Development

In early fetal life, the lungs bud off the esophagus and form a connection with the trachea to the oropharynx. Continued cell division produces greater volume of the lungs. The most prominent structures early on are the bronchi and bronchioles. Under 16 weeks gestational age, a histologic section of lung parenchyma will reveal mainly small round bronchioles, and this stage is known as the tubular (glandular) phase of development. There is so little surface area for gas exchange through thick bronchioles that survival is not possible if birth occurs. From 16 weeks to 26 weeks gestation, the bronchioles begin to give rise to more complex structure with branching to respiratory bronchioles and alveolar ducts. This is the canalicular phase of development. From 23 to 25 weeks gestation on, there is enough lung to survive (barely) if birth occurs, supported by mechanical ventilation. Beyond 26 weeks, there is continued branching with formation of alveoli, and this is the saccular phase of development. Alveolar type II cells become more numerous, but actual fetal lung maturity with enough surfactant to survive extrauterine life without serious complications is reached between 34 and 36 weeks gestation.

Nose

Air inhaled through the nostrils is warmed and filtered in the vestibule lined by stratified squamous epithelium. Beyond the vestibule, the nasal passages are lined by pseudostratified ciliated columnar epithelium ("respiratory epithelium"). Most of the cells comprising the respiratory epithelium are columnar cells with cilia. However, there are scattered admixed goblet cells secreting mucus, brush cells with a sensory function, and neuroendocrine cells.

Larynx

The nasopharynx and oropharynx meet at the epiglottis. The epiglottis is a flap valve structure that closes off the airway when swallowing to prevent aspiration. The portion of airway below the epiglottis is known as the larynx. The larynx functions to modulate sound for speech. The larynx is supported by cartilage and has skeletal muscle to adjust tension on the vocal folds. The folds just below the epiglottis at the top of the larynx are known as the aryepiglottic folds. Within the larynx proper, there is an upper set of false vocal folds lined by respiratory epithelium and a lower set of true vocal folds lined by stratified squamous epithelium. In the lamina propria beneath the epithelium in the ventricle (between the false and true cords) and above are mixed mucus and serous glands. Beneath the thin lamina propria of the true vocal folds is skeletal muscle.

Trachea

The trachea connects the larynx to the mainstem bronchi leading to the lungs. The trachea is a stiff tube that is anatomically positioned anterior to the esophagus. There are rigid circular tracheal ring cartilages with a "C" shape (the open side faces the esophagus posteriorly and is connected by smooth muscle) that keep the tracheal lumen open but provide flexibility for movement. The trachea is lined by respiratory epithelium. There is a thin underlying lamina propria, beneath which is a submucosa in which are scattered serous and mucinous glands. Also in the submucosa are scattered plasma cells that secrete primarily immunoglobulin A and help in mucosal defense against pathogens.

Major Bronchi

The right and left mainstem bronchi divide at the carina at the lower end of the trachea. The mainstem bronchi give rise to secondary bronchi that branch about 9 to 12 times while extending into the lungs. These bronchi have cartilage arranged circumferentially in discontinuous plates. The cartilage keeps the bronchi stiff and open but provides flexibility. The larger bronchi have a complete ring of smooth muscle between the lamina propria and the submucosa with seromucinous glands. As secondary bronchi extending to lung lobes divide into tertiary bronchi extending to lobar segments, there is less smooth muscle, less cartilage, and less submucosa distally. The number of elastic fibers adjacent to smooth muscle diminishes distally.

Lungs

The tertiary bronchi eventually branch into bronchioles, airways less than a millimeter in diameter, which lack cartilage and glands but still have smooth muscle. The smaller branches are lined by a simple ciliated epithelium that gradually decreases in height from columnar to cuboidal. A terminal bronchiole defines the smallest functional unit of lung--the lung acinus (terminal respiratory unit). Goblet cells are absent in terminal bronchioles. Each terminal bronchiole branches into two respiratory bronchioles which in turn lead into several smaller alveolar ducts, from which the blind-ended alveolar sacs branch. Gas exchange is possible in respiratory bronchioles and alveolar ducts, but mainly occurs in the alveoli. The alveolar ducts have a few elastic and collagen fibers to support them. Tiny smooth muscle bundles in respiratory bronchioles and alveolar ducts can control air movement in acini. A cluster of three to five terminal bronchioles with their acini form a lung lobule. The lobules are arranged into segments that comprise the lung lobes.

Between the lobules run the secondary bronchial branches and the pulmonary arterial branches. The lung also has a systemic blood supply--the bronchial arteries--but this system supplies only 1% of the blood to the lungs and is, in histologic sections, difficult to identify. The majority of the blood to the lungs is supplied by the pulmonary arterial system coming from the right side of the heart.

The ciliated cuboidal epithelium of terminal bronchioles becomes the flattened cuboidal non-ciliated epithelium of respiratory bronchioles, which have little smooth muscle, along with some elastic fibers. Tiny peripheral branches of pulmonary artery accompany the bronchioles before branching to the alveolar wall capillaries. There are some scattered specialized cells lining bronchioles, including serous secreting club cells and neuroendocrine cells. Scattered brush cells with short microvilli serve as afferent nerve ending receptors. Club cells secrete a lipoprotein with properties similar to surfactant to prevent airway collapse.

The alveolar sacs have very thin walls--less than 1 micron. There is an attenuated epithelium consisting of type I pneumonocytes through which oxygen diffuses into and carbon dioxide diffuses out of the capillary running through the wall. The capillaries have a very thin endothelium. There are scattered type II pneumonocytes along the alveolar walls which have the important function of producing surfactant. The surfactant is stored in structures called lamellar bodies (because of their structure seen on electron microscopy) and released into the alveoli. Surfactant has a detergent-like property that helps to reduce surface tension and keep the alveoli from collapsing. There are normally a few alveolar macrophages trundling around the alveoli scavenging for debris that is not removed by the mucociliary apparatus. When more debris collects with pathologic processes, then blood monocytes migrate into the alveoli and become macrophages.

The mucociliary apparatus consists of all the ciliated epithelium, along with the submucosal glands and goblet cells, that secrete serous and mucinous secretions. The function of the mucociliary apparatus is to trap and expel debris that has been inhaled. In general, particles above 10 microns in size do not get past the nasopharynx; particles averaging 5 to 10 microns are trapped by the mucociliary apparatus. Particles 1 to 5 microns in size must be phagocytozed by macrophages in the alveoli. Particles less than 1 micron remain suspended and are exhaled.

Lymphatic channels are present in the lungs. They run in conjunction with the bronchi and bronchioles. The peripheral lymphatics drain to the pleural surface and the central lymphatics drain to the hilar lymph nodes. Macrophages in the alveoli that have phagocytized debris transfer that debris to the lymphatics. In our modern world, there is a significant amount of carbon dust in the air, which is breathed in and trapped by macrophages. This anthracotic pigment outlines the larger lymphatic channels, particularly between lung lobules and on the pleural surface. Most adults have hilar nodes that appear grossly black because of this pigment. Persons who smoke have much more anthracotic pigmentation.

Pleura

The outer surface of the lungs, the pleura, is bounded by a thin layer of mesothelium supported by a thin layer of collagenous connective tissue. There is a visceral pleural lining over the lungs, and a parietal pleural lining on the chest wall. Between these layers is a potential space called the pleural cavity in which fluid, blood, and inflammatory cells can collect with pathologic processes.