As shown in Table 1-2 and Figure 1-1, A to D, the lungs are asymmetrically paired. The right lung is divided by major and minor fissures into three lobes: the upper, lower, and middle lobes. By contrast, the left lung has a single fissure dividing it into upper (superior) and lower (inferior) lobes. In the left lung, the homologue of the right lung’s middle lobe is the lingula, made up of the anterior and inferior portions of the upper lobe. In some persons there may be an incomplete fissure separating the lingula from the upper lobe. Bronchopulmonary segments are subunits of the lobes that derive from the first generation of bronchi below the lobar bronchi. These also are asymmetric between lungs; Table 1-1 shows the nomenclature.

Table 1-2 Segments of Lung

Right Lung	Left Lung
*Upper Lobe*	*Upper Lobe*
1. Apical	1, 2. Apical-posterior
2. Posterior
3. Anterior	3. Anterior
*Middle Lobe*	*Lingula*
4. Lateral	4. Superior
5. Medial	5. Inferior
*Lower Lobe*	*Lower Lobe*
6. Superior	6. Superior
7. Medial basal
8. Anterior basal	8. Anterior basal
9. Lateral basal	9. Lateral basal
10. Posterior basal	10. Posterior basal

Figure 1-1 Lobes for left (A and B) and right (C and D) lungs. The numbered segments are identified in Table 1-2.

The next-smallest unit of the lung below the gross level of definition is the pulmonary lobule, also known as the secondary lobule of Miller. On the pleural surface, the secondary lobule is outlined by connective septa and has a roughly polygonal shape, measuring between 1 and 2 cm in diameter. Examination of the cut surface of lung again shows the interlobular septa demarcating the edges of the lobule (Figures 1-2 and 1-e1); these are best seen in the periphery, because interlobular septa are less well developed in the center of the lungs. Lobules also can be identified on microscopic examination (Figures 1-e2 and 1-e3). Each lobule contains three to five acini, which are the basic units of gas exchange. An acinus is defined as the lung parenchyma that derives from a single terminal membranous bronchiole and includes three successive generations of respiratory bronchioles and their subtending alveolar ducts, alveolar saccules, and alveoli. The terminal bronchioles branch near the center of the lobules, and their acini abut the interlobular septa. This relationship allows assessment of alterations in the lung parenchyma in terms of its location within the lung lobule (centrilobular, panlobular, paraseptal).

Figure 1-2 Gross specimen of a secondary lobule of Miller, identified as the lung parenchyma surrounded by venous septa, or pleura and venous septa.

(Photo obtained from Gough section.)

Figure 1-e1 Gross photo of Gough section showing multiple normal lung lobules.

Figure 1-e3 Whole-mount histologic section demonstrating the microscopic equivalent of a secondary lobule of Miller. The arrows point to the pleura and the venous septa. Note the several respiratory bronchioles within the lobule.

Airways

The bronchial system generally is divided into conducting and respiratory airways. The conducting airways extend from the trachea to the membranous bronchioles, and the architecture changes as the airways decrease in size. The trachea has a membranous posterior aspect composed of transverse smooth muscle bundles that together make up the trachealis muscle, with protective cartilaginous rings on the anterior aspect (Figure 1-e4). In the cartilaginous bronchi, the cartilage plates enclose but do not completely surround the airway, and the muscle fibers wind around the airway in a spiral. These airways are surrounded by loose connective tissue, which contains the bronchial arteries, venous trunks, lymphatics, and nerves (Figures 1-3 and 1-e5). In the upper airways, the epithelium is predominantly ciliated, with a modest number of goblet cells. The cells are supported by a thin basement membrane. The bronchial mucous glands lie deep to the epithelium, with the mucous gland pits emptying onto the surface of the airway (Figure 1-e6). The glands contain both serous and mucous cells, with myoepithelial cells, all enclosed within the basal lamina of the glands (Figure 1-e7).

Figure 1-3 A cartilaginous intrapulmonary conducting airway with adjacent pulmonary artery. Of note, the diameters of airway and artery are similar. Bar indicates 2 mm.

Figure 1-e4 Low-power view of trachea demonstrating epithelium, mucous gland and pit, hyaline cartilage, and perichondral fibrous tissue.

Figure 1-e5 Segmental cartilaginous bronchus with adjacent bronchial lymphoid tissue.

Figure 1-e6 Higher-power view of trachea from the same specimen as in Figure 1-e4 demonstrating the pseudostratified epithelium with goblet cells and the mixed seromucinous nature of the bronchial gland.

Figure 1-e7 Smooth muscle actin immunohistochemical staining of bronchial gland reveals the myoepithelial cells surrounding the acini.

The noncartilaginous conducting airways extend from approximately generation 5 to generation 14 and are termed membranous bronchioles (Figure 1-4). The more proximal airways have a ciliated cell predominance (Figure 1-5), whereas the more distal airways acquire increasing numbers of nonciliated bronchiolar (Clara) cells until they account for approximately 11% of the total epithelial cell numbers in the terminal membranous bronchioles. Each bronchiole has a complete fibromuscular wall, with the muscle arranged in a tight spiral. An inconspicuous compartment located between the basement membrane and the muscle layer contains a few collagen fibers and longitudinally oriented elastic fibers. The bronchioles have an adventitial sheath into which adjacent alveoli insert.

Figure 1-4 Membranous bronchiole with adjacent pulmonary artery. The diameters of the airway and the artery are roughly similar.

Figure 1-5 Bronchiolar epithelium with predominantly ciliated cells.

The respiratory bronchioles have an incomplete fibromuscular wall, because they are partially alveolarized (Figure 1-6); the degree of alveolarization increases in each generation. The muscle bundles continue down the walls of the alveolar ducts, which are airways with completely alveolate walls, and end at the alveolar saccule entrance rings (Figure 1-e8).

Figure 1-6 Terminal membranous bronchiole bifurcating into two respiratory bronchioles, which in turn have subtending alveolar ducts, saccules, and alveoli.

Figure 1-e8 Smooth muscle actin immunohistochemical staining reveals muscle bundles in the mouths of the alveolar ducts and alveolar saccules.

Airway Epithelial Cells

Mucin-secreting cells are differentiated toward goblet cells and are characterized by a bulging apex distended by secretory vacuoles.

The ciliated cells arise from differentiation of the basal and nonciliated cells; they are columnar in type and attach to the basal lamina. The cilia are complex structures with dynein arms, nexin links, and radial spokes, all configured to utilize adenosine triphosphatase to control cilial beat.

Clara cells are nonciliated secretory cells that produce Clara cell secretory protein, some of the surfactant apoproteins, and antileukoproteinase and are a rich source of oxidases.

Neuroendocrine cells are known by several different names: Feyrter cells and Kulchitsky cells are more modern terms, but amine precursor uptake and decarboxylation (APUD) cells and “small granular” cells are found in earlier literature. The cells are roughly flask-shaped, with an apical protrusion found between the columnar cells extending to the airway surface. They express immunohistochemical neural markers such as chromogranin and synaptophysin, in addition to peptide hormones such as substance P, calcitonin, and gastrin-releasing peptide.

Alveolus

The alveolus is the main gas exchange area of the lung and is composed of a thin epithelial layer supported by its basement membrane, a capillary endothelium supported by its own basement membrane, and the interstitium between the two basement membranes (Figures 1-7 and 1-e9). Where the two basement membranes are fused, the alveolus is optimized for gas exchange; this region is known as the “thin” portion of the blood-air barrier. In the “thick” portion, by contrast, the basement membranes are separate, and there are fibroblasts, collagen and elastin fibers, and contractile interstitial cells (myofibroblasts, pericytes, and smooth muscle cells).

Figure 1-7 Plastic section showing the components of an alveolus.

Figure 1-e9 Transmission electron micrograph showing the relationships of type I and type II alveolar cells to the capillaries and interstitium of alveolar wall.

The alveolus is penetrated by openings known as the pores of Kohn (Figure 1-8). These appear early in postnatal life and increase in number with age. A majority of the pores are filled by alveolar lining fluid, but their geometry is affected by lung volumes. They may be important in collateral ventilation or may represent an acquired degenerative lesion.

Figure 1-8 Scanning electron micrograph of pore of Kohn.

(Courtesy Dr. William Thurlbeck.)

Alveolar Epithelial Cells

Most of the alveolar surface is covered by simple squamous cells known as type I pneumocytes (Figure 1-9). These cells have a small nucleus with highly branched cytoplasmic processes covering 4000 to 5000 µm². The cytoplasm contains sparse organelles. Type I cells form by mitotic division and transformation of type II cells. The normal ratio of type I to type II cells is 1:2.

Figure 1-9 Transmission electron micrograph of a type I cell.

Type II epithelial cells have a granular appearance and, in humans, are noted to protrude into the alveolar space (Figure 1-10). They have abundant mitochondria, endoplasmic reticulum, and a large Golgi apparatus, in addition to conspicuous secretory granules, called lamellar bodies, which are composed of surfactant. Surfactant is approximately 90% lipid in nature, the major portion of which is phosphatidylcholine; surfactant apoproteins A, B, C, and D make up the remainder.