Lecture 3 MoD

Question 1

How to maintain a healthy living cell?

Answer 1

Preservation of genetic integrity
Normal enzyme content
Intact membranes and transmembrane proteins
Adequate supply of substrates and oxygen

Question 2

What is cell injury?

Answer 2

Biochemical and/or morphological changes that occur when the steady state is perturbed by adverse influences.

Question 3

Draw cell injury pathway

Answer 3

refer lecture

Question 4

What is hyperplasia?

Answer 4

Increase in number of cells

Question 5

What is hypertrophy?

Answer 5

Increase in the volume of an organ or tissue due to the enlargement of its component cells. (Increase cell size)

Question 6

What is atrophy?

Answer 6

decrease in the size of cell

Question 7

What is metaplasia?

Answer 7

Change in cell morphology

Question 8

What are the different types of cellular adaptation?

Answer 8

Hyperplasia
Metaplasia
Hypertrophy
Atrophy

Question 9

What are the aetiology of cell injury? (5)

Answer 9

Low oxygen availability
Physical trauma
Chemical agents
Infectious organisms
Irradiation
Others:
-Immunological
-Lack of essential nutrients/vitamin
-Genetic disorders
-Ageing

Question 10

What are the meaning of hypoxia, anoxia and ischaemia?

Answer 10

Hypoxia = lack of oxygen
Anoxia = absence of oxygen
Ischaemia = lack of blood flow.

Question 11

What causes hypoxia and anoxia?

Answer 11

reduction or loss respectively of oxygen delivered to cells, often caused by ischaemia

Question 12

What will happen as the result of reoxygenation?

Answer 12

Reperfusion - generation of oxygen free radicals

Question 13

What are the factors that cause physical trauma?

Answer 13

Mechanical trauma
-Disruption of cell structure
-Thrombosis leading to ischaemia
Extremes of temperature
-Heat denaturation of proteins
-Ice crystals
-Fever

Question 14

What are the examples of chemical agents that cause cell injury?

Answer 14

Alcohol
Tobacco smoke
Drugs
Poisons
Environmental
Occupational

Question 15

What are the examples of infectious organisms that cause cell injury?

Answer 15

Bacterial toxin

• Exotoxins
• Endotoxins

Question 16

In what way does infectious organisms infect normal cells?

Answer 16

Hijacking of cell machinery by viral infection -> cell lysis

Collateral damage by inflammation

Question 17

Which organs have high sensitivity to radiation?

Answer 17

in bone marrow, gonads, intestines

Question 18

Which organs have low sensitivity to radiation?

Answer 18

Uterus, pancreas and adrenal

Question 19

What is the effect of radiation?

Answer 19

can induce inflammatory response several

hours after exposure

Question 20

What are the targets of cell injury?

Answer 20

Mitochondrial function
Membrane integrity and function
Protein synthesis
Cytoskeleton
Genetic apparatus

Question 21

What are the events that have a central role in mediating effects on multiple intracellular systems?

Answer 21

Diminished oxidative phosphorylation and reduced ATP level

Question 22

What are the factors that lead to cellular swelling, loss of microvilli, blebs and ER swelling?

Answer 22

Activity of plasma membrane ATP-driven “sodium pump” is reduced, with consequent influx of sodium and calcium,

Question 23

What are the sequence of events that lead to lipid deposition?

Answer 23

Decreasing pH and ATP levels cause ribosomes to detach from rough endoplasmic reticulum and reduction in protein synthesis which lead to lipid deposition

Question 24

What can cause sublethal cell injury?

Answer 24

Cell (cloudy) swelling

Fatty change

Question 25

What is oxygen free radicals?

Answer 25

- Highly reactive ions or molecules with single unpaired electron in outer orbital

Question 26

Explain oxygen free radicals toxicity?

Answer 26

Effector pathway of various types of cell injury Chain reaction with molecules in membranes to produce additional free radicals Also damages proteins and nucleic acids - apoptosis Detoxification by superoxide dismutase and antioxidants e.g. vitamins A, C & E

Question 27

What are the things that can compromise cell membrane?

Answer 27

Can be compromised by bacterial toxins, viral proteins, complement, cytolytic lymphocytes, and various physical and chemical agents

Question 28

What are the effect of loss of membrane barriers?

Answer 28

Loss of membrane barriers leads to breakdown in metabolite gradients - point of no return?

Question 29

Due to loss of membrane barriers, Ca2+ will increased. What is the effect of that?

Answer 29

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 30

What is necrosis?

Answer 30

Cell death as result of lethal cell injury Passive process Incites an inflammatory reaction

Question 31

What are the different types of necrosis?

Answer 31

``` Coagulative - most common Caseous - tuberculosis Colliquative - brain Gangrene - wet and dry Fat, fibrinoid ```

Question 32

What are the characteristics of coagulative necrosis?

Answer 32

Denaturation of intracytoplasmic protein 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

Question 33

What happened to the brain with colliquative necrosis?

Answer 33

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

Question 34

What are the characteristics of caseous necrosis?

Answer 34

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

Question 35

What is apoptosis?

Answer 35

‘Programmed cell death’ or ‘apoptosis’ (from Greek: falling off, as in leaves from trees)

Question 36

What is the mechanisms of apoptosis?

Answer 36

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. Two important molecules you will hear about in cancer biology are involved. 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 and become malignant. 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.