Disorders of Cell Growth, Differentiation, and Maturation

Question 1

How does cell injury occur?

Answer 1

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

Question 2

What are the possible causes of cell injury?

Answer 2

• Hypoxia
• Immunological
• Infection by micro-organisms
• Genetic
• Thermal injury
• Physical
• Chemical
• Aging

Question 3

Give examples of immunological causes of cell injury

Answer 3

Thyroid damage caused by autoantibodies

Antibodies produced by the body against its own tissues

Question 4

Give examples of genetic causes of cell injury

Answer 4

Duchenne muscular dystrophy

Sickle cell disease

Question 5

Give examples of physical causes of cell injury

Answer 5

Ionising radiation (sunburn due to UV light damage to the skin), trauma, heat, cold

Question 6

Give an example of a chemical caused cell injury

Answer 6

Acid damage to oesophageal mucosa

Question 7

Give an example of age induced cell injury

Answer 7

Cellular senescence leads to alterations in replication and repair abilities of the cell

Question 8

Define hyperplasia

Answer 8

An increase in the number of cells in an organ or tissue, usually resulting in increased volume

Question 9

What causes hyperplasia?

Answer 9

Increased workload
Hormonal stimulation
Decreased tissue

Question 10

Give examples of physiologic hyperplasia

Answer 10

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)

Question 11

What causes pathologic hyperplasia?

Answer 11

Most are caused by excessive hormonal stimulation or growth factors acting on cells

Question 12

Give examples of pathologic hyperplasia

Answer 12

Endometrial hyperplasia

Benign prostatic hyperplasia

Question 13

Is hyperplasia irreversible?

Answer 13

Hyperplasia will regress if the hormonal stimulation is eliminated, however will result in an increased risk of cancer

Question 14

Define hypertrophy

Answer 14

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)

Question 15

Why does hypertrophy occur in nondividing cells?

Answer 15

In nondividing cells, (e.g. myocardial fibres) hypertrophy may be the response to stress

Question 16

Which organs have an increased susceptibility to hypertrophy?

Answer 16

Heart

Kidneys

Question 17

What causes hypertrophy?

Answer 17

Hypertrophy may be caused by mechanical signals (e.g., stretch) or trophic signals (e.g., growth factors).

Question 18

Give an example of physiologic hypertrophy

Answer 18

An example of physiologic hypertrophy is in skeletal muscle with sustained weight bearing exercise

Question 19

Give an example of pathologic hypertrophy

Answer 19

An example of pathologic hypertrophy is in cardiac muscle as a result of hypertension.

Question 20

Define atrophy

Answer 20

Shrinkage in cell size by the loss of cell substance.

It is a form of adaptive response and may culminate in cell death

Question 21

Is atrophy reversible?

Answer 21

Yes

Question 22

What causes atrophy?

Answer 22

Disease
Insufficient blood flow
Malnutrition
Denervation
Reduced endocrine stimulation
Aging
Pressure

Question 23

When does a tissue or organ become atrophic?

Answer 23

When sufficient numbers of cells are involved

Question 24

Give an example of physiologic atrophy

Answer 24

Physiologic atrophy is common during early development

The uterus decreases in size shortly after partruition

Question 25

Give examples of pathologic atrophy

Answer 25

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

Question 26

Are the cell changes associated with atrophy different in different cells?

Answer 26

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

Question 27

What are the different acquired disorders of cell growth and differentiation?

Answer 27

Metaplasia Dysplasia Neoplasia

Question 28

Define metaplasia

Answer 28

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

Question 29

Give examples of causes of metaplasia

Answer 29

Stones in the excretory ducts of the salivary glands, pancreas or bile ducts Chronic inflammation Nutritional defeiciency

Question 30

What is the most common epithelial metaplasia?

Answer 30

Columnar to squamous It occurs in the respiratory tract in response to chronic inflammation

Question 31

Describe the metaplasia that commonly occurs in smokers

Answer 31

In the habitual cigarette smoker, the normal columnar ciliated epithelial cells of the trachea and bronchi are often replaced by stratified squamous epithelial cells

Question 32

Give an example of metaplasia due to nutritional deficiency

Answer 32

Vitamin A deficiency causing nasal squamous metaplasia

Question 33

Why is metaplasia problematic?

Answer 33

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

Question 34

What problem occurs with metaplasia of the respiratory tract?

Answer 34

Although the metastatic squamous cells are capable of surviving, an important protective mechanism (mucus secretion) is lost

Question 35

Give an example of metaplasia from squamous to columnar cell type

Answer 35

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

Question 36

What cancer is linked to Barrett's oesophagus?

Answer 36

Typically glandular adneocarcinomas

Question 37

Describe the mechanism of metaplasia

Answer 37

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

Question 38

Define dysplasia

Answer 38

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

Question 39

What causes dysplasia?

Answer 39

May be caused by longstanding irritation of a tissue with chronic inflammation or by exposure to carcinogenic substances

Question 40

What are the signs of dysplasia?

Answer 40

Dysplasia may be recognised by: 1. Evidence of increased growth 2. Presence of cellular atypia 3. Decreased differentiation

Question 41

Describe the features of evidence of increased growth

Answer 41

Increased bulk tissue (e.g. increased epithelial thickness) | Increased number of mitoses

Question 42

Describe the features of presence of cellular atypia

Answer 42

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

Question 43

Describe the features of decreased differentiation

Answer 43

Cells appear more primitive than normal May not show the normal differentiation Show loss of epithelial polarity

Question 44

How is observing dysplasia clinically useful?

Answer 44

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

Question 45

Define neoplasia

Answer 45

‘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.

Question 46

How do neoplasms occur?

Answer 46

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