Session 7 - Cellular adaptations Flashcards
How do cell populations increase in cell number?
- Increased proliferation
- Decreased death
What determines the size of cell populations?
- The rate of cell proliferation
- The rate of cellular differentiation
- The rate of apoptosis
What are proteo-oncogenes?
-Genes which regulate cellular cellular proliferation
What are the final possible outcomes of cellular signalling?
- Survive
- Divide
- Differentiate
- Die
How does cell-cell signalling occur?
- Hormones
- Local mediators
- Direct cell-cell contact or cell-stroma contact
What is intracrine signalling?
-Cells synthesise a factor but does not secrete it and it binds to its own intracellular receptors
What are growth factors?
-Polypeptides which work through cell-surface receptors to act as local mediators for cellular proliferation
What genes encode for growth factors?
-Proto-oncogenes
How do growth factors effect cellular proliferation?
-Bind specific receptors and stimulate the transcription of genes which regulate entry into the cell cycle
Other than cellular proliferation, briefly name a few events which are controlled by growth factors
- Differentiation
- Contractilitty
- Angiogenesis
- Migration
What is EGF?
- Epidermal growth factor
- Mitogenic for epithelial cells, hepatocytes and fibroblasts
- Produced by macrophages and keratinocytes
What is VEGF?
- Vascular endothelial growth factor
- Potent inducer of BV development and angiogenesis in wound healing, chronic inflammation and tumours
What is PDGF?
- Platelet-derived growth factor
- Stored in platelet a-granules and released upon activation
- Causes migration of fibroblasts, smooth muscle cells and monocytes
What is GCSF?
- Granulocyte colony-stimulating factor
- Stimulates BM to produce blood cells, especially neutrophils
- Used after chemotherapy
Briefly describe the cell cycle
G0- resting phase
G1 -Gap 1, presynthetic, cell grows,check point after
S-DNA replication
G2 - gap 2, premitotic, cell prepares to divide, check point after
M-> mitosis
How does increased proliferation occur in terms of cell cycle?
- Shortening the cycle (can take a few hours)
- Conversion of G0 cells to proliferating cells through making them enter the cel cycle
Which check point is most significant?
- R after G1
- Majority of cells which pass the point of R will complete the full cell cycle-> point of no return
- Most commonly altered check point in cancer cells
If a cell is damaged and detected by R, what happens?
-The cell cycle is delayed, DNA repair mechanisms are triggered or apoptosis through p53 is induced
What are cyclins?
-A family of proteins which control the progression of cells through the cell cycle by activating cyclin-dependant kinase enzymes
How do cyclins activate CDK?
-Bind to it and induce its phosphorylation to become fully activated
What do activated CDK do?
-Control other enzymes which are responsible for progression through the phases of the cell cycle
What cells are responsible for cellular proliferation?
-Stem cells
What is self-renewal during stem cell division?
-Stem cell undergoes asymmetric division so one daughter cell differentiates and the other remains a stem cell
What is a labile population?
-Population of cells in which stem cells divide persistently to replenish loss
What is a stable cell population?
-Population of cells which is normally stable, but quiescent cells can proliferate persistently when required
What are permanent cell populations?
-Stem cells present but cannot mount an effective proliferative response to significant cell loss
Give an example of labile populations
- Epidermis
- Gut epithelia
- BM
Give an example of stable cell populations
- Hepatocytes
- Osteoblasts
Give an example of permanent cell population
- Brain neurones (replaced by glial cells)
- Cardiac and skeletal muscle
What are the 5 important types of cell adaption?
- Regeneration
- Hyperplasia
- Hypertrophy
- Atrohpy
- Metaplasia
What is regeneration?
-The replacement of cell losses by identical cells to maintain tissue or organ size (cells multiply to replace losses)
What are the two possible outcomes of regeneration?
- Resolution with negligible scar tissue
- Scarring
When does resolution occur in regeneration?
- Removal of harmful agent
- Limited tissue damage
When does scarring occur in regeneration?
- Persistent harmful agent
- Extensive tissue damage
- Permanent cell populations
Is regeneration always due to injury?
-No occurs physiologically eg RBC replacement, epithelia
What is the main factor which determines the outcome of regeneration?
-The regenerative capacity of the tissue, ie whether it is a labile/permanent population eg epithelial vs CNS
Do tendons have good regenerative capacity?
-No, there are few/if any BVs in them so regeneration is often poor and leads to secondary rupture
If CNS neurones cannot regenerate, how is it possible to recover from a stroke?
- Regeneration is replacement by identical cells
- The plasticity of neurones means alternative pathways are generated, it is not the same
Are regenerated cells as good as the original cells? Why may this be beneficial?
- Usually but not always-> can take weeks/years to reach morphological maturity
- When exposed to certain viruses which infect mature cells eg influenzae, immature endothelia do not have influenzae receptor and so are protected
What is the role of retinoblastoma susceptibility protein in cell cycle?
-Restricts the cells ability to replicate its DNA by preventing progression from G1
How is RB protein inhibited?
-Phosphorylation by activated CDK
Describe the regeneration capacity of the following tissues:
Bone, Cartilage, Adipocytes, Epithelia, Liver, Melanocytes, Smooth muscle, Striated muscle, peripheral nerves, CNS
Bone-> Very good; Cartilage -> Poor; Adipocytes-> nil; Epithelia -> very good; Liver -> Very good; Melanocytes -> Tend to regenerate too little (hypopigmentation); Smooth muscle -> very well; Striated muscle -> Limited (regenertaion from satellite cells); Peripheral nerves -> predicatble (sprouts 1-3mm/day); CNS -> none
When does a neuroma form?
-When regenerating axons of peripheral nerves have to cross a wide gap and a disordered tangle forms
What induces cells to regenerate?
- Growth factors
- Cell-cell communication
What is reconstitution?
-The replacement of a lost part of the body eg blood vessels in wound healing
What is hyperplasia?
-Increase in tissue/organ size due to increased cell number in response to increased functional demand or external stimulation
Does hyperplasia occur in all tissues?
-No only in labile and stable populations
Is hyperplasia physiological or pathological?
- It is under physiological control
- Can be secondary to pathological cause, however the proliferation itself is a normal response to another abnormal condition
What are the disadvantages of repeated cell divisions in hyperplasia?
-Exposes cells to the risk of mutations and neoplasia
Give a physiological example of hyperplasia?
- Proliferative endometrium influenced by oestrogen
- BM producing more RBC in response to hypoxia (altitude)
Give a pathological example of hyperplasia?
- Thyroid goitre
- Epidermal thickening in eczema/psoriasis
Is hyperplasia reversible?
-Yes
What is hypertrophy?
-Increase in tissue/organ size due to increased cell size
Does hypertrophy occur in all cells?
-Yes, but especially permanent cell populations as they cannot divide
What are the main causes for hypertrophy?
- Increased functional demand
- Increased hormonal stimulation
What happens on a cellular level in hypertrophy?
- Cell increases in size
- Organelles increase in number
Give physiological examples of hypertrophy
- Pregnant uterus (Hypertrophy+hyperplasia)
- Skeletal muscle
Give pathological examples of hypertrophy
- Ventricular hypertrophy (hypertension/abnormal valves/pulmonary)
- Urinary bladder during prostate enlargement -> bladder has to work harder to empty as urethra narrows
Is hypertrophy of cardiac muscle always pathological?
-No, can occur in athletes without the pathological consequences as the heart is not constantly working hard as in hypertension
What is compensatory hypertrophy?
-Occurs in paired organs when one is removed or hypoplastic; the other organ hypertrophies due to extra work load
Define hypoplasia
-The underdevelopment of an organ or tissue at the embryonic stage eg heart, kidneys, breasts
Define aplasia
-Total failure of development of an organ or tissue at the embryonic stage
Is hypertrophy reversible?
-Yes
What is atrophy?
-Shrinkage of a tissue or organ due to an acquired decrease in cell size or number
Why is cardiac hypertrophy a problem?
-The number of capillaries increase but not enough to satisfy the increased muscle mass, leads to anoxia and fibrosis. This decreases compliance and effectiveness and can eventually lead to myocardial exhaustion
What are the main causes of atrophy?
- Reduced functional demand
- Reduced hormonal stimulation
How do cells reduce in size?
- Reduce the number of structural components by eliminating organelles into residual bodies which are digested.
- Removal of proteins by ubiquitin binding and targeting them for destruction
How do organs/tissue reduce in cell number?
- Cells are picked to undergo apoptosis
- If they are situated on an external surface then cell remnants are lost into the lumen or from the surface of the body
- Otherwise they will be removed by phagocytosis by macrophages or neighbouring cells
In organs undergoing atrophy, why part of the organ is effected first?
-Parenchyma thus atrophic tissues contain large amounts of connective tissue
Is atrophy reversible?
-Upto a point, after that it becomes permanent with reduced function
Give a physiological example of atrophy
- Decrease in uterus after parturition
- Ovarian atrophy in post-menopausal women
Provide examples of pathological atrophy
- Dis-use atrophy (reduced functional demand/workload)
- Denervation atrophy (loss of innervation)
- Inadequate blood supply
- Inadequate nutrition
- Loss of hormonal stimulation
- Persistant injury
- Ageing
What is metaplasia?
-The reversible change of one cell type to another
What happens in metaplasia to change the cell type present to a different one?
-Original cells die due to stress -> altered stem cell differentiation and they produce another fully differentiated cell more capable of withstanding the stress
Where is metaplasia the most adaptive?
-Epithelia
Does metaplasia occur in all tissues?
-No, only those which can replicate
Give an example of metaplasia in the bronchi
How does this affect function?
- Psuedostratified ciliated epithelia -> stratified squamous epithelia due to cigarette smoking
- No mucocilliary esculator
What can result from metaplasia in the bronchi to stratified squamous epithelia?
-Squamous cell carcinoma
Give an example of metaplasia in the oesaphagus, what it can mead to and what causes it?
- Stratified squamous epithelium -> gastric glandular epithelium
- Oesophageal adenocarcinoma
- Persistent acid reflux
What is involution?
- Normal programmed shrinkage of an organ (overlaps with atrophy)
- Uterus after child birth
- feotal organs (Pro- and mesonephros)
Define atresia
-No development of an orifice eg anus, vagina, gut
Define dysplasia
-Premalignant lesions of irregular and disorganised epithelia
