Cell Injury & Death III & IV - Parsa Flashcards
What are the main biochemical events leading to cell injury?
- ATP depletion
- Mitochondrial damage
- Influx of Ca and loss of Ca homeostasis
- Accumulation of oxygen derived free radicals (oxidative stress)
- Defects in membrane permeability
- Damage to proteins and DNA
ATP depletion
- Associated with hypoxic and chemical injury
- Reduces the oxygen supply to cell
- Cells with lots of glycogen stores survive longer than those without
Mitochondrial damage
- Anything that effects the cell membrane and certain hereditary diseases can cause problems
- Causes cellular apoptosis
Influx of Ca and loss of Ca homeostasis
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
Accumulation of oxygen derived free radicals (oxidative stress)
- 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
Defects in membrane permeability
• Necrosis results from significant damage
Damage to proteins and DNA
• Typically cause apoptosis
Ischemic and hypoxic injury
• Associated with inflammation
•Different cells respond differently
• Reperfusion helps recovery
o But also promotes generation of ROS (BAD)
How do neurons respond to ischemia?
Die after 5 min
How do myocardial fibers respond to ischemia?
Die after 30-40 min
How do fibroblasts respond to ischemia?
Last much longer
What protein is used clinically to diagnose tissue damage in cardiac muscle?
- Cardiac troponin-T
2. Creatine kinase
What protein is used clinically to diagnose tissue damage in hepatocytes?
- Alanine transaminase (ALT)
2. Aspartate transaminase (AST)
What protein is used clinically to diagnose tissue damage in striated muscle?
Creatine kinase (MM isoform)
What protein is used clinically to diagnose tissue damage in exocrine pancreas cells?
Amylase
Coagulative necrosis
- 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
Hemorrhagic necrosis
• Occurs when venous component if blocked off
Liquefactive necrosis
- 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
Gangrenous necrosis
- 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
Caseous necrosis
- Most often in foci of TB infection
* Name means cheese-like
Gumma
• 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
Enzymatic fat necrosis
- 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
Fibrinoid necrosis
- Seen in immune reactions involving blood vessels
* Occurs when complexes of antigens and antibodies are deposited in the walls of arteries
Direct injury
- Mercury binds to cell membrane sulfhydryl groups (absorb/excrete cells of G.I. and kidney)
- Cyanide inhibits mitochondrial oxidative phosphorylation
