Lect 3 - Cell Injury

Question 1

What is Atrophy?

Answer 1

a decease in cell number

Question 2

What is Hypertrophy?

Answer 2

individual cells getting bigger

Question 3

What is Hyperplasia?

Answer 3

more cells develop to try to keep up demand

Question 4

what is Metaplasia?

Answer 4

a change in cell morphology

Question 5

What types of cell death are there?

Answer 5

Necrosis/Apoptosis

Question 6

what mechanisms can cause cell injury?

Answer 6

lack of Oxygen availability
Physical Trauma
Chemical agents
Infectious organisms
Irradiation
(Also can be Immunological, Lack of essential nutrients/vitamins or Genetic disorders)

Question 7

what is cell injury due to lack of oxygen known as?

Answer 7

Hypoxia and anoxia (Reduction or loss respectively of oxygen delivered to cells, often caused by ischaemia)

Question 8

how can reoxygenation of a hypoxic cell further injure it?

Answer 8

re-perfusion injury - can cause generation of oxygen free radicals which can kill cells.

Question 9

How can Physical trauma damage cells?

Answer 9

• Disruption of cell structure
• Thrombosis leading to ischaemia is often a secondary effect.
• Extremes of temperature leading to Frostbite or heat denaturation.

Question 10

Give some examples of Chemical agents that can cause cell injury

Answer 10

–	Alcohol
–	 Tobacco smoke
–	 Drugs
–	 Poisons
–	 Environmental
–	 Occupational

Question 11

How does irradiation damage cells?

Answer 11

• e.g. X-rays, radioactive particles
• Generation of free radicals and direct damage to macromolecules
• different organs have different sensitivity
• v.high in bone marrow, gonads, intestines
• v.low in uterus, pancreas, adrenal
• e.g. UV-light
• can induce inflammatory response several
hours after exposure

Question 12

What happens when mitochondria are damaged in a cell?

Answer 12

cell gets less ATP, therefore has to try to pick up its rate of glycolysis. in addition, Na Pumps fail, so Ca H20 and Na come flowing in. this causes swelling and other problems.

Ribosomes become detached, meaning protein synthesis slows.

YOU GET LIPID DEPOSITION,

Question 13

what patient group has tissues which show signs of mitochondrial damage well?

Answer 13

Alcoholics.

Alcohol damages mitochondria. this causes swelling and fatty change which is easily seen histologically.

Question 14

give examples of agents that could compromise a cell’s membrane.

Answer 14

bacterial toxins, viral proteins, complement, cytolytic lymphocytes, and various physical and chemical agents

Question 15

why is a compromised cell membrane bad?

Answer 15

• Loss of membrane barriers leads to breakdown in metabolite gradients
• Increased Ca2+ in turn activates a number of enzymes, with potential deleterious cellular effects.
– ATPases (thereby hastening ATP depletion),
– phospholipases (which cause membrane damage),
– proteases (break down membrane and cytoskeletal proteins)
– endonucleases (responsible for DNA fragmentation)

Question 16

what is necrosis?

Answer 16

• Cell death as result of lethal cell injury

Question 17

what types of necrosis are there?

Answer 17

– Coagulative
– Caseous
– Colliquative
– Gangrene

also fibrinoid (fat)

Question 18

Describe Coagulative necrosis

Answer 18

• Dead tissue becomes firm and slightly swollen
• Tissue shows retention of microscopic architecture
• Typical of ischaemic injury (except in brain)
• Cellular proteins may leak into blood

(Note, this is the most common type)

Question 19

Describe Caseous necrosis and in what disease it is associated?

Answer 19

• Characteristic of tuberculosis
• Cheese like
• Cellular detail destroyed in this area, which is surrounded by granulomatous inflammation.
• Dead tissue lacks any structure

Question 20

Describe Colliquative necrosis and what tissue does it tend to happen in?

Answer 20

• Necrotic neural tissue is liable to total liquefaction and site is eventually marked by a cyst

Question 21

what types of gangrene are there?

Answer 21

wet and dry

Question 22

What is apoptosis?

Answer 22

programmed cell death

Question 23

In what processes does Physiological Apoptosis happen?

Answer 23

Embryogenesis
Involution
Elimination of self reacting lymphocytes

Question 24

what what processes does pathological apoptosis occur?

Answer 24

Pathological
DNA/protein damage
Viral infections
Cell killing by cytotoxic T-cells
(Chemo/radiotherapy?)

Question 25

describe apoptosis

Answer 25

Apoptosis initiating factor (AIF) and cytochrome C are normally sequestered in mitochondria, but when released into the cytosol activate caspases, which are the effector molecules of apoptosis.

Question 26

what two molecules cause lack of apoptosis in cancer?

Answer 26

P53 (the ‘guardian of the genome’) is activated by DNA damage and causes the elimination of damaged cells by apoptosis. Mutations to p53 are very common in malignant tumours, thus allowing cells to accumulate genetic abnormalities

Bcl-2 sequesters cytochrome C and thus inhibits apoptosis. Activating mutations leading to bcl-2 overexpression are another way that some tumours gain the ability to proliferate in an uncontrolled way.

Question 27

describe what a cell undergoing apoptosis would look like

Answer 27

reduced size, fragmented nucleus forming apoptotic bodies. other parts intact until phagocytosed.