Mechanisms of cell injury Flashcards
במה תלויה התגובה התאית לפגיעה?
סוג הפגיעה, משך הפגיעה, וחומרת הפגיעה
במה תלויה התוצאה בעקבות פגיעה?
סוג התא, מצבו, ויכולת האדפטציה שלו
perturbations in which elements cause cell injury?
one of five essential cellular elements:
- ATP production
- Mitochondrial integrity (independent of ATP prod.)
- Plasma Membrane integrity - ionic & osmotic homeostasis.
- Protein Synthesis - folding, degradation &re-folding
- Integrity of Nuclear Apparatus.
What are the six general pathways of intracellular cell injury?
- ATP depletion:
- common both as a result of hypoxia & toxins.
- lead to increased glycolysis, lactic acid accumulation, and intracellular acidosis.
- No money to pay for ion transporters and protein makers. - Mitochondrial Damage:
- Causes:
- Hypoxia & Toxins
- Oxidative Stress
- Increases cytosolic Ca.
- Phospholipid Breakdown
- Dissipates the electromotive force
- Leakage of Cytochrome C (Apoptosis trigger) - Influx of Calcium:
- Across the PM or release from organelles.
- The Calcium activates phospholipases, proteases, ATPases, and endonucleases (chromatin fragmentation) - Accumulation of ROS:
- Causes damage to lipids, proteins & nucleic acids.
- Vitamin A&E are antioxidants that either block ROS formation or scavenge them.
- Transition metals levels remain low thanks to protein binding ( ferritin, transferring, etc.) - Defects in Membrane Permeability:
- increased permeability of PM results in osmolarity change & enzymatic activity.
- increased permeability of the mitochondrial membrane results in reduced ATP synthesis and can drive apoptosis via Cyt C.
- increased lysosomal permeability releases potent enzymes and lowers pH. - DNA & Proteins Damage:
- too much damage to DNA activates apoptosis.
- too many improperly folded proteins lead to stress response that also triggers apoptosis.
The transition from reversible to irreversible injury is difficult to identify, although two phenomena are associated with irreversible injury specifically.
What are they?
- Inability to restore mitochondrial function.
- Impropriate membrane function.
Leakage of cytosolic enzymes to the bloodstream may serve as a clinical marker of cell death.
Elevation of Creatinine Kinase and Troponin certain isoforms indicates:
- Necrosis to Mayocardium cells
Elevation of Alkaline phosphatase specific isoform indicates:
- Necrosis to Epithelial cells lining the bile ducts.
Elevation of alanine & aspartate transaminases indicates:
- Necrosis to liver cells.
What is the difference between hypoxia and ischemia?
- Hypoxia is reduced oxygen-carrying capacity
- Ischemia is reduced blood flow
- Ischemia causes hypoxia and tends to injure tissues faster than hypoxia ( because hypoxia does not interfere with substrates delivery and waste removal )
- When the injury is considered reversible, re-oxygenation would let the cell recover, whereas in irreversible injury the cells will continue to die even though there is oxygen around.