Atlas of plant and animal histology

The respiratory system is responsible for providing oxygen needed for cellular respiration while also removing carbon dioxide generated during cellular metabolism. Both molecules are exchanged between the blood and the atmosphere. The respiratory system also performs other functions, such as providing air to produce sounds, renewing the air over the olfactory epithelium of the nasal cavity to allow smelling, and producing some hormones.

The respiratory system consists of a series of ducts through which the air is driven (Figure 1). It begins in the oral and nasal cavities, as both are airways through which air enters and exits. The nasal cavity houses the olfactory epithelium. Olfaction is closely related to the acto of breathing in pulmonary animals, and the rhythm of breathing may be adapted to enhance the intake and perception of odors.

The pharynx communicates the oral and nasal cavities with the larynx. It is a resonance chamber during sound production. Besides being an air-conducting structure, the larynx is the phonation organ since it contains the vocal cords. The larynx connects the pharynx with the trachea.

The trachea is a tubular structure that starts in the larynx and ends in the thoracic zone, where it branches out into two tubes that are called the main or primary bronchi. The trachea is lined with a mucosa composed of pseudostratified ciliated epithelium, containing some goblet cells (mucus-producing cells), and a lamina propria of connective tissue with many elastic fibers. More innerly, there is a submucosa constituted by connective tissue that contains the secretory portions of some glands, mostly formed by mucous acini, although some glands are mixed (serous and mucous). Underneath the submucosa, there are incomplete rings of hyaline cartilage, which in cross-sections (perpendicular to the major axis of the trachea) are C-shaped. These incomplete rings are distributed throughout the length of the trachea. The muscle cells within the trachea connect the ends of these incomplete rings. The cartilage provides rigidity and elasticity to the trachea. The adventitia limits the external part of the cartilage.

The primary bronchi are the initial two branches of the trachea. They further divide into the secondary bronchi and later into bronchopulmonary segments, according to the lobes of the lung. The bronchi share a similar histological structure with the trachea, but as they enter the lungs, irregular cartilage plates replace the cartilage rings. As the diameter of the ducts decreases and new branches emerge, the cartilage becomes more scarce. At the same time, the smooth muscle layer increases in proportion. When the diameter of the respiratory duct is close to 1 millimeter, the cartilage is no longer observed, and then these ducts are called bronchioles. In addition, bronchioles lack glandules.

Bronchioles give rise to terminal bronchioles, which subsequently lead to respiratory bronchioles, and then to pulmonary alveoli, which are organized as alveolar ducts and sacs. In bronchioles, there is a transition from pseudostratified to simple epithelium, which changes from simple columnar to simple cuboidal, until reaching the alveoli, where the epithelium is simple and squamous. The goblet cells are scarce in bronchioles and do not appear in terminal bronchioles.

Alveoli are the terminal zones of the airways. Gas exchange takes place through their walls. Alveoli are formed of a simple, squamous epithelium surrounded by blood capillaries. The internal cavity of the alveoli communicates with the alveolar sacs or with the alveolar ducts. The walls of alveolar sacs and alveolar ducts are the alveoli themselves. Both structures communicate with the bronchioles.

Respiratory epithelium

The respiratory epithelium lines the respiratory airways. It changes from ciliated and pseudostratified in the trachea to columnar and cuboidal in the bronchi and bronchioles and finally simple and squamous in the alveoli.

The respiratory epithelium protects against pathogens, pollutants, and allergenic substances. It comprises various protecting elements, such as a layer of mucus, the movement of cilia, the glycocalyx, and the cell-cell adhesion complexes between the epithelial cells that form a sealed barrier. The asthmatic conditions disrupt this epithelial barrier and allow the invasion of pathogens and harmful substances that otherwise cannot cross the epithelium.

The glycocalyx can extend as far as 150 nm from the epithelial cell membrane and is found in all epithelial cells of the respiratory system. It performs various functions, such as retaining water to sustain the mucous layer and compacting the mucous layer in a way that it can be moved by cilia. Additionally, the glycocalyx prevents particles larger than 100 nm, including bacteria and many viruses, from contacting the epithelial cell membrane. Nevertheless, not all the functions performed by the glycocalyx are fully understood.

The mucus is released onto the epithelial surface and functions as a protective and defensive layer. This layer is moved toward the oral cavity by propelling forces generated by the movement of cilia. Only the smaller molecules can cross the mucous layer, while pathogens and potentially dangerous particles are directed to the oral cavity. The mucus is composed of water, salts, lipids, and proteins. It is viscous, adhesive, and shows some elasticity. These properties are provided by mucins, proteins that are released and adhere to the glycocalyx or remain free on the epithelial surface. There are 21 different types of mucins, which are released by goblet cells and mucous glands.

TThe respiratory epithelium also releases lysozymes, transferrin, and antimicrobial peptides. Lysozymes are secreted by serous glands and attack bacteria. The transferrin removes iron, a necessary element for bacterial proliferation. The respiratory epithelium is also capable of translocating IgM and IgA immunoglobulins, so they can cross from the blood to the surface of the respiratory ducts.

Up to 40 cell types are found within the lung respiratory epithelium. Three regions can be distinguished in this epithelium: the proximal zone (trachea and bronchi), the distal zone (bronchioles), and the gas exchange region (alveoli). Each of these regions show specific types of epithelial cells.

The proximal zone comprises columnar pseudostratified epithelium, containing ciliated cells, goblet cells, club cells, and basal cells. Each ciliated cell bears between 200 and 300 cilia and accounts for more than half of the total epithelial cells. The distal zone contains secretory club cells, neuroendocrine cells, and goblet cells. Type I (flat cells that exchange gases) and type II (cuboidal cells that release surfactant substances) pneumocytes are found in the alveolar epithelium. Type II pneumocytes are also progenitor cells that develop into type I pneumocytes.

Tn the airways containing cartilage, the basal cells are stem cells found mostly as part of the glands. In addition, the epithelium can be divided into conducting and respiratory types. These two types perform different functions: the conducting epithelium acts as a protective barrier against microorganisms thanks to the mucous layer released by glands and goblet cells, while the cilia of the columnar to cuboidal pseudostratified epithelium move this mucous layer towards the oral cavity.

• Bibliography ↷

  • Davis JD, Wypych TP. 2021. Cellular and functional heterogeneity of the airway epithelium. Mucosal immunology. 14:978 – 990. DOI: 10.1038/s41385-020-00370-7.

    Li F, He J, Cho Wc, Liu X. 2015. Diversity of Epithelial Stem Cell Types in Adult Lung. Stem cells interantional. 728307. DOI: 10.1155/2015/728307.