Kevin O. Leslie, MD, and Mark R. Wick, MD
Development and Gross Anatomy
Airway Development
During early embryogenesis (at approximately day 21 after fertilization), the lungs begin as a groove in the ventral floor of the foregut (Fig. 1.1). This foregut depression becomes a diverticulum of endoderm, surrounded by an amorphous condensation of splanchnic mesoderm that lengthens caudally in the midline, anterior to the esophagus. By the fourth week of gestation, two lung buds form as distal outpouchings.1,2 A series of repetitive nondichotomous branchings begins during week 5 and results in the formation of the primordial bronchial tree by the eighth week of gestation.
By 17 weeks, the rudimentary structure of the conducting airways has formed. This phase of lung development is referred to as the pseudoglandular stage because the fetal (postgestational week 7) lung is composed entirely of tubular elements that appear as circular glandlike structures in two-dimensional tissue sections (Fig. 1.2). The subsequent stages of development (canalicular, 13-25 weeks; terminal sac, 24 weeks to birth; and alveolar, late fetal to the age of 8-10 years) are dedicated to the formation of the essential units of respiration, the acini (Fig. 1.3).1 5 the postnatal lung continues to accrue alveoli until the age of approximately 10 years (Fig. 1.4).
Pleura
Immediately after their formation, the lung buds grow into the medial walls of the pericardioperitoneal canals (splanchnic mesoderm) and in doing so become invested with a membrane that will be the visceral pleura (analogous to a fist being pushed into a balloon). In this process, the lateral wall of the pericardioperitoneal canal becomes the parietal pleura, and the compressed space between becomes the pleural space (Fig. 1.5).
Lung Lobes
By the end of gestation, five well-defined lung lobes are present, three on the right (upper, middle, and lower lobes) and two on the left (upper and lower lobes).3,6,7 Each of the five primary lobar buds is invested with visceral pleura. Each lobe in turn is composed of one or more segments, resulting in a total of 10 segments per lung (Fig. 1.6). The presence of the heart leads to the formation of a rudimentary third lobe on the left side, termed the lingula (more properly regarded as a part of the left upper lobe than as an independent structure). In fact, the right middle lobe and the lingula are analogous structures: Each has an excessively long and narrow bronchus, predisposing these lobes to the pathologic effects of bronchial compression by adjacent lymph nodes or other masses. When such compression occurs, the consequent chronic inflammatory changes in the respective lobe are referred to as middle lobe syndrome.8
As gestation proceeds, airway branching continues to the level of the alveolar sacs, with a total of about 23 final subdivisions (20 of which occur proximal to the respiratory bronchioles). In successive order proceeding distally, the anatomic units formed are the lung segments, secondary and primary lobules (Fig. 1.7), and finally the acini. With each successive division, the resulting airway branches are smaller than their predecessors, but each has a diameter greater than 50% of the airway parent. This phenomenon leads to a progressive increase in airway volume with each successive branching and a significant reduction in airway resistance in more distal lung. The acinus consists of a central respiratory bronchiole that leads to an alveolar duct and terminates in an alveolar sac, composed of many alveoli (Fig. 1.8).
Figure 1.1 Diagrammatic representation of the successive stages in the development of the bronchi and lungs: (A to D) 4 weeks; (E and F) 5 weeks; (G) 6 weeks; (H) 8 weeks. (From Moore K. The Developing Human. Philadelphia: WB Saunders; 1973.)
Figure 1.2 (A) In the early stage of lung development, the bronchi resemble tubular glands and are surrounded by undifferentiated mesenchyme. This stage is referred to as pseudoglandular because of this appearance (at 5-17 weeks of gestation). (B) Immunohistochemical staining for thyroid transcription factor-1 (brown chromogen, hematoxylin counterstain) is positive in the nuclei of the immature airway cells.
Figure 1.4 the mature lung lobule consists of terminal bronchioles with their respective respiratory bronchioles, alveolar ducts, and alveolar sacs. Here the Y-shaped division of the terminal bronchiole into respiratory bronchioles and alveolar ducts can be seen in the lung of a child. AD, Alveolar duct; RB, respiratory bronchiole; TB, terminal bronchiole.
Figure 1.5 View of the collapsed lung during thoracoscopic surgery demonstrates the visceral and parietal pleural surfaces.
Figure 1.6 Ten distinct segments are present in each lung. (From Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore: University Park Press; 1972.)
Figure 1.7 the pulmonary lobules are configured into two layers that probably play important roles in the physical dynamics of respiration. The superficial layer is 3 to 4 cm thick. (From Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore: University Park Press; 1972.)
Figure 1.8 This three-dimensional schematic diagram demonstrates the relationship between the pulmonary artery and the airway and also illustrates the junction of a terminal bronchiole with the acinus. (From Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore: University Park Press; 1972.)
Microscopic Anatomy
The microscopic lung structure relevant to this chapter begins with the trachea and conducting airways and ends with the alveolar gas exchange units. This overview is intended to refresh the surgical pathologist’s existing knowledge of the normal lung. For the reader interested in greater detail, the comprehensive and authoritative review of gross and microscopic lung anatomy by Nagaishi is recommended.4
Conducting Airways
Each of the major divisions of the tracheobronchial tree—trachea, bronchi, and bronchioles—has a specific role in lung function, as reflected in their respective microscopic anatomy.
Trachea
The trachea is the gateway to the lung and is exposed to environmental factors in highest concentration. This rigid tube is designed for conducting gas, with rigid C-shaped cartilage rings that protect it from frontal injury and also prevent collapse during the negative changes in intrathoracic pressure that occur during respiration. The open side of the cartilage ring faces posteriorly, where the trachealis muscle completes the tracheal circumference. This arrangement allows the esophagus to abut the soft side of the trachea, down to the level of the carina. Respiratory epithelium (pseudostratified, ciliated, columnar-type), submucous glands, and smooth muscle combine to prepare inspired air for use in the lung by adding moisture and warmth (Fig. 1.9), while trapping dust particles and chemical vapor droplets before they can reach more delicate peripheral lung. For all of these reasons, when diseases affect the trachea, the potential for impact on general respiratory function is significant.
Bronchi
The bronchi begin at the carina and extend into the substance of the lung. They are large conducting airways that have cartilage in their walls. As in the trachea, the cartilage of the primary bronchi is C-shaped, but this configuration changes to that of puzzle piece-like plates once the bronchus enters the lung parenchyma. Within the substance of the lung, the cartilage plates decrease in density progressively as the bronchial diameter decreases, resulting in increasing area between individual plates. Mucous glands are positioned just beneath the surface epithelium and may be seen in endobronchial biopsy specimens (Fig. 1.10). When inflamed or distorted by crush artifact, they may simulate granulomas or tumor. These glands are connected to the airway lumen by a short duct. The bronchi divide and subdivide successively, becoming ever smaller on their way to the peripheral lung.
Bronchioles
The bronchioles are the final air conductors, and by definition, lack cartilage altogether (and are There fore sometimes referred to as membranous) (Fig. 1.11). The bronchioles have no alveoli; alveoli are acquired more distally in the pulmonary acinus. The terminal bronchiole is the smallest conducting airway without alveoli in its walls. There are about 30,000 terminal bronchioles in the lungs, and each of these, in turn, directs air to approximately 10,000 alveoli. The cells that line the airways are columnar in shape and ciliated. Their nuclei are present at multiple levels in each cell—a phenomenon referred to as pseudostratification (Fig. 1.12).
Pseudostratified columnar epithelium is typically identifiable as far distal as the smallest terminal bronchioles, where the cells then rapidly become more cuboidal in shape and their nuclei more basally situated (Fig. 1.13). In the normal mucosa, mucus-secreting cells (goblet cells) are typically present in low numbers, most often as individual units. It may be quite difficult to identify any goblet cells in the epithelium of small bronchioles. When these cells are numerous, they may be distended with mucus; this finding should suggest the presence of underlying airway disease (Fig. 1.14).
Airway Mucosal Neuroendocrine Cells
Airway mucosal neuroendocrine cells typically present as single cells in the respiratory epithelium with clear cytoplasm (Fig. 1.15). Rarely, these cells may aggregate to form so-called neuroepithelial bodies.
Figure 1.9 (A) the tracheal mucosa is closely applied to the anterior cartilaginous portion, with scant subepithelial tissue. (B) Posteriorly, cartilage is absent, tracheal glands are abundant, and muscle is prominent.
Figure 1.10 (A) Segmental bronchus in cross section demonstrates the relationship of the structural elements of the cartilaginous airways. Discontinuous cartilage plates and a seromucous gland are evident (center right). (B) the relationship between serous and mucous glands in this structure is better seen at higher magnification.
Figure 1.11 the membranous airways (bronchioles) lack cartilage in their walls, but rather have prominent smooth muscle. The mucosa is respiratory in type, with uniform delicate cilia.
Figure 1.12 the respiratory epithelium is columnar, pseudostratified, and ciliated. Scattered goblet cells can be seen interspersed between ciliated columnar cells (arrows), and the nuclei of the columnar cells are present at varying levels within the cell. The subepithelial region is loose areolar tissue, and a basal lamina beneath the epithelium is easily recognizable, although not overly distinct or thickened.
Immunohistochemical stains decorate these cells when addressed with antibodies directed against the common neuroendocrine markers chromogranin A and synaptophysin, as well as a number of more esoteric neuropeptides. The exact function of these cells is unknown. It has been suggested that lung neuroendocrine cells play a role in regulating ventilation-perfusion relationships and also may be important in airway morphogenesis.9
Airway-Associated Lymphoid Tissue
Airway-associated lymphoid tissue may be present in the normal lung, but in such instances it is very sparse and typically occurs at the bifurcation points of the airways (Fig. 1.16). This lung lymphoid tissue is generally referred to as bronchus-associated lymphoid tissue (BALT) and is believed to be analogous to the mucosa-associated lymphoid tissue (MALT) of the gastrointestinal tract.10 the strategic localization of BALT at airway divisions may be a consequence of exposure to inhaled antigens and other airstream particles that are likely to strike these areas.11 BALT foci are associated with specialized epithelial cells in the mucosa, and the constituent lymphoid cells (mainly T lymphocytes) are admixed with macrophages and dendritic cells. The epithelial and dendritic cells of the BALT presumably play a role in the detection of inhaled allergens, viruses, and bacteria; accordingly, BALT is considered to be a critical component of the lung’s immune defense system. The bronchial BALT may become hyperplastic, with follicular germinal center formation. Such germinal centers may be sampled at bronchoscopic biopsy, presenting a potential diagnostic challenge when crushed or cut in such a way that the follicular center lymphoid cells appear as a nodule or sheet in the specimen. BALT may also be important in diseases of immunologic origin that produce bronchiolitis, such as connective tissue diseases (e.g., Sjogren syndrome, rheumatoid arthritis), as well as graft-versus-host disease in organ transplantation, immunoglobulin deficiency states, and even inflammatory bowel disease.
Figure 1.13 the transition from respiratory columnar epithelium to flattened alveolar lining cells is rather abrupt, with a recognized zone of cuboidal nonciliated cells present although difficult to identify with consistency in lung sections.
Figure 1.15 Very sparse (and rare) neuroendocrine cells are present in the normal lung. (Immunohistochemical stain for synaptophysin with red chromogen, hematoxylin counterstain.)
Figure 1.14 After irritation of the airway epithelium from any cause, goblet cell hyperplasia may occur (arrow on goblet cell). This finding is typical in patients with asthma, as is prominent thickening of the basement membrane (BM) (arrowhead) beneath the epithelium. SM, Smooth muscle.
Epithelial Basement Membrane
The epithelial basement membrane lies immediately beneath the airway epithelium and is routinely visible in association with an eosinophilic matrix of type III collagen. A fine layer of elastic tissue is present beneath the epithelial basement membrane. Collagen may come to separate this elastic tissue from the overlying basement membrane in airway injury associated with subepithelial fibrosis.
Figure 1.16 Bronchus-associated lymphoid tissue is uncommon in normal lungs but may be increased in the lungs of smokers and in a number of other settings. These small aggregations of benign lymphoid cells are closely approximated to the airway epithelium (boxedarea), typically with an intraepithelial component analogous to tonsillar epithelium.
Smooth Muscle of the Airways
The smooth muscle of the airways is arranged in a complex spiral pattern. The bronchovascular bundle encompasses the airway, the accompanying pulmonary artery, a network of lymphatic channels, a common adventitia, and a sheath of loose connective tissue. The connective tissue of the bronchovascular bundle diminishes progressively in the smallest bronchioles of the lung.
Acinus
The acinus begins distal to the terminal bronchiole and is where most of the gas exchange occurs in the lungs. The acinus includes (in order proceeding distally) the respiratory bronchioles (primary and secondary), the alveolar ducts, and the alveolar sacs (Fig. 1.17).
Figure 1.17 Scanning magnification view of the acinus. A branched respiratory bronchiole (RB) can be seen leading into two primary alveolar ducts (AD), fully lined with alveoli.
Respiratory bronchioles have progressively more alveoli in their walls with successive distal generations. The last conducting structure, the alveolar duct, is entirely lined by alveoli. The alveolar ducts terminate in alveolar sacs, which are globular aggregations of adjacent alveoli. As the airways of the acinus branch and diminish in diameter progressively, an abrupt transition from cuboidal cells to flattened epithelium is seen.
Alveoli
Most of the alveolar surface that faces the inspired air is covered by extremely flat type I epithelial cells that are not readily seen with the light microscope. These thin and flattened cells are well suited to gas exchange (Fig. 1.18). The type II epithelial cells are cuboidal in shape, and although they cover less surface area, they are greater in total number than the type I cells. They are present at the angular junctions of alveolar walls ( The alveolus being more like a geodesic dome than a sphere). The surface of the type II cell facing the alveolar airspace has microvilli that can sometimes be appreciated on light microscopy as slight roughening. Type II cells contain large numbers of organelles and are responsible for the production of surfactant, a substance that lowers surface tension and is essential for preventing alveolar collapse at low intraalveolar pressures. Type II cells are the progenitor cells of the alveolar type I cells and, after an injury, divide and replace them. Type I and type II cells have tight junctions that present a physical barrier between the interstitial fluid and the alveolar air.
Alveolar Walls
The alveolar walls are composed of a capillary net (Fig. 1.19), the extracellular matrix, and sparse cellular elements including mast cells, smooth muscle cells, pericytes, fibroblast-like cells, and occasional lymphocytes.12 the mesenchymal cells of the interstitium have been the subject of considerable study. Unstimulated, they resemble fibroblasts and have few organelles. During the repair phase of an injury, actin and myosin appear in the cytoplasm and develop contractile properties that play an important role in lung repair.13-15 Capillary endothelial cells within the acinus are joined by tight or semitight junctions. The semitight junctions exist to allow larger molecules to traverse the capillary wall.
Figure 1.18 (A) High-magnification view of five adjacent alveoli with delicate alveolar walls. Most of the visible nuclei in the normal alveolar wall belong to endothelial cells. (B) Electron microscopy emphasizes this point: A prominent endothelial cell nucleus is seen adjacent to two red blood cells (RBCs). Note the extremely attenuated fusion of endothelial cytoplasm, basal laminae, and type I cell cytoplasm above these RBCs (not readily visible, even on ultrastructural examination). (From Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore: University Park Press; 1972.)
Alveolar Macrophages
Alveolar macrophages play an essential role as phagocytes and, under appropriate stimulation, secrete soluble factors that are an essential part of the lung’s immunologic defense and response to injury. As mobile cellular elements, they are capable of removing engulfed particulates by migrating into the interstitium (and eventually, lymphatic channels) or ascending the mucociliary escalator of the airways.
Pulmonary Arteries
The pulmonary arteries carry venous blood to the lungs for gas exchange with the inspired air in the alveolar spaces. The pulmonary circulation is a low-pressure system (with a mean systolic pressure of 14 mm Hg) and is considerably shorter in length than the systemic circulation.16,17 Nevertheless, a doubling of the resting blood flow to the lung results in only a small increase (by approximately 5 mm Hg) in pressure.
The pulmonary arteries arise from the conus arteriosus of the right ventricle of the heart and run in parallel with the airways within the lung.18,19 the main trunk of the pulmonary artery bifurcates into right and left main trunks at the fourth thoracic vertebral body. These trunks follow the right and left main bronchi into the lung (Fig. 1.20). The diameter of the pulmonary artery and that of the accompanying airway in cross section are roughly equal. The pulmonary arteries branch at a rate similar to that of the airways, but they also have a second distinctive branching pattern identifiable in peripheral lung, with right-angle origins for branches having significantly smaller caliber (Fig. 1.21) designed to supply peribronchiolar alveoli.
Figure 1.19 (A) Scanning electron micrograph of adult human lung showing the internal aspect of the alveolus. The liberal communication between alveoli in adjacent alveolar sacs is made possible by the pores of Kohn. (B) the capillary network of the alveolus is demonstrated in this scanning electron micrograph of a methacrylate vascular cast. ([A] From Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore: University Park Press; 1972. [B] Courtesy A. Churg, MD, and J. Wright, MD, Vancouver, Canada.)
The pulmonary arteries are composed of three layers, the intima, the media, and the adventitia, similar to the systemic arteries; however, for arteries of the same diameter, systemic vessels have a significantly thicker muscular layer. In the adult, two or more elastic laminae are present in arteries larger than 1 mm in diameter. Arteries between 100 and 200 µm (between 0.1 and 0.2 mm) in diameter are muscular and have internal and external elastic laminae (Fig. 1.22). Smaller arteries may be muscular or nonmuscular. The two elastic laminae appear fused in smaller arteries as a result of progressive attenuation of smooth muscle. Where muscle is absent, a single fragmented elastic lamina is all that separates the intima from the adventitia. In the adult, arterial muscle extends down to the level of the alveoli. The ratio of arterial wall thickness to external arterial diameter often is a useful marker for abnormality. Nondistended muscular arteries have a medial thickness that should represent approximately 5% of the external arterial diameter.
Figure 1.20 This microscopic section of fetal lung shows the characteristic early relationship of pulmonary artery branches to bronchi. The smooth muscle layer of each of these structures is outlined in brown. (Immunohistochemical stain for alpha smooth muscle actin, brown chromogen, hematoxylin counterstain.) BR, Bronchus; PA, pulmonary artery.
Figure 1.21 the distinctive pattern of pulmonary artery branching in the lung parenchyma is nicely illustrated in this fetal lung. (Immunohistochemical stain with monoclonal antibody directed against alpha smooth muscle actin, brown chromogen, hematoxylin counterstain.)
Pulmonary Veins
The pulmonary veins carry oxygenated blood back to the heart for systemic distribution. The large veins are present adjacent to the main arteries at the hilum, but the pulmonary veins within the lung parenchyma travel along a separate course within the interlobular septa, beginning on the venous side of the alveolar capillary bed. The intralobular pulmonary veins coalesce to form larger channels that join the interlobular septa at the periphery of the acinus (Fig. 1.23). The veins are indistinct structures in the lung and are often difficult to identify.18,20 Most of the vascular structures identifiable at scanning magnification in tissue sections of lung are pulmonary arteries (with their adjacent airway). The most reliable method for locating a pulmonary vein in tissue sections is to find the junction of the pleura with an interlobular septum (Fig. 1.24). This is an important technique because every lung biopsy for diffuse disease should be evaluated systematically in search of pathologic alterations in each of the main compartments (airways, arteries, veins, acinar structures, and pleura). The veins have a single elastic lamina (Fig. 1.25) and sparse smooth muscle.
Figure 1.22 Pulmonary artery in peripheral lung showing internal and external elastic lamina. (Elastic van Gieson histochemical stain.)
Bronchial Arteries
The bronchial arteries supply arterial blood to the lung and arise most commonly from the descending aorta, although a number of anomalous origins are described. The bronchial arteries run parallel to the airways within the bronchovascular sheath, where small branches supply capillary networks of the mucosa, airway smooth muscle, and adventitia.20,21 the largest-diameter bronchial arteries can be seen in the adventitia of the airway. Submucosal branches are nearly imperceptible. On the venous side of the bronchial artery-supplied capillary net, bronchial veins within the lung eventually join pulmonary veins and return their blood to the left atrium.
Figure 1.23 the lobular relationship of pulmonary arteries and veins is illustrated in this simplified diagram. (From Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore: University Park Press; 1972.)
Figure 1.24 (A) Study of the pulmonary veins and lymphatics is facilitated by finding junctions of pleura with interlobular septa. (B) At higher magnification of the oval area in part (A), the delicate vessels, with red blood cells in their lumens, are seen to be veins. The veins have slightly thicker walls than those of adjacent lymphatics. Large arrow, Pleural vein; small arrow, peripheral lobular vein.
Figure 1.25 A larger pulmonary vein stained for elastic tissue shows a single elastic lamina. (Elastic van Gieson histochemical stain.) ILS, Interlobular septum.
Pulmonary Lymphatics
The lymphatic vessels of the peripheral lung begin at the outer edge of the acinus, draining along interlobular septa to coalesce finally at the hilum.22 A separate centriacinar system is present in the bronchovascular sheaths, beginning around the level of the respiratory bronchiole.23 No lymphatics are present in the alveolar sacs, where it is believed that the interstitial space serves the purpose of extracellular fluid collection and drainage to more proximal regions. The lymphatic net of the pulmonary arteries extends farther distally in the acinus than does that associated with the terminal airways.23 the lymphatic networks of the airways and pulmonary arteries anastomose freely during their course back to the hilum. The lymphatics (and veins) are also distributed over the surface of the lobes within the pleura. The relationship among airways, arteries, veins, and lymphatics is nicely illustrated by Okada23 in Fig. 1.26. When affected by certain diseases such as diffuse lymphangiomatosis (Fig. 1.27A) or lymphangiectasis (see Fig. 1.27B), the distribution of the pulmonary lymphatics becomes much more apparent.
Other Pulmonary Lymphoid Tissue
Lymphoid Aggregates
Lymphoid aggregates are uncommon in the lung under normal circumstances. They have no capsule and are composed of B cells, T cells, and dendritic cells. Lymphoid aggregates increase in the lungs of cigare. The smokers11,24 and may be present within interlobular septa or the pleura (Fig. 1.28) and in the subpleural connective tissue.25 Lymphoid aggregates may be one of the sources for the condition known as diffuse lymphoid hyperplasia.
Dendritic Cells
Dendritic cells are antigen-presenting cells that function in concert with T lymphocytes to develop acquired immunity. Dendritic cells occur in the epithelium and subepithelial tissue of the airways. Their kidney-shaped nucleus is eccentrically placed, and they feature prominent cytoplasmic protrusions. Dendritic cells strongly express the major histocompatibility complex (MHC) antigens.26 A subpopulation of dendritic cells carry the Langerhans cell marker24 and contain Birbeck granules in their cytoplasm on ultrastructural examination.27 Langerhans cells are increased in the lungs of smokers and can be identified by immunohistochemical techniques using antibodies directed against S100 protein and CD1a. The Langerhans cell is involved in the smoking-related disease known as pulmonary Langerhans cell histiocytosis (formerly known as pulmonary eosinophilic granuloma or histiocytosis X).
Self-assessment questions related to this chapter can be found online at ExpertConsult.com.
Figure 1.26 Schematic illustration of the relationships among airways, pulmonary arteries, pulmonary veins, and lymphatics. (From Okada Y Lymphatic System of the Human Lung. Siga, Japan: Kinpodo Publishing; 1989.)
Figure 1.27 (A) the pleural (P) and septal (ILS) distribution of lymphatics is dramatically accentuated in this example of the rare disorder known as diffuse pulmonary lymphangiomatosis. (B) Similar accentuation is produced by lymphangiectasis. ILS, Interlobular septum; L, lobule.
Figure 1.28 Lymphoid aggregates in the lung may occur along interlobular septa (A), and in the pleura (P), as seen in (B). Germinal centers may be evident.
References
1. Moore K. he Developing Human. Philadelphia: WB Saunders; 1973.
2. Langeman J. Medical Embryology. 2nd ed. Baltimore, MD: Williams & Wilkins; 1969.
3. Wells LJ, Boyden EA. The development of the bronchopulmonary segments in human embryos of horizons XVII to XIX. Am JAnat. 1954;95(2):163-201.
4. Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore, MD: University Park Press; 1972.
5. Boyden EA. Development of the pulmonary airways. Minn Med. 1971;54(11):894-897.
6. Boyden EA. Observations on the anatomy and development of the lungs. Lancet. 1953;73(12):509-512.
7. Boyden EA. Observations on the history of the bronchopulmonary segments. Minn Med. 1955;38(9):597-598.
8. Kwon KY, Myers JL, Swensen SJ, Colby TV. Middle lobe syndrome: a clinicopathological study of 21 patients. Hum Pathol. 1995;26(3):302-307.
9. Aguayo SM, Schuyler WE, Murtagh JJ Jr, Roman J. Regulation of branching morphogenesis by bombesin-like peptides and neutral endopeptidase. Am J Respir Cell Mol Biol. 1994;10:635-642.
10. Bienenstock J, Johnston N, Perey D. Bronchial lymphoid tissue I. Morphological characteristics. Lab Invest 1973;28:686-692.
11. Richmond I, Pritchard G, Ashcroft T, et al. Bronchus associated lymphoid tissue (BALT) in human lung: its distribution in smokers and non-smokers. Thorax. 1993;48:1130-1134.
12. Thurlbeck W. Chronic airflow obstruction. In: Churg A, ed. Pathology of the Lung. 2nd ed. New York, NY: Thieme Medical Publishers; 1995:739-825.
13. Fukuda Y, Ishizaki M, Masuda Y, et al. The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. Am J Pathol. 1987;126(1):171-182.
14. Leslie K, King TE Jr, Low R. Smooth muscle actin is expressed by air space fibroblast-like cells in idiopathic pulmonaiy fibrosis and hypersensitivity pneumonitis. Chest. 1991;99(suppl 3):47S-48S.
15. Leslie KO, Mitchell J, Low R. Lung myofibroblasts. Cell Motl Cytoskeleton. 1992;22(2):92-98.
16. Parker JC, Cave CB, Ardell JL, Hamm CR, Williams SG. Vascular tree structure affects lung blood flow heterogeneity simulated in three dimensions. J Appl Physiol. 1997;83(4):1370-1382.
17. Li CW, Cheng HD. A nonlinear fluid model for pulmonary blood circulation. J Biomech. 1993;26(6):653-664.
18. Huang W, Yen RT, McLaurine M, Bledsoe G. Morphometry of the human pulmonary vasculature. J Appl Physiol. 1996;81(5):2123-2133.
19. Hislop AA. Airway and blood vessel interaction during lung development. J Anat. 2002;201(4):325-334.
20. Boyden EA. Human growth and development. Am J Anat. 1971;132(1):1-3.
21. Boyden EA. The developing bronchial arteries in a fetus of the twelfth week. Am J Anat. 1970;129(3):357-368.
22. Okada Y, Ito M, Nagaishi C. Anatomical study of the pulmonary lymphatics. Lymphology. 1979;12(3):118-124.
23. Okada Y Lymphatic System of the Human Lung. Siga, Japan: Kinpodo Publishing; 1989.
24. van Haarst J, de Wit H, Drexhage H, Hoogsteden HC. Distribution and immunophenotype of mononuclear phagocytes and dendritic cells in the human lung. Am J Respir Cell Mol Biol. 1994;10(5):487-492.
25. Kradin R, Mark E. Benign lymphoid disorders of the lung, with a theory regarding their development. Hum Pathol. 1983;14:857-867.
26. Van Voorhis W, Hair L, Steinman R, Kaplan G. Human dendritic cells. Enrichment and purification from peripheral blood. J Exp Med. 1982;155(4):1172-1187.
27. Soler P, Moreau A, Basset F, Hance AJ. Cigare The smoking-induced changes in the number and differentiated state of pulmonary dendritic/Langerhans cells. Am Rev Respir Dis. 1989;139(5):1112-1117.
1. The lungs are derived embryologically from:
A. Ectoderm
B. Neuroectoderm
C. En do derm
D. A combination of ectoderm and endoderm
E. None of the above
ANSWER: C
2. The pleural surfaces derive from:
A. Splanchnic mesoderm
B. Undifferentiated ectomesenchyme
C. Endodermal foregut buds
D. The third pharyngeal pouches
E. Rostral neuroectoderm
ANSWER: A
3. In the process of airway branching with lung growth:
A. Progenitor airways give rise to successive branches of the same size
B. Muscularization of the most peripheral airways is maintained
C. Airway volume increases
D. Airway resistance increases
E. All of the above
ANSWER: C
4. In the trachea, the trachealis muscle is:
A. Anterior
B. Posterior
C. Circumferential
D. Lateral
E. Present only just below the larynx ANSWER: B
5. Tracheal ciliated columnar respiratory epithelium and its adnexa:
A. Remove moisture from inspired air
B. Cool the inspired air
C. Remove particulate matter from inspired air
D. Do not affect inspired chemical vapors
E. Are present only at the carina of the bronchopulmonary tree
ANSWER: C
6. Bronchial cartilage plates become discontinuous:
A. As bronchi enter the lung parenchyma
B. In the segmental bronchi
C. In the respiratory bronchioles
D. In the immediate postcarinal bronchi
E. None of the above
ANSWER: A
7. Which of the following normal structures can be mistaken for pathologic ones in crushed or inflamed endobronchial biopsy specimens?
A. Submucosal mucous glands
B. Mucosal reserve cells
C. Bronchial smooth muscle bundles
D. Segmental bronchial cartilage plates
E. All of the above
ANSWER: A
8. In the airways, pseudostratified columnar epithelium is seen:
A. In the main bronchi only
B. As far distal as the smallest terminal bronchioles
C. Out into the alveolar ducts of the upper lobes
D. Out into the respiratory bronchioles of the lower lobes
E. None of the above
ANSWER: B
9. Which of the following statements regarding neuroendocrine cells of the normal airways is/are TRUE?
A. They are seen with hematoxylin and eosin as dark basal cells in the respiratory epithelium
B. They are always singly dispersed
C. They may play a role in ventilation-perfusion relationships in the lungs
D. They can be identified only ultrastructurally, because they are chromogranin-negative in conventional immunostains
E. All of the above
ANSWER: C
10. Which of the following structures is/are part of the bronchovascular bundles?
A. Bronchial smooth muscle
B. Tubular airways
C. Pulmonary artery branches
D. Lymphatic vessels
E. All of the above
ANSWER: E
11. Type II epithelial cells:
A. Are present in terminal bronchioles and the alveoli
B. Account for fewer cells than type I epithelia in the airways
C. Produce surfactant
D. Are derivatives of type I epithelial cells
E. Contain scant cytoplasmic organelles ultrastructurally
ANSWER: C
12. After injuries to the lung parenchyma, interstitial mesenchymal cells:
A. Are often replaced by neuroendocrine elements
B. Acquire aberrant immunoreactivity for keratin
C. Participate in the formation of chemoreceptors
D. May become facultatively myoid
E. None of the above
ANSWER: D
13. Alveolar macrophages:
A. Are part of the defensive mononuclear cell population of the lungs
B. Are motile cellular elements
C. Demonstrate phagocytosis of many particulates in the airways
D. May enter and traverse intrapulmonary lymphatics
E. All of the above
ANSWER: E
14. Elastic laminae in intrapulmonary vessels can be demonstrated with which ONE of the following histochemical preparations?
A. Von Kossa stain
B. Macchiavello stain
C. Pinkerton stain
D. Van Gieson stain
E. Acridine orange stain
ANSWER: D
15. The pulmonary arterial trunk bifurcates at the level of which vertebral body?
A. Fifth cervical
B. Second thoracic
C. Fourth thoracic
D. Sixth thoracic
E. None of the above
ANSWER: C
16. Pulmonary arterial branches:
A. Roughly equal the diameters of their companion tubular airways
B. Comprise an intima, media, and adventitia
C. Contain two elastic laminae when they are greater than or equal to 1 mm in diameter
D. Normally have a medial thickness that is 5% of the external arterial diameter
E. All of the above
ANSWER: E
17. Pulmonary veins are best seen microscopically:
A. At the junctions of visceral pleura and interlobular septa
B. Next to segmental bronchi
C. Adjacent to alveolar ducts
D. With immunostains for desmin
E. None of the above
ANSWER: A
18. Intrapulmonary lymphatics:
A. Comprise two separate systems
B. May follow the interlobular septa
C. May accompany bronchovascular bundles
D. Are distributed over the surfaces of the lobes in the pleura
E. All of the above
ANSWER: E
19. Airway-associated lymphoid tissue:
A. Is very different structurally from mucosal lymphoid tissue of the gut
B. Is least visible microscopically at bifurcation points of the airways
C. Comprises a majority population of B lymphocytes
D. Plays a role in processing allergens and infectious agents
E. Usually lacks dendritic cells and macrophages
ANSWER: D
20. Intrapulmonary dendritic cells:
A. Function immunologically in concert with B lymphocytes
B. Are located principally in the pulmonary interstitium
C. Rarely if ever express class II histocompatibility antigens
D. May contain Birbeck granules ultrastructurally
E. Have intensely granular cytoplasm in hematoxylin and eosin stains
ANSWER: D