7. Cellular Adaptations Flashcards
How is cell proliferation controlled
—-> Largely by chemical signals from the microenvironment which either stimulate or inhibit cell proliferation by binding to receptors
How do cells survive
• Cell needs prosurvive signals
○ Survive – resist apoptosis
○ An no division
○ Always need the pro survival signals to maintain cell life
Cell death
Apoptosis
Stages of cell cycle
G1
S
G2
M – mitosis
Mitosis
Stages
- Prophase
- Metaphase
- Anaphase
- Telophase
G0 phase
• Terminal differentiation
• Permamnt exit from cell cycle
• Where quiscent cells are that have stopped dividing
○ Some cells can move in and out of G0 phase
Increased growth occurs by:
- Shortening the cell cycle = go through cycle faster
* Conversion of quiescent cells to proliferating cells by making them enter the cell cycle.
3 Cell cycle checkpoints
• G1 – detect nutrients for ccell cycle like growth factos
G2 – check forcorrectly replicated DNA
Metaphase to anaphase – check spindle is connected to chromosome
Restriction (R) checkpoint
Majority of cells that pass R point will complete cell cycle - point of no return
This checkpoint is most commonly altered in cancer cells
• Mutate genes to inactivate checkpoint and go through without control
Chrcpoint activation delays cell cycle, triggers DNA repair, apoptosis via p53
CDK activation
- Cyclin and CDK bind together
- When they come togeter they are partially active then fully active
- Once active it can phosphorylate other targets
Control CDK cyclin interactions
- The regulation of Cdk activity by phosphorylation
* The inhibition of a cyclin–Cdk complex by a CKI – inhibitor proteins bind to and inactivate proteins
Leonard Hayflick - Hayflick numbers/limits (1961)
- Limit to how much the cells can divide
- Nnumber of cell divisions human cell can go through
- Humans = 40-60 divisions normally until it stops
Why does cell division eventually stop
• As with each division you lose some part of the telomeres
• When the telomeres become too short = cells become senscent
○ Somatic cells don’t have enough telomerase - loose ability to express telomerase to maintain telomeres ends
➢ How to cancer cells survive?
- Cell override the stopping and can continue to divide
- Cancer cells use and reexpress telomerase which maintains the telomere sites
- Normlly telomerase is expressed at low levels in somatic cells
Proliferation:
• increase in numbers of cells
Growth:
• increase in size of the cell ○ Multiplicative growth ○ Ausectic growth ○ Accretionary growth ○ Combined pattern of growth
Differentiation:
• acquiring a specific morphology and function
Factors impacting size of a cell population
Depends on
• rate of cell proliferation
• cell differentiation
• cell death by apoptosis
• Increased numbers are seen with increased proliferation or decreased cell death
Regeneration:
• the ability to replace cells or tissues, destroyed by injury or disease (identical functionality)
3 types of cells
Labile
Stable
Permanent
Table cells
•Labile cells: high regenerative ability and turnover (e.g. intestinal epithelium)
Stable cells
• Stable cells: good regenerative ability and low turnover (e.g. hepatocytes) - can return to G1 and start regenerating
Permanent cells
• Permanent cells: no regenerative ability (e.g. neurones, cardiac, skeletal muscle cells)
Hyperplasia
• Hyperplasia – cells increase in number above normal
Hypertrophy
• Hypertrophy – cells increase in size
Atrophy
• Atrophy – cells become smaller
Metaplasia
• Metaplasia – cells are replaced by cells of a different type
Hyperplasia - features
• Only happens to labile or stable tissues as they can divide
• Caused by increased functional demand or hormonal stimulation
• Remains under physiological control and is reversible (cf. neoplasia)
○ Under some cases if you keep dividing you increase the risk of accumualting mutation
* Can occur secondary to a pathological cause but the proliferation itself is a normal response (cf. neoplasia – the proliferation itself is abnormal) * Repeated cell divisions exposes the cell to the risk of mutations and neoplasia
Hyperplasia - physiological examples
○ Proliferative endometrium under influence of oestrogen
○ Bone marrow produces erythrocytes in response to hypoxia (high altitude training)
Hyperplasia - physiological examples pathological
○ Exczema – proliferation of skin cells
○ Thyroid goitre in iodine deficiency – thyroid becomes much bigger
Hypertrophy features
- Labile, stable and especially permanent tissues
- Like hyperplasia, caused by increased functional demand or hormonal stimulation
- Cells contain more structural components – workload is shared by a greater mass of cellular components
- Cells become bigger and add to the functionality
- In labile and stable tissues hypertrophy usually occurs along with hyperplasia
- physiological examples hypertrophy
○ Atheltes body builders – skeletal muscle
○ Pregnant uterus (hypertrophy +hyperplasia)
Pathological examples- hypertrophy
○ Cardiac muscle in response to pulmonary hypertension
○ Bladder smooth muscle obstructed due to enlarged prostate gland – tissue has to try harder to remove urine
○ Smooth muscle hypertrophy before an intestinal stenosis – intestine becomes bigger to push contents through
Compensatory hypertrophy
• One kidney does more work to make up for removed kidney
Atrophy - features
- Shrinkage in the size of the cell to a size at which survival is still possible
- Reduced structural components of the cell and cell function
- May eventually result in cell death
- Organ/tissue atrophy typically due to combination of cellular atrophy and apoptosis
- Is reversible, but only up to a point
Atrophy physiological example
- Ovarian atrophy in post menopausal women
* Decrease in size of uterus after parturition
Atrophy example pathological
• Reduced functional demand/workload = atrophy of disuse muscle atrophy after disuse, reversible with activity
• Loss of innervation = denervation atrophy: wasted hand muscles after median nerve damage, muscle does not receive right signals
• 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 = less hormones
• Persistent injury: polymyositis (inflammation of muscle)
• Aging = senile atrophy: brain, heart become smaller
Pressure: tissues around an enlarging benign tumour (probably secondary to ischaem
Atrophy of extracellular matrix -bone
- In bed ridden patients or astronauts as they don’t use bone much
- Osteroporosis
Apoptosis - features
- Enzymes
- Growth factor withdrawal
- Engulf
- This can be reversible up to a certain point
Metaplasia- features
- May represent 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 (cf. dysplasia and cancer)
- Sometimes a prelude to dysplasia and cancer
- Occurs only in labile or stable cell types
- Involves expression of a new genetic programme
Metaplasia examples
- Bronchi in smokers - Bronchial pseudostratified ciliated epithelium is changed to → stratified squamous epithelium due to effect of cigarette smoke, stratifed sqaumous cells are betetr at dealing with smoke but they don’t produce mucous
- Acid reflux - Stratified squamous epithelium becomes → gastric glandular epithelium with persistent acid reflux (Barrett’s oesophagus)
Myeloid metaplasia
• Myeloid metaplasia – bone marrow is destroyed but spleen undergoes metaplasia to become bone marrow
Myosotis ossificans
• Myositis ossificans, metaplasia of fibroblasts in muscle that becoem osteoblasts that produce bone
Does metaplasia predispose to cancer?
• Epithelial metaplasia can be a prelude to dysplasia and cancer.
• Barrett’s epithelium and oesophageal adenocarcinoma
• Intestinal metaplasia of the stomach and gastric adenocarcinoma
Mechanism is not clear
Aplasia
—> organ fails to form
• Complete failure of a specific tissue or organ to develop
• An embryonic developmental disorder
Aphasia - examples
- Thymic aplasia - infections and auto-immune problems
- Aplasia of a kidney
• Also 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
• Not opposite of hyperplasia as it is a congenital condition
Hypoplasia - excemples
- Renal
- Breast
- Testicular in Klinefelter’s syndrome
- Chambers of the heart
Involution
—> Overlaps with atrophy = Normal programmed shrinkage of an organ
• Uterus after childbirth, thymus in early life, proand mesonephros
Reconstitution
—> Replacement of a lost part of the body normally in animals
Humans have angiogenesis
• Form new capillaries
• Basis for wound healing
• Important in cancer – angiogeneis helps cancer survive
Atresia
—> no lumen, lumen is not continus
- ‘No orifice’
- Congenital imperforation of an opening
- Examples: Pulmonary valve Anus Vagina Small bowel
Dysplasia
—> Abnormal maturation of cells within a tissue – go from a normal tissue to an abnormal tissue
- Potentially reversible
- Often pre-cancerous condition
Dysplasia - example
e.g. cervix – smear test
• Dysplaisia in hpv develops abnormal looking cells
Look for how many and what kind of abnormal cells are observed
