Goblet cells metaplasia

More serious respiratory effects were seen upon histological examination of the respiratory tract at the end of this study. Gross lung changes observed in the rabbits included collapsed dark red areas, hyperemia, and the accumulation of mucous material. The trachea and the major bronchi showed areas of epithelial desquamation, relative atrophy, flattening of the mucosa, and foci of goblet cell metaplasia. 

If the insult persists, hyperplasia (cell proliferation) proceeds and leads to an abnormal epithelium. Injury produced by chronic exposure to irritants such as SO2, NO2, O3, formaldehyde, and tobacco smoke includes undifferentiated basal cells (hyperplasia), squamous metaplasia, and goblet cell metaplasia. In practice, many irritants produce responses between mild and severe, and various combinations of degeneration, inflammation, and proliferation may be observed. 

Note intestinal goblet cell metaplasia (arrows)... 

Figure 12-2 y-Secretase inhibitors that modulate Notch processing cause intestinal goblet cell metaplasia. (A) Duodenum from vehicle control and (B) goblet cell metaplasia (arrows) in duodenum after 3 days of 30 pmol/kg benzodiazepine. Adapted by permission from Oxford University... 

Milano J, McKay J, Dagenais C, et al. Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicol Sci. 2004 82(l) 341-358. 

It has been postulated that wood dust carcinoma results from a multistep process Exposure causes loss of cilia and hyperplasia of the goblet cells and initiation of cuboidal cell metaplasia, followed (after a quiescent period) by squamous cell metaplasia. Decades later, cellular aplasia leads to nasal adenocarcinoma. The time between first occupational exposure to wood dust and the development of nasal cavity adenocarcinoma averages 40 years. Other cancers, including lung cancer, Hodgkin disease, multiple myeloma, stomach cancer, and colorectal cancer and lymphosarcoma, have been mentioned in relation to wood... 

The intestinal mucosa shows a reduction in the number of goblet cells without keratinization. Alterations in intestinal epithelium and metaplasia of pancreatic ductal epithelium are common. They may be responsible for the diarrhea occasionally seen in vitamin A deficiency. 

In chronic studies, male and female rats and mice tolerated up to 2.5 ppm chlorine gas for 6 h/day, 5 days/week for 2 years (CUT, 1993 Wolf et al, 1995). Concentration-dependent lesions confined to the nasal passages were observed in all animals. These lesions were most severe in the anterior nasal cavity and included respiratory and olfactory epithelial degeneration, septal fenestration, mucosal inflammation, respiratory epithelial hyperplasia, squamous metaplasia and goblet cell hypertrophy and hyperplasia, and secretory metaplasia of the transitional epithelium of the lateral meatus. Body weight was depressed compared to controls but no early deaths occurred. A similar lack of lower respiratory tract effects was seen in monkeys exposed to 2.3 ppm chlorine for 6 h/day, 5 days/week, for 1 year (Klonne et al, 1987). At these concentrations, chlorine is effectively scrubbed in the anterior nasal passages as indicated by the absence of lesions in the lung. 

Epidermal keratinization and mucous membrane squamous metaplasia respond to both oral and topical vitamin A therapy. Vitamin A exists in three forms retinol, retinal, and retinoic acid.VitaminA increases the mucous production of goblet cells and perhaps the aqueous and lipid components of the tears as well. Tretinoin is a normal metabolite and the carboxylic form of retinol. Retinol is present in tears and the lacrimal gland appears to be its major provider. Retinoic acid has been shown to be effective in ocular surfece disorders such as squamous metaplasia by reversing the corneal and conjunctival keratinization and improving epithelium wound healing rate. 

M (in the nasal epithelium Monticello et al. 1989 loss of goblet cells cilia epithelial hyperplasia squamous metaplasia neutrophil inflammatory response erosion of the metaplastic epithelium increased cell proliferation in nasal transitional epithelium, nasal passage epithelium, trachea carina. 

Larynx/trachea/carina loss of cilia, goblet cells, mild epithelial hyperplasia, early squamous metaplasia.)... 

A chronic inhalation MRL of 0.008 ppm was derived based on a minimal LOAEL of 0.24 ppm for histological evidence of mild damage to the nasal epithelial tissue (squamous metaplasia, loss of ciliated cells, goblet cell hyperplasia, and mild dysplasia in biopsied tissue) in formaldehyde exposed chemical workers (Holmstrom et al. 1989c). To derive the MRL, the minimal LOAEL was divided by an uncertainty factor of 30 (3 for the use of a minimal LOAEL and 10 for human variability). 

A number of studies have shown the association of gastric adenocarcinogenesis with intestinal metaplasia. Metaplasia means transformation of a mature form of cells into another type of mature cells in response to certain stimuli. In this case, gastric mucosal cells are converted to intestinal mucosal cells, especially goblet cells and Paneth cells. Indeed, it is believed that approximately one-third of all gastric adenocarcinoma is associated with intestinal metaplasia. " " ... 

Mucosal changes in the large airways that may precede or accompany invasive squamous cell carcinoma include hyperplasia of basal and goblet cells, squamous metaplasia, squamous dysplasia and carcinoma in situ (Saccomanno et al. 1976). Gersing... 

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