Cell Injury & Death III & IV - Parsa

Question 1

What are the main biochemical events leading to cell injury?

Answer 1

1. ATP depletion
2. Mitochondrial damage
3. Influx of Ca and loss of Ca homeostasis
4. Accumulation of oxygen derived free radicals (oxidative stress)
5. Defects in membrane permeability
6. Damage to proteins and DNA

Question 2

ATP depletion

Answer 2

• Associated with hypoxic and chemical injury
• Reduces the oxygen supply to cell
• Cells with lots of glycogen stores survive longer than those without

Question 3

Mitochondrial damage

Answer 3

• Anything that effects the cell membrane and certain hereditary diseases can cause problems
• Causes cellular apoptosis

Question 4

Influx of Ca and loss of Ca homeostasis

Answer 4

Three things can happen:
1. Mitochondrial permeability transition pore enter mitochondria, diminishing phosphorylation of ADP → diminished ATP production
2. Ca is an active promoter of cellular enzymes
• Makes everything in the cell activate improperly and fucks shit up
3. Ca can activate caspases independent of anything else
• Leads to apoptosis

Question 5

Accumulation of oxygen derived free radicals (oxidative stress)

Answer 5

• Cells lose ability to regulate production of ROS so then there is an excess of free radicals leaving to oxidative stress
• Oxidative stress has been linked to cell injury, cancer, aging and some degenerative diseases

Question 6

Defects in membrane permeability

Answer 6

• Necrosis results from significant damage

Question 7

Damage to proteins and DNA

Answer 7

• Typically cause apoptosis

Question 8

Ischemic and hypoxic injury

Answer 8

• Associated with inflammation
•Different cells respond differently
• Reperfusion helps recovery
o But also promotes generation of ROS (BAD)

Question 9

How do neurons respond to ischemia?

Answer 9

Die after 5 min

Question 10

How do myocardial fibers respond to ischemia?

Answer 10

Die after 30-40 min

Question 11

How do fibroblasts respond to ischemia?

Answer 11

Last much longer

Question 12

What protein is used clinically to diagnose tissue damage in cardiac muscle?

Answer 12

1. Cardiac troponin-T

2. Creatine kinase

Question 13

What protein is used clinically to diagnose tissue damage in hepatocytes?

Answer 13

1. Alanine transaminase (ALT)

2. Aspartate transaminase (AST)

Question 14

What protein is used clinically to diagnose tissue damage in striated muscle?

Answer 14

Creatine kinase (MM isoform)

Question 15

What protein is used clinically to diagnose tissue damage in exocrine pancreas cells?

Answer 15

Amylase

Question 16

Coagulative necrosis

Answer 16

• A form of necrosis in which the architecture of dead tissues is preserved for a span of at least some days
• Affected tissues exhibit a firm texture
• Injury denatures structural proteins and enzymes so proteolysis of dead cells is blocked
• Necrotic cells removed by phagocytosis
• Infarct = a localized area of coagulative necrosis

Question 17

Hemorrhagic necrosis

Answer 17

• Occurs when venous component if blocked off

Question 18

Liquefactive necrosis

Answer 18

• Characterized by digestion of dead cells resulting in transformation of tissue into a liquid viscous mass
• Seen most commonly in the brain after stroke
• Any place with an abcess is liquefactive necrosis

Question 19

Gangrenous necrosis

Answer 19

• Not a specific pattern of cell death
• Usually applied to a limb that has lost its blood supply and undergone necrosis (typically coagulative necrosis)
• Involved multiple tissue planes

Question 20

Caseous necrosis

Answer 20

• Most often in foci of TB infection

* Name means cheese-like

Question 21

Gumma

Answer 21

• Much less common
• Implies secondary or tertiary syphilitic infection
• Looks like a granuloma
• White-gray and rubbery
• Can occur singly or multiply
• Different b/n this and TB is
o Clinical presentation
o Presence of plasma cells in area surrounding necrosis

Question 22

Enzymatic fat necrosis

Answer 22

• Associated with pancreatitis
• Chalky-white mesenteric deposits
• Refer to focal areas of fat destruction
• Results from release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity

Question 23

Fibrinoid necrosis

Answer 23

• Seen in immune reactions involving blood vessels

* Occurs when complexes of antigens and antibodies are deposited in the walls of arteries

Question 24

Direct injury

Answer 24

• Mercury binds to cell membrane sulfhydryl groups (absorb/excrete cells of G.I. and kidney)
• Cyanide inhibits mitochondrial oxidative phosphorylation

Question 25

Reactive toxic metabolites

Answer 25

• CCl4 → highly reactive free radical •CCl3
• Acetaminophen → NAPQI (electrophilic toxic metabolite)
o Converted to cytochrome P-450 oxidases → increase electrophilic toxic metabolite

Question 26

Mitochondrial (intrinsic) pathway of apoptosis

Answer 26

• Involves the action of sensors and effectors of the Bcl family
• Induce leakage of mitochondrial proteins
• Other Bcl family members are anti-apoptotic proteins

Question 27

Death receptor (extrinsic) pathway of apoptosis

Answer 27

• Engagement of death receptors leads directly to caspase activation
• FADD = Fas-associated death domain