Irreversible Injury Flashcards
Cell Injury
injury:
- hypoxia
- membrane injury
cell response depends on:
- cell type
- injury
Result:
- adaptive
- degenerative
- reversible
- irreversible = DEATH
Cell Death
Simple version:
1) homestasis / physiologic
- development
- adult animal - compensation for cell duplication
- adult - tissue remodeling
2) pathology
- response to severe injury
- 2 morphologic forms = necrosis + apoptosis
Advanced version:
- ACD = accidental cell death
- RCD = regulated cell death
- synthesis of morphology, enzymology, functional aspects, immunological aspects
Necrosis
cell swells (oncosis - reversible change) -> eventually bursts
internal structure falls apart
often group of cells
Sequelae:
- inflammation
- scarring
- loss of function
Histological Features of Necrosis/Apoptosis
Pyknosis v Karyorhexis v Karyolysis
Pyknosis = condensation of chromatin + nuclear membrane (thin arrows)
Karyorhexis = fragmentation of chromatin + nuclear membrane (circle)
Karyolysis = dissolution of chromatin + nuclear membrane (fat arrows)
Types of Necrosis
descriptive terms -> don’t reflect specific pathogenesis
Coagulative
Liquefactive
Caseuous
forms can overlap at times:
- coagulative + bacteria = suppurative
- liquefactive + time = dehydration/caseous
Coagulative Necrosis
tissue structure maintained, all cells are dead
inflammation is minor
original strucutre evident, looks cooked
initally pallor from blood loss
subsequent reddening -> hemorrhage, inflammation
seen with infarctions
Histo:
cell outlines preserved, details lacking
cell shadows
Liquefactive Necrosis
tissues are liquid, structure is lost
inflammation prominent -> many neutrophils
Caseous Necrosis
tissue develops caseous semi-solid quality, loss of structure
inflammation is prominent -> many macrophages
tissue pale, yellow + pasty
mycobacteria + corynebacterium
chronic
Gangrene
coagulative necrosis with other modifier/changes
coagulative + dessication = dry gangrene (mummification)
coagulative + moisture + saprophytic bacteria = wet gangrene
coagulative necrosis of adipose = fat necrosis
coagulative + saprophytic anaerobic bacteria = gas gangrene
Dry gangrene
AKA mummification
coagulative + dessication
Wet gangrene
coagulative + moisture + saprophytic bacteria
Fat Necrosis
coagulative necrosis of adipose
FAs combine with Ca, Na, K in dead tissue -> forms soaps (saponification)
Gas gangrene
coagulative + saprophytic anaerobic bacteria
Apoptosis
“single cell necrosis”
- different from necrosis mechanistically + morphologically
cells round up, fragment + ingested by neighbors (heterophagy)
tightly regulated -> controlled by cell itself
cell fragments self contained (intact membranes + organelles)
no inflammation
Apoptosis on Histology
cell shrinkage + condensation = rounded w/ clear halo
hyperbasophillia or hypereosinophillia
nuclear changes = chromatin caps/crescents + nuclear membrane stays intact
late stages = cell fragmentation into membrane bound bodies
NO inflammation
Pathogenesis of Cell Death
lethal injury by 2 basic mechanisms:
- interference w/ energy supply
- damage to cell membranes
Energy Supply Interruptions
Pathogenesis of Cell Death
1) hypoxia = decreased O2
2) ischemia = no blood flow (no nutrient + waste exchange)
3) infarction = tissue death d/t ischemia
4) anoxia = no O2 in tissue
myocardium, prox. renal tubules + neurons need constant ATP -> very susceptible to hypoxia/ischemia
- for other cell types, hypoxia not the most common cause
Reperfusion Injury
Pathogenesis of Cell Death
return of blood flow to damaged but living cells
much of injury to cells occurs at this stage -> damage to mitochondria end up with free electrons = produces radicals
inefficient ATP production
calcium + water flood cells -> pumps don’t work well -> increased swelling
Membrane Damage
Pathogenesis of Cell Death
causes = irradiation, toxins, metabolic products, depleted antioxidants, immune-mediated reactions
liver + kidney susceptible
toxic intermediates - drugs
free radicals = attack membranes
- superoxide = most common
- hydroxyl radical = most damaging
How do free radicals relate to disease?
leukocytes produce them to kill bacteria
leukocytes produce them without bacteria as well -> inflammatory free radical damage
hemorrhage releases iron which catalyzes free radical reactions -> esp. in CNS
injury releases arachidonic acids from CMs -> produce free radicals
ischemia -> reperfusion injury/free radical damage
sunlight - free radical prod.
x-rays - produce free radicals
drugs, toxins, pollutants
IC cause of radicals = 1% in transport chain stray + react with oxygen enzymes in redox reactions == cytychromes that contain transitional metals (Fe, Cu, Zn)
Radicals
Pathogenesis of Cell Death
initiate chain reactions, esp. w/ unsaturated lipids in CM:
1) initiation
2) propagation
3) termination
Reaction:
- oxygen accepts 1 electron = superoxide
- superoxide donates it to iron = divalent iron
- oxygen accepts 2 electrons = hydrogen peroxide
- hydrogen peroxide + divalent iron = hydroxyl radical
- hydroxyl radical (OH) = reacts with anything
OH lets loose = reaction that bend + break + polymerize proteins, DNA, CHOs + Lipids
Radicals induce the MPT
Detoxification
antioxidant scavengers freezes radicals
- Vit E = lipid soluble, eats up radicals in membranes
- Vit C = eats up radicals + regenerates vit E
Scavenger Enzymes:
- superoxide dismutase (SOD) = gets rid of O2- in cytosol + mitochondria
- catalase + peroxidase = remove hydrogen peroxide
- glutathione peroxidase detoxifis H2O2 (requires selenium)
tissues with high O2 consumption (muscle, liver) prone to damage without adequate selenium
Apoptosis Basic Mechanism
Cell death with:
- cytoplasmic shrinkage
- pyknosis
- karyorhexis
- membrane blebbing
- apoptotic bodies/vesicles
Intrinsic + Extrinsic Apoptosis
- perturbation of intrinsic or extrinsic environment
