(01) Mechanisms of Cell Injury Flashcards
What are 6 common mechanisms of cell injury?
- Depletion of ATP
- Mitochondrial Damage and Dysfunction
- Influx of Calcium
- Accumulation of Oxygen-Derived Free Radicals
- Defects in Membrane Permeability
- Damage to DNA and Proteins
What are the 4 main consequences of ATP depletion?
- Plasma membrane ATP-dependent sodium pumps activity is reduced
- Failure of ATP-dependent Ca2+ pumps leads to and influx of Ca2+
- Increase in anaerobic glycolysis to try to maintain energy
- Ribosomal detachment from the ER resulting in Protein Synthesis problems
What are the 3 main consequences of mitrochondrial damage?
- Failure/abnormal oxidative phosphorylation
- Increased permeability of the membrane with loss of membrane potential and pH changes
- Release of proteins causing apoptosis
What are the some types of signals/physiologic conditions that lead to mitochondrial damage?
- No O2 supply
- Toxins
- Radiation
- Loss of survival signals
- DNA, protein damage
What are 2 ways that cytosolic calcium can be increased?
- Release from intracellular stores
- smooth ER, and mito - Influx across plasma membrane
- after injury
What are the 2 ways that calcium release leads to cell damage?
- Increased Ca2+ activates enzymes that are potentially harmful
- Ca2+ may activate caspases that increase mitochodrial permeability causing APOPTOSIS
What are the 2 major pathways that can cause oxidative stress in the cell?
- Oxidative burst in neutrophils and macrophages
2. ETC which can produce NITRIC OXIDE and peroxides
What does oxidative stress lead to?
Covalent modification of proteins, lipids, and nucleic acids
What are some sources of free radicals in the body?
- Absorption of Radiant energy (UV rays, X-rays)
- Enzymatic Metabolism of exogenous chemicals (CCl4)
- Imflammation in which leukocytes make free radicals
What methods do cells use to reduce free radical damage?
- Superoxide Dismutases (SODs)
- Glutathione Peroxidases
- Catalase (in peroxisomes)
- Endogenous or exogenous antioxidants
What are some examples of endogenous and exogenous antioxidants?
- vit. E
- vit. A
- vit. C
- ß-carotene
What are some causes of defects of membrane permeability?
- Decreased Phospholipid synthesis
- Increased Phospholipid breakdown
- ROS
- Cytoskeletol Abnormalities
- Lipid breakdown produces
What do unrepairable defects in DNA (and proteins) cause?
Apoptosis
How will an apoptotic cell appear on H and E?
Shunken, Eosinophilic, and Pyknotic
What does elevated serum lactate dehydrogenase indicate?
Lactate Dehydrogenase in the serum is indicative of cell death.
