11. Cellular Adaptations Flashcards
How can the size of a cell population change?
Rate of cell proliferation
Rate of cell differentiation
Rate of cell death by apoptosis
What regulates normal cell proliferation?
Proto-oncogenes and tumour suppressor genes
E.g. chemical mediators/signals from the microenvironment - either stimulate or inhibit cell proliferation
Signalling molecules binds to a receptor leading to modulation of gene expression
Where are the checkpoints in cell division?
Between G1 and S
Between G2 and M
What is checked at G1 checkpoint?
Is cell big enough?
Is environment favourable?
Is DNA damaged?
What is checked at G2 checkpoint?
Is all DNA replicated?
Is cell big enough?
What is the restriction point?
Most critical checkpoint
Majority of cell that pass R point will complete cell cycle
Most commonly altered checkpoint in cancer cells
Takes place near end of G1
Checkpoint activation delays cell cycle and triggers DNA repair mechanisms or apoptosis via p53
What happens if DNA damage is found at the checkpoint?
DNA damage
Leads to increase in activated p53 which can either lead to:
-induce apoptosis
-increase p21, so preventing phosphorylation of cycles, causing cell cycle arrest and allowing DNA repair
What is the retinoblastoma protein?
Usually acts to prevent DNA replication
Inactivated by phosphorylation by cyclin D/CDK4 complex
Give examples of tumour suppressor genes
Rb - brakes on G1/S
p53 - arrests if cell damage and DNA repair or apoptosis
What is hyperplasia?
Increase in tissue or organ size due to increased cell numbers
In labile or stable tissues
Remains under physiological control and is reversible
Repeated cell divisions exposes cell to risk of mutations and neoplasia
Give examples of physiological hyperplasia
Proliferative endometrium under influence of oestrogen
Bone marrow produces erythrocytes in response to hypoxia
Give examples of pathological hyperplasia
Eczema/psoriasis
Thyroid goitre in iodine deficiency
What is hypertrophy?
Increase in tissue or organ size due to increased cell size
Labile, stable but especially in permanent tissues
Increased functional demand or hormonal stimulation
In labile and stable tissues, hypertrophy usually occurs along with hyperplasia
Give examples of physiological hypertrophy?
Skeletal muscle
Pregnant uterus
Give examples of pathological hypertrophy
Right ventricular
Intestinal fibrosis
Prostatic hypertrophy
Compensatory hypertrophy
What is atrophy?
Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells
Shrinkage in size of cell to a size at which survival is still possible
What can atrophy eventually result in?
Cell death
What is tissue atrophy usually a result of?
Due to combination of cellular atrophy and apoptosis
Reversible up to a point
Give examples of physiological atrophy
Ovarian atrophy in post menopausal women
Postpartum uterus
Give examples of pathological atrophy
Reduced functional demand/workload - atrophy of disuse Loss of innervation - denervation atrophy Inadequate blood supply Inadequate nutrition Loss of endocrine stimuli Persistent injury Ageing - senile atrophy Pressure
What is metaplasia?
Reversible change of one differentiated cell type to another
Labile or stable cell types
Altered stem cell differentiation
Adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment
Not across germ layers
What can metaplasia lead to?
Dysplasia and cancer
Give examples of metaplasia
Bronchial pseudostratified ciliated epithelium to stratified squamous epithelium due to effect of cigarette smoke
Stratified squamous epithelium to gastric glandular epithelium with persistent acid reflux
Does metaplasia predispose to cancer?
Epithelial metaplasia can lead to dysplasia and cancer
E.g:
- squamous metaplasia and lung squamous cell carcinoma
- Barrett’s epithelium and oesophageal adenocarcinoma
