Next Lesson - Introduction to Neoplasia
Core
In response to physiological and pathological stimuli, cells can undergo changes which make them more suited for their environment. Chemical mediators (signalling molecules, such as hormones) are able to signal cells to undertake a number of actions. These chemicals can prompt apoptosis, cell division and cell differentiation, or resist apoptosis.
Hypertrophy is the increase in the size of a tissue via the enlargement of cells. The intracellular organelles, cytoplasm and structural proteins all increase in these enlarged cells, but the number of cells in the tissue remains the same.
Hypertrophy can occur both physiologically and pathologically. A common cause of physiological hypertrophy is increased skeletal muscle mass gained through anabolic metabolism (building up proteins and tissue) following exercise. Smooth muscle hypertrophy occurs in the uterus during pregnancy (after an early phase of hyperplasia), stimulated by hormonal changes.
In hypertension there is often pathological hypertrophy of the cardiac tissue, due to the increased strain on the heart, mainly the left ventricle, which has to pump against a higher pressure. Excessive cardiac hypertrophy makes the muscular walls of the heart too thick. This can impair pumping and contribute to heart failure, especially if the underlying cause is not treated.
Hyperplasia is the increase in the size of a tissue by an increase in the number of cells in that tissue.
Physiological hyperplasia occurs in the endometrium (the lining) of the uterus upon stimulation by oestrogen during the menstrual cycle. Hyperplasia is also the method by which the liver restores itself from a partial resection (surgical removal of part of the liver).
Pathological hyperplasia can occur in overstimulation of endometrial tissue with oestrogen, for example in women who still have a uterus and take oestrogen on its own (unopposed, without a progestogen) as hormone replacement therapy after the menopause. This is why women with a uterus are given a progestogen (a progesterone-like drug) alongside the oestrogen. The increased cell replication increases the chance of dysplasia (abnormal, disordered growth, discussed later) and then of neoplasia (the formation of a tumour).
Diagram - The differences between hyperplasia and hypertrophy
Creative commons source by SchwarzeMelancholie [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Atrophy is the opposite of hyperplasia and hypertrophy: in essence, it is the shrinkage of tissue. This can happen by a decrease in cell number and/or cell size.
Atrophy occurs physiologically in involution, when a tissue reduces in size after having increased in size. For example, the uterus and breasts both reduce in size post-pregnancy. Atrophy will also occur with old age. When an individual gets older, most systems and tissues undergo some level of atrophy.
Pathological atrophy can happen through catabolic metabolism (the breakdown of body tissue for energy) due to malnutrition, whether this be caused by diseases such as cancer or by nutritional deficit. It can also occur due to inactivity, pressure, ischaemia, and chronic inflammation.
Diagram - The difference between normal and atrophied muscle
Creative commons source by OpenStax [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Metaplasia is the transformation of tissue in which one differentiated (specialised) cell type is replaced by another. This happens through changes in the differentiation of stem cells or progenitor cells (immature cells that can develop into specialised cells). An example is the replacement of columnar epithelium (tall, column-shaped cells) by stratified squamous epithelium (flat cells in many layers).
An example of a common and usually benign adaptive metaplasia is the squamous metaplasia that occurs in the cervix (the neck of the womb). When the cervix everts (turns outwards), the columnar epithelium that lines it meets the acidic environment of the vagina. The epithelium undergoes metaplasia to become stratified squamous epithelium like the rest of the vagina as this is better suited to the conditions. The area where this metaplasia happens is called the transformation zone.
Pathological metaplasia is a common response to chronic stimulation from chemical or physical factors. Metaplastic change can be associated with an increased risk of malignancy (for example in Barrett’s oesophagus, described below), however metaplasia itself is not cancer. Some metaplastic changes may regress to their original type if the stimulus is removed, while others may persist and increase the risk of malignant transformation.
Some common examples of pathological metaplasia are:
- Transformation of the pseudostratified columnar epithelium (one layer of cells that looks layered) of the bronchi to stratified squamous epithelium in smokers due to cigarette smoke.
- Squamous metaplasia of the bladder due to infection or urinary calculi (stones).
- Stratified squamous epithelium at the bottom of the oesophagus transforms to intestinal-type columnar epithelium with persistent acid reflux. This is called Barrett’s oesophagus.
Dysplasia is disordered growth of epithelium characterised by frequent mitotic figures (cells seen part-way through dividing, under the microscope) and loss of cell orientation and uniformity (size, shape). Dysplasia can progress to carcinoma in situ (abnormal cells that look like cancer cells under the microscope but are found only in the place where they first formed). Some of these go on to become invasive cancer, which spreads into nearby tissue. The key difference between dysplasia and neoplasia (the formation of a tumour, which can be benign or malignant) is that dysplasia can be reversible if the stimulus is removed, while neoplasia is not.
Persistent infection with high-risk types of the human papillomavirus (HPV) can cause dysplasia of the cervix in the transformation zone. During cervical screening, the sample is first tested for high-risk types of HPV. Only if high-risk HPV is found are the cells then examined under the microscope (cytology) for changes that suggest dysplasia, because persistent dysplasia can progress to cervical cancer.
Diagram - Non-neoplastic cell changes
Creative commons source by DennisHansen [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Anaplasia
Anaplasia refers to a lack of cellular differentiation seen in malignant tumours, where cells show marked atypia (abnormal, irregular-looking cells) and loss of normal structural features. It reflects malignant transformation rather than a normal stage of tissue adaptation. For more information on the cellular changes associated with malignancy, see the Introduction to Neoplasia article.
Proliferation is an increase in the number of cells in a tissue due to replication (cell division). There are several tissue types that have different rates of proliferation, and this decides how well each can repair itself after injury:
- Labile
- These cells are short lived, and can easily be replaced by replication and maturation of stem cells
- This means these tissues have a high reproductive capacity
- For example, epithelial cells (such as those in the gastrointestinal tract)
- Stable
- These cells normally have a slow rate of cell replication
- However, they can divide rapidly when required
- Hepatocytes and renal tubular cells are examples of stable cells
- Permanent
- These cells are unable to undergo effective replication
- Only a few stem cells are present
- Neurones are an example of permanent cells
Edited by: Dr. Bethany Turner and Dr. Marcus Judge
Reviewed by: Dr. Thomas Burnell
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