Session 7 - Cellular adaptations Flashcards
0
Q
How do cell populations increase in cell number?
A
- Increased proliferation
- Decreased death
1
Q
What determines the size of cell populations?
A
- The rate of cell proliferation
- The rate of cellular differentiation
- The rate of apoptosis
2
Q
What are proteo-oncogenes?
A
-Genes which regulate cellular cellular proliferation
3
Q
What are the final possible outcomes of cellular signalling?
A
- Survive
- Divide
- Differentiate
- Die
4
Q
How does cell-cell signalling occur?
A
- Hormones
- Local mediators
- Direct cell-cell contact or cell-stroma contact
5
Q
What is intracrine signalling?
A
-Cells synthesise a factor but does not secrete it and it binds to its own intracellular receptors
6
Q
What are growth factors?
A
-Polypeptides which work through cell-surface receptors to act as local mediators for cellular proliferation
7
Q
What genes encode for growth factors?
A
-Proto-oncogenes
8
Q
How do growth factors effect cellular proliferation?
A
-Bind specific receptors and stimulate the transcription of genes which regulate entry into the cell cycle
9
Q
Other than cellular proliferation, briefly name a few events which are controlled by growth factors
A
- Differentiation
- Contractilitty
- Angiogenesis
- Migration
10
Q
What is EGF?
A
- Epidermal growth factor
- Mitogenic for epithelial cells, hepatocytes and fibroblasts
- Produced by macrophages and keratinocytes
11
Q
What is VEGF?
A
- Vascular endothelial growth factor
- Potent inducer of BV development and angiogenesis in wound healing, chronic inflammation and tumours
12
Q
What is PDGF?
A
- Platelet-derived growth factor
- Stored in platelet a-granules and released upon activation
- Causes migration of fibroblasts, smooth muscle cells and monocytes
13
Q
What is GCSF?
A
- Granulocyte colony-stimulating factor
- Stimulates BM to produce blood cells, especially neutrophils
- Used after chemotherapy
14
Q
Briefly describe the cell cycle
A
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
15
Q
How does increased proliferation occur in terms of cell cycle?
A
- Shortening the cycle (can take a few hours)
- Conversion of G0 cells to proliferating cells through making them enter the cel cycle
16
Q
Which check point is most significant?
A
- 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
17
Q
If a cell is damaged and detected by R, what happens?
A
-The cell cycle is delayed, DNA repair mechanisms are triggered or apoptosis through p53 is induced
18
Q
What are cyclins?
A
-A family of proteins which control the progression of cells through the cell cycle by activating cyclin-dependant kinase enzymes
19
Q
How do cyclins activate CDK?
A
-Bind to it and induce its phosphorylation to become fully activated
20
Q
What do activated CDK do?
A
-Control other enzymes which are responsible for progression through the phases of the cell cycle
21
Q
What cells are responsible for cellular proliferation?
A
-Stem cells
22
Q
What is self-renewal during stem cell division?
A
-Stem cell undergoes asymmetric division so one daughter cell differentiates and the other remains a stem cell
23
Q
What is a labile population?
A
-Population of cells in which stem cells divide persistently to replenish loss
24
What is a stable cell population?
-Population of cells which is normally stable, but quiescent cells can proliferate persistently when required
25
What are permanent cell populations?
-Stem cells present but cannot mount an effective proliferative response to significant cell loss
26
Give an example of labile populations
- Epidermis
- Gut epithelia
- BM
27
Give an example of stable cell populations
- Hepatocytes
| - Osteoblasts
28
Give an example of permanent cell population
- Brain neurones (replaced by glial cells)
| - Cardiac and skeletal muscle
29
What are the 5 important types of cell adaption?
- Regeneration
- Hyperplasia
- Hypertrophy
- Atrohpy
- Metaplasia
30
What is regeneration?
-The replacement of cell losses by identical cells to maintain tissue or organ size (cells multiply to replace losses)
31
What are the two possible outcomes of regeneration?
- Resolution with negligible scar tissue
| - Scarring
32
When does resolution occur in regeneration?
- Removal of harmful agent
| - Limited tissue damage
33
When does scarring occur in regeneration?
- Persistent harmful agent
- Extensive tissue damage
- Permanent cell populations
34
Is regeneration always due to injury?
-No occurs physiologically eg RBC replacement, epithelia
35
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
36
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
37
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
38
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
39
What is the role of retinoblastoma susceptibility protein in cell cycle?
-Restricts the cells ability to replicate its DNA by preventing progression from G1
40
How is RB protein inhibited?
-Phosphorylation by activated CDK
41
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
42
When does a neuroma form?
-When regenerating axons of peripheral nerves have to cross a wide gap and a disordered tangle forms
43
What induces cells to regenerate?
- Growth factors
| - Cell-cell communication
44
What is reconstitution?
-The replacement of a lost part of the body eg blood vessels in wound healing
45
What is hyperplasia?
-Increase in tissue/organ size due to increased cell number in response to increased functional demand or external stimulation
46
Does hyperplasia occur in all tissues?
-No only in labile and stable populations
47
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
48
What are the disadvantages of repeated cell divisions in hyperplasia?
-Exposes cells to the risk of mutations and neoplasia
49
Give a physiological example of hyperplasia?
- Proliferative endometrium influenced by oestrogen
| - BM producing more RBC in response to hypoxia (altitude)
50
Give a pathological example of hyperplasia?
- Thyroid goitre
| - Epidermal thickening in eczema/psoriasis
51
Is hyperplasia reversible?
-Yes
52
What is hypertrophy?
-Increase in tissue/organ size due to increased cell size
53
Does hypertrophy occur in all cells?
-Yes, but especially permanent cell populations as they cannot divide
54
What are the main causes for hypertrophy?
- Increased functional demand
| - Increased hormonal stimulation
55
What happens on a cellular level in hypertrophy?
- Cell increases in size
| - Organelles increase in number
56
Give physiological examples of hypertrophy
- Pregnant uterus (Hypertrophy+hyperplasia)
| - Skeletal muscle
57
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
58
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
59
What is compensatory hypertrophy?
-Occurs in paired organs when one is removed or hypoplastic; the other organ hypertrophies due to extra work load
60
Define hypoplasia
-The underdevelopment of an organ or tissue at the embryonic stage eg heart, kidneys, breasts
61
Define aplasia
-Total failure of development of an organ or tissue at the embryonic stage
62
Is hypertrophy reversible?
-Yes
63
What is atrophy?
-Shrinkage of a tissue or organ due to an acquired decrease in cell size or number
64
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
65
What are the main causes of atrophy?
- Reduced functional demand
| - Reduced hormonal stimulation
66
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
67
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
68
In organs undergoing atrophy, why part of the organ is effected first?
-Parenchyma thus atrophic tissues contain large amounts of connective tissue
69
Is atrophy reversible?
-Upto a point, after that it becomes permanent with reduced function
70
Give a physiological example of atrophy
- Decrease in uterus after parturition
| - Ovarian atrophy in post-menopausal women
71
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
72
What is metaplasia?
-The reversible change of one cell type to another
73
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
74
Where is metaplasia the most adaptive?
-Epithelia
75
Does metaplasia occur in all tissues?
-No, only those which can replicate
76
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
77
What can result from metaplasia in the bronchi to stratified squamous epithelia?
-Squamous cell carcinoma
78
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
79
What is involution?
- Normal programmed shrinkage of an organ (overlaps with atrophy)
- Uterus after child birth
- feotal organs (Pro- and mesonephros)
80
Define atresia
-No development of an orifice eg anus, vagina, gut
81
Define dysplasia
-Premalignant lesions of irregular and disorganised epithelia
