Metaplasia
Encyclopedia
Metaplasia is the reversible replacement of one differentiated
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

 cell type
Cell type
A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...

 with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or 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
Dysplasia
Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...

 and is not directly considered carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...

ic. It is also contrasted with heteroplasia, which is the abnormal growth of cytologic and histologic elements without a stimulus.

Causes

When cells are faced with physiological or pathological stresses, they respond by adapting in any of several ways, one of which 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 pseudostratified columnar respiratory epithelial cells that line the airways to be replaced by stratified squamous epithelium, or a stone in the bile duct that causes the replacement of the secretory columnar epithelium with stratified squamous epithelium (Squamous metaplasia
Squamous metaplasia
Squamous metaplasia refers to benign changes in the epithelial linings of certain organs within the body. These cells assume a more squamous morphology. Common sites for squamous metaplasia include the bladder and cervix. Smokers often exhibit squamous metaplasia in the linings of their airways...

). 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.
Specialized 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 reprogram differentiation of cells rather than by transdifferentiation
Transdifferentiation
Transdifferentiation in biology takes place when a non-stem cell transforms into a different type of cell, or when an already differentiated stem cell creates cells outside its already established differentiation path...

.

Therapy

The medical significance of metaplasia is that in some sites cells may progress from metaplasia, to develop dysplasia, and then malignant neoplasia
Neoplasia
Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...

 (cancer). Thus, at sites where metaplasia is detected, efforts are made to remove the causative irritant, thereby decreasing the risk of progression to malignancy
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...

. 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
Barrett's esophagus
Barrett's esophagus refers to an abnormal change in the cells of the inferior portion of the esophagus. A positive diagnosis generally requires observing specific macroscopic and microscopic changes...

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

The following table lists some common tissues susceptible to metaplasia, and the stimuli that can cause the change:
Tissue Normal Metaplasia Stimulus
Airways Pseudostratified columnar epithelium Squamous epithelium Cigarette smoke
Urinary bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...

Transitional epithelium Squamous epithelium Bladder stone
Esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...

Squamous epithelium Columnar epithelium Gastro-esophageal reflux (Barrett's Esophagus)
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