What are the 9 main causes of cell injury?
- Hypoxia
- Chemical agents
- Infectious agents
- Immunologic reactions
- Genetic defects
- Workload imbalance
- Nutritional imbalance
- Physical agents
- Aging
What are the 5 most important targets of injurious stimuli?
- Mitochondria
- Cell membranes
- Protein synthesis
- Cytoskeleton
- Genetic apparatus
What are the molecular mechanisms of cell injury?
- Calcium entry
- ATP depletion
- DNA damage
- Mitochondrial damage
- Membrane damage
- Oxidative stress (free radicals)
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Name 6 antioxidants
- Superoxide dimutase (SOD)
- Catalase
- Glutathione peroxidase
- Vitamins A, C, and E
What is the initial response to cell injury?
Acute cell swelling
Hydropic degeneration
Swelling in hepatocytes and renal epithelial cells
Ballooning degeneration
Swelling in keratinocytes
Cytotoxic edema
Swelling in glial cells of SNC
PAS stain
Glycogen
Sudan black stain
Lipid
What are 4 ultrastructural signs of acute cell swelling?
- Swelling of mitochondria
- Detachment of ribosomes from rER
- Clumping of chromatin
- Membrane blebs
What are the consequences of ATP depletion?
- Lose Na/K pump -> Na retention -> water retention/swelling
- Increased anaerobic glycolysis -> lactic acid accumulation
- Ca pump failure
- Protein synthesis failure -> unfolded protein response -> apoptosis
Cytochrome C
A proapoptotic enzyme released by damaged mitochondria
Effects of intracellular calcium retention
Activation of:
- ATPases
- Phospholipases -> membrane damage
- Proteases -> cytoskeletal damage
- Endonucleases -> DNA damage
Describe the histologic appearance of acute cell swelling
Finely vacuolated (and swollen) cytoplasm
