MoD Session 7 Flashcards
What regulates proliferation in physiological and pathological conditions?
Proto-oncogenes
What does the size of a cell population depend on?
Proliferation
Cell death
How are cells stimulated to divide?
Signal molecule binds to a receptor modulating gene expression and causing the cell to enter the cell cycle
How can increased cell growth arise?
Shortening of cell cycle
Conversion of quiescent cells
Where can receptors for signal molecules modulating gene expression be found in a cell?
Usually membrane but can be cytosol or nucleus
How can cell to cell signalling occur to cause cells to divide?
Hormones
Local mediators
Direct cell-cell/cell-stroma contact
How does endocrine signalling take place?
Cell secretes molecules into circulation which then act on a distant cell
How does autocrine signalling work?
Cell secretes molecules and expresses receptors for them on CSM
How does intracrine cell signalling work?
Cell synthesises signalling molecules but does not secrete it so it can act on receptors present in the cell
How does paracrine cell singling work?
Cell releases molecules that act on a nearby cell
What is G1?
Gap 1 stage in the cell cycle before DNA synthesis where the cell grows
What happens in the S stage of the cell cycle?
DNA synthesis
What is G2?
Gap 2 stage of the cell cycle where the cell prepares to divide
What happens in the M stage of the cell cycle?
Mitosis
Where are the checkpoints in the cell cycle located?
Between G1 and S
Between G2 and M
What distinctive processes occur during the M stage of the cell cycle that can be seen under the light microscope?
Mitosis
Cytokinesis
What regulates transition of a cell from G1 to S in the cell cycle?
Cyclin E
CDK2
What regulates transition of a cell from S to G2 in the cell cycle?
Cyclin A
CDK2
What regulates transition of a cell from G2 to M in the cell cycle?
Cyclin B
CDK1
What regulates transition of a cell from M to G1 in the cell cycle?
Cyclin D
CDK2
What is permanent exit from the cell cycle called?
Terminal differentiation
How long does it take for a cell to enter the cell cycle
A few hours
During which stages of the cell cycle does interphase occur?
G1
S
G2
Which is the most critical point in control of the cell cycle?
Restriction point towards the end of G1
What happens to the majority of cells that pass the restriction point?
Complete the full cell cycle
What can the restriction point towards the end of G1 also be considered as?
Point of no return
What is the most commonly altered checkpoint in cancer cells?
Restriction point
What can checkpoint activation trigger?
DNA repair
Apoptosis via p53
What action does p53 have when a checkpoint is activated?
Stops cell cycle and stimulates DNA repair which if not possible will then stimulate apoptosis
What are cells responsive to up until the restriction point?
Mitogenic growth factors
TGF-beta
How do cyclins tightly regulate the transition of cells from G to S?
Bind with enzymes needed causing phosphorylation of the substrate activating the cyclin dependent kinase
What tightly regulates the CDK-cyclin complex?
CDK inhibitors
What are growth factors?
Polypeptides that act on specific CSM receptors to regulate transcription of genes regulating entry and passage of the cell through the cell cycle
What effects do growth factors have on a cell?
Proliferation Inhibition Locomotion Contractility Differentiation Viability Activation Angiogenesis
Give four named examples of growth factors.
Epidermal growth factor
Vascular endothelial growth factor
Platelet derived growth factor
Granulocyte colony-stimulating factor
Why is GCSF given after chemotherapy?
Used pharmacologically to stimulate neutrophil release from bone marrow
What is the difference between adult and embryonic stem cells?
Adult have one mature type
Embryonic have multiple mature types
What replenishes loss of differentiated cells?
Tissue stem cells present in most but not all adult tissues
Compare the proliferation of labile, stable and permanent stem cells.
Labile: divide persistently to replenish losses
Stable: normally quiescent/slowly proliferating but proliferate persistently when needed
Permanent: cannot mount an effective proliferative response to significant cell loss
How long do labile mature cells live?
Short amount of time
Can stable mature cells proliferate if needed?
Yes
Can cell adaptation be reversed?
Yep as long as cell isn’t injured
What is regeneration?
Replacement of cell losses by identical cells to maintain tissue/organ size
How does the effectiveness of cells after regeneration change?
After a short delay they are as effective as the original cells
Why are immature respiratory epithelial cells immune to flu virus?
Lack receptors as not fully functional yet
What happens in regeneration if a harmful agent persists?
Causes extensive damage including to permanent cells leading to scar formation
What happens in regeneration if a harmful agent is removed?
Tissue damage is limited so regeneration can occur in non-permanent tissue causing a negligible scar which does not affect function therefore achieving resolution
What is the Hayflick number?
Number of regenerations cells can undergo dependent on species and its life expectancy
What is hyperplasia biologically similar to?
Regeneration
What is characteristic about the increase in size seen in hyperplasia?
It is not uniform
When can hyperplasia occur?
Only in labile or stable cell populations under reversible physiological control
What can hyperplasia be in response to?
Normal response to abnormal condition
Secondary response to pathological cause
What does hyperplasia expose a cell to?
Risk of mutations - neoplasia
Why is hyperplasia seen physiologically in the endometrium and bone marrow?
To increase functionality of the tissue
What stimulates physiological hyperplasia?
Hormones
Give two examples of pathological hyperplasia.
Eczema
Goitre
What is hyperplasia?
Increase in tissue/organ size due to increased cell number
What is hypertrophy?
Increase in tissue/organ size due to increase in cell size
What causes hypertrophy in permanent cells?
Increased workload by increased functional demand or hormonal stimulation
Why do hypertrophied cells contain more structural components?
So workload is shared and therefore less likely to injure individual components
What can hypertrophy occur alongside?
Hyperplasia
In what tissues is physiological hypertrophy seen?
Skeletal muscle
Pregnant uterus
In what tissues can pathological hypertrophy be seen?
Ventricular muscle
Bladder muscle due to compression by prostrate
What is atrophy?
Shrinkage of a tissue/organ due to an acquired decrease in size and/or number of cells
How does the reversibility of atrophy change with time?
Possible but becomes less so with increased time
How are residual bodies formed in atrophy?
Cells get rid of what they can manage without
In what order are tissues lost in atrophy?
Functional tissues are lost before connective tissue support
In what order does pancreatic tissue atrophy?
Leaves islets of Langerhans in islands of CT as parenchyma lost before stroma
What is metaplasia?
Reversible change of one differentiated cell type to another
Is atrophy associated more with physiology or pathology?
Pathology
What do many metaplasias represent?
Adaptive substitution
What allows metaplasia to happen?
Altered stem cell differentiation
How does metaplastic tissue differ from dysplastic and cancerous epithelium?
It is fully differentiated so is organised
What can metaplasia sometimes prelude?
Dysplastia and cancer
What cells can metaplasia happen in?
Only in cells that replicate
What causes the new phenotype in metaplasia?
New genetic programme expression
What is reconstitution?
Replacement of a lost part of the body
How does reconstitution differ from proliferation?
Requires coordination of lots of different cell types not just one
When is reconstitution seen in adults?
Angiogenesis
Shay are scars hairless?
Hair follicles cannot reconstitute
Why is physiological hypertrophy of cardiac muscle not dangerous?
There is a period of rest from the increased resistance to blood flow causing the hypertrophy
When does physiological hypertrophy of the heart become pathological?
If the increased angiogenesis for the heart is insufficient and causes relative ischaemia
What is compensatory hypertrophy?
Removal of one of a paired organ causes functional overstrain on the remaining organ thus causing hypertrophy
What is seen in functional overstrain of the kidney?
Hypertrophy
Hyperplasia
What happens if the functional overstrain is removed in compensatory hypertrophy?
Hypertrophy is resolved
What can cause pathological atrophy?
Loss of endocrine stimuli Inadequate nutrition Senile atrophy Inadequate blood supply Denervation Persistent injury Pressure Disuse
In what organs is senile atrophy seen in?
Spleen Liver Heart Brain Kidneys
Why does only partial or gradual inadequate blood supply cause pathological atrophy?
Sudden inadequate blood supply causes cell injury
In what circumstances is physiological atrophy seen?
Post menopausal ovaries
Post childbirth
What causes physiological atrophy?
Loss of endocrine stimuli
Which disease is an example of cerebral pathological atrophy?
Alzheimer’s
How can atrophy of disuse be reversed?
With activity
Why does smoking cause metaplasia?
The end tissue is better able to withstand the irritating effects of smoke
What change in phenotype is seen in metaplasia caused by cigarette smoking?
Bronchial pseudostratified ciliated epithelium to stratified squamous epithelium
What is lost in metaplasia caused by cigarette smoke?
Mucociliratory escalator
What metaplasia is seen in persistent acid reflux?
Stratified squamous to gastric/intestinal glandular epithelium
What is metaplasia due to persistent acid reflux called?
Barrett’s oesophagus
How does muscle injury lead to metaplasia?
Fibroblasts turn into osteoblasts so bone is laid down in muscle
What causes metaplasia in muscle injury?
Returning to activity prematurely after injury
What is hypoplasia?
Congenital condition in which there is an underdevelopment/incomplete development of a tissue/organ at the embryonic stage due to an inadequate number of cells
Where might hypoplasia be seen?
Kidneys
Breasts
Testes in Klinefelter’s syndrome
Chambers of the heart
Who discovered the function of platelets, described helicon acted pylori and classified cells by stheir ability to multiply?
Giulio Bizzozero
What is aplasia?
Embryonic developmental disorder causing complete failure of a specific tissue/organ to develop
What does thymic aplasia cause?
Infections and autoimmune problems
What is seen in aplasia of a kidney?
Only one kidney present
What term is used to describe an organ whose cells no longer proliferate?
Aplasia
What is seen in aplastic anaemia?
Aplasia of bone marrow
What is involution?
Normal programmed shrinkage of an organ
When is involution seen?
Uterus after childbirth
Thymus in early life
Foetal organs (pro- and mesonephros)
What is atresia?
Lack of an opening which can be seen in part of the gut/anus/vagina
What is dysplasia?
Potentially reversible abnormal cells in a tissue
What is dysplasia often seen before?
Cancer
Why is the regenerative capacity of a tendon poor?
It is avascular
Why is secondary rupture of a tendon common?
Due to abnormal use of other tendons to compensate
What is the regenerative capacity of the skin?
Good
What is the regenerative capacity of the liver?
Good
What happens to transplant livers which demonstrates its good regenerative capacity?
It will regrow to almost the exact same size of the removed liver
In what circumstances is peripheral nerve regeneration capacity not OK?
If injury is severe
If distance to be branched is too far
Why is hypopigmentation seen in scars?
Poor regenerative capacity of melanocytes
What causes a neuroma?
Disorganised regeneration of a peripheral nerve
What does the CNS have instead of good regenerative capacity?
Plasticity to form alternative pathways around damage
Why is improvement in symptoms seen following strokes with therapy?
CNS forms alternative pathways around the damage
