Cells + Cell Injury

Question 1

What is cell injury?

Answer 1

Effect of stresses from changes in the internal and/or external environment.

Question 2

What does cellular response to injury depend on? (4)

Answer 2

1. Type of cell and tissue involved
2. Extent and type of injury
3. Intracellular phenomena
4. Morphological consequences

Question 3

What are 3 types (levels) of stresses on a cell and how is it classified?

Answer 3

1. Adaptations: normal cell is restored due to minor stressor
2. Reversible cell injury: repair and heal due to moderate stressor
3. Irreversible cell injury: severe and persistent stress resulting in cell death

Question 4

What are some examples of adaptive cell injuries?

Answer 4

• Atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia.

Question 5

What are some examples of reversible cell injuries?

Answer 5

Degenerations, subcellular alterations, intracellular accumulations

Question 6

T/F - Cell injury can be both genetic and acquired.

Answer 6

True

Question 7

What is ischemia?

Answer 7

Loss of arterial blood flow

Question 8

What is hypoxia?

Answer 8

Loss of ability to carry on sufficient aerobic oxidative respiration (ischemia can lead to hypoxia).

Question 9

What is the most common cause of injury?

Answer 9

Hypoxia

Question 10

How can ischemia cause hypoxia? (2)

Answer 10

1. Local causes: the occlusion of arteries or veins or the shunting of blood elsewhere.
2. Systemic causes: failure of heart to pump enough blood

Question 11

What is hypoxemia?

Answer 11

Too little available oxygen in the blood.

Question 12

What causes oxygen problems in hypoxemia?

Answer 12

1. Too little oxygen in the air
2. Failure to properly ventilate the lungs
3. Failure of lungs to properly oxygenate blood
4. Failure of heart to pump enough blood through lungs
5. Increased lung dead space

Question 13

What causes hemoglobin problems in hypoxemia?

Answer 13

1. Inadequate circulating red cell mass (anemia)
2. Inability of hemoglobin to carry oxygen because of either CO poisoning or methemoglobinemia
3. High affinity hemoglobin

Question 14

What are three causes of hypoxia?

Answer 14

1. Ischemia
2. Hypoxemia
3. Failure of cytochromes (histotoxic hypoxia)

Question 15

How can failure of cytochromes cause hypoxia?

Answer 15

• CO and cyanide poisoning

- DNP poisoning

Question 16

How does DNP poisoning cause failure of cytochromes?

Answer 16

• Proton leakage will cause uncoupling

Question 17

What happens if uncoupling of protons takes place in ETC?

Answer 17

Results in insufficient production of ATP and instead everything is released as heat.

Question 18

How do metabolic demands affect cells?

Answer 18

Increased metabolic demands will exacerbate hypoxic conditions temporarily

Question 19

What are some physical causes of cell damage?

Answer 19

• mechanical trauma
• thermal trauma
• electricity
• rapid pressure changes

Question 20

What are some examples of rapid pressure changes causing damage of cells?

Answer 20

• Intracranial pressure
• tumors
• lung disease

Question 21

What are some chemical causes of cell damage?

Answer 21

• Oxygen in high concentrations
• Hypertonic glucose
• Alcohol and narcotics

Question 22

What are some microbial causes of cell damage?

Answer 22

• Bacteria, fungi, viruses, protozoa and metazoa

Question 23

How do cytolytic and cytopathic viruses cause cell damage?

Answer 23

Cytolytic viruses: scramble genes that are needed to maintain cell structure and multiply so fast that cells explode
- Cytopathic: alter morphology

Question 24

What are some immunologic causes of cell damage?

Answer 24

• hypersensitivity reactions
• anaphylactic reactions
• autoimmune disease due to auto-antibodies

Question 25

What are some nutritional derangement causes of cell damage? (2)

Answer 25

1. Deficiency - overall starvation - Kwashiorkor (protein deficiency in later years) and marasmus (protein deficiency in earlier years) 2. lack of glucose leading to same brain damage as hypoxia

Question 26

How does aging contribute to cell injury?

Answer 26

The impaired ability to replicate and repair eventually leads to cell death

Question 27

What can be an example of an idiopathic cause of cell injury?

Answer 27

Essential hypertension or cancer

Question 28

What happens when a small dose of toxin or short duration of ischemia is experienced?

Answer 28

Damage is reversible

Question 29

What happens when a large dose of toxin or persistent ischemia is experienced?

Answer 29

Will result in cell death

Question 30

How do skeletal muscles respond to hypoxia?

Answer 30

They can withstand hypoxia for a long time

Question 31

How do cardiac muscles respond to hypoxia?

Answer 31

Irreversible damage after about 20-30 minutes of ischemia

Question 32

How do neurons respond to hypoxia?

Answer 32

Will die after 3-5 minutes without oxygen

Question 33

How do liver cells respond to hypoxia?

Answer 33

Can last about 1-2 hours without oxygen

Question 34

How does intracellular phenomena affect cell damage? (3)

Answer 34

1. Mitochondrial damage (the depletion of ATP) 2. Cell membrane damage (disturbs metabolic and transmembrane exchange) 3. Release of toxic free radicals

Question 35

Pathogenesis of hypoxia and ischemic reversible injuries

Answer 35

1. Decreased ATP 2. Intracellular lactic acidosis 3. Damage to plasma membrane pumps 4. Reduced protein synthesis

Question 36

Relationship between ischemia and aerobic respiration

Answer 36

- In ischemia, aerobic respiration and glucose availability is compromised resulting in severe and faster effects of cell injury and accumulation of wastes in cells

Question 37

Relationship between hypoxia and anaerobic respiration

Answer 37

- In hypoxia, anaerobic glycolytic ATP generation is able to continue to result in a less severe injury

Question 38

Why do specialized cells (such as myocardium, PT cells, and neurons) suffer effects of ischemia more rapidly and severely?

Answer 38

Because they depend solely on aerobic respiration for ATP

Question 39

How do ischemia and hypoxia lead to intracellular lactic acidosis?

Answer 39

Aerobic respiration will eventually fail and switch to anaerobic which causes glycogen depletion and lactic acid accumulation

Question 40

Why does the forced switch to anaerobic respiration cause glycogen depletion and lactic acid accumulation?

Answer 40

Because glucose and glycogen are needed to start anaerobic glycolysis and results in an end product of pyruvate and lactate

Question 41

How do ischemia and hypoxia lead to damage to plasma membrane pumps?

Answer 41

A lack of ATP interferes with the generation of phospholipids which in turn damages the pumps

Question 42

How are sodium-potassium pumps affected by ischemia and hypoxia (Na+ out, K- in)

Answer 42

Intracellular sodium will accumulate while potassium will passively flow out causing intracellular water and hydropic swelling

Question 43

How are calcium pumps affected by ischemia and hypoxia?

Answer 43

When membrane is damaged, excess calcium will move into the cell

Question 44

How does reduced protein synthesis progress from ischemia and hypoxia?

Answer 44

- membranes of ER and Golgi will swell - ribosomes will detach from RER - polysomes will degrade to monosomes (inactivated)

Question 45

What makes cell injury irreversible? (2)

Answer 45

1. mitochondrial dysfunction not reversible upon reperfusion or re-oxygenation 2. disturbance in cell membrane function

Question 46

What are biochemical changes that affect ultrastructure? (5)

Answer 46

1. Calcium influx 2. Activated phospholipases 3. Intracellular proteases 4. Activated endonucleases Lysosomal hydrolytic enzymes

Question 47

How does calcium influx affect ultrastructure?

Answer 47

Large influx of calcium collects in mitochondria and disables function

Question 48

How do activated phospholipases affect ultrastructure?

Answer 48

- Cause membrane damage | - The low replacement and synthesis of phospholipids results in low ATP and activated ATPase

Question 49

How do intracellular proteases affect ultrastructure?

Answer 49

- Cause cytoskeletal damage

Question 50

How do activated endonucleases affect ultrastructure?

Answer 50

Nucleoproteins are damaged by lysosomal enzymes

Question 51

What are 3 forms of irreversible nuclear damage?

Answer 51

1. Karyolysis: nuclear fading 2. Pyknosis: nuclear shrinkage 3. Karyorrhexis: nuclear fragmentation

Question 52

What do karyolysis, pyknosis, and karyorrhexis all lead to?

Answer 52

Nuclear dissolution and a nuclear necrotic cell

Question 53

How do lysosomal hydrolytic enzymes affect ultrastructure?

Answer 53

The damage of lysosomes releases hydrolytic enzymes that lead to the digestion of cellular components and cell death

Question 54

How are hydrolytic enzymes activated?

Answer 54

by low oxygen and pH

Question 55

What are dead cells replaced by?

Answer 55

Myelin figures

Question 56

What are the clinical parameters of cell death?

Answer 56

When liberated enzymes leak into serum