1. Cellular Adaptations to Cell Injury
Biology of Disease
Cellular Adaptations to Cell Injury
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2. Atrophy A decrease in the size and function of a cell.
Most often seen clinically as a reduction in the size and differentiated function of an organ.
Atrophy can occur in a range of conditions:
A reduced functional demand
Inadequate supply of oxygen
Insufficient nutrients
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3. Atrophy II
Interruption to trophic signals
Persistent cell injury/stress
Ageing.
Atrophy is an adaptive response to reversible cell injury .If the injuring agent or assault is removed the atrophic cells and tissues revert back to normal, both in terms of size and function.
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4. Hypertrophy
An increase in the size of a cell, along with an augmented functional capacity
Unlike hydropic swelling, there is not merely an increased water content of the cell.
Hypertrophy is generally a response to trophic signals or an increased functional demand, often physiological
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5. Hypertrophy Examples of hypertrophy:
Physiological (hormonal) hypertrophy: A normal response to physiological levels of circulating hormones e.g. puberty & lactation.
Pathological (hormonal) hypertrophy: It can often be the result of abnormal (non-physiological) levels of circulating hormones.
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6. Hypertrophy Increased functional demand:
E.g. Exogenous anabolic steroids
Thyroid goitre seen in nutritional iodine deficiency
Abnormal hormone production from tumours
Increased functional demand:
Muscular exercise
Liver detoxification of drugs.
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7. Cellular Mechanisms of Hypertrophy
The cell enlargement seen is brought about by an increased synthesis of structural components.
It is associated with an accelerated cellular metabolism and a rise in levels of RNA and organelles associated with protein synthesis.
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8. Mechanisms of Hypertrophy
It is mainly seen in response to an increased functional demand made on tissues made up of non-dividing cells.
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9. Hyperplasia
An increase in the number of cells which comprise a tissue or organ.
Hyperplasia and hypertrophy are often seen together, producing a tissue with an increased size and augmented function.
The two cellular adaptations are not mutually exclusive.
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10. Hyperplasia Hyperplasia can result from a range of stimuli:-
Hormonal stimulation (trophic signals)
Physiological
Pathological
Increased functional demand
EPO at altitude, chronic blood loss, immunity.
Persistent cell injury/stress
Corns & calluses, chronic cystitis.
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11. Hyperplasia
Hyperplastic response is not always uniformly seen within a tissue:
So called ‘nodular hyperplasia’ may be seen.
This nodular form of adaptive response is most often seen in tissues in which the cells are responding to a specific trophic signal.
E.g. thyroid, prostate or breast tissue.
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12. Hyperplasia/Hypertrophy
Both of these adaptive mechanisms are REVERSIBLE.
By definition, following the removal of the stimulus of the response, the tissue reverts completely back to normal, both in terms of its size and its functional capacity.
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13. Metaplasia The conversion of one differentiated cell type to another
Most often seen as the replacement of a glandular epithelium with a much simpler,less differentiated, squamous epithelium.
It is almost invariably a response to a persistent cell injury/stress
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14. Metaplasia
Cells adapt to a change in their environment by differentiating to a new mature stable cell type, better equipped to cope with and withstand the harsh environmental stress imposed upon it.
It is very often concomitant with hyperplasia.
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15. Metaplasia
Although essentially a protective mechanism, metaplasia is not always harmless:
squamous metaplasia can impair bronchial function, increasing the likelihood of infection.
Neoplastic transformation can occur in metaplastic epithelium.
Metaplasia is fully reversible.
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16. Triggering Mechanisms
The mechanisms which trigger the adaptive responses of hypertrophy, hyperplasia and metaplasia are not clearly understood.
Growth factors are involved
Alterations in either:
Local concentrations of growth factors
Increased expression of receptors will result in altered cellular growth patterns
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17. Triggering Mechanisms
Growth Factors
EGF family
CSF
Interferons
PDGF
FGF
TGF
Interleukins
EPO
NGF
CNGF
Many of these are manufactured by recombinant gene technology and used as therapeutic agents.
Possibly severe side effects!
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18. Dysplasia
Cellular dysplasia refers to an alteration in the size, shape and general organisation of the cells within a tissue.
There are variations in the size and shape of cells within an epithelium.
Nuclei may be enlarged, irregular and also hyperchromatic.
Generally disorderly organisation of the cells within the tissue.
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19. Dysplasia
Dysplasia most often occurs in areas of squamous metaplasia or in areas of hyperplastic squamous epithelium.
The dysplastic cell is generally less differentiated than its metaplastic or hyperplastic neighbours.
It is likely to be more resistant to injury
It has found ways to survive in a hostile environment
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20. Dysplasia
It should be stressed that dysplasia is fully reversible as long as there is prompt removal of injuring agent!
Dysplasia shares many cytological features with cancer, there is hence a very fine line between the two!
Difficult for the pathologist to discriminate between severe dysplasia and neoplasia.
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21. Dysplasia Dysplasia should be considered as a pre-neoplastic lesion.
Severe dysplasia is considered as an indication for rapid and aggressive therapies.
This adaptation should still be seen as a protective adaptation, enhancing and prolonging the survival of the cell.
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22. Key Facts on Adaptations
Cells are adaptable within physiological limits.
Cells can respond to injury by producing cell stress proteins, which help protect against injury, and allow the cell time to adapt.
Increased demands upon a cell are met by hypertrophy and hyperplasia.
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23. Key Facts on Adaptations
Decreased demands upon a cell are met by atrophy.
Tissues can adapt to persistent injury by a change in differentiation, known as metaplasia.
Further prolonged exposure to a damaging agent may result in dysplasia.
A fine line exists between dysplasia and neoplasia.
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