Structure and development of the lower respiratory system


  • Lungs increase in volume from about 250 mL at birth to 6000 mL in the adult.

  • Each lung lobe is subdivided into 19 bronchopulmonary segments, which receive a primary segmental bronchus and a tertiary pulmonary artery branch and are drained by pulmonary veins.

  • The airway branching pattern in the lung undergoes multiple generations, yielding a total of 27 or 28 divisions when counting begins from the primary bronchus.

  • The aggregate length of the airways in the adult lung spans approximately 1500 miles (2400 km).

  • The bronchial mucosa contains several epithelial cell types, with the ciliated cell comprising more than 90% of the epithelial cell population in the conducting airways, but the proportion and number of cilia per cell decrease from the proximal to distal airways.

  • The acinus, which is approximately spherical in shape and has a diameter of about 7 mm and a length of 0.5 to 1 cm, is the gas-exchange portion of the lung.

  • At the alveolar level, many changes occur in the postnatal period. Although there is disparity concerning the time in which alveolarization is completed, alveoli in a normal adult number from 300 to 500 million and have a diameter of 150 to 200 μm.

  • The two epithelial cells of the alveolus are the gas-exchanging type I cell and type II cell, which are responsible for the production of pulmonary surfactant and have a central role in repair.

  • The alveolar-capillary unit is composed of three major constituents: the epithelial lining of the alveolus, capillary endothelial cells, and a mixture of cellular and extracellular interstitial components.

  • Following birth, the pulmonary vasculature undergoes extensive remodeling. When fully matured, the thickness of the pulmonary artery is only about 60% that of the aorta.

  • The large pulmonary arteries traverse the lung with the cartilaginous airways and extend from the hilum nearly halfway down the bronchial tree.

  • Smaller pulmonary arteries measure between 100 and 1000 μm in diameter, branch with the bronchial tree, and lie close to bronchi and bronchioles.

  • Pulmonary veins do not course with the bronchial tree; instead, they are seen within the interlobular septae.

Lower respiratory system

Overview of the lungs

While the upper airway of the respiratory system is involved in uptake of air for delivery to the lungs and in the removal of large particulates from the air, the primary purpose of the lower respiratory tract is to efficiently deliver oxygen to the blood and remove expired carbon dioxide. The main components of the lower respiratory tract are the trachea, bronchial tubes, and lungs. The lungs are dense, spongy structures composed of smaller branches of the bronchi called bronchiolar tubes. After several branching generations, the bronchiolar tubes terminate at alveolar sacs, where oxygen and carbon dioxide are exchanged with the blood of alveolar sac–associated capillaries. The trachea, bronchial tubes, and bronchioles provide rapid delivery of large volumes of air; the alveolar sacs provide the large surface area required for sufficient gas diffusion.

Externally, the lungs are paired structures that, with the mediastinum, fill the thoracic cavity. Normally, the right lung is composed of three lobes and the left lung consists of two lobes and the lingula, arising from the left upper lobe. The lobes are separated by fissures and have hili that receive a primary lobar bronchus, pulmonary artery and veins, bronchial arteries and veins, lymphatics, and nerves. , The lobes are further subdivided into 19 bronchopulmonary segments that receive primary segmental bronchi and a tertiary pulmonary artery branch and are drained by pulmonary veins. Pulmonary veins do not course with the airway and pulmonary artery; instead, they course midway between the dyads and can be readily identified in the intersegmental septa. The connective tissue septa that demarcate each bronchopulmonary segment define the smallest surgically resectable portions of the lung.

The lung bud develops in the first month of the embryonic period, after which extensive branching progresses (≈20 generations) forming the bronchial tree by the middle of the second trimester. The most rapid period of human lung development occurs between 22 weeks’ gestational age and term (≈40 weeks). This is during the saccular period, when alveolarization is initiated and accelerates, yielding approximately 20,000,000 to 50,000,000 alveoli at birth—only 6% to 16% of that in the full-grown adult lung. The beginning of the third trimester (22–27 weeks) is not only critical with respect to premature births but also because early development of fetal human lungs primarily occurs in the presence of fetal hemoglobin (α 2 γ 2 ). Later stages (∼27 to ∼38 weeks) of human fetal lung development (which include initiation of both pulmonary surfactant expression and accelerated alveolarization) occur during the main γ to β globin transition—that is, from fetal to adult hemoglobin (α 2 β 2 ). Fetal hemoglobin binds oxygen more efficiently than adult hemoglobin, yielding higher oxygen tensions in the lung tissue of developing human fetuses. Therefore, treatment of premature infants with regard to oxygen delivery should consider potential risks associated with the oxygen-binding properties of the predominant hemoglobin form.

At birth, the lungs weigh about 40 g and double in weight by 6 months. Lung volume increases from about 250 mL at birth to 6000 mL in the adult. Mature respiratory alveoli appear at approximately 36 weeks of gestation and continue to develop until about 2 years of age, with an approximate total surface area of 2.8 m 2 . By age 2 years, most of the alveolarization process is complete, but newly formed alveolar septa still contain a double capillary network rather than the single one observed in adult lungs. Therefore, over the next several years the capillary bed will reorganize well after alveolar formation. After 8 years of age, the lung enters the phase of natural growth.


In the lung, the airway undergoes multiple generations of branching, yielding a total of 23 to 28 divisions when counting begins from the primary bronchus. The bronchi are the larger intrinsic cartilaginous airways, comprising 9 to 12 generations, starting with the primary bronchus and terminating in bronchi with a diameter of approximately 1 mm. Bronchioles, sometimes called membranous bronchioles or distal noncartilaginous airways , are conducting airways. They comprise an additional 12 generations before ending as terminal bronchioles, the last purely conducting structure in the lung. Horsfield and Cumming showed that the course from the trachea to the alveolar level may comprise as few as 8 or as many as 24 airway branch points. The first 16 generations of branching are genetically determined, while more distal branching and alveolarization are more plastic and are much more likely to be influenced by maternal nutrition and other extrinsic factors. For this reason, a particular airway diameter may be found at various points along the course of the airway. Determination of the total cross-section of airways is important in understanding the distribution of airway resistance. Weibel showed that as the peripheral generations of the airways are approached, the total cross-sectional area of the lung is markedly increased, suggesting that peripheral airways account for only a small proportion of total airway resistance. In the adult, an asymmetric dichotomous branching pattern is seen, each daughter branch having a cross-sectional area about 75% of its parent branch. This results in an increase of combined cross-sectional area of the two daughter branches. It is well known, however, that peripheral airway resistance in children’s lungs is disproportionately high. The size of the conducting airways is related to stature; thus, the airways’ cross-sectional area in children increases at a slow rate with growth and aging. Because the peripheral airways make up a significant portion of the total respiratory resistance in children, disease in the bronchioles can be serious.

The bronchi maintain the histologic appearance of the trachea in that mucosa, submucosa, muscularis, adventitia, and cartilaginous support are present. As the bronchi branch deeper into the lung parenchyma, the cartilage rings become plates and less regular, and the muscularis becomes continuous, being located between the submucosa and cartilage plates. Also contained within the bronchial submucosa are mucus-secreting submucosal glands, nerves, ganglia, and bronchial arterial branches ( Fig. 41.1 ). As the bronchi decrease in diameter, the pseudostratified columnar epithelium becomes lower and the mucoserous glands become fewer in number. Although the glands decrease in number in the more distal parts of the lung, mucous cells persist and can be found in very small bronchi and some membranous bronchioles.

• Fig. 41.1

Bronchus (B) with surrounding smooth muscle (M) and cartilage (C). The airway mucosa (inset) is composed of ciliated epithelial cells and vacuolated goblet cells (arrowheads). (Gomori trichrome, ×40 and ×400.)

The bronchial mucosa contains several epithelial cell types: ciliated, mucus-producing (goblet cells), basal, brush, and neuroendocrine. , The ciliated cell constitutes more than 90% of the epithelial cell population in the conducting airways, but the proportion and number of cilia per cell decrease from the proximal to distal airways. The 9 + 2 microtubular structure within the cilia has been shown to be altered in the primary ciliary syndromes ( Fig. 41.2 ). In addition to its ciliary beating movement, the ciliated columnar cells regulate the depth of the composition of the periciliary fluid and transport ions across the epithelium. The basal cell has a progenitor cell role and functions to maintain adherence of columnar cells to the basement membrane. The brush cell, thought to have a role in fluid absorption and/or chemoreceptor function, is found rarely in the tracheobronchial and alveolar epithelia.

• Fig. 41.2

Internal structure of a cilium (no cell membrane evident) in which two axial tubules and nine peripheral duplex tubules are seen. Dynein arms are attached to several of the peripheral duplex tubules (×13,500).

The mucociliary apparatus is the primary defense mechanism in the respiratory system. Although mucous goblet cells secrete mucin, it is the submucosal glands that produce more than 90% of the mucus needed for mucociliary function. The glandular unit of the bronchial submucosa comprises mucous, serous, myoepithelial cells, collecting duct cells, and, occasionally, neuroendocrine (Kulchitsky) cells. , The physical characteristics of the mucous layer reveal that the superficial layer is more viscous than the deeper layer. This difference in consistency of the mucous layer allows the cilia to function properly, allowing a power and recovery stroke mechanism. The secretions include lysozyme, antileukoprotease, lactoferrin, and immunoglobulin A (IgA). The secretory component of IgA is synthesized in bronchial gland cells and expressed on their basolateral cell surfaces, to which IgA dimers synthesized by plasma cells bind. The complex is endocytosed by the glandular cell and then is secreted from its luminal surface. Neuroendocrine cells can be solitary near the basal lamina between columnar cells or in collections called neuroepithelial bodies that occur near branch points of bronchi. The neuroendocrine cells are more abundant in the fetus and likely have a role in lung growth or maturation.

Although originally defined as having a lumen diameter of less than 2 mm, the term small airway usually refers to a bronchiole. Histologically, the bronchiole is characterized by a transition from pseudostratified tall columnar epithelium to a more cuboidal ciliated form. In addition, the mucous goblet cell is replaced by the nonciliated club cell, formerly known as the Clara cell ( Figs. 41.3 and 41.4 ). In the bronchiolar epithelium, a ratio of about three ciliated cells to two nonciliated cells lines the lower airways. The club cell is identified as a dome- or tongue-shaped cell that protrudes into the bronchiolar lumen among the shorter ciliated cells. The club cell has varying features according to species but possesses an abundance of agranular reticulum and secretory granules. Club cells synthesize and secrete club cell secretory protein (CC10, CC16), a unique 10-kDa protein similar to rabbit uteroglobin that has antiinflammatory and immunoregulatory functions. In addition, club cells secrete surfactant-associated proteins A, B, and D. Importantly, the club cell also functions as a progenitor cell that differentiates into ciliated cells following injury. Some investigators have shown that the club cell can differentiate into a type II epithelial cell.

• Fig. 41.3

Distal conducting airway mucosa composed of some ciliated epithelial cells showing a terminal bar (arrows) and a nonciliated club cell (arrowheads). (Hematoxylin-eosin stain, ×400.)

• Fig. 41.4

Respiratory tract epithelia. There is a progression from pseudostratified columnar epithelium with ciliated, goblet, and basal cells in the large conducting airways (top circle) to a more cuboidal ciliated epithelium in the small conducting airways with nonciliated club cells (middle circle) . In the alveolar epithelium, flattened type I pneumocytes and cuboidal type II pneumocytes are present and are associated with an extensive capillary network (box) .

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

May 20, 2021 | Posted by in RHEUMATOLOGY | Comments Off on Structure and development of the lower respiratory system

Full access? Get Clinical Tree

Get Clinical Tree app for offline access