Air enters the respiratory system through the nose or mouth. Air entering through the nose is filtered, heated to body temperature, and humidified as it passes through the nose and nasal turbinates. These protective mechanisms are discussed in Chapter 10. The upper airways are shown in Figure 10–1. Air breathed through the nose enters the airways via the nasopharynx and through the mouth via the oropharynx. It then passes through the glottis and the larynx and enters the tracheobronchial tree. After passing through the conducting airways, the inspired air enters the alveoli, where it comes into contact with the mixed venous blood in the pulmonary capillaries.
After passing through the nose or mouth, the pharynx, and the larynx (the upper airways), air enters the tracheobronchial tree. Starting with the trachea, the air may pass through as few as 10 or as many as 23 generations, or branchings, on its way to the alveoli. The branchings of the tracheobronchial tree and its nomenclature are shown in Figure 1–2. Alveolar gas exchange units are denoted by the U-shaped sacs.
Schematic representation of airway branching in the human lung with approximate dimensions. (Reproduced with permission, Figure after Weibel, 1963. Data from Bouhuys, 1977.)
The first 16 generations of airways, the conducting zone, contain no alveoli and thus are anatomically incapable of gas exchange with the venous blood. They constitute the anatomic dead space, which is discussed in Chapter 3. Alveoli start to appear at the 17th through the 19th generations, in the respiratory bronchioles, which constitute the transitional zone. The 20th to 22nd generations are lined with alveoli. These alveolar ducts and the alveolar sacs, which terminate the tracheobronchial tree, are referred to as the respiratory zone.
Respiratory bronchioles have some alveoli, as shown in Figure 1–2. Each respiratory bronchiole branches into about 100 alveolar ducts and 2000 alveoli in the adult human lung. An acinus contains 10 to 12 of these respiratory bronchioles and their branches; they are called terminal respiratory units. All of the airways of an acinus participate in gas exchange. The numerous branchings of the airways result in a tremendous total cross-sectional area of the distal portions of the tracheobronchial tree, even though the diameters of the individual airways are quite small. This can be seen in the table within Figure 1–2.
The structure of the airways varies considerably, depending on their location in the tracheobronchial tree. The trachea is a fibromuscular tube supported ventrolaterally by C-shaped cartilage and completed dorsally by smooth muscle. The cartilage of the large bronchi is semicircular, like that of the trachea, but as the bronchi enter the lungs, the cartilage rings disappear and are replaced by irregularly shaped cartilage plates. They completely surround the bronchi and give the intrapulmonary bronchi their cylindrical shape. These plates, which help support the larger airways, diminish progressively in the distal airways and disappear in airways about 1 mm in diameter. By definition, airways with no cartilage are termed bronchioles. Because the bronchioles and alveolar ducts contain no cartilage support, they are subject to collapse when compressed. This tendency is partly opposed by the attachment of the alveolar septa, containing elastic tissue, to their walls, as seen in Figure 1–3 and shown schematically in Figure 2–18. As the cartilage plates become irregularly distributed around distal airways, the muscular layer completely surrounds these airways. The muscular layer is intermingled with elastic fibers. As the bronchioles proceed toward the alveoli, the muscle layer becomes thinner, although smooth muscle can even be found in the walls of the alveolar ducts. The outermost layer of the bronchiolar wall is surrounded by dense connective tissue with many elastic fibers.
Scanning electron micrograph of human lung parenchyma. A = alveolus; S = alveolar septa; D = alveolar duct; PK = pore of Kohn; PA = small branch of the pulmonary artery. (Reproduced with permission from Weibel, 1998.)
The Lining of the Airways
The entire respiratory tract, except for part of the pharynx, the anterior third of the nose, and the respiratory units distal to the terminal bronchioles, is lined with ciliated cells interspersed with mucus-secreting goblet cells and other secretory cells. The ciliated cells are pseudostratified columnar cells in the larger airways and become cuboidal in the bronchioles. In the bronchioles, the goblet cells become less frequent and are replaced by another type of secretory cell, the Clara cell. Clara cells secrete proteins (including surfactant apoproteins SpA, SpB, and SpD—see Chapter 2), lipids, glycoproteins, and modulators of inflammation. They also act as progenitor cells for Clara cells and for ciliated epithelial cells, metabolize some foreign material, and participate in airway fluid balance. The ciliated epithelium, along with mucus secreted by glands along the airways and the goblet cells and the secretory products of the Clara cells, constitutes an important mechanism for the protection of the lung. This mechanism is discussed in detail in Chapter 10.
Mast cells are also found in the airways. They contain membrane-bound secretory granules that consist of many inflammatory mediators, including histamine, proteoglycans, lysosomal enzymes, and metabolites of arachidonic acid that can induce bronchoconstriction, stimulate mucus secretion, and induce mucosal edema by increasing permeability of bronchial vessels.
The Alveolar-Capillary Unit
The alveolar-capillary unit is the site of gas exchange in the lung. The alveoli, traditionally estimated to number about 300 million in the adult (a more recent study calculated the mean number of alveoli to be 480 million), are almost completely enveloped in pulmonary capillaries. There may be as many as 280 billion pulmonary capillaries, or approximately 500 to 1000 pulmonary capillaries per alveolus. These staggering numbers of alveoli and pulmonary capillaries result in a vast area of contact between alveoli and pulmonary capillaries—probably 50 to 100 m2 of surface area available for gas exchange by diffusion. The alveoli are about 200 to 250 μm in diameter.
Figure 1–3 is a scanning electron micrograph of the alveolar-capillary surface. Figure 1–4 shows an even greater magnification of the site of gas exchange.
Scanning electron micrograph of the surface and cross section of an alveolar septum. Capillaries (C) are seen sectioned in the foreground, with erythrocytes (EC) within them. A = alveolus; D = alveolar duct; PK = pore of Kohn; AR = alveolar entrance to duct; * = connective tissue fibers. The encircled asterisk is at a junction of 3 septa. (Reproduced with permission from Weibel, 1998.)
In Figure 1–4 the alveolar septum appears to be almost entirely composed of pulmonary capillaries. Red blood cells (erythrocytes) can be seen inside the capillaries at the point of section. Elastic and connective tissue fibers, not visible in the figure, are found between the capillaries in the alveolar septa. Also shown in these figures are the pores of Kohn or interalveolar communications.
The alveolar surface is mainly composed of a thin layer of squamous epithelial cells, the type I alveolar cells. Interspersed among these are the cuboidal type II alveolar cells, which produce the fluid layer that lines the alveoli. Although there are about twice as many type II cells as there are type I cells in the human lung, type I cells cover 90% to 95% of the alveolar surface because the average type I cell has a much larger surface area than the average type II cell does. The thin-walled type I cells allow most of the gas exchange between the alveolar air and the pulmonary capillary blood; type I alveolar epithelial cells may also help remove liquid from the alveolar surface by actively pumping sodium and water from the alveolar surface into the interstitium.
The alveolar surface fluid layer is discussed in detail in Chapter 2. A third cell type, the free-ranging phagocytic alveolar macrophage, is found in varying numbers in the extracellular lining of the alveolar surface. These cells patrol the alveolar surface and phagocytize inspired particles such as bacteria. Their function is discussed in Chapter 10.
The Capillary Endothelium
A cross section of a pulmonary capillary is shown in the transmission electron micrograph in Figure 1–5. An erythrocyte is seen in cross section in the lumen of the capillary. Capillaries are formed by a single layer of squamous epithelial cells that are aligned to form tubes. The nucleus of one of the capillary endothelial cells can be seen in the micrograph.
Transmission electron micrograph of a cross section of a pulmonary capillary. An erythrocyte (EC) is seen within the capillary. C = capillary; EN = capillary endothelial cell (note its large nucleus); EP = alveolar epithelial cell; IN = interstitial space; BM = basement membrane; FB = fibroblast processes; 2,3,4 = diffusion pathway through the alveolar-capillary barrier, the plasma, and the erythrocyte, respectively. Note that the alveolar-capillary barrier appears to have a thin side and a thick side that has a greater interstitial space and more connective tissue. (Reproduced with permission from Weibel, 1970.)
The barrier to gas exchange between the alveoli and pulmonary capillaries can also be seen in Figure 1–5. It consists of the alveolar epithelium, the capillary endothelium, and the interstitial space between them. Gases must also pass through the fluid lining the alveolar surface (not visible in Figure 1–5) and the plasma in the capillary. The barrier to diffusion is normally 0.2- to 0.5-μm thick. Gas exchange by diffusion is discussed in Chapter 6.
The Muscles of Respiration and the Chest Wall
The muscles of respiration and the chest wall are essential components of the respiratory system. The lungs are not capable of inflating themselves—the force for this inflation must be supplied by the muscles of respiration. The chest wall must be intact and able to expand if air is to enter the alveoli normally. The interactions among the muscles of respiration and the chest wall and the lungs are discussed in detail in the next chapter.
The primary components of the chest wall are shown schematically in Figure 1–6. These include the rib cage; the external and internal intercostal muscles and the diaphragm, which are the main muscles of respiration; and the lining of the chest wall, the visceral and parietal pleura. Other muscles of respiration include the abdominal muscles, including the rectus abdominis; the parasternal intercartilaginous muscles; and the sternocleidomastoid and scalenus muscles.
The primary components of the chest wall. (Reproduced with permission from Weibel, 1998.)
The Central Nervous System and the Neural Pathways
Another important component of the respiratory system is the central nervous system. Unlike cardiac muscle, the muscles of respiration do not contract spontaneously. Each breath is initiated in the brain, and this message is carried to the respiratory muscles via the spinal cord and the nerves innervating the respiratory muscles.
Spontaneous automatic breathing is generated by groups of neurons located in the medulla. This medullary respiratory center is also the final integration point for influences from higher brain centers; for information from chemoreceptors in the blood and cerebrospinal fluid; and for afferent information from neural receptors in the airways, joints, muscles, skin, and elsewhere in the body. The control of breathing is discussed in Chapter 9.