2.3 Path: Cell Death Flashcards
What are hypoxia, anoxia, and ischemia?
HYPOXIA: relative loss of oxygen
ANOXIA: complete loss of oxygen
Ischemia: Failure of vascular supply
What is the order of operations in a hypoxic cell injury?
lood vessel with thrombus (clot) —> blood supply blocked (ISCHEMIA) —> within the cell the mitochondria are the first cell affected. Without O2, the normal process of oxidative phosphorylation slows then stops. —> If no O2, then anaerobic pathways kick in (capacity varies by cell type, eg muscle cells have a large capacity for anaerobic metabolism, neuro cells not so much). Cell will consume glycogen, then cell function will not be maintained. Other early change: ATP-dependent Na+ pump (that maintains water balance) fails, and water starts to accumulate in the cell. Na+ stays in the cell and water follows salt.
= Water in cell, aerobic glycolysis
What are the consequences of anaerobic metabolism within the cell?
Increased Lactic Acid decreases Intracellular pH
Clumping of DNA
Cessation of RNA synthesis
Cessation of the Plasma Membrane Energy dependent Sodium Pump
Increased Intracellular Sodium and Water
Results in INTRACELLULAR EDEMA
What is the fatal step that leads to irreversible cell death?
Disruption of the plasma membrane
What happens once the cell membrane has been disrupted?
Once plasma membrane ruptures, the organelles lyse and stop functioning. Remember: organelles are membrane-bound. If something breaks the cell membrane, it can break the organelle.
Once the internal membrane is broke, lysosomes (SUICIDE BAG) rupture and kill anything else
Same with ionized Ca++ —> very potent cell disrupter/ It’s a potent catalyst, moves cell death along
Ca++ can be a marker of cell death (latent)
What is the morphology (on histo) of hypoxic cell death?
Increased Cytoplasmic Eosinophilia (more pink)
Loss of DNA, RNA, Glycogen (loss of blue)
Protein clumping of myocardial fibers.
What is karyolysis?
faded nucleus
What is pyknosis?
shrunken nucleus
What is karyorrhexis?
fragmented nucleus
What is necrosis? What kind of response does it provoke?
Spectrum of morphologic change of cell death in living tissues
Progressive enzymatic cell degradation
Invokes INFLAMMATORY Response
What is free-radical induced cell injury? How does this occur?
A direct membrane attack
High Reactivity with Cell Membranes and Nucleic Acid
Sources include: radiant energy, endogenous oxidative reactions, exogenous chemicals/drugs, reperfusion
NO SWELLING. Don’t go through stages of reversible cell injury. Straight to cell breaking apart
What is a reprofusion injury?
There’s a cost to reestablishing blood supply after ischemia (eg stent s/p MI)
When you bring in fresh blood, with fresh neutrophils (who search and destroy with powerful enzymes). Neutrophils release their granules which damage the membranes of cells that are still alive. *granules can be indiscriminate.
TRADEOFF- weigh benefits of reestablishing blood supply vs risk of repercussion injury. Are clinical guidelines for heart, brain injury.
What is apoptosis? How does it work?
Planned/orchestrated cell death
Signal- often something purposeful eg in embryonic development. Tissue laid down in development then “sculpted out”
DOESN’T CAUSE INFLAMMATORY RESPONSE. A clean way to kill off cells.
Requires activation of a sophisticated pathway that ends in cell death. Ex: endometrial tissue every month, tissue dies by apoptosis and bleeds out.
What is the order of operations in apoptosis?
Cell Shrinkage
Chromatin condenses with peripheral clumping
Fragmentation into “Apoptotic Bodies”
Ingested by Macrophages
What is steatosis?
“Fatty liver” Accumulation of lipids within hepatocytes
