n addition to their primary function of gas exchange, the lungs act as a primary barrier between the outside world and the inside of the body, with host defense functions. They are also active organs in the metabolism of xenobiotic and endogenous compounds.
To cope with the inhalation of foreign substances, the respiratory system and, in particular, the conducting airways have developed unique structural features: the mucociliary clearance system and specialized adaptive and innate immune response mechanisms.
The mucociliary clearance system protects the conducting airways by trapping and removing inhaled pathogenic viruses and bacteria, in addition to nontoxic and toxic particulates (e.g., pollen, ash, mineral dust, mold spores, and organic particles), from the lungs. These particulates are inhaled with each breath and must be removed. The three major components of the mucociliary clearance system are two fluid layers, referred to as the sol (periciliary fluid) and gel (mucus) layers, and cilia, which are positioned on the surface of bronchial epithelial cells (
Fig. 26.1 ). Inhaled material is trapped on the viscoelastic (sticky) mucus layer, whereas the watery periciliary fluid allows the cilia to move freely and establish an upward flow to clear particulates from the lung. Effective clearance requires both ciliary activity and the appropriate balance of periciliary fluid and mucus.
The periciliary fluid layer is composed of nonviscous serous fluid, which is produced by the pseudostratified ciliated columnar epithelial cells that line the airways. These cells have the ability to either secrete fluid, a process that is mediated by activation of cystic fibrosis transmembrane regulator (CFTR) chloride (Cl−) ion channels (Na+ secretion follows passively between cells across the tight junctions) or reabsorb fluid, a process that is mediated by activation of epithelial sodium channels (ENaC; Cl− absorption follows passively between cells across the tight junctions). NaCl secretion or reabsorption temporarily establishes an osmotic gradient across the pseudostratified epithelium, which provides the driving force for passive water movement. The balance between CFTR-mediated Cl− secretion and ENaC-mediated Na+ absorption is regulated by a variety of hormones and determines the volume of the periciliary fluid, which in the healthy lung is 5 to 6 µm deep, a level that is optimal for rhythmic beating of the cilia and mucociliary clearance.
The mucus layer lies on top of the periciliary fluid layer and is composed of a complex mixture of macromolecules and electrolytes. Because the mucus layer is in direct contact with air, it entraps inhaled substances, including pathogens. The mucus layer is predominantly water (95% to 97%), 5 to 10 µm thick and exists as a discontinuous blanket (i.e., islands of mucus). Mucus has low viscosity and high elasticity and is composed of glycoproteins with groups of oligosaccharides attached to a protein backbone. Healthy •Fig. 26.1 Overview of the Epithelial Lining and Innervation of the Tracheobronchial Tree. Theciliaoftheepithelialcellresideinthepericiliaryfluidlayer,andthemucuslayerisontop.Interspersedbetweentheciliatedepithelialcellsaresurfacesecretory(goblet)cellsandsubmucosalglands.Sympatheticandparasympatheticnervefibersdescendintothesubmucosalglandsandsmoothmuscles.