Cell Turnover and Disorders of Cell Proliferation and Differentiation

Question 1

Answer 1

Question 2

Answer 2

Question 3

What are the factors controlling cell division

Answer 3

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)

Question 4

What pathways contol cell growth and differentiation?

Answer 4

Question 5

Patterns of Increased Growth (excluding neoplasia) General Principles

Answer 5

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)

Question 6

Patterns of Increased Growth (excluding neoplasia) Two main types are?

Answer 6

Hyperplasia

• increase in number of cells
• stimulus is usually hormonal or chemical

Hypertrophy

• increase in size of cells
• stimulus is usually mechanical

Question 7

Answer 7

Question 8

What are physiological changes that causes increased growth>?

Answer 8

Physiological

– changes largely reversible if the stimulus causing them is removed.

Question 9

Examples of Increased Growth - Pathological

Answer 9

1. Left ventricular hypertrophy
2. Thyroid gland hyperplasia (Graves disease)
3. Cystic hyperplasia of the breast

Question 10

Left ventricular hypertrophy

What are the causes and consequences?

Answer 10

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)

Question 11

What problems does bicuspid aortic valves cause?

Answer 11

bicuspid aortic valve -> aortic stenosis -> infective endocarditis

Question 12

What happened to these thyroid tissues?

Answer 12

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

Question 13

What happened to this breast lobule?

Answer 13

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

Question 14

What is hypoplasia

Answer 14

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

Question 15

What is atrophy?

What are the causes of pathological atrophy?

Answer 15

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

Question 16

Factors maintaining normal cell integrity

Answer 16

Cell membrane

• ATP generation (mitochondria)
• Protein synthesis
• Genetic apparatus

Question 17

What causes cell injury?

Answer 17

Hypoxia

Pro-inflammatory cytokines

• Chemical toxins
• Bacterial toxins

Question 18

Early (Reversible) Cell Injury

What are the factors involved?

What are morphological terms?

Answer 18

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

Question 19

What can you see that is wrong in this hepatocyte?

Answer 19

Hepatocyte Ballooning

Mallory’s Hyaline - globular red hyaline within hepatocytes - intermediate filament breaking down after chronic damage

Question 20

Late (Irreversible) Cell Injury leads to ______

Nuclear changes causing:

• Pyknosis
• karyorrehexis

Karyolysis

what cytoplasmic changes occur?

Answer 20

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

Question 21

Late (Irreversible) Cell Injury leads to ______

Nuclear changes causing:

• Pyknosis
• karyorrehexis

Karyolysis

what cytoplasmic changes occur?

Answer 21

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

Question 22

Label this

Answer 22

Question 23

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?

Answer 23

1) 4-12 hours after irreversible injury has occured
2) 24 hours after cell death

Question 24

What has happened to this myocardium after infarction

Answer 24

Question 25

What changes are seen here with someone with acute hepatitis

Answer 25

Confluent Centrilobular Necrosis (lytic pattern – cell outlines no longer visible)

Question 26

Answer 26

Question 27

What causes apoptosis to be signalled?

Answer 27

Question 28

What can be seen here with a person with acute hepatitis

Answer 28

Acidophil Body

Question 29

Define metaplasia

Answer 29

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 30

Answer 30

Question 31

What are the consequences of metaplasia?

Answer 31

1. Loss of normal cell function e.g. chest infections due to squamous metaplasia in bronchi 2. Increased risk of malignancy

Question 32

What happenes to this normal bronchial mucosa?

Answer 32

Squamous Metaplasia (+ dysplasia)

Question 33

Dysplasia - Definition

Answer 33

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

Question 34

Dysplasia as a Premalignant Condition Why is that? What happnes in severe dysplacia?

Answer 34

* 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