METAPLASIA 

Metaplasia is a cellular adaptation that involves the replacement of one differentiated cell type with another that has the same embryonic origin. This replacement occurs because the goal is to change the histotype to better overcome and resist an environmental stress. 

The pulmonary epithelium is a cylindrical ciliated epithelium and if for a long time it is subjected to a stress (for example a chemical stress represented by cigarette smoke) it will undergo a metaplasia: the normal cylindrical ciliated epithelium will be replaced with one more resistant to stress (for example a keratinized epithelium = squamous epithelium). Thus, a more resistant epithelium is obtained but at the same time a loss of function because the ciliated epithelium, in that district, has the function of removing impurities through the cilia.

This adaptation can involve epithelial cells, therefore epithelial metaplasia or mesenchymal cells, mesenchymal metaplasia. In order for this replacement to occur there must be changes in the expression of genes typical of that differentiation. At the base there will be a phenotypic change that has a change at the gene level. 

Metaplasia, as an adaptation, represents a condition that predisposes to the onset of malignancy. Very often on what starts as metaplasia is superimposed a neoplasm. 

Examples of epithelial metaplasia:

• transition from columnar to squamous epithelium in respiratory epithelium that is exposed to chronic irritation
• transition from columnar to squamous epithelium in epithelia of the secretory ducts of the glands as a result of calculosis phenomena. In this case the stressful event is mechanical, not chemical
• "Reverse" metaplasia: a squamous epithelium is replaced by columnar epithelium. This condition occurs in Barret's esophagus as a result of gastric reflux. 
• from transitional epithelium (which we find at the level of the bladder) to squamous epithelium: this transition is caused by the presence of stones at the bladder level and will cause a loss of function as the transitional epithelium is able to modulate its thickness while the squamous one does not.

Mesenchymal metaplasia: there is the formation of a tissue in a district where it is not normally present. We are therefore talking about cartilage, bone and adipose tissue. If a tissue is formed in a site other than normal we will speak of tissue formation in ectopic site: 

• myositis ossificans following intramuscular hemorrhage: formation of bone tissue at the level of a muscle in which a hemorrhage has formed 
• deposition of bone tissue within a scar tissue (scar) in which there is normally connective tissue 
• deposition of bone tissue at the level of atherosclerotic plaques. This deposition will lead to serious consequences in the atherosclerotic phenomenon. 

ORAL LEUKOPLAKIA. In this metaplasia, white plaques form at the level of the oral cavity. (Many oral pathologies will result in white plaques).

Adaptations can be reversible but, in the case of metaplasia, very often this results in a precancerous situation. So potentially, even metaplasia, is reversible unless the transition to a neoplastic condition has already occurred.

DIFFERENCE BETWEEN NEOPLASIA AND METAPLASIA

In neoplasms, cells have alterations at the gene level. These have a different genotype from normal cells that also causes a phenotypic change. 

In metaplasia by replacing the cells there is no mutation at the gene level, only the epithelium varies but remains "normal". Therefore the type of differentiation changes: epithelia tend to renew themselves and if there is an abnormal stimulus, when the cells are replaced, a different epithelium is formed, always consisting of "normal" cells, there are no abnormalities.

CELL DAMAGE 

The capacity of a cell is not unlimited and if it is not able to adapt it will undergo cellular damage. In cellular damage all alterations that affect tissues, organs and our organism in general can be involved. If we adapt the concept of homeostatic condition to each cell we can say that this condition depends on the genetic program of the cell itself, that is it will be conditioned by the function that it performs. A cell of skeletal muscle tissue will need optimal conditions to function that will be different than those of a hepatocyte. Therefore the homeostatic condition of a cell depends on its type of differentiation. It is known that, especially for normal cells, the homeostatic condition of a cell depends on contacts with neighboring cells: normal cells that are part of a tissue do not live alone but in a "condominium" of cells and therefore the homeostatic condition of each depends on contacts with neighboring cells. A cell will be able to live a homeostatic condition even if it has an adequate presence of metabolic substrates and therefore receives a correct amount of nutrients and oxygen. If the cell is in a particularly stressful condition or different from normal it responds adapting itself but if it can't adapt completely it will face a cellular damage that can be of two types:

• REVERSIBLE: if the cell can return to homeostatic conditions 
• IRREVERSIBLE: the cell can no longer return to its original condition and is destined to die

If the exposure to a damaging agent persists over time it causes irreversible damage and the cell can go from a situation of reversible damage to one of irreversible damage that culminates in death. When the cell passes from reversible to irreversible damage, it exceeds the point of no return. This is not a philosophical concept but, in the cell, corresponds to certain changes of biochemical, functional and morphological nature. Therefore, the crossing of the point of no return implies further changes than those that occurred in the reversible damage. If you go along this road from left to right,you will observe an increasing impairment at the level of the cell's functionality, structure and shape.

The effects, which the exposure to the harmful stimulus determines, are correlated with: 

• duration of the harmful stimulus
• intensity of the damaging stimulus
• cell type: a cell in a condition of hypoxia (lack of oxygen) can be damaged, but the severity of this damage will also be related to the cell type. In fact, there are cell types that are much more sensitive to oxygen deficiency (e.g. cardiomyocytes or SN cells). At the same time, this depends on the ability of the cell to adapt, in particular, to chemical injury agents. The effect depends on the ability of the cell to decode chemicals (e.g. cytochromeP 450)
• type of damage: if the damaging agent alters the mitochondrial respiration chain or selectively inhibits a certain enzyme that the cell uses once in a while, different situations occur. The first damaging agent will have a greater effect because it will compromise one of the main functions performed by the cell (ATP production) while the second will act on a "secondary" situation. 

Therefore the exposure to a lesive agent determines a damage that is a function of these aspects.