Cellular Injury Mechanisms

Question 1

Rudolph Virchow

Answer 1

father of modern pathology

Question 2

Homeostasis

Answer 2

cellular ability to handle physiologic demands to maintain a steady state

Question 3

What sorts of things can cause cell stress and injury?

Answer 3

BASICALLY EVERYTHING

oxygen deficiency, physical agents, infectious agents, nutritional deficiencies/imbalances, genetic derangements, chemicals/drugs/toxins, aging

Question 4

Does stress always cause pathology?

Answer 4

No - cells are able to adapt to handle the increased level of stress, until it becomes too much

Question 5

Main Mechanisms of Injury

Answer 5

1. Decreased ATP
2. Mitochondrial Damage
3. Calcium entry
4. Increase reactive oxygen species
5. Membrane damage
6. Protein misfolding and DNA damage

Question 6

ATP from Oxidative Phosphorylation

Answer 6

32 ATP (requires oxygen - aerobic respiration)

Question 7

ATP from Glycolysis

Answer 7

2 ATP (no oxygen - anaerobic respiration)

Question 8

Byproduct of glycolysis?

Answer 8

lactic acid

Question 9

Most efficient process for production of ATP?

Answer 9

oxidative phosphorylation

Question 10

3 Major Causes of ATP Depletion

Answer 10

1. Decreased oxygen and nutrients (ischemia, resp failure, heart failure, anemia)
2. Mitochondrial Damage
3. Specific Targeting of ATP-generating mechanisms by toxins

Question 11

Effect of Decreased ATP on Sodium-Potassium Pump

Answer 11

Decrease NaK pump leading to efflux of potassium leading to cell swelling, loss of microvilli, and blebs

also influx of calcium causing mitochondrial damage, enzymatic actions, and apoptosis

Question 12

Effect of Decreased ATP on Glycolysis

Answer 12

Increase glycolysis which decreases glycogen and increases lactic acid which decreases the pH, potentially causing clumping of nuclear chromatin

Question 13

Effect of Decreased ATP on Ribosomes

Answer 13

ribosomes will start detaching therefore decreasing protein synthesis and increasing lipid deposition

Question 14

What percentage of ATP depletion will start to cause problems?

Answer 14

5-10%

Question 15

4 Ways Mitochondrial Damage might occur

Answer 15

1. Influx of calcium
2. Increase of reactive oxygen species
3. Oxygen deprivation
4. Mutations of mitochondrial genes

Question 16

Two Possible Results of Mitochondrial Damage

Answer 16

1. Necrosis (more likely)
2. Apoptosis

Question 17

Free Radicals

Answer 17

chemicals that have an unpaired electron in their outer orbit and are therefore unstable

Question 18

Reactive Oxygen Species

Answer 18

free radical derived from oxygen

Question 19

Are free radicals produced from normal processes?

Answer 19

YES

Question 20

Mechanisms that Regulate Free Radicals

Answer 20

1. Spontaneous Decay
2. Antioxidants
3. Iron and copper based transport proteins
4. Enzymes of the Radical-Scavenging System

Question 21

3 Enzymes of the Radical Scavenging System

Answer 21

1. Catalase
2. Superoxide dismutase
3. Glutathione peroxidase

Question 22

Consequences of Membrane Damage

Answer 22

1. Lysosomal injury (enzymes released into cytoplasm)
2. Mitochondrial Damage (dec. ATP, pore opens and proteins trigger apoptosis)
3. Plasma Membrane Leakage (lose osmotic balance, lose metabolites for ATP –> dec. ATP, other constituents into blood)

Question 23

4 Ways Membrane Damage Can Occur

Answer 23

1. ROS
2. Decreased phospholipid synthesis
3. Increased phospholipid breakdown
4. Cytoskeletal Abnormalities

Question 24

What bloodwork constituents might indicate cellular membrane damage?

Answer 24

inc. ALT, ALP, ADT(liver), creatine kinase (CK) (muscle)