Cell turnover and disorders of cell proliferation and differentiation

Question 1

What are examples of labile cells and what is their proliferative activity and capacity for increased proliferation?

Answer 1

Surface epithelia e.g. skin, gut, haemopoetic cells
High proliferative activity
They have the capacity for increased proliferation

Question 2

What are examples of stable cells (conditional renewal) and what is their proliferative activity and capacity for increased proliferation?

Answer 2

Parenchymal cells of glandular organs e.g. liver, kidney and thyroid
- low proliferative activity but they do have the capacity for increased proliferation

Question 3

What are examples of permanent cells (non-replacing) and what is their proliferative activity and capacity for increased proliferation?

Answer 3

Neurones, cardiac muscle

- no proliferative capacity and no capacity for increased proliferation

Question 4

What are the different states of cell division ?

Answer 4

Stem cells - proliferative compartment

Transit cells - maturing cells, limited capacity for division

Mature functional cells - non-dividing, programmed to die and require replacement

Question 5

Which layer of the epidermis contains stem cells and which later loses the ability to proliferate?

Answer 5

Basal cell layer = stem cells which high mitotic activity

Prickle cell layer = lose ability to proliferate

Question 6

What are the different phases of the cell cycle (Go, G1, S, G2 and M)?

Answer 6

G0 - quiescent - majority of cells in this phase
G1 - pre-synthetic
s- DNA synthesis
G2 - pre-mitotic
M- mitotic
Terminal differentiation - no longer re-enter cell cycle - programmed to die

Question 7

What factors control cell division and how?

Answer 7

Polypeptide GFs and cytokines - act on R cell surfaces, forming second messengers in the cytoplasm and DNA synthesis in the nucleus

Cyclins - activate proteins involved in DNA replication an other events in cell cycle

Inhibitory factors - polypeptide GFs/cytokines, tumour suppressor genes (p53) and cyclin-dependent kinase inhibitors (p21, p27)

Question 8

What can increased growth be due to and why does it usually occur and how?

Answer 8

increased growth can be due to an increase in number or size of cells, usually occurs as a result of increased demand for function (physiological or pathological) and stimuli may be mechanical, chemical or hormonal
Capacity for cell division governs the pattern of increased growth

Question 9

What are the 2 main patterns of increased growth?

Answer 9

hyperplasia - increase in number of cells, stimulus usually hormonal or chemical

hypertrophy - increase in size of cells, stimulus usually mechanical

Question 10

What are labile cells response to increased demand in function, what stimulus drives it and what are their responses to injury?

Answer 10

• hyperplasia
• chemical or hormonal
• regeneration

Question 11

What are stable cells response to increased demand in function, what stimulus drives it and what are their responses to injury?

Answer 11

• hyperplasia
• chemical or hormonal
• regeneration

Question 12

What are permanent cells response to increased demand in function, what stimulus drives it and what are their responses to injury?

Answer 12

• hypertrophy
• mechanical
• repair

Question 13

How does physiological increased growth and pathological increased growth differ?

Answer 13

Physiological - changes largely reversible if the stimulus causing them is removed

Pathological - changes less readily reversible, if excessive growth persists may predispose to neoplastic transformation

Question 14

What are some examples of increased physiological growth?

Answer 14

1) Pregnancy
- uterus - myometrial hypertrophy and hyperplasia due to mechanical factors and oestrogen
- breast- glandular hyperplasia due to oestrogen and progesterone
2) skeletal muscle - hypertrophy occurring in athletes
3) Bone marrow- hyperplasia of erythroid cells in response to blood loss

Question 15

What are some examples of increased pathological growth?

Answer 15

1) Left ventricular hypertrophy
2) Thyroid gland hyperplasia
3) Cystic hyperplasia of the breast

Question 16

What are the causes of left ventricular hypertrophy?

Answer 16

Systemic hypertension
Aortic valve disease (aortic stenosis or incompetence) - has to work harder or doesn’t close properly
Mitral incompetence - blood goes back into the atrium
Coronary artery atheroma - death of muscle cells

Question 17

Wha are the consequences of left ventricular hypertrophy?

Answer 17

Initially compensates for increased demand

Later leads to cardiac failure (myocardial ischaemia may also occur)

Question 18

What can happen when the aortic valve undergoes calcification?

Answer 18

Leads to aortic stenosis which can lead to infective endocarditis - bacterial growth leads to damage and perforates valve cuffs

Question 19

What happens in graves disease?

Answer 19

Hyperplasia of the thyroid gland with increased production of thyroxine
Due to production of thyroid stimulating autoantibodies which act on same receptors as thyroid stimulating hormone
Not susceptible to normal negative feedback mechanism

Question 20

What happens in cystic hyperplasia of the breast?

Answer 20

Proliferation of glandular elements with formation of cysts
Probably due to hormonal factors
- occurs in women between menarche and menopause
- normal variations in breast tissue during menstrual cycle

Question 21

Define hypoplasia:

Answer 21

NOT the opposite to hyperplasia

• failure of a tissue or organ to reach normal size during development
• causes include genetic defects, intrauterine infection, toxic insults

Question 22

Define atrophy:

Answer 22

opposite to hyperplasia and hypertrophy

• decrease in size of tissue or organ at a stage after initial development
• may be due to a decrease in cell size or number
• can be physiological
• part of normal ageing process

Question 23

What are the causes of pathological atrophy?

Answer 23

Loss of hormonal stimulation
Reduction in blood supply
Decreased workload
Loss of innervation

Question 24

What factors maintain normal cell integrity?

Answer 24

cell membrane
ATP generation (mitochondria)
Protein synthesis
Genetic apparatus

Question 25

What are some causes of cell injury?

Answer 25

hypoxia
Pro-inflammatory cytokines
Chemical toxins
Bacterial toxins

Question 26

What are the early (reversible) cell injury factors?

Answer 26

Normally associated with cell swelling 
Factors involved:
- entry of sodium and water into the cell (membrane dysfunction)
- mitochondrial swelling
- dilatation of endoplasmic reticulum 
Morphological changes:
- hydropic changes
- vacuolar degeneration 
- ballooning degeneration

Question 27

What are the late (irreversible) cell injury factors (necrosis)?

Answer 27

Nuclear changes
- shrinkage (pyknosis)
- fragmentation (karyorrhexis)
- disappearance (karyolysis)
Cytoplasmic changes
- denaturation of proteins- increased cytoplasmic eosinophilia, typically occurs in hypoxic/ischaemic injury
- enzymatic digestion of cell - disappearance of cells, more common with cytokine-mediated injury

Question 28

How long does necrosis take and what does it typically elicit?

Answer 28

Morphological features take several hours to develop

- typically elicits an acute inflammatory reaction

Question 29

What are the difference between apoptosis and necrosis in the following areas?

• cellular changes
• pattern of cell involvement
• pathogenetic mechanisms
• tissue reaction
• physiological examples
• pathological examples

Answer 29

Cellular changes
- apoptosis- shrinkage, fragmentation (apoptotic bodies)
- necrosis- swelling, coagulative of lytic changes
Pattern of cell involvement
- apoptosis - single cells
- necrosis - group of cells
Tissue reaction
- apoptosis - phagocytosis of apoptotic bodies, no inflammation
- necrosis - inflammation
Physiological examples
- apoptosis - normal cell turnover, organ development
- necrosis - no
Pathological examples
- apoptosis - yes
- necrosis - yes

Question 30

Define metaplasia:

Answer 30

replacement (potentially reversible) of one differentiated cell type by another differentiated cell type
Usually occurs as response to unfavourable environment for the original cell type

Question 31

What is the original cell type, the metaplastic cell type and cause for the change at the bronchus?

Answer 31

Original - ciliated columnar epithelium
Metaplastic - squamous epithelium
Cause - cigarette smoking

Question 32

What is the original cell type, the metaplastic cell type and cause for the change at the lower oesophagus?

Answer 32

Original - squamous epithelium
Metaplastic - gastric columnar lined distal oesophagus
Cause - acid reflux

Question 33

What is the original cell type, the metaplastic cell type and cause for the change at the stomach?

Answer 33

Original - columnar epithelium
Metaplastic - intestinal
Cause - chronic inflammation e.g. H.Pylori

Question 34

What are the consequences of metaplasia?

Answer 34

loss of normal cell function
increased risk of malignancy
Metaplasia is NOT a pre-malignant condition but it does increase risk

Question 35

Define dysplasia:

Answer 35

Literally - “disordered development”
Development abnormalities
Tumour like malformations
Premalignant changes

Question 36

What does it mean by dysplasia as a premalignant condition?

Answer 36

changes resemble those seen in neoplastic cells
not yet invasive but potential for progression to invasive carcinoma if untreated
Increasing grades of dysplasia described (mild, moderate, severe)- potential for reversibility diminishes with progression in grade
Intraepithelial neoplasia now preferred term in many situations
Basis for screening