T2: Cell Injury

Question 1

What is oncosis?

Answer 1

Pre-lethal changes preceding cell death.

Question 2

What are the causes of cell injury?

Answer 2

• Hypoxia - lack of oxygen in the area

• Physical agents
  
  • Temperature, trauma, radiation (causes direct damage to DNA). In trauma there is mechanical disruption of the.
• Chemical agents
  
  • Drugs etc. For example paracetamol overdose leads to metabolites binding ti liver cell proteins and lipoproteins.
• Immunologic reactions
• Infectious agents - Toxins and enzymes produced by the bacteria are damaging to the tissue.
• Genetic derangements
• Nutritional imbalances

This is not an exhaustive list.

Question 3

What are the general biochemical mechanisms of cell injury?

Answer 3

• ATP depletions
• Oxygen and oxygen derived free radicals - free radicals to bind to various things on the cell and destroy things.
• Loss of intercellular calcium haemostasis.
• Defects in membrane permeability - changes to the concentration gradient.
Irreversible mitochondrial damage.

Question 4

What are the types of cell injury?

Answer 4

Reversible cell injury - shows Cell swelling, pallor, hydropic change (Hydropic changerefers to the accumulation of water in the cell) and vacuolar degeneration. The lack of ATP means the sodium-potassium pump is not working, increasing the amount of sodium in the cell and therefore causing swelling of the cell by osmosis.

Irreversible cell injury - There is leakage of lysosomal enzymes into the cytosol. Also increase of calcium in the call causing the activation of proteins that deaerates the cell. Calcium alongside the cytochrome C leakage, leads to apoptosis.

Reperfusion injury - New damage on reperfusion mediated by free oxygen radicals.

Question 5

What are the differences between apoptosis and necrosis?

Hint: Think SUMO

Answer 5

Size: Apoptosis leads to cellular shrinkage and only one cell is affected. In necrosis, there is cellular swelling and many cells are affected.

Uptake: In apoptosis cell contents ingested by neighbouring cells and there is no inflammatory response. In necrosis the cell contents are ingested by macrophages and there is significant inflammation.

Membrane: In apoptosis there is membrane blobbing but the integrity remains - apoptotic bodies form. In necrosis there is a loss of membrane integrity and cell lysis occurs.

Organelles: In apoptosis mitochondria release pro-apoptotic proteins and chromatin condensation and there is non-random DNA degeneration. In necrosis there is organelle swelling and lysosomal leakage. There is also Random degeneration of DNA.

Question 6

What is the most common type of necrosis?

Answer 6

Coagulative necrosis

Question 7

What is the main cause of caseous necrosis?

Answer 7

Tuberculosis

Question 8

What are the different types of necrosis?

Answer 8

• Coagulative - The cells retain their outlines and the proteins coagulate and metabolic activity ceases. The predominant method is enzyme degeneration.
• Liquefactive (or Colliquative) - such as in a Bacterial or fungal infection, CNS hypoxia. Seen in the brain. Due to the lack of substantial supporting stroma, the cells all liquify. The main method is enzyme digestion.
• Gangrenous - this is necrosis with putrefaction of the tissue. The cause is mostly infectious or bacterial. The limb (usually) appears black. It can be wet, dry or gas gangrene.
• Caseous - Cheese like structure. It is a structureless form of death. Macrophages cannot fully digest the problem leading to an over reaction.
• Fat necrosis - Due to the leakage of the structure and enzymes being released form the pancreas. It can also be due to trauma. Adipocytes are broken down.
• Fibroid necrosis - It is seen in malignant HTN and autoimmune disease.