This article discusses cellular effects of toxicity. However, cell and chemical effects can not be conveniently separated as cells are constructed of a variety of chemicals of diverse types. Specific intracellular chemical changes may be manifest as changes in the cell, either its appearance or function. Indeed, the actual mechanisms leading to cell damage are usually biochemical in nature.
- constantly adapt to changes in the tissue environment
- attempt to respond to external stimuli so as to cope with new demands placed on them
- are usually capable of an amazing degree of cellular adaptability
- adaptability may be beneficial in nature (physiological) or detrimental (pathological).
Examples of physiological adaptation are:
- an increase in skeletal muscle cells in athletes due to exercise and increased metabolic demand
- the increase in number and size of epithelial cells in breasts of women resulting from endocrine stimulation during pregnancy.
When these cells or tissues are damaged, the body attempts to adapt and repair or limit the harmful effects. Often the adaptive changes result in cells or organs that can not function normally. This imperfect adaptation is a pathological change.
Examples of pathological adaptations are:
- Change from ciliated columnar epithelium to non-ciliated squamous epithelium in the trachea and bronchi of cigarette smokers. The replacement of squamous epithelium can better withstand the irritation of the cigarette smoke. However, the loss of cilia and mucous secretions of columnar epithelium diminish the tracheo-bronchial defense mechanisms.
- Replacement of normal liver cells by fibrotic cells in chronic alcoholics (known as cirrhosis of the liver). A severely cirrhotic liver is incapable of normal metabolism, maintenance of nutrition, and detoxification of xenobiotics.
If the change is minor, cellular adaptation may result and healing with a return to normal. When damage is very severe, the result may be cell death or permanent functional incapacitation.
Cellular adaptation to toxic agents is of three basic types:
- Increase in cell activity
- Decrease in cell activity
- Alteration in cell morphology (structure and appearance) or cell function
Specific Types of Cellular Adaptations
- reduced oxygen needs
- reduced protein synthesis
- decrease in number and size of the organelles.
The most common causes of atrophy are: reduced use of the cells, lack of hormonal or nerve stimulation, decrease in nutrition, a reduced blood flow to the tissue, and natural aging. An example of atrophy is the decrease in size of muscles and muscle cells in persons whose legs are paralyzed, in a cast, or infrequently used (e.g., bed-ridden patients).
Hypertrophy is an increase in size of individual cells. This frequently results in an increase in the size of a tissue or organ. When cells hypertrophy, components of the cell increase in numbers with increased functional capacity to meeting increased cell needs. Hypertrophy generally occurs in situations where the organ or tissue can not adapt to an increased demand by formation of more cells. This is commonly seen in cardiac and skeletal muscle cells, which do not divide to form more cells. Common causes for hypertrophy are increased work or stress placed on an organ or hormonal stimulation. An example of hypertrophy is the compensatory increase in the size of cells in one kidney after the other kidney has been removed or is in a diseased state.
Hyperplasia is an increase in the number of cells in a tissue. This generally results in an enlargement of tissue mass and organ size. It occurs only in tissues capable of mitosis such as the epithelium of skin, intestine, and glands. Some cells do not divide and thus can not undergo hyperplasia, for example, nerve and muscle cells. Hyperplasia is often a compensatory measure to meet an increase in body demands. Hyperplasia is a frequent response to toxic agents and damage to tissues such as wounds or trauma. In wound healing, hyperplasia of connective tissue (e.g., fibroblasts and blood vessels) contributes to the wound repair. In many cases, when the toxic stress is removed, the tissue returns to normal. Hyperplasia may result from hormonal stimulation, for example, breast and uterine enlargement due to increased estrogen production during pregnancy.
Metaplasia is the conversion from one type of mature cell to another type of mature cell. It is a cellular replacement process. A metaplastic response often occurs with chronic irritation and inflammation. This results in a tissue more resistant to the external stress as the replacement cells are capable of survival under circumstances in which the original cell type could not survive. The cellular changes, however, usually result in a loss of function, which was performed by the original cells that were lost and replaced.
Examples of metaplasia are:
- The common condition in which a person suffers from chronic reflux of acid from the stomach into the esophagus (Gastroeosphageal Reflux Disease). The normal esophageal cells (squamous epithelium) are sensitive to the refluxed acid and die. They are replaced with the columnar cells of the stomach that are resistant to the stomach's acidity. This pathological condition is known as "Barrett's syndrome".
- The change in the cells of the trachea and bronchi of chronic cigarette smokers from ciliated columnar epithelium to non-ciliated stratified squamous epithelium. The sites of metaplasia frequently are also sites for neoplastic transformations. The replacement cells lack the defense mechanism performed by the cilia in movement of particles up and out of the trachea.
- With cirrhosis of the liver, which is a common condition of chronic alcoholics, the normal functional hepatic cells are replaced by nonfunctional fibrous tissue.
Dysplasia is a condition of abnormal cell changes or deranged cell growth in which the cells are structurally changed in size, shape, and appearance from the original cell type. Cellular organelles also become abnormal. A common feature of dysplastic cells is that the nuclei are larger than normal and the dysplastic cells have a mitotic rate higher than the predecessor normal cells. Causes of dysplasia include chronic irritation and infection. In many cases, the dysplasia can be reversed if the stress is removed and normal cells return. In other cases, dysplasia may be permanent or represent a precancerous change. An example of dysplasia is the atypical cervical cells that precede cervical cancer. Routine examination of cervical cells is a routine screening test for dysplasia and possible early stage cervical cancer (Papanicolaou test). Cancer occurs at the site of Barrett's syndrome and in the bronchi of chronic smokers (bronchogenic squamous cell carcinoma).
Anaplasia refers to cells that are undifferentiated. They have irregular nuclei and cell structure with numerous mitotic figures. Anaplasia is frequently associated with malignancies and serves as one criterion for grading the aggressiveness of a cancer. For example, an anaplastic carcinoma is one in which the cell appearance has changed from the highly-differentiated cell of origin to a cell type lacking the normal characteristics of the original cell. In general, anaplastic cells have lost the normal cellular controls, which regulate division and differentiation.
Neoplasia is basically a new growth of tissue and is commonly referred to as a tumor. There are two types of neoplasia, benign and malignant. Malignant neoplasias are cancers. Since cancer is such an important and complex medical problem, a separate section is devoted to cancer.
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