Disorders of Cell Growth, Differentiation, and Maturation Flashcards
How does cell injury occur?
Cell injury occurs when cells are stressed so severely that they are no longer able to adapt – or when cells are exposed to inherently damaging agents
What are the possible causes of cell injury?
- Hypoxia
- Immunological
- Infection by micro-organisms
- Genetic
- Thermal injury
- Physical
- Chemical
- Aging
Give examples of immunological causes of cell injury
Thyroid damage caused by autoantibodies
Antibodies produced by the body against its own tissues
Give examples of genetic causes of cell injury
Duchenne muscular dystrophy
Sickle cell disease
Give examples of physical causes of cell injury
Ionising radiation (sunburn due to UV light damage to the skin), trauma, heat, cold
Give an example of a chemical caused cell injury
Acid damage to oesophageal mucosa
Give an example of age induced cell injury
Cellular senescence leads to alterations in replication and repair abilities of the cell
Define hyperplasia
An increase in the number of cells in an organ or tissue, usually resulting in increased volume
What causes hyperplasia?
Increased workload
Hormonal stimulation
Decreased tissue
Give examples of physiologic hyperplasia
Hormonal - increases functional capacity (e.g. the estrogen-dependent uterine cells undergo hyperplasia and hypertrophy following pregnancy)
Compensatory - increases tissue mass after damage or resection (e.g. liver regeneration)
What causes pathologic hyperplasia?
Most are caused by excessive hormonal stimulation or growth factors acting on cells
Give examples of pathologic hyperplasia
Endometrial hyperplasia
Benign prostatic hyperplasia
Is hyperplasia irreversible?
Hyperplasia will regress if the hormonal stimulation is eliminated, however will result in an increased risk of cancer
Define hypertrophy
Increase in cell size, resulting in an increase in the size of the organ.
The increase in cell size is not due to cellular swelling, but to the synthesis of more structural components (e.g. proteins and organelles)
Why does hypertrophy occur in nondividing cells?
In nondividing cells, (e.g. myocardial fibres) hypertrophy may be the response to stress
Which organs have an increased susceptibility to hypertrophy?
Heart
Kidneys
What causes hypertrophy?
Hypertrophy may be caused by mechanical signals (e.g., stretch) or trophic signals (e.g., growth factors).
Give an example of physiologic hypertrophy
An example of physiologic hypertrophy is in skeletal muscle with sustained weight bearing exercise
Give an example of pathologic hypertrophy
An example of pathologic hypertrophy is in cardiac muscle as a result of hypertension.
Define atrophy
Shrinkage in cell size by the loss of cell substance.
It is a form of adaptive response and may culminate in cell death
Is atrophy reversible?
Yes
What causes atrophy?
Disease Insufficient blood flow Malnutrition Denervation Reduced endocrine stimulation Aging Pressure
When does a tissue or organ become atrophic?
When sufficient numbers of cells are involved
Give an example of physiologic atrophy
Physiologic atrophy is common during early development
The uterus decreases in size shortly after partruition
Give examples of pathologic atrophy
Pathologic atrophy depends on the underlying cause:
Decrease in workload
- atrophy of disuse (e.g. broken limb in a plaster cast)
Loss of innervation
- damage to the nerves leads to rapid atrophy of the muscle fibres supplied by those nerves
Diminished blood supply
- e.g. as result of arterial occlusive disease due to progressive cell loss
Malnutrition
- Profound protein/calorie malnutrition is associated with the use of skeletal muscle as a source of energy after other reserves (adipose tissue) have been depleted (e.g. marked muscle wasting)
Loss of endocrine function
- many endocrine glands are dependant on endocrine stimulation for normal metabolism and function
Aging
- process associated with cell loss, typically seen in tissues containing permanent cells, particularly the brain and heart
Pressure
- tissue compression for any length of time can cause atrophy
Are the cell changes associated with atrophy different in different cells?
No, the fundamental cellular changes associated with atrophy are identical in all cells, regardless of the cause of atrophy - representing a retreat to a smaller cell size at which survival is still possible
What are the different acquired disorders of cell growth and differentiation?
Metaplasia
Dysplasia
Neoplasia
Define metaplasia
Metaplasia is a reversible change in which one adult cell type is replaced by another adult cell type
It may represent an adaptive substitution of cells that are sensitive to stress, to cell types that are better able to withstand the adverse environment
Give examples of causes of metaplasia
Stones in the excretory ducts of the salivary glands, pancreas or bile ducts
Chronic inflammation
Nutritional defeiciency
What is the most common epithelial metaplasia?
Columnar to squamous
It occurs in the respiratory tract in response to chronic inflammation
Describe the metaplasia that commonly occurs in smokers
In the habitual cigarette smoker, the normal columnar ciliated epithelial cells of the trachea and bronchi are often replaced by stratified squamous epithelial cells
Give an example of metaplasia due to nutritional deficiency
Vitamin A deficiency causing nasal squamous metaplasia
Why is metaplasia problematic?
In most circumstances metaplasia represents and undesirable change.
The influences the predispose to metaplasia, if persistent may induce cancer transformation in metastatic epithelium
Thus the common form of cancer in the respiratory tract is composed of squamous cells
What problem occurs with metaplasia of the respiratory tract?
Although the metastatic squamous cells are capable of surviving, an important protective mechanism (mucus secretion) is lost
Give an example of metaplasia from squamous to columnar cell type
Barrett’s oesophagus
- in which the oesophageal squamous epithelium is replaced by intestinal-like columnar cells under the influence of long standing refluxed gastric acid
What cancer is linked to Barrett’s oesophagus?
Typically glandular adneocarcinomas
Describe the mechanism of metaplasia
Metaplasia does not result from a change in the phenotype of a differentiated cell type
Instead it is the result of a reprogramming of stem cells that are known to exist in normal tissues or of undifferentiated mesenchymal cells present in connective tissue
In a metaplastic change, these precursor cells differentiate along a new pathway
Define dysplasia
A premalignant condition characterised by increased cell growth, the presence of cellular atypia and decreased differentiation
Early mild forms may be reversible if the initial stimulus is removed
Severe dysplasia will progress to a malignant neoplasm unless it is adequately treated
What causes dysplasia?
May be caused by longstanding irritation of a tissue with chronic inflammation or by exposure to carcinogenic substances
What are the signs of dysplasia?
Dysplasia may be recognised by:
- Evidence of increased growth
- Presence of cellular atypia
- Decreased differentiation
Describe the features of evidence of increased growth
Increased bulk tissue (e.g. increased epithelial thickness)
Increased number of mitoses
Describe the features of presence of cellular atypia
Pleomorphism (variation of size and shape of cells and their nuclei)
High nuclear/cytoplasmic ratio
Increased nuclear DNA
- recognised by hyperchromatism (more darkly stained nuclei
Describe the features of decreased differentiation
Cells appear more primitive than normal
May not show the normal differentiation
Show loss of epithelial polarity
How is observing dysplasia clinically useful?
Dysplasia may develop without co-existing metaplasia
(e.g. in squamous epithelium of cervix, glandular epithelium of stomach, in the liver)
Dysplasia may be present for years before a malignant neoplasm develops.
This observation can be used to screen populations at high risk of developing tumours
Define neoplasia
‘Neoplasia’ means ‘new growth’
- lesion produced is a ‘neoplasm’
A neoplasm is an abnormal tissue mass, the excessive growth of which is uncoordinated with that of normal tissues and which persists after the removal of the neoplasm-inducing stimulus.
How do neoplasms occur?
Neoplasms result from uncontrolled growth & often disordered differentiation which is excessive & purposeless
The growth of neoplasms continues in an autonomous manner in the absence of normal physiological stimuli & without negative feedback mechanisms to arrest the cellular proliferation
