Chapter 2: Mechanisms of Cellular Injury

Question 1

The cellular response to injurious stimuli depends on what?

Answer 1

Nature of the injury, its duration, and its severity (dose/ischemic time)

Question 2

The consequences of cell injury depend on what?

Answer 2

The type, state, and adaptability of the injured cell

Question 3

What are the principal targets of injurious stimuli?

Answer 3

Mitochondria, cell membranes, the machinery of protein synthesis and secretion, and DNA

Question 4

How can mitochondria be damaged?

Answer 4

Increases of cystolic Ca2+, ROS, and oxygen deprivation

Question 5

What are the three major consequences of mitochondrial damage?

Answer 5

ATP depletion, formation of ROS, and leakage of mitochondrial proteins

Question 6

What is decreased ATP synthesis and ATP depletion frequently associated with?

Answer 6

Both hypoxic and chemical injury

Question 7

What are the major causes of ATP depletion?

Answer 7

Reduced supply of oxygen and nutrients (because of ischemia and hypoxia), mitochondrial damage and the actions of some toxins (cyanide)

Question 8

What is the high-conductance channel that forms in the mitochondrial membrane as a result of mitochondrial damage?

Answer 8

The mitochondrial permeability transition pore

Question 9

What is the effect of the mitochondrial permeability transition pore opening?

Answer 9

It leads to the loss of the mitochondrial membrane potential, which leads to a failure of oxidative phosphorylation and progressive ATP depletion that leads to necrosis

Question 10

What are the cellular systems affected by ATP depletion?

Answer 10

The plasma membrane energy dependent sodium pump, cellular energy metabolism (so there will be increased rates of glycogenolysis and glycolysis), glycogen stores will be depleted, accumulation of lactic acid, and a reduction in protein synthesis

Question 11

What does incomplete oxidative phosphorylation lead to?

Answer 11

Formation of ROS

Question 12

What is a consistent feature of most forms of cell injury (except apoptosis)?

Answer 12

Early loss of the selective membrane permeability which leads to overt membrane damage

Question 13

What are the most important sites of selective membrane damage during cell injury?

Answer 13

Mitochondrial membrane, the plasma membrane, and membranes of lysosomes

Question 14

What are some mechanisms that contribute to membrane damage?

Answer 14

ROS, decreased phospholipid synthesis, increased phospholipid breakdown, cytoskeletal damage

Question 15

What is the effect of plasma membrane damage?

Answer 15

It results in the loss of osmotic balance and influx of fluids and ions

Question 16

What is the effect of injury to the lysosomal membranes?

Answer 16

Leakage of their enzymes into the cytoplasm and activation of acid hydrolases push cells into necrosis

Question 17

Increased production or decreased scavenging of ROS may lead to an excess of free radicals. This condition is known as what?

Answer 17

Oxidative stress

Question 18

What 3 things could cause the production of ROS?

Answer 18

Radiation, toxins, or reperfusion

Question 19

What enzyme converts superoxide into H2O2?

Answer 19

Superoxidase dismutase (SOD)

Question 20

How is H2O2 decomposed to H2O?

Answer 20

By glutathione peroxidase or catalase

Question 21

ROS are also produced in large amounts by activated what?

Answer 21

Leukocytes, particularly neutrophils and macrophages, during inflammatory reactions aimed at destroying microbes and cleaning up dead cells

Question 22

What effect does ROS accumulation have on lipids?

Answer 22

They damage lipids through lipid peroxidation, which damages membranes

Question 23

What effect does ROS accumulation have on proteins?

Answer 23

ROS accumulation leads to protein modifications, which leads to protein breakdowns or misfolding

Question 24

What effect does ROS accumulation have on DNA?

Answer 24

It leads to mutations

Question 25

How can you get increased intracellular Ca2+?

Answer 25

Ischemia and certain toxins

Question 26

What effect does excessive Ca2+ in the mitochondria have?

Answer 26

Failure of ATP generation

Question 27

What does increased cytosolic Ca2+ activate?

Answer 27

Phospholipases, proteases, endonucleases, and ATPase

Question 28

What is the difference between ischemia and hypoxia?

Answer 28

Blood flow is maintained in hypoxia, ischemia is hypoxia induced by reduced blood flow

Question 29

Why is ischemia more severe than hypoxia?

Answer 29

In ischemia, not only does aerobic metabolism cease, but anerobic energy generation also fails after glycolytic substrates are exhausted

Question 30

What three things happen when there is a loss of ATP?

Answer 30

Decreased Na+ pump action, increased anaerobic glycolysis, and detachment of ribosomes

Question 31

What are four possible mechanisms for ischemia-reperfusion injury?

Answer 31

Oxidative stress, intracellular calcium overload, inflammation, and activation of the complement system

Question 32

What does mild ischemia cause?

Answer 32

Reversible cell injury

Question 33

What does severe/prolonged ischemia cause?

Answer 33

Death by necrosis and apoptosis

Question 34

What causes reperfusion injury?

Answer 34

Oxidative stress due to release of free radicals from leukocytes and endothelial cells. Also intracellular calcium overload, inflammation, and activation of complement

Question 35

Chemicals induce cell injury by one of two general mechanisms. What are they?

Answer 35

Direct toxicity and conversion to toxic metabolites