Pathology: Cell Injury Flashcards
Prior to damage/death, how do body cells cope with changes (stress)?
Adaptations
What are examples of adaptions of body cells due to stress?
- Increased demand on cells - hyperplasia, hypertrophy
- Decreased demand - atrophy
- Altered stimulus - metaplasia
In which 2 ways does the body grow?
- Hypertrophy - cells get bigger
* Hyperplasia - cells increase in number
Do hyperplasia and hypertrophy occur randomly?
No, they require specific instructions to grow
How are signals for growth (hypertrophy) produced?
- Produce more growth factors
* Produce more growth factor receptors
What are the 3 categories of growth receptors?
- Receptors with intrinsic tyrosine kinase activity
- 7 transmembrane G-protein coupled receptors
- Receptors without intrinsic tyrosine kinase activity
Does hyperplasia and hypertrophy occur in a disordered fashion?
No, occurs in a stepwise progression
What can mistakes in signals for growth and cell division lead to?
Cancer
What are the stages of the cell cycle (G1, S, G2, M) controlled by?
Cyclin dependent kinases (CDKs)
What do CDKs do?
Activate each other and other enzymes in a stepwise fashion
What are CDKs activated by?
A specific cyclin
Do cyclins and CDKs vary in concentration throughout the cell?
- Cyclins vary in concentration throughout the cell
* CDKs do not
What are the 4 types of cyclin?
- Cyclin D
- Cyclin E
- Cyclin A
- Cyclin B
What is G1?
Growth phase
What happens in G1?
- Cell increases in size and synthesises proteins
- CDK4 is activated by cyclin D
- CDK4 phosphorylates retinoblastoma protein
What is the role of activated CDK4?
Phosphorylates Rb, which means it cannot bind to EF2 - allows cell cycle to progress
What is retinoblastoma?
Protein that is important in cell growth and malignancy
How does Rb inhibit the cell cycle?
Normally bound to EF2, which prevents EF2 from stimulating cell division
What is EF2?
A protein that stimulates cell cycle
What is the S phase?
Synthesis - DNA replication
What happens in the S phase?
- EF2 initiates DNA replication
- EF2 increases levels of cyclin A
- Cyclin A activates CDK2
- CDK2 also promotes DNA replication
How many copies of the genome are there at the end of the S phase?
2 copies of the genome
What is G2?
Second growth phase
What happens in G2?
- More cell growth and protein synthesis
Where does the main checkpoint of the cell cycle occur?
End of G2 (G2 checkpoint - P53)
What is the role of P53 at the G2 checkpoint?
- Checks for DNA damage
What happens if mistake in DNA is found by P53?
- Pauses cell cycle and attempts repair
- If repair successful = cell cycle progresses
- If repair unsuccessful = P53 triggers apoptosis
How do cancer cells avoid apoptosis at the G2 checkpoint?
They avoid checking by P53 - they can keep dividing despite faults in DNA
What checkpoint is present in the mitotic phase?
Mitotic checkpoint - checks chromosomes are correctly aligned on the spindle
What happens once mitotic checkpoint is passed?
- Nucleus divides
* Cytokinesis can then occur
What is replicative senescence?
Cells which cannot/can no longer divide
What does it mean if a cell is terminally differentiated?
Once specialised, lose ability to replicate e.g. neurones
How do people recover from brain damage if neurones are terminally differentiated?
- New cells are not formed in response to damage
* Instead, undamaged areas of the brain take on the function of the damaged area
Do cells divide less in younger people than in older people?
No
- Young people - cells divide lots of times
- Older people - fewer times
Why can cells only divide a certain number of times?
Due to telomere repeats at the end of chromosomes
* With every division, number of telomere repeats gets smaller until you can’t divide anymore
What is the function of telomeres?
Provide protection and stop chromosome ends from degrading or fusing
What are TTAGGG repeats?
Telomere repeats
What must be present for hyperplasia to occur?
External stimulus - growth signals
What will happen to hyperplasia if growth signals are withdrawn?
Hyperplasia will regress
Is hyperplasia pathological?
Can be pathological or physiological
What are examples of physiological hyperplasia?
- Hormonal - puberty (breast tissue growth), pregnancy (hyperplasia of endometrium)
- Compensatory - occurs after loss of tissues (not common in many tissues) e.g. liver, bone marrow
What are examples of pathological hyperplasia?
- Hormonally-induced - excess oestrogen leads to endometrial hyperplasia and abnormal menstrual bleeding (e.g. postmenopausal bleeding), prostatic hyperplasia in response to androgens
- Infection - lymph nodes undergo hyperplasia in response to infection
Is hyperplasia reversible?
Yes, upon withdrawal of stimulus
Does cancer require an external stimulus?
No, cancer can keep growing even when stimulus is withdrawn
What is hyperplasia a risk factor for?
Hyperplastic tissue is at risk for development of cancer
What is hypertrophy?
Increase in cell size
What does hypertrophy often occur in response to?
Mechanical stress - increased demand e.g. athletes have a big heart
- However, big heart can also occur in response to pathology (hypertension) - heart has to work harder to pump blood
When does compensatory hypertrophy of the heart become pathologic?
When heart is pushed too hard
- Can no longer function
- Requires more blood than is supplied
What can pathologic hypertrophy of the heart result in?
Heart failure - inability of heart to pump normally
What is atrophy?
Reduction in cell size
Is atrophy pathological?
Can be pathological or physiological
What are examples of physiological atrophy?
- Embryological structures - if remain, can become pathological
- Uterus undergoes rapid atrophy after child birth (parturition)
What are examples of pathological atrophy?
- Decreased demand (workload) e.g. broken limb immobilised in cast
- Loss of innervation
- Blocked blood supply
- Loss of hormonal stimulation
- Inadequate nutrition
- Ageing
- Pressure - endogenous (internal) or exogenous (external) structures, often seen in tissues adjacent to tumours
What does loss of blood supply to 1 kidney result in?
- Atrophy of the affected kidney
* Other kidney then undergoes compensatory hyperplasia due to increased demand
What are the mechanisms of atrophy?
- Reduced cellular components
- Protein degradation
Both result in a decrease in cell size
How are proteins degraded in atrophy?
- ‘Digested’ by enzymes
* degraded by ubiquitin proteasome pathway
Which hormones promote degradation and atrophy?
- Glucocorticoids
* Thyroid hormone
Which hormone opposes atrophy and promotes growth?
- Insulin
Why must atrophy and growth be balanced?
To maintain homeostasis
