Cellular Adaptations Flashcards
What determines the size of a cel population?
- Depends on rate of cell proliferation, cell
differentiation and cell death by apoptosis - Increased numbers are seen with increased proliferation or decreased cell death
- Cell proliferation occurs in physiological and pathological conditions
- Excessive physiological stimulation can become pathological, e.g., prostatic hypertrophy
- Proto-oncogenes regulate normal cell proliferation
How is cell proliferation controlled?
- Largely by chemical signals from the
microenvironment, mainly growth factors, which either stimulate or inhibit cell proliferation - When a signalling molecule binds to a receptor it results in the modulation of gene expression - proliferation, halt, or apoptosis
- Receptors usually in cell membrane but can be in the cytoplasm or nucleus (e.g., steroid receptors)
What can chemical signals make the cell do?
Survive – resist apoptosis
Divide – enter cell cycle
Differentiate – take on specialised form and function
Die – undergo apoptosis
How can a cell population increase its numbers?
Increased growth occurs by
- shortening of the cell cycle
- conversion of quiescent cells to proliferating by making them enter the cell cycle
G0 - can go back into cell cycle i required, unless they become totally differentiated in which case they exit the cycle?
Can you see the cell cycle by light microscopy?
Everything we see is in mitosis and cytokinesis - dont see interphase
Can cells with damaged DNA replicate? And what are the checkpoints?
Dont want them to replicate -
Neoplasia is a result of changes in genetic material
Don’t want them to replicate
3 main checkpoints to prevent them from completing cell cycle
1 at end of g1 - restriction joint
B/w g1 and s - makes sure that dna is ok before its is replicated
B/e g2 and m - makes sure there is no problem with dna after replicated
What is the restriction point?
Period during which cells re responsive to mitogenic GFs and to TGF-beta
• Most critical checkpoint
• Majority of cells that pass R point will complete cell cycle – point of no return
• Most commonly altered checkpoint in cancer cells
• Checkpoint activation delays cell cycle and triggers DNA repair mechanisms or apoptosis via p53
If checkpoint is not functioning properly, cells with abnormal dna can proliferate
• if checkpoint is activated p53 protein halts cell cycle and tries to get dna repaires
• I it cant be repaired p53 will push cell into apoptosis
How is the cell cycle controlled?
- Cyclins and cyclin dependent kinases (CDKs)
- CDKs become active by binding with cyclins
- also CDK inhibitors
Different cyclins are åre produced at different phases - bind with CDC’s - allows cell to pass through cell cycle
Cyclin bind with cdk and activate it - CDK phosphorylates target protein - this then allows cell to pass around cycle
Cyclin bind to CDK and target protein which allows target to be phosphorylated
How many times can cells divide?
- Leonard Hayflick discovered Hayflick numbers/limits in 1961
- Humans = 61.3
Number varies according to species - size of the organism being considered
Humans 60-70
How can cells adapt?
- Hyperplasia – cells increase in number above normal
- Hypertrophy – increase in tissue or organ size due to cells increase in size
- Atrophy – Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells
- Metaplasia – cells are replaced by cells of a different type - reversible
Are cellular adaptations reversible?
Stress on cell - cell has to adapt - if pushed further if may get injured then killed
Cell adaptations are generally reversible though
In which type of tissues does hyperplasia occur?
- Labile or stable tissues - cells can divide
- Caused by increased functional demand or hormonal stimulation
- Remains under physiological control and is reversible (cf neoplasia) - Not under physiological control in neoplasia
- Can occur secondary to a pathological cause but the proliferation itself is a normal response (cf neoplasia – the proliferation itself is abnormal)
- Repeated cell divisions exposes the cell to the risk of mutations and neoplasia - Hyperplasia can open the door to neoplasia - when cells divide -prone to getting abnormality in dna - if you have repeate cell divisions - many chances for dna problems to arise
What exazmpels are there of physiological hyperplasia?
Proliferative endometrium under influence of oestrogen
Bone marrow produces erythrocytes in response to hypoxia
What examples are there of pathological hyperplasia?
Eczema - epidermis thickens - hypoplastic response
Thyroid goitre in iodine deficiency - thyroid undergoes hyperplasia
In which type of tissue does hypertrophy occur?
- Labile, stable but especially permanent tissues
- Like hyperplasia, caused by increased functional demand or hormonal stimulation
- Cells contain more structural components – workload is shared by a greater mass of cellular components
- In labile and stable tissues hypertrophy usually occurs along with hyperplasia- Classically seen a lone in permanent.
What examples are there of physiological hypertrophy?
Skeletal muscle
Pregnant uterus - (hypertrophy up to 70% size and hyperplasia)
What examples are there of pathological hypertrophy?
Ventricular hypertrophy - if heart is having to work hard eg hypertension or valvular heart disease - cells undergo hypertrophy
Pathological cardiac hypertrophy - increase in capillaries but not as much as required for myocytes - results re little area o fibrosis secondary to ischaemia throughout heart - heart not working efficiently - can affect action potential - arrhythmia problems
Atheete has time to rest but in hypertension there is no rest time
bladder hypertrophy due to enlarged prostate
Stenosis - smooth muscle hypertrophy proximal to bowel stenosis as cells working harder to propel contents
What is compensatory hypertrophy?
Paired organ - if one malformed etc. The other will increase in a compensatory way so body can mange with one eg kidney
What is happening in the cell in atrophy?
Cell atrophy,
issue/organ atrophy - shrinkage of cells as well as apoptosis
- Shrinkage in the size of the cell to a size at which survival is still possible
- Reduced structural components of the cellphone at it can just about do without
- May eventually result in cell death
Is tissue atrophy only a result of cell atrophy?
Organ/tissue atrophy typically due to
combination of cellular atrophy and apoptosis
Is reversible but only up to a point - if stress prolonged then it becomes irreversible
What happens in tissue atrophy?
Cells which become atrophied and apoptosis cells are often parenchyma cells ie cells that are doing the job - process continues - those cells die and become replaced by connectivetissue
Eg stone blocking pancreatic duct - this can cause atrophy of secreting organ being blocked - vale pale area of fibrosis of connective tissue - paranchymal cells undergone strophe
In pancreas its the exocrine cells that are most affected by blocking - left with longer larger ducts and endocrine islets
Also occurs in panreatitis
Exocrine tissue replaced by fibrosis
Structural components broken down in autophagosomes - parked in residual bodies
What examples are there of physiological atrophy?
Ovarian atrophy in post menopausal women
Withdrawal
Decrease in size of uterus - component of atrophy
What examples are there of pathological atrophy?
• Reduced functional demand/workload = atrophy
of disuse: muscle atrophy after disuse, reversible with activity
• Loss of innervation = denervation atrophy: wasted
hand muscles after median nerve damage
• Inadequate blood supply: thinning of skin on legs with peripheral vascular disease
• Inadequate nutrition: wasting of muscles with malnutrition
What examples are there of pathological atrophy?
• Loss of endocrine stimuli: breast, reproductive organs
• Persistent injury: polymyositis (inflammation of skeletal muscle)
• Aging = senile atrophy: brain, heart
• Pressure: tissues around an enlarging benign tumour (probably secondary to ischaemia)
-Calf muscle atrophy after plaster cast
Thenar atrophy
Tumour causing atrophy or brain tissue
Aneurism causing atrophy and erosion through terbium
