Flashcards in MOD S7 Deck (67):
What does the size of the cell population depend on?
How might a cell population increase in size?
Rate of cell proliferation, differentiation and apoptosis.
Increased numbers seen with:
- Increased proliferation
-Decreased cell death
What regulates cell proliferation under normal conditions?
Directly controlled by chemical signals from the microenvironment that stimulate or inhibit proliferation.
Signalling molecule binds to cell surface receptor (sometimes` cytoplasmic or nuclear) and modulation of gene expression occurs.
What are the 4 outcomes of cellular signalling that might influence the size of cell populations?
Survive - resist apoptosis, Divide - enter cell cycle, Differentiate, Die - undergo apoptosis
Cell to cell signalling is achieved by which 3 things?
Hormones, Local mediators, Direct cell to cell stroma contact
What are the 3 modes of signalling? give a brief description of each type
-Cell produces and secretes a molecule which then acts on surface receptors of the same cell.
-Intracrine is an example but the factors aren't released from the cell and act on intracellular receptors.
-Cell produces a signalling molecule which then acts on adjacent cells.
-The responding cells are close to the secreting cell and are often of a different type
- Molecule produced and secreted, then travels in blood to a distant cell and binds to receptors.
What are growth factors an example of? Give some details about their propertes
Examples of local mediators.
- They are polypeptides that act on specific cell surface receptors.
- Are considered local hormones because they act over a short distance.
- Coded for by proto-oncogenes
- Stimulate (but can inhibit) transcription of genes that regulate entry of a cell into the cell cycle and the cell's passage through the cycle.
What processes can growth factors effect?
Cell proliferation and inhibition, Locomotion, Contractility, Differentiaion, Liability, Activation and Angiogenesis.
Give some examples of growth factors and their functions
Epidermal growth factor:
- Mitogenic for epithelial cells, hepatocytes and fibroblasts; produced by keratinocytes, macrophages and inflammatory cells; binds to epidermal growth factor receptor (EGFR)
Vascular endothelial growth factor:
- Potent inducer of blood vessel development (vasculogenesis) and role in growth of new blood vessels (angiogenesis) in tumours, chronic inflammation and wound healing.
Platelet derived growth factor:
- Stored in platelet alpha granules and released on platelet activation
-Also produced by macrophages, endothelial cells, smooth muscle cells and tumour cells
-Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes
Granulocyte colony-stimulating factor:
-Stimulates bone marrow to produce granulocyes, particularly neutrophils, and release them into the blood
What does it mean if something is mitogenic?
It promotes mitosis
When do cells permanently exit the cell cycle? What stage do they enter?
When they have terminally differentiated. G0.
What are the stages of the cell cycle?
What about when cells are not actively proliferating?
Interphase: G1, S, G2
Cell not active in the cell cycle enter G0 after G1
What are quiescent cells?
Inactive cells (usually found in g0)
How can cell behaviour be altered to increase growth of a tissue? (Refer to the cell cycle)
Shortening of the cell cycle
Converting quiescent cells to proliferating cells by making them enter the cell cycle.
What feature of the cell cycle can be seen under a microscope?
Only mitosis and cytokinesis
What are the cell cycle checkpoints and why are the important?
Events where the cell's DNA is checked for errors before continuing in the cell cycle.
2 important checkpoints at the end of G1 and before M.
Prevent cells with abnormal DNA from passing this onto daughter cell and causing dysfunction/malignancy.
What is p53 known as? Why?
The guardian of the genomes. It mediates apoptosis in response to DNA damage.
What is the restriction point? Where is it found?
It is found at the end of G1 and is the most important checkpoint.
Give some facts about the restriction point:
Majority of cells that pass the R point will complete the cell cycle
It is the the most commonly altered checkpoint in cancer cells
Checkpoint activation delays the cell cycle and either DNA repair mechanism are activated or apoptosis by p53
What are defective cell cycle checkpoints a major cause of?
Genetic instability in cancer cells.
What proteins are responsible for cell cycle regulation?
Cyclins, Cyclin-dependent kinases (CDKs)
Describe cell cycle regulation
Cyclins bind to cyclin-dependent kinases (CDKs) and the cyclin CDK comples.
These phosphorylate proteins that are critical for progression to the next stage (e.g retinoblastoma susceptibility protein)
Cyclin-CDK complexes tightly regulates by CDK inhibitors
Growth factors also involved:
- Some stimulate cyclin production
- Some inhibit CDK inhibitor production
What is the major function of adult stem cells?
-Replenish the loss of differentiated cells while maintaining their own population
-They achieve this through symmetric replication (one daughter cell is a stem cell, one will mature and differentiate)
-Only one mature cell type can be produces (aka lineage specific ) - c.f embryonic stem cells.
What is the difference between labile, stable and permanent cells?
Labile: Cells continue to multiply throughout life
Stable: Cells can multiply in a regenerative burst but are usually quiescent (inactive)
Permanent: cells that cannot proliferate.
Give examples of labile, stable and permanent cell populations
- Surface epithelia (skin and gut epithelia)
- Brain neurones
- Cardiac and skeletal muscle
What is cell adaptation
When the cell is stressed, but not enough to cause cell injury changes take place to help the cell to survive that stress.
They are always reversible changes - irreversible cell changes are cell injury.
List the 5 important types of cellular adaptation
Give a very short description of each
Regeneration - cells multiply to replace loses (identical cells)
Hyperplasia - cells increase in number above normal
Hypertrophy - cells increase in size
Atrophy - cells become smaller
Metaplasia - cells are replaced by cells of a different type
Briefly explain the two major outcomes of cell regeneration
- Harmful agent removed
- Limited cell damage
- Harmful agent persists
- Extensive tissue damage due to permanent cells
What is the definition of cell regeneration? Give examples of when complete cell regeneration might occur
It is the replacement of cell losses by identical cells in order to maintain the size of a tissue or organ.
Liver regeneration following a partial hepatectomy
Replacement of skin epithelia
Are regenerated cells as good as the cells they replace?
Sometimes immediately as good, but can take weeks/months/years to be as good as predecessors if at all.
How many times can a cell regenerate?
Humans = mean of 61.3 (hayflick number)
Related to telomere shortening upon replication, after telomere shortening reaches max, cannot regenerate further
What is re-constitution? Give an example. Where does it appear in humans?
The replacement of a lost body (multiple tissues) E.g regrowing lizards tail or deers antlers
In humans, angiogenesis occurs and in children less than 4.5 years they can reconstiture the tip of a finger if it is cleanly severed.
How can cells be induced to regenerate?
By growth factors in the microenvironment, cell-to-cell communication. electric current and nervous stimuli also appear to play a role in the reconstitution of limbs in amphibians
In what types of cell population can hyperplasia occur?
Only in labile and stable populations
Is hyperplasia a normal or abnormal process?
Normal, under physiological control, only occurs secondary to abnormal conditions
When hyperplasia is abnormal is it called neoplasia
Why does hyperplasia occur?
In response to increased functional demand and/or external stimulation
What is a key differences between hyperplasia and neoplasia?
Hyperplasia remains under physiological control and is reversible - opposite to neoplasia
What is the major risk involved in a tissue undergoing hyperplasia?
Repeated cell divisions expose the cell to the risk of mutations and neoplasia
Give examples of physiological hyperplasia an the (abnormal) condition that the example is responding
Proliferation of endometrium:
Bone marrow producing erythrocytes:
Give examples of pathological hyperplasia
What is pathologica hyperplasia normally caused by?
Secondary to excessive hormonal stimulation of growth factor production
Where is hypertrophy mainly seen? When does it occur in ther cells?
It is mainly seen in permanent cells (as they cannot increase in number) but also occurs in labile and stable cells alongside hyperplasia.
Why does hypertrophy occur? Why is it advantageous?
Due to increased functional demand and/or hormonal stimulation
Greater cell demand can then be met by a greater mass of cellular components to prevent cell damage (workload can be shared)
Give examples of physiological hypertrophy
Skeletal muscle growth
Pregnant uterus (alongside hyperplasia)
Cardiac muscle (in response to exercise)
Give examples of pathological hypertrophy and include the condition that it is responding to
- In response to hypertension/valve stenosis
- In response to enlarged prostate blocking the urethra
Smooth muscle upstream of intestinal stenosis:
- Extra work of having to push lumen contents through the narrowed lumen
What is compensatory hyperplasia?
Hyperplasia in response to removal of tissue
For example, when a kidney is removes, the remaining kidney will undergo hypertrophy to meet demand
What happens if the stimulus for hypertrophy or hyperplasia disappears?
The cells and organs become normal size once again
When is cardiac hypertrophy an example of physiological hypertrophy?
In athletes. because they are only under strain for a short period of time and then they are able to rest
How is childhood obesity an example of hypertrophy?
In childhood there is an increase in fat tissue and protein synthesis, causing there to be lots of adipocytes. These then remain present al thought life so can always fill with fat again.
What are the two types of atrophy?
Cellular - Decrease in cell size
Organ/Tissue atrophy - cellular atrophy and apoptosis.
Describe the main mechanism of tissue/organ atrophy (aka cellular deletion)
Cells are picked out to undergo apoptosis
Often in atrophic organs parenchycmal cells will under apoptosis before stromal cells
What is involved in cellular atrophy (aka cell shrinkage)?
Cells shrink via auto-digestion to a size at which survival is still possible
Cell contains reduced number of structural components and has reduced function.
Give an example of extracellular matrix atrophy
Loss of bone matrix do to bed rest/spaceflight
This is due to lack of mechanical stress which stimulates bone matrix regeneration.
Give two examples of physiological atrophy
Post menopausal ovary and uterus atrophy
Post partum / natal (after giving birth) atrophy
What mneumonic should you remember for the pathological examples of atrophy?
Give a list of 8 causative factors for atrophy and an examples of where each might cause atrophy
Loss of innervation (Disuse) - Muscles atrophy when not in use (e.g bed rest)
Reduced funtional demand/workload (Denervation) - Muscle atropy in the hand after median nerve damage
Inadequate blood supply - Thinning of the skin on the legs with peripheral vascular disease
Inadequate nutrition - Wasting of muscles
Loss of endocrine stimuli - Breast and reproductive organ atrophy
Persistint injury - polymyositis (muscle inflammation)
Ageing - Senile atrophy of braing and heart
pressure - tissues around a beningn tumour
What causes metaplasia and why is it advantageous?
Due to altered stem cell differentiation
May represent adaptive substitution of cells that are sensitive to stress with those better able to withstand the adverse environment.
In what cells can metaplasia occur?
Only cells which can replicate
What is the mechanism of metaplasia?
One phenotype of cells is eliminated and they a new genetic 'program' is expressed by cells so a new phenotype is produced.
Give an example of abnormal metaplasia
Give a brief description of abnormal cells that have undergone metaplasia
Dysplastic and cancerous epthelium (cancerous tissue is irreversible)
Disorganised and abnormal differentiation
Sometimes a prelude to dysplasia and cancer
What cell type mose commonly undergoes mtaplasia and what is it replaced with?
Columnar epithelium undergoes metaplasia and becomes the more resilient squamous epithelium
How is differentiation into new cell types limited in metaplasia?
Can only differentiation into cell type of the same germ layer.
What is a germ layer?
It is a primary layer of cells tat form during embryogenesis. The three germ layers in humans and endo, ecto and mesoderm.
Give 2 examples of metaplasia, include the causative factor
Bronchial pseudostratified columnar epithelium to stratified squamous epithelium. Due to cigarette smoke exposure.
Stratified squamous epithelium to gastric glandular epithelium - persistent acid reflux.
Describe hypoplasia and give an example
Underdevelopment of a tissue/organ at the embryonic stage, inadequate number of cells.
In a spectrum with aplasia
Not the opposite of hyperplasia and it's congenital only, it's not atrophy
E.g hypoplastic left heart
Describe aplasia and give an example.
Complete failure of a specific tissue/organ to develop
Also used to describe an organ whose stem cell have stopped proliferation.
E.g bone marrow in aplastic anaemia or kidney aplasia
What is involution? Give an example
The normal, programmed shrinkage of an organ. Overlaps with atrophy.
Uterus shrinkage post partum or thymus is early life.
What is atresia?
Lack of embryonic development of an orifice (opening) E.g anus or vagina