Types and Patterns of Response in the Larynx Following Inhalation

Abstract

The laryngeal mucosa responds to insult similarly to other epithelial tissues but the response depends on location within the larynx since important anatomic differences exist, even within rodent species. Although dogs and nonhuman primates are also utilized for inhalation toxicology studies, little published information is available regarding sites of injury from inhaled toxicants in these species. Accurate and consistent fixation, trimming, and microtomy of laryngeal sections allow the pathologist to compare the morphology of laryngeal mucosa from exposed and control animals and detect and interpret subtle differences resulting from inhalation exposure. There are anatomic landmarks that are keys to providing consistent sections through important areas of the laryngeal mucosa. Repeated inhalation of toxic concentrations of chemicals, drugs, or environmental contaminants induces a wide range of responses, depending on the physical properties and concentration of the toxic substance and duration of exposure. Responses include edema, acute to chronic inflammation, fibrosis, mucosal ulceration, degeneration, and necrosis. Attempts at repair include regeneration, hyperplasia, squamous metaplasia, hyperkeratosis, and neoplasia. Awareness of normal histology and zones of transition from squamous to respiratory epithelium in different areas of the larynx in different species is critical to avoid confusing normal epithelium with metaplasia or hyperplasia. Microscopic examination of laryngeal mucosa from animals exposed via inhalation and necropsied following a recovery period provides the opportunity to determine the degree of regression or progression of exposure-induced laryngeal lesions.

Upper Respiratory Tract Lesions in Inhalation Toxicology

“…1, 2007 RESPIRATORY TRACT LESIONS 167 normally lined by stratified squamous epithelium such as the medial surface of the vocal processes of the arytenoids, may undergo hyperplasia and hyperkeratosis. Areas normally covered with a thin layer of squamous epithelium such as the mucosa adjacent to the ventral pouch may also become hyperplastic and hyperkeratotic, and may be accompanied by inflammatory cell infiltrates in the adjacent submucosa, depending on severity and duration of the stimulus (Renne and Gideon, 2006). If squamous metaplasia extends downward into the ducts of submucosal glands, the ducts may plug with hyperkeratotic debris, causing dilatation and inflammation of the affected glands.…”

“…Exposure-induced laryngeal lesions are frequently reported in inhalation studies in rodents; thus, there is considerable information available on laryngeal lesions in these species (Lewis, 1991;Miller and Renne, 1996;Renne and Gideon, 2006). The laryngeal epithelium responds similarly to the epithelium lining the nose.…”

“…In most reported studies and in the authors' experience, removal of the inciting stimulus for a period of 6 to 13 weeks following subchronic (13 weeks) exposure results in regression of the lesions and return of the affected epithelium to normal morphology. Morphometry using image analysis tools to measure the total area of epithelium lining the base of the epiglottis has proven useful in quantitating hyperplasia and hyperkeratosis in rodents (Renne and Gideon, 2006).…”

“…One key is access to interpretable sections through the area of transition from squamous to respiratory epithelium at the base of the epiglottis. The submucosal glands and cartilages at the level of the base of the epiglottis, ventral pouch, and vocal processes of the arytenoids in rodent larynges can be visualized in unstained sections at microtomy by adjusting the light diffraction in the microscope (Renne and Gideon, 2006). Microscopic examination of unstained sections through these key areas at microtomy enables the histotechnologist to accurately determine the location of the section and provide the pathologist with consistent sections through key areas of the larynx.…”

“…Microscopic examination of unstained sections through these key areas at microtomy enables the histotechnologist to accurately determine the location of the section and provide the pathologist with consistent sections through key areas of the larynx. Publications providing information on the most frequent sites and typical morphology of laryngeal lesions induced in rodents from inhalation exposure are available in the literature (Lewis, 1991;Miller and Renne, 1996;Renne and Gideon, 2006).…”