Stress on cells results in an attempt at adaptation
Adaptations to increased demand
Hyperplasia
Hyperplasia: Increase in cell number in response to external stimulus
Can be physiological or pathological
Physiological e.g. breast tissue in puberty, response after loss of tissue
Pathological - hormonally induced e.g. excess oestrogen → endometrial hypoplasia, hyperplasia of lymph nodes in response to infection
Reversed on withdrawal of stimulus
Cancer keeps growing on absence of stimulus
Hyperplastic tissue = risk site for development of cancer
Hypertrophy
Hypertropy: increase in cell size
Often occurs:
In conjunction with hyperplasia
In isolation in non-dividing cells (e.g. skeletal muscle)
In response to mechanical stress
Becomes pathological when heart/muscle can no longer function
Requires more blood supply etc. than it is supplied
Heart failure
Growth receptors
Stress growth factors lead to cell division
To increase cell division:
Produce more growth factors
Produce more growth factor receptors
Three categories of receptor:
Receptors with intrinsic tyrosine kinase activity
7 transmembrane G protein coupled receptors
Receptors without intrinsic tyrosine kinase receptors
Cell cycle
Tightly controlled - checkpoints
Faulty cells may not perform function; may predispose to cancers
Each stage of the cell cycle is controlled by CDKs, which are activated by a specific cyclin
G1
Cells get bigger, increased protein synthesis
Cyclin D activates CDK4 which phosphorylates Rb
Rb is normally bound to E2F, stopping it from initiating cell division
When Rb is phosphorylated it is unable to bind to E2F, and E2F will initiate cell division
p53 can cause cell cycle arrest between G1 and S phase
S phase
E2F initiates DNA replication and increases levels of cyclin A
Cyclin A activates CDK2 – also promotes DNA replication
By end – cell contains 2 copies of genome
G2
Cell gets bigger, more protein synthesis
Main p53 checkpoint occurs at end of G2
Checks cell for mistakes
Pauses cell cycle and repair is attempted
Success → cycle continues
Fails → cell death
Important in cancer – if cells can avoid p53 they can keep dividing despite faults in DNA
M phase
Mitosis
Variations in cell cycle
Not all cells divide - some are terminally differentiated (neurons etc.)
Replicative senescence
Telomeres: caps which protect chromosome ends from degradation and fusion
Get smaller with each division - cells can only divide so many times
Atrophy
Atrophy: reduction in cell size
Can be physiological (e.g. embryological structures, post-menopausal uterus) or pathological (e.g. decreased workload, blocked blood supply, loss of innervation)
Mechanism
Reduced cellular components
Protein degradation
Some hormones promote degradation (thyroid hormone), others promote growth (insulin)
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