Epithelial metaplasia is a reversible conversion of one mature epithelial cell type to another mature epithelial cell type. Metaplasia is generally an adaptive response to stress, chronic inflammation, or other abnormal stimuli. The original cells are substituted by cells that are better suited to the new environment and more resistant to the effects of abnor-mal stimuli. Metaplasia results from reprogramming of ep-ithelial stem cells that changes the patterns of their gene expression. The most common epithelial metaplasia is columnar-to-squamous and occurs in the glandular ep-ithelium, where the columnar cells become replaced by the stratified squamous epithelium. For example, squamous metaplasia frequently occurs in the pseudostratified respi-ratory epithelium of the trachea and bronchi in response to prolonged exposure to cigarette smoke. It also occurs in the cervical canal in women with chronic infections. In this exam-ple, simple columnar epithelium of the cervical canal is re-placed by the stratified squamous nonkeratinized epithelium (Fig F5.1.1). In addition, squamous metaplasia is noticeable in the urothelium (transitional epithelium) and is associated with chronic parasitic infections such as schistosomiasis. Squamous-to-columnar epithelial metaplasia may also occur. For example, as a result of gastroesophageal reflux (Barrett’s esophagus), the stratified squamous nonkeratinized epithelium of the lower part of the esopha-gus can undergo metaplastic transformation into an intestinal-like simple columnar epithelium containing gob-let cells. Metaplasia is usually a reversible phenomenon, and if the stimulus that caused metaplasia is removed, tissues re-turn to their normal pattern of differentiation. If abnormal stimuli persist for a long time, squamous metaplastic cells may transform into squamous cell carcinoma. Cancers of the lung, cervix, and bladder often originate from squamous metaplastic epithelium. Squamous columnar epithelium may give rise to glandular adenocarcinomas. When metaplasia is diagnosed, all efforts should be di-rected toward removing the pathogenic stimulus (i.e., ces-sation of smoking, eradication of infectious agents, etc.) and monitoring the metaplastic site to ensure that cancer-ous changes do not begin to develop. FIGURE F5.1.1 • Squamous metaplasia of the uterine cervix. Photomicrograph of a cervical canal lined by simple columnar epithelium. Note that the center of the image is occupied by an island containing squamous stratified epithelium. This metaplastic epithelium is surrounded on both sides by simple columnar epithelium. Since metaplasia is triggered by reprogramming of stem cells, metaplastic squamous cells have the same characteristics as normal stratified squamous epithelium. 240. (Courtesy of Dr. Fabiola Medeiros.)
The molecular mechanism responsible for establishing polarity in epithelial cells is required to first create a fully functional barrier between adjucent cells. Junctional complexes (which will be discussed later in this chapter) are being formed in the apical parts of the epithelial cells. These specialized attachment sites not only are responsible for tight cell adhesions but also allow epithelium to regulate paracellular movements of solutes down their electroosmotic gradients. In addition, junctional complexes separate the apical plasma membrane domain from basal and lateral domains and allow them to specialize and recognize different molecular signals.