Cellular adaptions Flashcards
cell population controlled by
- Rate of cell proliferation
- Physiological and pathological
- Rate of cell differentiation
- Rate of cell death by apoptosis
Increased numbers=
Decreased=
Increased numbers= proliferation
Decreased= cell death
Control of cell proliferation by
- proto-oncogenes and tumour suppressor genes
- chemical mediators from microenvironemnt
signalling moelcules modulate gene expression by binding to receptors on the :
- cell membrane
- cytoplasm
- nucleus
cell cycle overview
G1
G1 checkpoint
S phase
G2
G2 checkpoint (restriction point)
M and cytokinesis
G1
cellular contents excluding the chromosome are duplicated
G1 checkpoint
- Is the cell big enough
- Is environment favourable
- Is DNA damaged?
S phase
each of the 46 chromosomes are duplicated by the cell
G2
cell doublechecks the duplicated chromosomes for error- makes repairs
G2 checkpoint (restriction point)
- Is all DNA replicated?
- Is the cell big enough?
- Enter M
M and cytokinesis- mitosis
- Division of cell to produce 2 identical sister cells
- Prophase
- Metaphase
- Anaphase
- Telophase and cytokinesis
if there are defects in checkpoints
uncontrolled division
what regulate checkpoints
cyclins
the restriction (R) point is governed by
P53
the majority of cells that pass the R point will
complete cell cycle- point of no return
the R point is the
most commonly altered checkpoint in cancer cells
checkpoint activation at the R point
delays cell cyel and triggers DNA repair mechanisms or apoptosis via P53
P53- the guardian of the genome - activators
- DNA damage
- Oncogene expression
- Hypoxia
- Oxidative stress
- Nutrient deprivation
what occurs as a reuslt of P53
- Senescence
- Cell cycle arrest
- Apoptosis
- DNA repair
all results of P53 activation result in
tumour supression
in 70% of cancers
P53 mutation
P53 pathway
- DNA is damaged
- Increase in activated P53 either induces
- Apoptosis
- Or Increase in p21
- Prevent phosphorylation of cyclins
- Cell cycle arrest
- Allow DNA repair
cyclins and CDK
- Cyclin dependent kinases (CDKs) become activated when cyclins bind
what do CDKs do
- phosphorylate proteins which have downstream effects such as increased transcription of proteins which increase cellular proliferation
For each part of the cell cycle to commence
specific cyclins must binds to CDKS
cyclin inhibitors e.g. retinablastoma (RB) protein and P21
e.g. retinoblastoma (RB) protein
- RB is bound to TF (e.g. E2F-DP1) preventing it from entering the nucleus and transcribing
- When cyclin binds to CDK the CDK phosphorylates the RB protein
- This releases the TF so it can enter the nucleus and transcribe proteins that will cause cellular division (protooncogenes)
How can cells adapt
- hyperplasia
- hypertrophy
- metaplasia
- aplasia
- hypoplasia
- involution
- reconsturction
- atresia
- dysplasia
hyperplasia simple
cells increase in number above normal
hypertrophy simple
icnrease in cell size
atrophy
cells become smaller
metaplasia
cells are replaced by cells of different type
hyperplasia occurs in
- Labile (resting/slow turnover) tissues
hyperplasia is caused by
- increased functional demand or hormonal stimulation (e.g. regeneration of the liver)
- Remains under physiological control and is reversible
- Can occur secondary to pathological cause but the proliferation itself is a normal response
risk of hyperplasia
exposes cell to risk of mutations and neoplasia
physiological hyperplasia
- Proliferative endometrium under influence of oestrogen
- Bone marrow produces erythrocytes in response to hypoxia
pathological hyperplasia
- Eczema
- Thyroid goitre iodine deficiency
hypertrophy occurs in
- Labile, stable but especially permanent tissues
when does hypertrophy occur
- Increased functional demand or hormonal stimulation
- Usually occurs alongside hyperplasia
why do cells need to grow
- Cells contain more structural components e.g. cytoplasm- workload is shared by a greater mass of cellular components
physiological hypertrophy
- Skeletal muscle e.g. building muscle in the gym
- Pregnant uterus (hypertrophy + hyperplasia)
pathological hypertrophy e.g.
- Hypertrophy of the heart
- Athletes and cardiac hypertrophy- no. of capillaries will increase- but only to a certain extent- can cause ischaemia–> heart arrhythmias
- Obstruction of the urethra increases amount of urine needed to be held in the bladder at any time
compensatory hypertrophy example
if you remove one kidney the other will grow
Atrophy
Shrinkage of a tissue or organ due to an acquired decrease in size and/ or normal number of cells
why foes atrophy need to occur
- shrinkage in the size of the cell to a size at which survival is still possible
- Reduced structural components of the cell (e.g. cytoplasm)
atrophy may result in
cell death
atrophy is reversible or irreversible
reversible up to a certain point
physiological atrophy
- E.g. ovarian atrophy in post menopausal women
pathological atrophy
- Reduced functional demand= atrophy of disuse
- Loss of innervation= denervation atrophy
- Inadequate blood supply
- Inadequate nutrition
- Loss of endocrine stimulinBreast, reproductive organs
- Persistent injury
- Ageing= senile atrophy
- Pressure
Reduced functional demand= atrophy of disuse
- Muscle atrophy after disuse
- Reversible with activity
Loss of innervation= denervation atrophy
Wasted hand muscles after median nerve damage
Inadequate blood supply
Thinning of skin on legs with peripheral vascular disease
Inadequate nutrition
Wasting of muscles with malnutrition
Loss of endocrine stimulation
Breast, reproductive organs
Persistent injury
Polymyositis (inflammation of muscle)
Ageing= senile atrophy
Brain, heart
Pressure
Tissues around an enlarging benign tumour (probs secondary to ischaemia)
metaplasia (reversible change of one differentiated cell type to another) occurs in
labile cell types
why does emtapalsia occur
- Altered stem cell differentiation
- Adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment
- Metaplastic cells are fully differentiated and the process is reversible
metaplasia can lead to
dysplasia and cancer (no metapalsia across germ layers)
example of metaplasia in lung tissue
Bronchial pseudostratified ciliated epithelium –> stratified squamous epithelium due to effect of cigarette smoke
example of metaplasia in the oesphagus
Stratified squamous epithelium –> gastric glandular epithelium with persistent acid reflux (Barretts oesophagus)
examples of how epitheilial metaplasia can lead to cancer
- Squamous metaplasia and lung squamous cell carcinoma
- Barrett’s epithelium and oesophageal adenocarcinoma
- Intestinal metaplasia of the stomach and gastric adenocarcinoma
aplasia
- Complete failure of specific tissue or organ to develop
aplasia is a
- Embryonical developmental disorder
- E.g. thymic aplasia- infections and auto-immune problem
- Aplasia of a kidney
aplasia can also be used to describe
- an organ whose cells have ceased to proliferate e.g. aplasia of bone marrow in aplastic anaemia
hypoplasia
- Underdevelopment or incomplete development of tissue or organ at embryonic stage- inadequate number of cells
hypoplasia is in a spectrum with
aplais
hypoplasia is not
the opposite of hyperplasia as it is a congenital condition
involution
- Overlaps with atrophy
- Normal programmed shrinkage of an organ
- Uterus after childbirth, thymus in early life, pro and mesonephros
atresia
- No orifice- failure for opening to form
- Congenital imperforation of an opening
- E.g.
- Pulmonary valve
- Anus
- Vagina
- Small bowel
Dysplasia
- Abnormal maturation of cells within a tissue
- Potentially reversible
- Often pre-cancerous condition
