Cell Turnover and Disorders of Cell Proliferation and Differentiation Flashcards
What are the factors controlling cell division
Polypeptide Growth Factors and Cytokines
- act on receptors on cell surface
- formation of second messenger in cytoplasm
- DNA synthesis in nucleus
Cyclins
• activate proteins involved in DNA replication and other events in cell cycle
Inhibitory Factors
- polypeptide growth factors/cytokines
- Tumour suppressor genes (e.g. p53)
- Cyclin –dependent kinase inhibitors (e.g. p21, p27)
What pathways contol cell growth and differentiation?
Patterns of Increased Growth (excluding neoplasia) General Principles
Increased growth can be due to an increase in NUMBER or SIZE of cells
- Usually occurs as a result of INCREASED DEMAND FOR FUNCTION
- Stimuli may be MECHANICAL, CHEMICAL or HORMONAL
- Capacity for cell division governs the pattern of increased growth (and also response to cell loss)
Patterns of Increased Growth (excluding neoplasia) Two main types are?
Hyperplasia
- increase in number of cells
- stimulus is usually hormonal or chemical
Hypertrophy
- increase in size of cells
- stimulus is usually mechanical
What are physiological changes that causes increased growth>?
Physiological
– changes largely reversible if the stimulus causing them is removed.
Examples of Increased Growth - Pathological
- Left ventricular hypertrophy
- Thyroid gland hyperplasia (Graves disease)
- Cystic hyperplasia of the breast
Left ventricular hypertrophy
What are the causes and consequences?
Causes
- Systemic hypertension
- Aortic valve disease (aortic stenosis or incompetence)
- Mitral incompetence
- Coronary artery atheroma
Consequences
- Initially compensates for increased demand.
- Later leads to cardiac failure (myocardial ischaemia may also occur)
What problems does bicuspid aortic valves cause?
bicuspid aortic valve -> aortic stenosis -> infective endocarditis
What happened to these thyroid tissues?
Grave’s disease
Hyperplasia of thyroid gland with increased production of thyroxine (thyrotoxicosis)
- Due to production of thyroid stimulating autoantibodies (immunoglobulins) which act on same receptors as thyroid stimulating hormone
- Not susceptible to normal negative feedback mechanism
What happened to this breast lobule?
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
What is hypoplasia
Hypoplasia (not the opposite of hyperplasia)
- Failure of a tissue or organ to reach normal size during development
- Causes include genetic defects, intrauterine infection, toxic insults - e.g. hypoplastic limbs related to thalidomide
What is atrophy?
What are the causes of pathological atrophy?
Decrease in size of tissue or organ at a stage after initial development
- May be due to a decrease in cell size or number (i.e. opposite of hyperplasia and hypertrophy)
- Can be physiological (e.g. post-pubertal atrophy of thymus gland)
- Part of “normal” ageing process
- Causes of pathological atrophy include:
– Loss of hormonal stimulation e.g. atrophy of endocrine organs secondary to pituitary disease
– Reduction in blood supply
– Decreased workload e.g. disuse atrophy of muscle
– Loss of innervation
Factors maintaining normal cell integrity
Cell membrane
- ATP generation (mitochondria)
- Protein synthesis
- Genetic apparatus
What causes cell injury?
Hypoxia
Pro-inflammatory cytokines
- Chemical toxins
- Bacterial toxins
Early (Reversible) Cell Injury
What are the factors involved?
What are morphological terms?
Typically associated with cell swelling
- Factors involved – Entry of sodium and water into cell (membrane dysfunction) – Mitochondrial swelling – Dilatation of endoplasmic reticulum
- Morphological terms
– Hydropic change - water in cells
– Vacuolar degeneration - loss of cytoplasmic
– Ballooning degeneration
What can you see that is wrong in this hepatocyte?
Hepatocyte Ballooning
Mallory’s Hyaline - globular red hyaline within hepatocytes - intermediate filament breaking down after chronic damage
Late (Irreversible) Cell Injury leads to ______
Nuclear changes causing:
- Pyknosis
- karyorrehexis
Karyolysis
what cytoplasmic changes occur?
Nuclear Changes
- Shrinkage (pyknosis)
- Fragmentaion (karyorrhexis)
- Disappearance (karyolysis)
Cytoplasmic changes
• Denaturation of proteins
– Increased cytoplasmic eosinophilia (Coagulative necrosis)
– Typically occurs in hypoxic/ischaemic injury e.g. myocardial infarction
• Enzymatic digestion of cell
– Disappearance of cells (Lytic necrosis)
– More common with cytokine-mediated injury e.g. acute viral hepatitis
Late (Irreversible) Cell Injury leads to ______
Nuclear changes causing:
- Pyknosis
- karyorrehexis
Karyolysis
what cytoplasmic changes occur?
Nuclear Changes
- Shrinkage (pyknosis)
- Fragmentaion (karyorrhexis)
- Disappearance (karyolysis)
Cytoplasmic changes
• Denaturation of proteins
– Increased cytoplasmic eosinophilia (Coagulative necrosis)
– Typically occurs in hypoxic/ischaemic injury e.g. myocardial infarction
• Enzymatic digestion of cell
– Disappearance of cells (Lytic necrosis)
– More common with cytokine-mediated injury e.g. acute viral hepatitis
Label this
1) How long does it take for histological features of MI to be apparent?
2) Necrosis causes an acute inflammatory reaction which begins around how long after cell death?
1) 4-12 hours after irreversible injury has occured
2) 24 hours after cell death
What has happened to this myocardium after infarction
What changes are seen here with someone with acute hepatitis
Confluent Centrilobular Necrosis (lytic pattern – cell outlines no longer visible)
What causes apoptosis to be signalled?
What can be seen here with a person with acute hepatitis
Acidophil Body
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 are the consequences of metaplasia?
- Loss of normal cell function e.g. chest infections due to squamous metaplasia in bronchi
- Increased risk of malignancy
What happenes to this normal bronchial mucosa?
Squamous Metaplasia (+ dysplasia)
Dysplasia - Definition
Literally ‘disordered development’
Controversial term due to varied usage:
- Developmental abnormalities – e.g. cystic renal dysplasia
- Tumour like malformations – e.g. fibrous dysplasia of bone
- Premalignant changes (usually epithelial) – e.g. epithelial dysplasia in ulcerative colitis
Dysplasia as a Premalignant Condition
Why is that?
What happnes in severe dysplacia?
- 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 – Severe dysplasia = carcinoma-in-situ.
- Intraepithelial neoplasia now preferred term in many situations – e.g. cervical intraepithelial neoplasia or CIN: • CIN grade 1 = mild dysplasia, CIN 2 = moderate dysplasia, CIN 3 = severe dysplasia • Basis for screening
