W1 2 Cellular Responses To Stress And Injury

Question 1

How do cells respond to stress and injury?

Answer 1

If injury is mild and transient - cells recover and return to normal - homeostasis
Cells can adapt to a change in environment - also homeostasis
If injury is more severe, irreversible, cell death occurs - necrosis or apoptosis

Question 2

What are adaptations?

Answer 2

Reversible changes in the size, number, phenotype, metabolic activity or functions of cells in response to stress. Beneficial for affected cell but might have pathological effects for the organism.

Question 3

What are the 4 main types of adaptation?

Answer 3

Hyperplasia
Hypertrophy
Atrophy
Metaplasia

Question 4

What is hyperplasia?

Answer 4

An increase in the NUMBER of cells, usually following a hormonal or chemical stimulus

Question 5

What is hyperplasia determined by?

Answer 5

Mitosis - some cells in quiescence can be stimulated to re-enter the cell cycle

Question 6

What is hypertrophy?

Answer 6

Increase in the SIZE of cells, usually following a mechanical stimulus

Question 7

Explain left ventricular hypertrophy - stimulus and the effect

Answer 7

Stimulus is mechanical pressure from systemic hypertension. Hypertrophy of left ventricular myocytes results in thickening of the ventricular wall and increase in weight of the heart. Whilst initially beneficial, if too thick can make heart stiff and impair diastolic filling.

Question 8

What is atrophy?

Answer 8

Decrease in size of tissue organ at a stage after initial development. May be due to a decrease in cell size and/or number.

Question 9

Is atrophy always abnormal?

Answer 9

Can be physiological and part of the ‘normal’ ageing process

Question 10

Give some causes of pathological (abnormal) atrophy

Answer 10

Loss of hormonal stimulation eg atrophy of endocrine organs from pituitary disease
Reduction in blood supply
Decreased workload
Loss of innervation

Question 11

Hypoplasia is not the opposite of hyperplasia. What is it?

Answer 11

Hypoplasia is the failure of a tissue or organ to reach normal size during development. Causes include genetic defects, toxic insults etc.

Question 12

What is metaplasia?

Answer 12

Replacement (potentially reversible) of one differentiated cell type by another differentiated cell type.

Question 13

Why does metaplasia occur?

Answer 13

Usually occurs as a response to unfavourable environment for the original cell type (gets lots of stress eg). Results from reprogramming of local stem cells or colonisation by differentiated cells from adjacent sites (rather than change in the already differentiated cell).

Question 14

Give some examples of metaplasia (site - original cell type - metaplastic cell type - cause)

Answer 14

Bronchus - ciliated columnar (respiratory epithelium) - squamous - cigarette smoking
Lower oesophagus (Barrett’s oesophagus) - squamous - gastric - acid reflux
Stomach - columnar (gastric) - intestinal - chronic inflammation

Question 15

Describe the mechanism of squamous metaplasia due to smoking

Answer 15

Reprogramming of local tissue stem cells or colonisation by differentiated cell populations from adjacent sites. Stem cells underneath change.
Ciliated columnar cells get irritated by smoke but squamous cells are more resistant, so cell type changes to protect itself from the smoke.

Question 16

What are the consequence of bronchial squamous metaplasia due to smoking?

Answer 16

Loss of normal cell function - leading to chest infections
Increased risk of malignancy - leading to squamous cell carcinoma of the lung
(Image pg7)

Question 17

Cellular injury can occur directly of following failure of adaptation - example

Answer 17

Pg8 image of heart hyperplasia

Question 18

Give some causes of cell injury

Answer 18

Toxins, ischaemia, inflammation, burns, radiation, trauma, infection, surgical
May be direct damage to cell membranes or DNA

Question 19

What are some early (reversible) cell injury characteristics?

Answer 19

Cell swelling
Reduction in cytoplasmic RNA

Question 20

Why does cell swelling occur in early cell injury?

Answer 20

Due to the entry of sodium and water into cell (from membrane dysfunction), and swelling of organelles

Question 21

Why does reduction in cytoplasmic RNA occur in early cell injury?

Answer 21

Due to reduced transcription. Gives cytoplasm a red appearance on H&E.

Question 22

Describe the H&E stain

Answer 22

RNA like DNA stains blue/purple. Reducing the amount of genetic RNA present in the cytoplasm, loses blue/purple colour so the cytoplasm becomes pinker.

Question 23

What can happen if cell injury is severe or prolonged and the damage is irreversible?

Answer 23

Cell death

Question 24

Although cell death is a failure of homeostasis, it can be beneficial. How?

Answer 24

Elimination of obsolete/dangerous cells.
Alerts the organism (immune system) to potential threats via DAMPs

Question 25

What are the 2 main types of cel death?

Answer 25

Necrosis and apoptosis

Question 26

Necrosis vs apoptosis table

Answer 26

Pg10 REVIEW PLEASE!

Question 27

Describe necrosis (table)

Answer 27

An energy independent loss of cell integrity. Results in enlarged cells and a disrupted plasma membrane, with groups of cells involved. The nucleus becomes: pyknosis (shrinkage), karyorrhexis (fragmentation) or karyolysis (disappearance). The tissue reacts by acute inflammation.

Question 28

Describe apoptosis (table)

Answer 28

An energy dependent tightly regulated mechanism resulting in shrinkage of cells. Plasma membrane remains intact and the nucleus becomes nuclear fragments (apoptotic bodies). Affects single cells. Tissue reacts via phagocytosis.

Question 29

Why do the tissues swell in necrosis.

Answer 29

Since cells don’t have enough energy for the sodium-potassium ATPase, so accumulated intracellular sodium.

Question 30

Why does inflammation occur in necrosis?

Answer 30

Since it releases DAMPs

Question 31

How is apoptosis more controlled?

Answer 31

Tends to occur in less severe forms of injury as it depends on energy for it to occur. The plasma membranes stay intact so substances within the cell are unable to elicit an extracellular response. Apoptotic bodies can be phagocytosed.

Question 32

Describe internal factors for apoptosis

Answer 32

Intrinsic pathways = triggered by cell injury, eg DNA damage, misfolded proteins etc
Activates a series of intracellular proteins which in the end cause release of cytochrome C from mitochondria.
This activates caspases = central enzymes involves in apoptosis. Cause a variety of further pathways to be activated ultimately resulting in fragmentation of the nucleus and apoptotic bodies.
(Image pg12)

Question 33

Describe external factors for apoptosis

Answer 33

Extrinsic pathway = tend to be Fas or Fas ligands interactions with inflammatory cells like NK cells or neutrophils, OR activation of the TNF receptors (inflammatory mediator)
These external factors bind to receptors and activate intracellular signalling pathways, which converge on caspases, leading to apoptosis
(Image pg12)

Question 34

What are DAMPs?

Answer 34

Damage-associated molecular patterns (DAMPs) are released from necrotic cells and activate the innate immune system.

Question 35

Give some examples of DAMPs

Answer 35

Histones, IL-1, DNA, RNA, heat-shock proteins, heparan sulfate

Question 36

What do DAMPs do if released by a cell?

Answer 36

If released by a cell, they elicit an inflammatory response, most commonly with toll-like receptors.
Important in the innate immune response, both for pathogens and damaged host cells.

Question 37

What are the consequences of dysfunctional cell death?

Answer 37

Excess cell death can result in loss of normal organ function
Impaired cell death can result in accumulation of genetic mutations contributing to cancer (eg loss of p53)

Question 38

What does a loss of p53 (guardian of the genome) lead to?

Answer 38

Leads to the inability to detect DNA damage, lack of BAX activation and failure to induce apoptosis, which can lead to cancer development.

Question 39

Functions of p53

Answer 39

Image on pg14