Cell Adaptation Flashcards
What types of cell to cell signalling largely control cell proliferation?
In the microenvironment
Autocrine
Paracrine
Direct cell to cell or cell to stroma contact
What genes regulate normal cell proliferation?
Proto-oncogenes
What are growth factors?
Chemical mediators involved locally in cell proliferation. They are polypeptides which act on cell surface receptors and coded by proto-oncogenes.
Affect cell proliferation, inhibition, locomotion and contractability.
What is the function of epidermal growth factor?
Mitogenic for epidermal cells.
What produces epidermal growth factor?
Keratinocytes
Macrophages
Inflammatory cells
What is the function of V-EGF
Stimulates vasculogenesis and angiogenesis.
What is the function of platelet-derived growth factor?
Stimulates the migration and proliferation of fibroblasts, smooth muscle and monocytes.
What produces platelet derived growth factor?
Alpha granules of platelets Macrophages Endothelial cells Smooth muscle Tumour cells
What is the function of G-CSF?
Promotes granulocyte production in the bone marrow.
Give a clinical application of G-CSF.
Treat poorly functioning bone marrow, such as when undergoing chemotherapy.
What is the difference between mitosis and cytokinesis?
Mitosis - nuclear division
Cytokinesis - cellular division
Briefly describe the four stages of the cell cycle.
G1 - cell growth, presynthetic
S - synthesis of DNA
G2 - premitotic, cell prepares to divide
M - mitosis. The only distinctive stage under a light microscope.
What is a particularly important check point in the cell cycle?
Restriction point - most cells which pass this will enter the cell cycle.
Most commonly changed in cancer cells.
Describe the role of p53 in the cell cycle.
Produced when a check point is activated. Suspends the cell cycle and triggers DNA repair, but pushes the cell into apoptosis if this doesn’t work.
What two types of molecule are especially important for controlling the cell cycle and why?
Cyclins and cyclin-dependent kinase.
CDK works on it’s substrate when cyclin is bound, such as retinoblastoma susceptability protein.
How do growth factors affect the cell cycle?
Can increase it’s rate or activate quiescent cells by increasing cyclin production or decreasing CDK inhibitors.
Describe labile cells.
Short lived.
Stem cells divide persistently to repair losses.
Give an example of where labile cells can be found.
Epithelia of the gut
Bone marrow
Skin
Describe stable cells.
Stem cells which are normally quiescent or divide very slowly.
They proliferate persistently when regeneration is needed.
Occurs in organs with slow turnover.
Give an example of where labile cells can be found.
Hepatocytes
Bone
Describe permanent cells.
Undergo terminal differentiation.
Stem cells are unable to mount an effective proliferative response.
Give an example of where permanent cells can be found.
Brain neurons
Cardiac muscle
Skeletal muscles
If neurons in the brain die, how does the body fill the space?
Proliferation of glial cells.
Explain what is meant by asymmetrical replication in stem cells.
They can divide to produce one stem cell and one differentiated cell.
What is the difference between adult-type and embryonic stem cells?
Adult can only divide into one or a few cell types whereas embryonic are pluripotent
Describe the meaning of regeneration.
Replacement of cell losses by identical cells to maintain the tissue or organ size.
Describe what determines whether a scar forms when there is tissue damage.
If the harmful agent is removed, there is a small amount of tissue damage and it is in labile or stable cells there can be resolution with minimal or no scarring.
If the agent persists, there is extensive damage or it is in permanent cells, scarring will occur.
What stimulates regeneration?
Growth factors
Cell-cell adhesions.
Why are tendons unable to heal well?
They are relatively avascular.
Why are scars and damaged skin generally hypopigmented?
Melanocytes are poor at regeneration
If there is a large gap between peripheral nerves which they need to repair, what can form and why?
A neuroma
Nerves become tangled.
How can the brain recover function to an extent after a stroke?
The CNS has plasticity which allows it to form alternative pathways.
Can regenerated cells be as good as those that they replace?
Yes
Describe a situation in which the long maturation time of regenerated cells is an advantage.
H1N1 virus infects and kills respiratory epithelial cells.
New immature cells don’t have the receptor which the virus uses to enter the cells.
Builds a level of immunity to the virus.
What is the number of regenerations of a cell dependent on?
Hayflick’s number
The number of times that a cell can divide.
Relys on telomer length which decreases with each division.
What is reconstitution?
The replacement of a lost part of the body.
Requires coordinated proliferation of different cell types.
Give some examples of reconstitution in people.
Small blood vessels, such as in the uterine lining in menstruation
In children less than four, a finger amputated distal to the distal interphalangeal joint will grow back.
What is hyperplasia?
An increase in tissue or organ size due to an increase in cell number.
Won’t return the organ to its original size.
Only occurs in labile or stable cell populations
Is a normal response to abnormal conditions.
What conditions can cause hyperplasia?
Increased functional demand
External stimulation
Is hyperplasia reversible?
Yes if the stimulus is reversed.
Give some examples of tissues that undergo hyperplasia, both as a normal and pathological response.
Endometrium by increased hormonal stimulation from oestrogen.
Bone marrow in response to hypoxia
Goitre in iodine deficiency
Secondary to excess hormone or growth factor
Eczema
Psoriasis
What is hypertrophy?
An increase in tissue or organ size due to an increase in cell size without proliferation.
Can be due to an increase in functional demand or external stimulation.
What cell type does hypertrophy usually occur in?
Permanent cells.
Can be in any tissue and alongside hyperplasia.
Give some examples of hypertrophy both due to normal and pathological situation.
Skeletal muscle in bodybuilding
Smooth muscle in the pregnant uterus (and hyperplasia)
Ventricular hypertrophy
Bladder smooth muscle when the prostate is enlarged
Intestine above an area of stenosis.
What is compensatory hypertrophy?
When one organ is damaged so another must take over
Give an example of where compensatory hypertrophy may occur.
Kidney
Is compensatory hypertrophy reversible?
Yes if the stimulus is removed.
Why can being obese as a child lead to an increased risk of being obese as an adult?
Over nutrition increases fat cells and protein synthesis.
The adipocytes never go away so always have the potential to fill.
What is atrophy?
The shrinkage of tissues or organs due to a decrease in the size or number of cells.
Can be due to low nutrition or decreased growth factor.
What mechanism is used to remove cells in atrophy, and what part of an organ is lost first?
Apoptosis - specific cells are identified.
Parenchyme lost first, then stroma
What is a residual body?
An autophagosome with lipofuscin and undigested remnants and can be viewed under a light microscope.
What is the function of ubiquitin in atrophy when cell contents are being reduced?
It binds to proteins that need to be removed, targeting them for destruction.
Is atrophy reversible?
Initially reversible by removing the stimulus.
Will become irreversible
Give some examples of atrophy, both in normal situations and pathological.
Ovaries in post-menopausal women
Atrophy of disuse (e.g. skeletal muscle)
Inadequate blood supply (if gradual)
Thin skin on the legs in peripheral vascular disease
Persistent inflammation such as polymyositis
Pressure such as tissue around a benign tumour, probably secondary to ischaemia
Cerebral atropy in Alzheimer’s disease
Senile atrophy
Immunological mechanisms such as atrophic gastric mucosa
Inadequate nutrition (brain will be the last to atrophy)
Decreased endocrine stimulation
What is metaplasia?
The reversible change of one differentiated cell type to another. Clearly adaptive in epithelial tissues.
Terminally differentiated cells are eliminated and stem cells are reprogrammed to replace them with different tissues.
It is an adaptive response.
What induces metaplasia?
Signal changes from cytokines or growth factors
Give some examples of metaplasia occurring.
Barrett's oesophagus Traumatic myositis ossificans Myeloid metaplasia in the spleen Squamous cell metaplasia of the lungs Intestinal metaplasia of the stomach
Why can metaplasia be dangerous?
It can increase the risk of dysplasia or cancerous cells with abnormal differentiation
Describe Barrett’s oesophagus.
Changes to the glandular epithelium so the function can be changed or lost.
Can be due to chronic Heliobacter pylori infection.
How can cigarette smoke cause metaplasia in the bronchi and trachea?
The smoke damages the pseudostratified ciliated columnar epithelia, and stem cells change to produce stratified squamous epithelia which eliminates the mucociliary escalator.
In what circumstance will the spleen undergo myeloid metaplasia?
When there is extensive damage to the bone marrow.
What is hypoplasia?
Incomplete or underdevelopment of a tissue or organ which is congenital.
Give an example of when hypoplasia occurs.
Testes in Klinefelter’s
Kidney
Breasts
Heart chambers
What is aplasia?
Complete failure of a specific tissue or organ to develop, or those in which the cells are unable to differentiate.
Give an example of when aplasia occurs.
Thymic aplasia leading to chronic infection or autoimmune problems
Aplasia of the kidney
Aplastic anaemia
What is involution?
Overlaps with atrophy. Normal, progressive shrinkage.
Give an example of when involution occurs.
Uterus after childbirth
Thymus in early life
Temporary foetal origins
What is atresia?
When an opening is lost
What is dysplasia?
Abnormal maturation of cells within tissues, often pre-cancerous. Potentially reversible.
