What is homeostasis?
The maintenance of a steady state/closely maintained
What does the body do if there is increased demand?
Hyperplasisa and hypertrophy
What will the body do if there is decreased demand?`
Atrophy
What will the body do if there is altered stimulus?
Metaplasia
What is hypertrophy?
Cells get bigger
What is hyperplasia?
More cells grow - this will only occur if there is specific cell signals and increased cell division
What are signals that can lead to hyperplasia?
More growth factor production
More growth factor receptor production
What are the three types of growth receptors?
Receptors with intrinsic tyrosine kinase activity
7 transmembrane G-protein couples receptors
Receptors without intrinsic tyrosine kinase activity
What happens if there are mistakes in the signals for growth and cell cycle development?
Cancer development
How id the cell cycle controlled?
It is a stepwise progression through a series of stages that has various checkpoints that ensure faulty cells are not made. Faulty cells may predispose to cancers
What are the 4 stages to the cell cycle?
G1, S, G2, M
What controls the cell cycle?
Cyclin dependent kinases (CDK’s) that will activate each other and other enzymes in a step wise fashion. Each CDK is activated by a specific cyclin. Can be Cyclin D, E, A or B
What occurs during G1?
The cell increases in size with increased protein synthesis
How is G1 controlled?
During G1 CKD4 is activated by cyclin D. CDK4 phophorylates retinoblastoma
What is retinoblastoma?
An important protein needed for normal cell growth. Normally Rb is bound to E2F
What is E2F?
A protein that will kick off cell division but is prevented to by Rb. When phosphorylated by CDK4, Rb can’t bind to E2F and therefore E2F is free to give a green light to cell division
What occurs during the S phase?
DNA synthesis occurs. E2F initiates DNA replication and increases levels of cyclin A.
What does cyclin A do?
Activated CDK2
What does CDK2 do?
Promotes DNA replication
What occurs during G2?
Second growth phase where the cell gets bigger and more protein synthesis occurs. Main checkpoint for cell cycle.
What is the main checkpoint protein at G2?
p53
What does p53 do?
Checks cell for mistakes
Pauses cell cycle to allow for DNA repair
Initiate apoptosis
What can a terminally differentiated cell not do?
Divide, an example is a neuron. These cells exhibit replicative senesence by qhich other cells must divide many times to either grow or replace lost cells
What is a telomere?
The caps on chromosomes to provide protection and to stop the chromosome ends from degradation and fusion
What does a telomere consist of?
A TTAGGG repeats and with every division , the number of repeats gets smaller
What is an example of normal hyperplasia?
Hormonal such a during puberty the growth of breast tissue or during pregnancy, the growth of the lining of the womb
What tissues will show compensatory hyperplasia?
Liver and bone marrow
What are some examples of pathological hyperplasia?
Excess oestrogen will lead to endometrial hyperplasia and abnormal menstrual bleeding - usually post menopausal.
Hormonally induced prostatic hyperplasia in response to androgen’s
What will occur during an infection?
The lymph nodes will undergo hyperplasia in response to an infection
What will occur if the stimulus is withdrawn in hyperplasia?
It will be reversed as hyperplasia is reversible growth. Hyperplastic tissue however is at a risk for developing cancer
When will hypertrophy occur?
Usually in conjuction with hyperplasia and often in isolation in non-divding cells e,g, cardiac myocytes or skeletal muscle
Often in response to mechanical stress
When will hypertrophy become pathologic?
When the heart can no linger function and requires more blood supply than it is given. The muscles will also become less function when hypertrophy has occured
What are physiolocical atrophy examples?
Embryological structures and the uterus after birth
What are examples of pathological atrophy?
Decreased workload - e.g. if a limb has been in a cast
Loss of innervation
Loss of function after a nerve supply is removed
Blocked blood supply
Loss of hormonal stimulation e.g. a post menopausal uterus
Inadequate nutrition
Ageing
Pressure due to endogenous or exogenous structures
What is the mechanism of atrophy?
The cellular components will be reduced and protein degradation will occur . The proteins will be digested in lysosomes.
What hormones promote degradation?
Thyroid and glucocoricoids
What hormones oppose atrophy and promote growth?
Insulin
What retains homeostasis?
A balance of growth and atrophy