5. Cell Injury And Death Flashcards
Describe the sequence of events that lead to cell injury and death
- Adaptation: stress induced change in cell
- Reversible injury: cell is able to return to steady state
- Irreversible injury: cell goes beyond point of no return and causes permanent pathological changes leading to cell death
Inability to restore mitochondrial function, loss of plasma membrane, loss of chromatin integrity - Cell death: necrosis/ apoptosis
Necrosis
Major pathway in cell death in many commonly encountered injuries ( ischemia, exposure to toxins, various infections, trauma)
ALWAYS pathological, unwanted, external agents
Happens in a lot of cells, inflammation is present
Mechanism of Necrosis
ATP depletion
Membrane pump falls out - needs ATP to function
Damage to cellular membranes - too much sodium comes in, water follows, cell bursts
Leakage of cellular contents- acidic enzymes (lysosomes) and eats cellular contents
Inflammation - cellular contents attract neutrophils who call for help and release more acidic enzymes
SIMPLY PUT:
- Disintegration of plasma membrane
- Degradation of intracellular proteins
- Enzymatic digestion of the cell
Example of Necrosis : Ischemia
Ischemia - reduction of blood supply
Cells not receiving oxygen and cannot undergo aerobic respiration so go through anaerobic respiration (by product is lactic acid)
Lactic acid changes cellular environment and degrades proteins
Coagulation necrosis
Loss of blood supply firm and opaque, occurs in solid organs except for the brain, organ architecture is maintained
Liquefaction necrosis
Enzymes are released and liquefy cells - brain and neurons
Caseous necrosis
Cheese-like partially digested debris (granulomas) - TB, syphillis, Fungi, Lung
Fatty necrosis
Chalky white lipase
Fatty acids + Ca2+ (chalky crystals)
Breast and pancreas
Apoptosis
Programmed cell death
Cell degrades it’s own DNA and nuclear cytoplasmic proteins by activation of caspases (nucelar fragmentation and formation of apoptotic bodies)
Can be external or internal agents, cell does not open, no inflammation
Apoptotic cells break up into fragments called apoptotic bodies - targets for phagocytes
Intrinsic and extrinsic pathways
Intrinsic pathway of apoptosis
Most common
Activates poor-apoptotic factors who put holes in mitochondria - cytochrome C is released and activated caspases
Extrinsic pathway of apoptosis
Usually caused by virus infection or T-lymphocyte death]
Receptors (Fas and TNF) are bound by ligand and those ligand are bound to a virus - cytotoxic T cells recognize though Fas ligand and activate caspases - apoptosis
No involvement of mitochondria
Pathological apoptosis
DNA damage
Accumulation of misfolded proteins
Infections - especially viral
Physiological apoptosis
During embryogenesis
Turnover of proliferation tissue (intestinal epithelium)
Involution of hormone-dependent tissues (endometrium)
Decline of leukocyte numbers at the end of immune and inflammatory response
Necrosis SUMO
Size- cellular swelling, many cells affected
Uptake - cell contents ingested by macrophages (inflammation)
Membrane - loss of membrane integrity (cell lysis occurs)
Organelles - organelle swelling and lysosomal leakage, random degradation of DNA
Apoptosis SUMO
Size - cell shrinkage, one cell affected, NO swelling and ONLY one affected rather then many
Uptake - cell contents ingested by neighboring cells, NOT macrophages
Membrane -membrane blebbing but integrity maintained, NO loss of membrane integrity no cell lysis
Organelles - mitochondria release pro-apoptotic proteins chromatin condensation and non-random DNA degradation, NO organelle swelling or lysosomal leakage NO random degradation of DNA
