Metaplasia

Overview
Metaplasia (Greek: "change in form") is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another is generally caused by some sort of abnormal stimulus. In simplistic terms, it is as if the original cells are not robust enough to withstand the new environment, and so they change into another type more suited to the new environment. If the stimulus that caused metaplasia is removed or ceases, tissues return to their normal pattern of differentiation. Metaplasia is not synonymous with dysplasia and is not considered carcinogenesis. It is also contrasted with heteroplasia, which is the abnormal growth of cytologic and histologic elements without a stimulus.

Heteroplasia and dysplasia are synonyms.

Causes
When cells are faced with physiological or pathological stresses, they respond by adapting in several ways; one of these cellular adaptations is metaplasia. It is a benign (i.e. non-cancerous) change that occurs as a response to chronic physical or chemical irritation, such as cigarette smoke that causes the mucus-secreting ciliated simple columnar respiratory epithelial cells that line the airways to be replaced by simple squamous epithelium, or a stone in the bile duct that causes the replacement of the secretory columnar epithelium with simple squamous epithelium (Squamous metaplasia). Although metaplasia is an adaptation that replaces delicate cells with hardier ones that are more likely to be able to withstand the stresses that the epithelium is faced with, it is also accompanied by a loss of epithelial function, and is considered undesirable; this undesirability is underscored by the propensity for metaplastic regions to eventually turn cancerous if the irritant is not eliminated. Specialised epithelial cells are already differentiated, and cannot simply transform their morphologies to change from one cell type to another. Metaplasia, then, does not occur as a result of any change in the pre-existing epithelial cells but rather as a result of reprogrammed stem cells present in the organ's connective tissue that are nudged along a different pathway of differentiation by cytokines, growth factors and other substances in the cell's environment. In a nutshell, metaplasia occurs by stem cells that reprogramme differentiation of cells rather than by transdifferentiation.

Therapy
The medical significance of metaplasia is that in some sites cells may progress from metaplasia, to develop dysplasia, and then malignant neoplasia (cancer). Thus, at sites where metaplasia is detected, efforts are made to remove the causative irritant, thereby decreasing the risk of progression to malignancy. The metaplastic area must be carefully monitored to ensure that dysplastic change does not begin to occur. A progression to significant dysplasia indicates that the area could need removal to prevent the development of cancer.

Examples
Barrett's esophagus is an abnormal change in the cells of the lower esophagus, thought to be caused by damage from chronic stomach acid exposure.

Metaplasia of the cervix, which occurs in cervical erosion, can be detected by a cervical smear test. The normal endocervical columnar epithelium is replaced by a squamous epithelium in an area termed the transformation zone. This is a normal physiological event that takes place around puberty. The stimulus is believed to be a change in the vaginal environment, which becomes acidic.

The following table lists some common tissues susceptible to metaplasia, and the stimuli that can cause the change: