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.

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.

(Reprinted with permission from Moore K. The Developing Human. Philadelphia: WB Saunders; 1973.)

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 gland-like 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^1–5 (Fig. 1-3). The postnatal lung continues to accrue alveoli until the age of approximately 10 years (Fig. 1-4).

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 1-3 The remaining stages in lung development are illustrated here in tissue sections from developing human lung. A, The canalicular period occurs in the interval between 13 and 25 weeks after fertilization. Airway lumens become dilated and more prominent, and the mesenchymal tissue surrounding them becomes progressively vascularized. B, The terminal sac period occurs from 24 weeks to birth. The terminal buds of the airways at this juncture are referred to as primitive alveoli. C, The final phase of lung development is referred to as the alveolar period and crosses into childhood (extending from the late fetal stage to 10 years of age). New alveoli continue to form well after birth. AD, alveolar duct; AS, alveolar sac; RB, respiratory bronchiole.

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.

The 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).

Figure 1-5 View of the collapsed lung during thoracoscopic surgery demonstrates the visceral and parietal pleural surfaces.

The 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

Figure 1-6 Ten distinct segments are present in each lung.

(Reprinted with permission from Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore: University Park Press; 1972.)

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 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 1-7 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.

(Reprinted with permission 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 pulmonary artery and airway and also illustrates the junction of a terminal bronchiole with the acinus.

(Reprinted with permission from Nagaishi C. Functional Anatomy and Histology of the Lung. Baltimore: University Park Press; 1972.)

The 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.

The 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.

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.

The 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 connect to the airway lumen by a short duct. The bronchi divide and subdivide successively, becoming ever smaller on their way to the peripheral lung.

Figure 1-10 A, 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.