Necrosis/irreversible cell death

reversible cell injury means the cell is able to go from survival mode back to

normal cell without scarring or evidence it was under stress

irreversible cell injury means the cell

cannot return to normal, cell death occurs

cellular necrosis

cell death by accident

with cellular necrosis by hypoxia ATP depletion

continues from cell injury

loss of intracellular homeostasis with necrosis

influx of Ca2+ continues from cell injury, lysosomes open up to the cell and digests organelle membranes (eats anything its in contact with), protease, endonuclease and ATPase functions continue

free radical

chemical species with a single unpaired electron

free radicals are capable to damage

cellular components

reactive oxygen species (ROS)

when oxygen picks up the extra electron of a free radical

reactive oxygen species will

damage anything it bumps into (targetless)

sources of reactive oxygen species

mitochondria with aerobic respiration (accidental byproduct) and neutrophils/macrophages (good at phagocytosis)

reactive oxygen species are

normal and necessary with a healthy balance

defense against reactive oxygen species

superoxide dismutase (enzyme in the cell neutralize free radicals immediately), anti-oxidants (vitamins C and E) and natural decay

intracellular antioxidants

destroy and neutralize free radicals

oxidative stress

accumulation of oxidative free radicals (can lead to cell death)

causes of oxidative stress

infections, ionizing radiation, chemicals, ischemia reperfusion injury (area not getting enough blood followed by sudden influx of BF to area) (increased production or compromised ability to neutralize free radicals)

oxidative stress on the cell will cause

lipid peroxidation (damage to membrane), crosslink/fragment proteins (lose normal function), DNA fragmentation (damage)

cellular nuclear damage by oxidative stress

visible changes of genetic cell material

pyknosis

nuclear condensation to one DNA chunk in the middle, this leads to karyorrhexis

karyorrhexis

fragmentation of pyknotic nucleus, which leads to karyloysis

karyolysis

destruction of the nucleus, no more DNA

following oxidative stress on the cell,

mitochondrial damage will occur, no going back

damaged mitochondrial membrane causes

decreased ATP formation (viscous cycle) (pumping ROS), abnormal oxidative phosphorylation

pohspholipase damage will eventually cause defects in

membrane permeability - cell contents leak out and fragments are released

DNA and proteins have been attacked for so long that

no longer functional due to protease and endonuclease

irreversible cell injury leading to necrosis summary

lysosome membrane not intact, nucleus lost, disrupted phospholipid layer, contents leaving the cell

physiological response to necrosis

inflammation (body cleaning up with white blood cells)

coagulative necrosis

caused by reduced blood flow to tissue

coagulative necrosis represents as

pale, firm and wedge shaped

coagulative necrosis can occur in

any solid organ with a blood clot (except the brain)

liquefactive necrosis

caused by bacterial or fungal infection in a tissue, tissue gets liquified in the area of tissue injury (invader triggers WBC to destroy)

abcess

accumulation of pus in an enclosed space (fluid substance formed at inflammatory sites)

ischemia in the brain causes

liquefactive necrosis

gangrenous necrosis

critically insufficient blood supply to limbs (NOT tissue)

dry grangrene

reduced blood flow to a limb (frost bite)

dry gangrene symptoms

numbness/pain, tissue colors blue and black, tissue dries up and often falls off

wet grangrene

reduced blood flow and bacterial infection of a limb

wet grangrene is a critical reason to

amputate - could die if not

symptoms of wet grangrene

painful, swelling/blisters, foul smelling discharge, tissue turns red then black

wet grangrene could cause

systemic problems like fever/sepsis, danger to whole person not just the limb

fat necrosis

result of digestive enzymes acting on fat in a tissue

fat necrosis is almost exclusive to

pancreatic cell death (ezymes spill out when pancrease dies and expose to fat)

fatty acids exposed to calcium form

soap (saponification), appears as white chalky deposits

caseous necrosis

caused by tuberculosis and certain types of fungi in a tissue, forms a case around the invader

with caseuous necrosis, the immune system builds a

defensive barrier of macrophages around the infection, granulomas wall off the cell in pockets (necrotic cells are not completely digested)

causeous necrosis result

tissue has cheese like appearance (leave cavity behind)