Cells adapt to injury primarily through four main mechanisms: atrophy, hypertrophy, hyperplasia, and metaplasia. These adaptations represent the cell's attempt to maintain viability and function in the face of stress.
Atrophy: Decreased Cell Size
Atrophy involves a reduction in cell size and function. This is essentially the cell shrinking to conserve resources.
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Causes:
- Decreased workload (e.g., immobilization of a limb)
- Loss of innervation
- Diminished blood supply (ischemia)
- Inadequate nutrition
- Loss of endocrine stimulation
- Aging (senile atrophy)
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Mechanism: Atrophy occurs through a combination of decreased protein synthesis and increased protein degradation. The ubiquitin-proteasome pathway plays a crucial role in protein breakdown. Autophagy, a process where the cell digests its own components, also contributes to atrophy.
Hypertrophy: Increased Cell Size
Hypertrophy represents an increase in cell size, leading to an increase in the size of the organ. This often occurs in response to increased functional demand.
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Causes:
- Increased workload (e.g., weightlifting causing muscle growth)
- Hormonal stimulation (e.g., estrogen causing uterine enlargement during pregnancy)
- Growth factors
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Mechanism: Hypertrophy involves increased synthesis of structural proteins and organelles. The cellular signaling pathways involved include:
- Mechanical sensors (detect stretch)
- Growth factors (e.g., TGF-β, IGF-1)
- Vasoactive agents (e.g., α-adrenergic agonists, endothelin-1)
Hyperplasia: Increased Cell Number
Hyperplasia involves an increase in the number of cells in an organ or tissue, resulting in increased volume. This is distinct from hypertrophy, which involves an increase in cell size.
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Causes:
- Hormonal stimulation (e.g., proliferation of the glandular epithelium of the breast at puberty and during pregnancy)
- Compensatory mechanisms (e.g., liver regeneration after partial hepatectomy)
- Chronic irritation
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Mechanism: Hyperplasia can only occur if the tissue contains cells capable of dividing. It is often triggered by growth factors produced by mature cells. Hyperplasia can be physiological (hormonal or compensatory) or pathological (often due to excessive hormonal stimulation or growth factors).
Metaplasia: Replacement of One Cell Type with Another
Metaplasia is the reversible change of one differentiated cell type to another mature differentiated cell type. It usually occurs as an adaptive response to chronic irritation or inflammation, allowing cells to better withstand the altered environment.
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Causes:
- Chronic irritation (e.g., squamous metaplasia of the respiratory epithelium in smokers)
- Vitamin A deficiency
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Mechanism: Metaplasia is thought to result from the reprogramming of stem cells to differentiate along a new pathway. It does not result from the transdifferentiation of already differentiated cells. For example, in the respiratory tract, columnar epithelial cells are replaced by stratified squamous epithelial cells, which are more resistant to chronic irritation. However, this metaplastic change can predispose to dysplasia and cancer if the stimulus persists.
In summary, cell adaptation to injury occurs through mechanisms aimed at preserving cell viability. However, these adaptive responses, while initially protective, can have consequences and may predispose to disease if the underlying stressor persists.
