Cellular adaptations refer to the changes made by cells in response to various stimuli or changes in their local environment. This can involve changing the number of cells or their morphological appearance. It can be physiological, where it occurs in normal tissues or organs, or pathological, i.e. occurring in disease states.
In this article, we will consider how the sizes of cell populations are controlled, how cells and tissues can adapt in response to stressors and how these processes can result in disease.
Control of cell populations
The size of cell populations depends on the rate of 3 factors:
- Cell proliferation
- Cell differentiation
- Cell death by apoptosis
Increased cell numbers are therefore seen with either increased cell proliferation or decreased cell death.
Cell proliferation occurs both in both physiological and pathological conditions. Physiological cell proliferation is primarily regulated by chemical signals which either promote or inhibit proliferation. Signalling may be via hormones, local mediators such as growth factors or direct cell to cell contact. If cell proliferation becomes uncontrolled, and cells no longer respond to inhibitory signals, cancer can develop.
Growth factors act on cell surface receptors, stimulating transcription of genes that regulate the cell cycle. Examples of growth factors include epidermal growth factor, vascular endothelial growth factor and platelet-derived growth factor.
Ultimately, cell signalling results in one of four outcomes:
- Cell survival, i.e. resistance of apoptosis
- Cell division – cell enters the cell cycle
- Cell differentiation – cell takes on specialised form and function
- Cell death via apoptosis
Stem cells are immature cells that can go on to differentiate into various specialised, mature cell types within a certain lineage. They are key to determining a tissue’s ability to replenish lost cells, as they are able to self-renew indefinitely. Thus where stem cells are present, new cells can be formed in response to disease, environmental stressors or normal replenishment of cells at the end of their lifespan.
Tissues can be classified into 3 types depending on the ability to self-repair, which depends on their stem cell activity:
|Tissue type||Stem cell activity||Examples|
|Labile||Stem cells divide repeatedly to replenish losses||· Surface epithelia, e.g. gut mucosa
· Bone marrow (haematopoietic cells)
|Stable||Stem cells proliferate very slowly or lie dormant, but can rapidly proliferate when required||· Hepatocytes
|Permanent||Stem cells are present but cannot proliferate effectively to replenish lost cells||· Neurons
· Cardiac and skeletal muscle
When cells experience environmental stressors or other stimuli, they undergo adaptations to allow them to function better and survive in this new environment. These adaptations can usually be reversed if the stressor is removed. However, if the stimulus continues these adaptations may be inadequate and the cell may become permanently injured or die.
Regeneration is the replacement of cell losses by identical cells to maintain tissue or organ size. Usually, regenerated cells are functionally identical to the cells they replace, however some cells take time to reach functional maturity.
When a tissue is exposed to a harmful agent, it undergoes some tissue damage. If the harmful agent is removed, damage is limited and regeneration can occur, resulting in full resolution of the damage. However, if the agent persists, extensive tissue damage occurs, often resulting in permanent damage and the formation of scar tissue instead of the regeneration of functional tissue.
Different tissues have different regeneration capacities. Epithelial cells and liver cells are very good at regeneration, whereas tendons have a poor ability to regenerate due to their poor blood supply, hence injury is very slow to heal. Neurones have no ability to regenerate at all, however, there is sometimes neuronal plasticity, whereby new neuronal pathways are formed to allowing the regaining of some function.
Hyperplasia is an increase in the tissue or organ size due to increased cell number, without an increase in cell size. It can only occur in labile or stable cell populations. The cell proliferation in hyperplasia remains under physiological control and is reversible, unlike in neoplasia (cancer) which is irreversible.
Hyperplasia may occur secondary to a pathological process, but the proliferation itself is not abnormal, only the trigger. However, repeated cell division raises the risk of mutations and hence neoplasia may follow after long-term hyperplasia.
Examples of hyperplasia include:
- Endometrial proliferation under the influence of oestrogen during the menstrual cycle
- Thyroid goitre in response to iodine deficiency
- Epidermal thickening in eczema
Hypertrophy is an increase in the tissue or organ size due to an increase in cell size, without an increase in cell number. Hypertrophy usually occurs where there is increased functional demand on a tissue, or where there is hormonal stimulation.
Hypertrophy is especially prevalent in permanent cell populations such as skeletal muscle, as these cells cannot divide to increase their cell number; the only way of increasing the size of the tissue is to increase the size of each constituent cell. In cell populations where division can occur, hypertrophy may occur alongside hyperplasia to increase both the number and size of the cells.
Examples of hypertrophy include:
- Right ventricular hypertrophy in response to pulmonary hypertension
- Compensatory hypertrophy in paired organs such as the kidneys, where one organ is removed or dysfunctional and the other hypertrophies to increase its functional ability
- Expansion of the pregnant uterus (combination of hypertrophy and hyperplasia)
Atrophy is the shrinkage of a tissue or organ due to a decrease in size and/or number of cells. It can occur physiologically, for example when the uterus decreases in size after birth following the cessation of production of hormones which stimulated its growth, or pathologically, for example atrophy of an organ due to inadequate blood or nutritional supply.
Examples of pathological atrophy include:
- Atrophy of disuse, where decreased functional demand leads to muscle atrophy. This is normally reversible with activity.
- Denervation atrophy where loss of innervation leads to muscle atrophy, for example, wasting of the thenar muscles of the hand in carpal tunnel syndrome.
- Atrophy of an endocrine organ due to loss of hormonal stimuli
Metaplasia is the reversible change of one differentiated cell type to another. It usually occurs in epithelial tissues as an adaptive response to cell stress; cells can be substituted by those types better suited to the environment. This occurs via altered stem cell differentiation and thus metaplasia can only occur in labile or stable tissues.
Metaplastic cells are fully differentiated, unlike dysplastic epithelium which is abnormally differentiated. However, metaplastic tissue can go on to become dysplastic and even cancerous, although the exact mechanisms leading to this are unclear.
Examples of metaplasia include:
- Bronchial pseudostratified ciliated epithelium becoming stratified squamous epithelium in response to cigarette smoke.
- Stratified squamous epithelium in the oesophagus becoming gastric epithelium when exposed to persistent acid reflux (Barrett’s oesophagus)
Clinical Relevance – Dysplasia
Dysplasia is the formation of abnormally differentiated cells within a tissue. Initially this change is reversible, but as the dysplasia becomes more severe, reversal becomes less likely and there is a greater chance of progression to neoplasia and cancer.
A common clinical example of dysplasia occurs in the cervix, in which abnormal cells appear in the cervix or endocervical canal. It is primarily caused by human papillomavirus (HPV) infection and can be detected via cervical smear test. Cervical dysplasia is usually highly treatable, but severe dysplasia indicates high risk of transformation to cervical cancer.