POM Lecture 1

Question 1

What are the causes of cell stress and injury?

Answer 1

Physical Injury
Chemical Injury
Biological causes
Immunologic Injury
Genetic Derangements 
Nutritional Imbalance

Question 2

Cell Suicide

Answer 2

Apoptosis

Question 3

Cell Murder

Answer 3

Oncosis/Necrosis

Question 4

Why is there depletion of ATP during cell injury?

Answer 4

Depletion of Oxygen
Damage to Enzymes
Damage to mitochondria

Question 5

What are the responses due to an injurious stimulous

Answer 5

Depletion of ATP
Membrane Damage
Increase of Intracellular Calcium
Reactive Oxygen species

Question 6

Low energy for sodium pumps means?

Answer 6

Influx intracellularly of sodium and water, cells and organelles swell

Question 7

Low energy for Calcium pumps means?

Answer 7

influx of calcium into the cytosol, inappropriate activation of calcium dependent channels. damage to cellular components.

Question 8

How can cell membrane damage occur?

Answer 8

Directly via free radicals,
or hypoxia (stress due to a lack of oxygen),
or due to a membrane targeting bacteria toxin
or following failure of plasma membrane Calcium pump

Question 9

Influx of calcium activates what destructive calcium dependent enzymes?

Answer 9

ATPases
Phospholipases
Proteases
Endonucleases

Question 10

Oxidative stress

Answer 10

the accumulation of free radicals

Question 11

Reactive Oxygen species

Answer 11

free radicals generated during cell injury,

Eg) O2 H2 NO

Question 12

Heat Shock Factors

Answer 12

Transcription factors that induce the transcription of Heat Shock Proteins.

Question 13

Heat shock Proteins

Answer 13

Proteins that are molecular chaperones, assist repair of damaged proteins.

Question 14

Stress Kinases

Answer 14

Are released following stress or injury, initiate signalling cascades that co-ordinate the cells response to damage

Question 15

What is bad about ATP depletion and how does this occur?

Answer 15

There is less energy for ATP membrane pumps (ionic/osmotic homeostasis ruined). Less energy for protein synthesis and DNA/protein repair.
this occurs during cell injury due to a lack of O2, enzyme or mitochondrial damage

Question 16

What is bad about Cell membrane damage

Answer 16

Causes loss of cell contents, osmotic balance and proteins (enzymes, coenzymes, RNA)

Question 17

What happens when lysosomal membranes leak?

Answer 17

leak enzymes into cytoplasm, and start digesting cell ; ‘autolysis’

Question 18

What happens when mitochondrial membrane damage occurs?

Answer 18

formation of nonselective high conductance channels in IMM, ‘mitochondrial permeability transition’, takes away transmembrane potential for oxidative phosphorylation.

Question 19

How do you get higher cytosolic Ca concentration?

Answer 19

when reduced activity of the plasma membrane calcium pump allows influx of Ca into cytosol.

Question 20

What are reactive oxygen species

Answer 20

Free radicals generated during cell injury. The accumulation of these is called oxidative stress, and these cause secondary damage.

Question 21

How do free radicals cause damage?

Answer 21

By attacking the double bonds in unsaturated fatty acids in membranes, oxidising aminoacids

Question 22

How do we defend against free radicals?

Answer 22

With antioxidants and some enzymes. When there are too many FR too be handled = oxidative stress

Question 23

Hyperplasia?

Answer 23

increase in cell numbers due to an increase functional demand or stimulation. Can be from the division of the cells in question or locally residing stem cells

Question 24

Hypertrophy?

Answer 24

increase in cell size due to an increase functional demand or stimulation.

Question 25

Atrophy?

Answer 25

Decrease in cell size. Cells responding to reduced functional demand/nutrient supply

Question 26

Metaplasia?

Answer 26

reversibly changing from one adult cell type to another. Response to continuous mild damage. Results from the reprogramming of stem cells, to differentiate down a new path

Question 27

Features of Necrosis

Answer 27

- no energy requirement - often with autolysis 'protein soup' - cytosolic contents also leak across damaged plasma membrane into extracellular space (induces inflammatory response) - uncontrolled messy process - featureless cytoplasm due to denaturation and protein digestion - fragmentation and fading of chromatin in nuclei - Pyknosis - usually quickly removed by phagocytosis

Question 28

Pyknosis

Answer 28

Chromatin shrinks into a dense mass at the margin of the nucleus, prior to karolysis

Question 29

Features of Apoptosis

Answer 29

requires energy - common after DNA damage, hypoxia, accumulation of damaged proteins - also eliminates unwanted cells - chromatin cleaves and condenses, membrane bound blebs break off cell and are phagocytosed

Question 30

what cascade of enzymes mediates apoptosis

Answer 30

Caspases

Question 31

How does apoptosis NOT initiate inflammation?

Answer 31

As pyknosis occurs, membrane bound 'blebs' containing contents break off and are phagocytosed by neighbouring cells, so cytosolic contents don't leak out