Cellular Adaptations to Cell Injury Biology of Disease Cellular Adaptations to Cell Injury RHY/CH0576

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 RHY/CH0576

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. RHY/CH0576

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 RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576

Mechanisms of Hypertrophy It is mainly seen in response to an increased functional demand made on tissues made up of non-dividing cells. RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576

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 RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576

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 RHY/CH0576

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! RHY/CH0576

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. RHY/CH0576

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 RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576

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. RHY/CH0576