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Biology of Disease

Cellular Adaptations to Cell Injury

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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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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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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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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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Hypertrophy

– 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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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.