tracheal epithelium.
Image 9.7a is a diagram of the major structures of the respiratory system. The larynx is mounted on top of the trachea, and the trachea is seen bifurcating at its base into a left and a right bronchus, each of which passes into a lung. The lungs are soft, spongy, cone-shaped organs located in the thoracic cavity on either side of the heart and mediastinum. Each lung sits above the diaphragm and is covered by a layer of serous membrane called the visceral pleura. The right lung is slightly larger than the left and is divided into three lobes-the superior, middle, and inferior. The left lung is divided only into two lobes-the superior and inferior. Each lobe is supplied by a major branch of the bronchial tree with attending blood and lymphatic vessels, so that all of the lobes are anatomically and functionally independent of one another.
Image 9.7b shows an example of a diseased lung as seen in an asthmatic. In asthma the airways become filled with thick, tenacious, mucus plugs and the lungs greatly distend with air (as can readily be seen in this specimen). The mucus plugs cause bronchial obstruction, and bronchiectasis occurs which is a permanent abnormal dilation of the bronchi. Note the enlargement of the left upper lobe and the right middle lobe. Asthma is a disease that is quite common with 7-10% of children and 5% of adults showing the disorder.
Image 9.7c is a lung specimen that that shows the effects of a tuberculosis infection on the lungs of a child. The disease is caused by Mycobacterium tuberculosis which are small, rod-shaped, aerobic bacteria that can be transmitted from one person to another on liquid droplets produced by coughing, sneezing, or just simply talking. Once deposited on the alveolar surface, they multiply freely, as phagocytosis is often ineffective against these organisms. They multiply producing infection "nodules" which initially contain dead cells but can become fibrotic and calcified with time. Tuberculosis can often reactivate and produce focal areas of necrosis (usually near the apical and posterior segments as in the picture) that produce large cavitations. Image 9.7d is a case of tuberculosis in an adult lung. Note the dead (necrotic) tissue throughout the lung and the white calcified nodules scattered through the parenchyma of the lung.
Image 9.7e is an example of atelectasis of the lung. In this specimen the left lung has collapsed. Atelectasis (the collapse of the expanded lung) is usually caused by an airway obstruction. Diffusion of gases from the alveoli into the blood collapses the blocked region. Aspiration of foreign objects, mucus obstruction of bronchial tubes, and pneumothorax of the lung can all cause this unfortunate pathology. Image 9.7f is an example of bulbous emphysema, a lung condition in which there is abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by the destruction of the alveolar walls. Note the large blue air spaces at the base of the specimen-as the alveoli are destroyed, a lacy network of supporting tissue is left behind, called the "cotton candy lung".
Image 9.7a: Diagram of major structures of the respiratory system.
Image 9.7b: Asthmatic lung.
Image 9.7c: Effects of tuberculosis on the lungs of a child.
Image 9.7d: Effects of tuberculosis on the lungs of an adult.
Image 9.7e: Example of atelectasis of the lung.
Image 9.7f: Example of bulbous emphysema.
At its base the trachea branches into the right and left bronchi which enter the right and left lungs respectively. Each primary bronchus then divides into smaller secondary bronchi, which in turn divide into tertiary (segmental) bronchi. These bronchi continue to sub-branch into smaller and smaller bronchial tubes until they finally subdivide into the smallest microscopic air-conduction tubes, the terminal bronchioles. Terminal bronchioles divide into tubes which exchange gases with the blood, the respiratory bronchioles, which then further divide into passageways in the alveolar sacs, the alveolar ducts. These alveolar ducts then conduct air into the final alveolar chambers in which the majority of all gas exchange takes place. The whole system looks so much like an upside-down tree that it is commonly called the "respiratory tree."
In image 9.8a, note the pulmonary artery (labeled "PA" in image 9.8a) accompanying the large primary bronchus (labeled "Br" in image 9.8a). Observe the rather thick ciliated columnar epithelial layer (labeled "EL" in image 9.8a) supported by its underlying lamina propria (labeled "LP" in image 9.8a). Also note the surrounding layer of smooth muscle (labeled "SM" in image 9.8a) which in this section is contracted so as to produce the scalloped, folded appearance of the inner mucosa. Surrounding the bronchus are numerous smaller blood vessels (labeled "BV" in image 9.8a) and, since this bronchus is intrapulmonary, you can see the surrounding alveoli (labeled "Al" in image 9.8a).
Image 9.8b is a cross-sectional view of a bronchus as seen with the light microscope. The arrow points to a supporting cartilage ring and the bronchus itself is a fibromuscular tube with a ciliated epithelium lining the interior. Note also the large blood vessel to the right of the bronchus and the numerous alveoli to the far right.
Image 9.8c is an example of bronchiectasis. This is a disease in which there is permanent, abnormal dilation of the bronchi. The cause is often obstruction of the central bronchi by inhaled bodies, tumors, mucus plugs, and inflammatory material. Note in the two pictures the severely and irregularly dilated bronchial tubes, giving the impression that the lungs are filled with massive pipes.
Image 9.8a: Bronchus (Br), pulmonary artery (PA), epithelial layer (EL), lamina propria (LP), smooth muscle (SM), blood vessels (BV), and alveoli (Al).
Image 9.8b: Cross-sectional view of bronchus with supporting cartilage ring (arrow).
Image 9.8c: Example of bronchiectasis.
Image 9.9a shows a surface view of the epithelium that lines the inside of the bronchi as seen with the scanning electron microscope. Note the numerous long cilia (labeled "Ci" in image 9.9a) and the interspersed mucus-secreting goblet cells (labeled "GC" in image 9.9a). The major bronchial tubes have pseudostratified ciliated columnar cells in the mucosa; whereas simple columnar lines the narrower, more terminal bronchial divisions. Small-granule cells are also present deep within the epithelium at various locations along the conducting airways, and these can release serotonin, polypeptide hormones, and other chemical mediators that can affect airway diameter and vascular resistance.
Image 9.9b is a light microscopic close-up of the bronchial epithelium. Note the distinctly columnar cells with large purple nuclei and the cilia on their top surface. Image 9.9c is another image of bronchial epithelium. Here you can easily appreciate the green columnar cells with their dark blue nuclei and also observe the distinctive reddish cilia on their apical surface.
Image 9.9d is an example of the effects of a disease called asthma on the bronchial mucosa. Note the thickened layer just below the basement membrane (at the tip of the black arrow) and the hyperplasic epithelium. Asthma, once considered a smooth muscle spasm disease exclusively, is now seen as a chronic inflammatory disease. It is not uncommon to see a mucus plug, a hyperplastic epithelium, a thickened collagenous sublayer, and white blood cell infiltration into the submucosa in mild asthmatics. This underlying inflammation then produces a "twitchy" airway, one that is hyper responsive to bronchio-spasm.
Image 9.9a: Cilia (Ci) and goblet cells (GC) of bronchial epithelium.
Image 9.9b: Bronchial epithelium.
Image 9.9c: Bronchial epithelium.
Image 9.9d: Asthma's effect on the lungs.
Bronchioles are extensions of the major bronchi, they lack cartilage plates, and the smaller divisions are devoid of any glands. Smooth muscle bands in the walls of the bronchioles form a distinctive muscularis mucosa layer and the epithelium of bronchioles varies from simple columnar to simple cuboidal (both ciliated and non-ciliated). Some anatomists consider any bronchial tube past a tertiary bronchus to be a bronchiole, and there are then reportedly some 20 generations of bronchioles, the smallest of which are called terminal bronchioles. In image 9.10a, you can observe a terminal bronchiole (labeled "TB" in image 9.10a) that branches into several respiratory bronchioles (labled "RB" in image 9.10a). Unlike terminal bronchioles, these respiratory bronchioles may exhibit numerous alveolar out-pocketings along their entry length. Image 9.10a illustrates a region of transition between terminal bronchiole, respiratory bronchioles, and alveolar ducts (labeled "AD" in image 9.10a). The terminal functional unit, the primary pulmonary lobule, usually includes a respiratory bronchiole, attached alveolar sacs, and attending alveoli.
Image 9.10b is a light microscope slide of lung tissue showing a cross-section of a terminal bronchiole. The bronchiole shows a dark purple, simple ciliated, columnar epithelium. Note also the outer halo area of smooth muscle (pinkish color) surrounding the epithelium. Image 9.10c is a light microscope slide of a respiratory bronchiole (arrow in image 9.10c). Observe that it is surrounded by alveoli, and it shares with them the ability to exchange respiratory gases with the blood. Image 9.10d is a more magnified, cross-sectional view of a respiratory bronchiole (shown occupying the entire left portion of image). Note that the epithelium is very thin and no longer composed of ciliated columnar or cuboidal cells. The pink spherical structure to the right is a blood vessel full of red and white blood cells.
Image 9.10a: Terminal bronchiole (TB), respiratory bronchiole (RB), and alveolar ducts (AD).
Image 9.10b: Lung tissue with cross-section of terminal bronchiole.
Image 9.10c: Respiratory bronchiole (arrow).
Image 9.10d: Magnified cross-section of respiratory bronchiole.
The functional units of the lungs are the alveoli. Each lung contains over 350 million alveoli, each surrounded by many capillaries. The alveoli are clustered into alveolar sacs, resembling bunches of grapes. The total interior area of adult human lungs provides about 60 to 70 square meters of gas diffusion surface area-that is 20 times greater than the surface area of the entire skin. Every time you inhale, you expose to fresh air an area of your lung roughly equal to that of a small tennis court. A single alveolus looks like a bubble, which is supported by a basement membrane (basal lamina). A group of several alveoli with a common opening into an alveolar duct is called an alveolar sac. The lining epithelium of alveoli consists mainly of a single layer of squamous cells, also called type I cells, which perform the major function of gas exchange with the blood. It also has septal cells, called type 11 cells-which are smaller, more scattered, cuboidal-shaped secretory cells. Type II cells secrete a detergent-like phospholipid called surfactant (dipalmityl lecithin), which helps keep alveoli inflated by reducing surface tension. Alveoli also contain phagocytic alveolar macrophages that adhere to the alveolar wall or circulate freely in the lumen of alveoli. These macrophages ingest and destroy microorganisms and other foreign particles.
Image 9.11a shows a low magnification view of alveolar structures of lung tissue. Note the bag-like configuration of the alveoli and how thin the walls of the alveoli are. The entire alveolar sac resembles a labyrinth of interconnected rooms with extremely thin walls that carry numerous capillaries for gas exchange. Image 9.11b is a low power light microscopic picture of an alveolus (marker/star in middle). Again, note the thin walls (simple squamous epithelia) and the numerous capillaries (showing dark nuclei between the alveoli) that are tightly applied to these alveoli.
Image 9.11a: Alveolar structures of lung tissue.
Image 9.11b: Alveolus (marker/star).
Image 9.12a shows a highly magnified view of the inner surface of an alveolar wall. Spaced among the capillaries (labeled "Ca" in image 9.12a), are two main types of cells that comprise the wall. The type I pneumocytes (labeled "I" in image 9.12a) are the very flat simple squamous cells which interlock to form the majority of the alveolar wall and also function in the exchange of respiratory gases with the blood (the arrows point to the intercellular junctions between the cells in image 9.12a). The type II pneumocytes (labeled "II" in image 9.12a), also called "septal cells" which secrete the surfactant that helps keep the alveoli expanded. Note that these type II pneumocytes project into the alveolar lumen and have numerous microvilli located on the inner surface.
Image 9.12b is a light microscopic picture of a type II pneumocyte (at the tip of the arrow). Note how these cells are typically cuboidal in shape and occur in clusters, projecting into the alveolar lumen. They function in the secretion of a phospholipid surfactant that reduces the surface tension of the liquid which lines the inner wall of the alveolus. Without this phospholipid the expansion of the alveolus would require excessive energy and inhalation would become laborious.
Image 9.12a: Inner surface of alveolar wall with capillaries (Ca), type I pneumocytes (I), type II pneumocytes (II), and intercellular junctions (arrows).
Image 9.12b: Type II pneumocyte (arrow).
Image 9.13a shows a vascular cast of the extensive capillary network that surrounds the alveoli of the lungs. A branch of the pulmonary artery is seen descending from the top right of the screen. It carries deoxygenated blood to the capillary bed that is tightly applied to the alveoli (seen as bag-like structures in this slide). The entire area in which capillary endothelium contacts the alveolar wall is known as respiratory membrane. It functions in the important role of internal respiration, a process by which oxygen diffuses from the alveolar lumen into the blood and carbon dioxide diffuses from the blood into the alveolar lumen.
Image 9.13b is a microscopic view of hyaline membrane disease of the lung. Insult to the lungs, for example the inhalation of toxic substances (herbicides, ozone, and other air pollutants) or even water (as in cases of near drowning) can precipitate a clinical condition called adult respiratory distress syndrome (ARDS). In this condition the alveolar-capillary membranes can be severely damaged and the patient may progress to respiratory failure. The toxic insult attacks the type I squamous cells of the alveolus and the cellular junctions of the endothelial capillary wall, allowing extensive leakage of protein and fluids into the alveolar space. This pulmonary edema can cause rapid and distressful breathing. As the alveolar cells die, white blood cells invade and surround the alveoli, and the type II pneumocytes proliferate in an attempt to reconstitute the alveolar lining. Fibroblasts also proliferate in the interstitial tissue. As fluids flow into the alveoli, a "hyaline membrane" forms along the inner surface of the alveoli. This is a thick, distinctive layer of proteinaceous exudate filled with cellular debris that lines the alveoli and alveolar ducts. In the slide note the large number of collapsed alveoli and the extensive cellular proliferation in the interstitial spaces between the alveoli. Observe the numerous neutrophils (masses of purple cells) surrounding the alveoli and note that some of these white blood cells have infiltrated into the air spaces themselves.
Image 9.13a: Capillary network surrounding alveoli of lungs.
Image 9.13b: Example of hyaline membrane disease of the lung.