MoD S8 - Cell Adaptations Flashcards
What does the size of a cell population depend on?
How might a cell population increase in size?
Rate of cell proliferation, differentiation and apoptosis
Increased numbers seen with:
- Increased proliferation
- Decreased cell death
What regulates cell proliferation under normal conditions?
Proto-oncogenes
Directly controlled by chemical signals from the microenvironment that stimulate or inhibit proliferation
Signalling molecule binds to cell surface receptor (sometimes cytoplasmic or nuclear) and modulation of gene expression occurs
What are the 4 outcomes of cellular signalling that might influence the size of cell populations?
Survive - Resist apoptosis
Divide - Enter cell cycle
Differentiate
Die - Undergo apoptosis
Cell to cell signalling is achieved by what 3 things?
Hormones
Local mediators
Direct cell to cell stroma contact
What are the 3 modes of cell signalling?
Give a brief description of each type
Autocrine:
- Cell produces and secretes molecule which then acts on surface receptors of the same cell
- When molecule is not secreted and acts on internal receptors this is called ‘intracrine signalling’
Paracrine:
- Cell produces a secretes a molecule that acts on a nearby cell (normally a different type of cell)
Endocrine:
- Molecule produced and secreted, then travels in blood to a distant cell and bind to receptors
Describe growth factors
Local mediators involved in cell proliferation
They’re polypeptides that act on surface receptors
Coded by proto-oncogenes
Stimulate (can inhibit) transcription of genes that regulate entry of a cell into the cell cycle and the cell’s passage through the cycle
What can growth factors affect?
Cell proliferation and inhibition Locomotion Contractility Differentiation Viability Activation Angiogenesis
Give some examples of growth factors add their functions
Epidermal growth factor:
- Mitogenic for epithelial cells, hepatocytes and fibroblasts
- Produces by macrophages, keratinocytes and inflammatory cells
- Bind to epidermal growth factor receptor
Vascular endothelial growth factor:
- Potent inducer of vasculogenesis and angiogenesis in tumours, chronic inflammation and wound healing
Platelet derived growth factor:
- Stored in platelet alpha granules, released on platelet activation
- Also produced by macrophages, endothelial cells, smooth muscle cells and tumour cells
- Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes
What are the stages of the cell cycle?
What about when cells are not actively proliferating?
Mitosis
Interphase:
G1
S
G2
Cell not active in the cell cycle enter G0 after G1
How can the cell behaviour be altered to increase growth?
Hint: Refer to the cell cycle
Shortening the cell cycle
Converting quiescent (G0) cells into proliferating cells (making them enter the cell cycle)
What features of the cell cycle can be seen under a microscope?
Only mitosis and cytokinesis
What are cell cycle checkpoints?
Why are they important?
Events where the cells DNA is checked for errors before continuing in the cell cycle
2 important checkpoints at the end of G1 and before M
Prevents cells with abnormal DNA from passing this on to daughter cells and causing dysfunction/malignancy
What is the restriction point?
Near the end of G1, the most important checkpoint
Majority of cells that pass the R point will complete the cell cycle
It is the most commonly altered checkpoint in cancer cells
Checkpoint activation delays the cell cycle and either DNA repair mechanisms are activated or apoptosis (via p53)
What proteins are responsible for cell cycle regulation?
Cyclins
Cyclin-dependent kinases (CDKs)
Describe cell cycle regulation
Cyclins bind to cyclin-dependent kinases (CDKs) and the cyclin CDK complex
These phosphorylate proteins that are critical for progression to the next stage (E.g. Retinoblastoma susceptibility protein)
Cyclin-CDK complexes tightly regulated by CDK inhibitors
Growth factors also involved:
- Some stimulate cyclin production
- Some inhibit CDK inhibitor production
What is the major function of adult stem cells?
Replenish the loss of differentiated cells while maintaining their own population
They achieve this through asymmetric replication (one daughter cell is stem cell, one will mature and differentiate)
Only one mature cell type can be produced (lineage specific)
Describe the role of adult stem cell in labile, stable and permanent cell populations
Labile:
- Divide persistently to replenish losses
Stable:
- Normally quiescent (G0) or proliferate slowly
- Can proliferate persistently when required
Permanent:
- Present however cannot mount effective proliferative response to significant cell loss
Give examples of labile, stable and permanent cell populations
Labile:
- Surface epithelia (E.g. Skin and gut epithelia)
- Bone marrow
Stable:
- Liver hepatocytes
- Bone osteoblasts
Permanent:
- Brain neurones
- Cardiac and skeletal muscle
What is cell adaptation?
Changes in a cell that is stressed that help the cell survive that stress
They are ALWAYS reversible changes, irreversible cell changes are cell injury
List the 5 important types of cellular adaptation
Give a very short description of each
Regeneration:
- Replacement of cell losses by identical cells to maintain organ or tissue size
Hyperplasia:
- Increase in tissue or organ size due to increased cell numbers
Hypertrophy:
- An increase in tissue/organ size due to increased cell size without increased cell number
Atrophy:
Shrinkage of a tissue/organ due to an acquired decrease in size and/or number of cells
Metaplasia:
- Reversible change of one differentiated cell type for another FULLY differentiated cell type
Briefly explain the two major outcomes of cell regeneration?
Resolution:
- Harmful agent removed
- Limited cell damage
- Regeneration
Scarring:
- Harmful agent persists
- Extensive tissue damage to permanent cells
- Scar
What is the definition of cell regeneration?
Give examples of when complete cell regeneration might occur
Liver regeneration following partial hepatectomy
Replacement of skin epithelia
Are regenerated cells as good as cells they replace?
Sometimes immediately as good (E.g. Epidermal skin cells)
Can take weeks/months/years to be as good as predecessors if at all
How many times can a cell regenerate?
Species specific,
Humans = mean of 61.3
Related to telomere shortening upon replication, after telomere shortening reaches max, cannot regenerate further
What is re-constitution?
Where does it appear in humans?
The replacement of a lost body part (multiple tissues)
E.g. Regrowing lizards tail
In humans, angiogenesis occurs
In what types of cell population can hyperplasia occur?
Only in labile and stable populations
Is hyperplasia a normal or abnormal process?
Normal, under physiological control, only occurs secondary to abnormal conditions
When hyperplasia is abnormal it is called neoplasia
What is the major risk involved in a tissue undergoing hyperplasia?
Repeated cell divisions expose the cell to the risk of mutations and neoplasia
Give examples of physiological hyperplasia and the condition that example is responding to
Proliferation of endometrium:
- Oestrogen
Bone marrow producing erythrocytes:
- Hypoxia
Give examples of pathological hyperplasia
What is pathological hyperplasia normally caused by?
Eczema
Thyroid Goitre
Secondary to excessive hormonal stimulation or growth factor production
In what types of cell can hypertrophy occur?
Labile:
- Often alongside hyperplasia
Stable:
- Often alongside hyperplasia
Permanent:
- Tissues cannot divide so organ size must occur via hypertrophy
Why does hyperplasia occur?
How is it advantageous?
Caused by increased demand on cells or hormonal stimulation
Greater cell demand can then be met by greater mass of cellular components to prevent cell damage
Give examples of physiological hypertrophy
Skeletal muscle growth Pregnant uterus (alongside hyperplasia) Cardiac muscle (in response to exercise)
Give examples of pathological hypertrophy and include the condition that it is responding to
Cardiac muscle:
- In response to hypertension/valve stenosis
Bladder muscle:
- In response to enlarged prostate blocking the urethra
Smooth muscle upstream of intestinal stenosis:
- Extra work of having to push lumen contents through the narrowed lumen
What is compensatory hyperplasia?
Hyperplasia in response to removal of tissue
For example when a kidney is removed, the remaining kidney will undergo hypertrophy to meet demand
What are the two ‘types’ of atrophy?
Cellular atrophy
Tissue/organ atrophy (apoptosis of cells)
Extracellular matrix atrophy
Describe the main mechanism of tissue/organ atrophy
Cells are picked out to undergo apoptosis
Often in atrophic organs parenchymal cells will undergo apoptosis before stromal cells
What is involved in cellular atrophy?
Cell shrinks via auto-digestion to a size at which survival is still possible
Cell contains reduced number of structural components and has reduced function
Give an example of extracellular matrix atrophy
Loss of bone matrix due to bed rest/spaceflight
This is due to lack of mechanical stress which stimulates bone matrix regeneration
Give two examples of physiological atrophy
Post menopausal ovary and uterus atrophy
Post partum uterus atrophy
Give a list of 8 causative factors for atrophy and an example of where each might cause atrophy
Disuse:
- Muscle atrophy when not in use (E.g. bed rest)
Denervation:
- Muscle atrophy in the hand after median nerve damage
Inadequate blood supply:
- Thinning of the skin on legs with peripheral vascular disease
Inadequate nutrition:
- Wasting of muscles
Loss of endocrine stimuli:
- Breast and reproductive organ atrophy
Persistent injury:
- Polymyositis (muscle inflammation)
Ageing:
- Senile atrophy of brain and heart
Pressure:
- Tissues around a benign tumour (probably secondary to ischaemia)
What causes metaplasia and why is it advantageous?
Due to altered stem cell differentiation
May represent adaptive substitution of cells that are sensitive to stress with those better able to withstand the adverse environment
In what cells can metaplasia occur?
Only cells which can replicated
What is the mechanism of metaplasia?
New genetic ‘program’ is expressed by cells
Give an example of abnormal metaplasia
Give an brief description of abnormal cells that have undergone metaplasia
Dysplastic and cancerous epithelium (Cancerous tissue is irreversible)
Disorganised and abnormal differentiation
Sometimes a prelude to dysplasia and cancer
What cell type most commonly undergoes metaplasia and what is it replaced with?
Columnar epithelium undergoes metapalsia and becomes the more resilient squamous epithelium
How is differentiation into new cell types limited in metaplasia?
Can only differentiate into cell types of cells in the same germ layer
Give 2 examples of metaplasia, include the causative factor
Bronchial pseudostratified ciliated epithelium to stratified squamous epithelium:
- Due to cigarette smoke exposure
Stratified squamous epithelium to gastric glandular epithelium
- Persistent acid reflux
Describe hypoplasia
Give an example
Underdevelopment or incomplete development of a tissue/organ at the embryonic stage, inadequate number of cells
In a spectrum with aplasia
Not the opposite of hyperplasia as it’s congenital only, it’s not atrophy
E.g. Hypoplastic left heart
Describe aplasia
Give an example
Complete failure of a specific tissue/organ to develop
Embryonic disorder
Also used to describe an organ whose stem cells have stopped proliferation
Kidney aplasia
What is involution?
Give an example
Normal, programmed shrinkage of an organ
Overlaps with atrophy
Uterus shrinkage post partum
What is atresia?
Lack of embryonic development of an orifice (E.g. Anus)
What is dysplasia?
Abnormal maturation of cells within a tissue
Potentially reversible but often pre-cancerous
