Cell turnover and disorders of cell proliferation and differentiation Flashcards
What are examples of labile cells and what is their proliferative activity and capacity for increased proliferation?
Surface epithelia e.g. skin, gut, haemopoetic cells
High proliferative activity
They have the capacity for increased proliferation
What are examples of stable cells (conditional renewal) and what is their proliferative activity and capacity for increased proliferation?
Parenchymal cells of glandular organs e.g. liver, kidney and thyroid
- low proliferative activity but they do have the capacity for increased proliferation
What are examples of permanent cells (non-replacing) and what is their proliferative activity and capacity for increased proliferation?
Neurones, cardiac muscle
- no proliferative capacity and no capacity for increased proliferation
What are the different states of cell division ?
Stem cells - proliferative compartment
Transit cells - maturing cells, limited capacity for division
Mature functional cells - non-dividing, programmed to die and require replacement
Which layer of the epidermis contains stem cells and which later loses the ability to proliferate?
Basal cell layer = stem cells which high mitotic activity
Prickle cell layer = lose ability to proliferate
What are the different phases of the cell cycle (Go, G1, S, G2 and M)?
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
What factors control cell division and how?
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)
What can increased growth be due to and why does it usually occur and how?
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
What are the 2 main patterns of increased growth?
hyperplasia - increase in number of cells, stimulus usually hormonal or chemical
hypertrophy - increase in size of cells, stimulus usually mechanical
What are labile cells response to increased demand in function, what stimulus drives it and what are their responses to injury?
- hyperplasia
- chemical or hormonal
- regeneration
What are stable cells response to increased demand in function, what stimulus drives it and what are their responses to injury?
- hyperplasia
- chemical or hormonal
- regeneration
What are permanent cells response to increased demand in function, what stimulus drives it and what are their responses to injury?
- hypertrophy
- mechanical
- repair
How does physiological increased growth and pathological increased growth differ?
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
What are some examples of increased physiological growth?
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
What are some examples of increased pathological growth?
1) Left ventricular hypertrophy
2) Thyroid gland hyperplasia
3) Cystic hyperplasia of the breast
What are the causes of left ventricular hypertrophy?
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
Wha are the consequences of left ventricular hypertrophy?
Initially compensates for increased demand
Later leads to cardiac failure (myocardial ischaemia may also occur)
What can happen when the aortic valve undergoes calcification?
Leads to aortic stenosis which can lead to infective endocarditis - bacterial growth leads to damage and perforates valve cuffs
What happens in graves disease?
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
What happens in cystic hyperplasia of the breast?
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
Define hypoplasia:
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
Define atrophy:
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
What are the causes of pathological atrophy?
Loss of hormonal stimulation
Reduction in blood supply
Decreased workload
Loss of innervation
What factors maintain normal cell integrity?
cell membrane
ATP generation (mitochondria)
Protein synthesis
Genetic apparatus
What are some causes of cell injury?
hypoxia
Pro-inflammatory cytokines
Chemical toxins
Bacterial toxins
What are the early (reversible) cell injury factors?
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
What are the late (irreversible) cell injury factors (necrosis)?
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
How long does necrosis take and what does it typically elicit?
Morphological features take several hours to develop
- typically elicits an acute inflammatory reaction
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
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
Define metaplasia:
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
What is the original cell type, the metaplastic cell type and cause for the change at the bronchus?
Original - ciliated columnar epithelium
Metaplastic - squamous epithelium
Cause - cigarette smoking
What is the original cell type, the metaplastic cell type and cause for the change at the lower oesophagus?
Original - squamous epithelium
Metaplastic - gastric columnar lined distal oesophagus
Cause - acid reflux
What is the original cell type, the metaplastic cell type and cause for the change at the stomach?
Original - columnar epithelium
Metaplastic - intestinal
Cause - chronic inflammation e.g. H.Pylori
What are the consequences of metaplasia?
loss of normal cell function
increased risk of malignancy
Metaplasia is NOT a pre-malignant condition but it does increase risk
Define dysplasia:
Literally - “disordered development”
Development abnormalities
Tumour like malformations
Premalignant changes
What does it mean by dysplasia as a premalignant condition?
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
