MoD S8 - Cell Adaptations Flashcards Preview

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Flashcards in MoD S8 - Cell Adaptations Deck (53):
1

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

2

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

3

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

4

Cell to cell signalling is achieved by what 3 things?

Hormones
Local mediators
Direct cell to cell stroma contact

5

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

6

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

7

What can growth factors affect?

Cell proliferation and inhibition
Locomotion
Contractility
Differentiation
Viability
Activation
Angiogenesis

8

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

9

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

10

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)

11

What features of the cell cycle can be seen under a microscope?

Only mitosis and cytokinesis

12

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

13

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)

14

What proteins are responsible for cell cycle regulation?

Cyclins
Cyclin-dependent kinases (CDKs)

15

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

16

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)

17

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

18

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

19

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

20

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

21

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

22

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

23

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

24

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

25

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

26

In what types of cell population can hyperplasia occur?

Only in labile and stable populations

27

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

28

What is the major risk involved in a tissue undergoing hyperplasia?

Repeated cell divisions expose the cell to the risk of mutations and neoplasia

29

Give examples of physiological hyperplasia and the condition that example is responding to

Proliferation of endometrium:
- Oestrogen

Bone marrow producing erythrocytes:
- Hypoxia

30

Give examples of pathological hyperplasia

What is pathological hyperplasia normally caused by?

Eczema
Thyroid Goitre

Secondary to excessive hormonal stimulation or growth factor production

31

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

32

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

33

Give examples of physiological hypertrophy

Skeletal muscle growth
Pregnant uterus (alongside hyperplasia)
Cardiac muscle (in response to exercise)

34

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

35

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

36

What are the two 'types' of atrophy?

Cellular atrophy
Tissue/organ atrophy (apoptosis of cells)
Extracellular matrix atrophy

37

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

38

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

39

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

40

Give two examples of physiological atrophy

Post menopausal ovary and uterus atrophy

Post partum uterus atrophy

41

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)

42

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

43

In what cells can metaplasia occur?

Only cells which can replicated

44

What is the mechanism of metaplasia?

New genetic 'program' is expressed by cells

45

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

46

What cell type most commonly undergoes metaplasia and what is it replaced with?

Columnar epithelium undergoes metapalsia and becomes the more resilient squamous epithelium

47

How is differentiation into new cell types limited in metaplasia?

Can only differentiate into cell types of cells in the same germ layer

48

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

49

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

50

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

51

What is involution?

Give an example

Normal, programmed shrinkage of an organ

Overlaps with atrophy

Uterus shrinkage post partum

52

What is atresia?

Lack of embryonic development of an orifice (E.g. Anus)

53

What is dysplasia?

Abnormal maturation of cells within a tissue

Potentially reversible but often pre-cancerous