Cell degeneration and death 2 Flashcards
Physical causes of cell injury
UV radiation
Excessive heat or cold
Mechanisms by which cells are deprived of O2
inadequate oxygenation of the blood- ie hypoxia
inadequate o2 carrying capacity of blood- anemia
inadequate delivery of blood to tissue- ischemia
-vascular occlusion
-vasospasm
-shock
-infarct
Describe the cellular events leading to necrosis in hypoxia/ischemia
blood flow stops
lack of O2 and glucose
Mitochondrial ATP down
Depletion of cellular ATP
1.failure of protein synthesis (as it requires ATP)
2. failure of membrane Na/K pump- swelling of ER
3. anaerobic metabolism- low pH- activation of enzymes at low pH-necrosis
4. free Ca in cytoplasm -necrosis cascade
5. mitochondrial swelling
Factors influencing significance of ischemia
pre-existing collateral circulation
rapidity of development of ischemia
type of tissue/degree of metabolic activity
whether ischemia is due to defect in atrial or venous perfusion
whether or not there is reperfusion injury
Anoxic cellular injury
inadequate oxygenation of blood
- anemia
- pneumonia
Arterial vs venous impairment of blood flow
arterial initially pale
venous deep red-balck congested
Appearance of an infarct is dependent on
vanous vs atrial infarct
tissue- dense or loose
age of infarct
presence or absence of reperfusion
Venous infarct commonly are associated with?
displacements or twists in the intestine
Reperfusion injury
- may damage ischemic tissue even more
- reflow of blood into an area of moderate hypoxic insult results in additional damage to sublethally injured cells and may tip cells over the edge to necrosis
- reflow increases free radical generation and inflammation
- must be kept in persepctive in veterinary medicine
Watershed
between arterial fields in the equine large bowel where collateral circulation is poorest
Renal papillary necrosis
due to reduced perfusion of the medulla/papilla associated with NSAIDS administration in horses
Describe the process of frostbite
cold–>vasoconstriction–>ischeia coupled with direct freezing injury to cells
Explain how Ergotism (mycotoxin-related disease) can produce a similar lesion to frostbite
ergotamine toxin–> vasoconstriction–>ischemia
Patterns of necrosis
Distribution of noxious insult
-blood-borne or inhaled
Relative susceptibility of the cells or tissue
-cell metabolism (zone 3 hepatocytes vs zone 1)
-blood supply (end-artery OR collateral circulation)
If necrosis is severe how does it heal?
heals by scarring