Cell Injury II

Question 1

What are the eight general causes of cell injury?

Answer 1

1. Oxygen deprivation
2. Chemical agents
3. Infectious agents
4. Immunologic reactions
5. Genetic factors
6. Nutritional imbalances
7. Physical agents
8. Aging

Question 2

Carbon monoxide poisoning causes what type of general cell injury?

Answer 2

Oxygen deprivation by irreversibly binding to heme

Question 3

Do different cells react differently to certain stresses?

Answer 3

Yeah

Question 4

In cell injury, what is the temporal arrangement of the following: gross morphological changes, cell death, cellular function?

Answer 4

Cellular function is lost first, then cell death occurs, then gross morphological changes happen.

Question 5

What are the four intracellular systems that are vulnerable to injury?

Answer 5

Cell membranes, aerobic respiration, protein synthesis, genetic integrity.

Question 6

What are the two most important phenomena that correlate with the irreversibility of cell injury?

Answer 6

Mitochondrial dysfunction and membrane dysfunction. Note that the two are interrelated.

Question 7

Does cell injury progress in steps, or in a continuous process?

Answer 7

In a continuous process

Question 8

What is the difference between ischemia and hypoxia?

Answer 8

Ischemia is characterized by a deprivation of both oxygen and substrates (often occurs as a loss of blood supply). Hypoxia is systemic oxygen deprivation (example: going to high altitudes).

Question 9

What are the three general changes that occur during reversible cell injury?

Answer 9

1. Volume - cells swell
2. Changes in energy metabolism
3. Morphological changes

Question 10

What causes cellular swelling that occurs during reversible cell injury?

Answer 10

Changes in membrane permeability and loss of function of ATP-driven ion pumps increase osmotic load in the cell from increased levels of Na+, Ca2+, and small molecules.

Question 11

Name the changes in energy metabolism that occur during reversible cell injury.

Answer 11

ATP production drops due to decreased aerobic respiration. Anaerobic metabolism increases, lowering pH. Glycogen stores are used, protein synthesis decreases.

Question 12

What morphological changes from reversible cell injury can be seen in a light microscope?

Answer 12

Cytoplasmic changes such as hydropic changes (vacuolar degeneration - ER buds that have pinched off into the cytoplasm; cell stains lighter, too). Nuclear changes like clumping of chromatin can be seen.

Question 13

What morphological changes from reversible cell injury can be seen in an electron microscope? (4)

Answer 13

Dilation of the ER (from habitual drug abuse), decreased glycogen stores, swollen mitochondria with small densities, blebbing of the plasma membrane.

Question 14

What causes the dysregulation of volume in cells that are irreversibly injured?

Answer 14

Caused by a permanent loss of selective permeability of the plasma membrane and leakage of large molecules out of the cell. Membrane phospholipids are lost due to enzymatic action and cytoskeletal abnormalities.

Question 15

What four changes in energy metabolism occur after irreversible cell injury?

Answer 15

1. OXPHOS decoupling
2. Decreased PO4: O2 ratio
3. Glycolysis increases, lactate increases, pH drops
4. Mitochondrial dysfunction, including mt permeability transition pore leakage

Question 16

An increase in eosinophilia and a decrease in basophilia in cells is indicative of what? What causes it?

Answer 16

Cell damage and swelling. Caused by denaturation of cytoplasmic proteins and a loss of RNA from the cell (RNA is basophilic), and increased osmotic load in the cytoplasm due to loss of selective permeability of the PM.

Question 17

What is:
1. Pyknosis
2. Karyorrhexis
3. Karyolysis?
What do these indicate?

Answer 17

Pyknosis is a shriveling of the nucleus and increased basophilia.
Karyorrhexis is nuclear fragmentation - looks like a chocolate chip cookie.
Karyolysis is the complete dissolution of the chromatin of a dying cell due to the enzymatic degradation by endonucleases.

They are indicative of necrosis.

Question 18

What morphologic changes to the mitochondria can be seen on EM during irreversible injury?

Answer 18

1. Dilation or rupture

2. Granules/amorphous densities

Question 19

What role does calcium play in cell injury?

Answer 19

It is usually found in low cytoplasmic concentrations. When the cell is injured, altered membrane permeability allows for Ca2+ influx. Mitochondria will suck up the Ca2+ from cytoplasm, resulting in decreased ATP production.

Question 20

What can increase rates of free radical formation? (4)

Answer 20

Radiant energy exposure, enzymatic reactions, transitional metals react with H2O2 to generate a hydroxyl radical via the Fenton reaction, Nitric oxide can produce free radicals.

Question 21

Name two examples of physiologic free radical generation.

Answer 21

1. Respiratory burst in neutrophils and macrophages.

2. Byproduct of aerobic respiration.

Question 22

What are the three main ways in which reactive oxygen species cause cell injury?

Answer 22

1. Lipid peroxidation of membranes.
2. Cross-linking of proteins - results in protein degradation.
3. DNA damage.

Question 23

What do scavengers do to free radicals?

Answer 23

Capture them!

Question 24

What are the five mechanisms by which cells deal with free radicals?

Answer 24

1. Superoxide dismutases
2. Glutathione peroxidases
3. Catalase
4. Antioxidants A, C, and E
5. Metal binding proteins (transferrins, ferritin, lactoferrin, etc.)

Question 25

What does CCl4 do to hepatocytes? How?

Answer 25

Causes fatty infiltration and necrosis by CYP450 conversion to a free radical containing compound that injures ER membranes (lipid peroxidation), leading to inhibition of apoprotein synthesis and a build up of lipids in the cells.

Question 26

What does ricin poisoning do?

Answer 26

Stops translation

Question 27

What morphological change constitutes the only unequivocal evidence that the cell is dead?

Answer 27

Nuclear changes seen by microscopy.

Question 28

What are the possible causes for reperfusion injury?

Answer 28

Suddenly increasing the O2 availability may rapidly increase O2-derived free radicals. Increased perfusion may also increase the number of infiltrating inflammatory cells and may also activate the complement system –> more cell death.