Effect on injury on cells (W10) Flashcards
causes of cell injury
lack of O2
physical agents (temp, psi, electricity, radiation)
chemicals and drugs
infectious agents
immune reactions
genetic defects
nutrition
reversible cell injury features?
rapid changes
swelling due to loss of ion/fluid homeostasis
fat accumulation (steatosis)
when does reversible cell injury become irreversable
if experiences persistent injury - no defined ‘point of no return’
fatty change histology?
large pale spaces - fat globules
2 types of cell death
apoptosis and necrosis
apoptosis overview?
membrane stays in tact
energy spent from own cell
apoptotic bodies spread off from cell
phagocytosis of cell and fragments
apoptosis 2 stages
intrinsic
extrinsic (signal from outside cell - YOU MUST KILL YOURSELF!!!)
apoptosis - extrinsic regulation
receptor ligand interactions
leads to series of intracellular protein-protein interactions
activates initiator caspase 8
apoptosis - intrinsic pathway?
less BCL2 (anti-apoptotic proteins), more BAX and BAK (pro-apoptotic proteins)
this allows leakage of cytochrome C and SMAC out mitochondria
these lead to activation of caspase 9
initiator caspase for intrinsic apoptosis pathway
caspase 9
normal intrinsic pathway before apoptosis
growth factors cause transcription of more anti-apoptotic (BCL-2) proteins, outnumbering pro-apoptotic proteins therefore keeping cell alive
initiator caspase for extrinsic apoptosis pathway
activates initiator caspase 8
what do active initiator caspases act on in apoptosis? what does this cause?
activate executioner caspases (‘cut’ off inhibitory part) which then disassemble the cell
what is autophagy
recycling and turnover of cytoplasmic cell constituents
what regulates autophagy
autophagy-related genes (ATGs)
what is autophagy a response to
extra/intracellular stress
autophagy summary?
intracellular constituents get packages into autophagosomes which fuse with lysosomes containing enzymes that degrade the components, then the original building blocks are released back into the cytoplasm and are reused
necrosis summary?
cell loses membrane integrity falls apart, contents outside cell cause inflammation. neutrophils are attracted to the area and cause more damage to other cells
what does necrosis look like in histology
pink blobs, nuclei not in cells, no properly defined cells
types of necrosis
coagulative
liquefactive
caseous
gangrenous (dry)
fat
coagulative necrosis? histology?
cell proteins denature (due to lack of blood supply?)
cells lose nuclei and stain more deeply. ghost outlines of cells.
liquefactive necrosis?
histology - tissue dissolves into mush, different causes:
inflammation (neutrophils destroy tissue)
bacteria into area of coagulative necrosis (pus, melted mushy tissue, smelly)
lipid rich tissue (eg in brain - cells don’t leave outlines, also go mushy)
caseous necrosis?
histology - ragged mess, ‘cottage cheese’. cell death you see in the middle of a TB caused granuloma
what is a granuloma
formed when immune cells clump together and create tiny nodules at the site of infection. the body’s way of containing an area of infection to stop it spreading
what is caseous necrosis caused by
TB
mycobacterial infection
dry gangrene?
extreme coagulative necrosis due to slowly developing vascular occlusion
fat necrosis?
degradation of fatty tissue by lipases, forming chalky deposits
necroptosis?
virus stops apoptosis, organism can cause organised necrosis to destroy cell as apoptosis cannot occur.
earliest changes apoptosis vs necrosis?
apoptosis - cell shrinking
necrosis - cell swelling
vesicles differences apoptosis vs necrosis?
apoptosis - formation of membrane enclosed vesicles
necrosis - no vesicle formation, lysis
termination apoptosis vs necrosis?
apoptosis - continued fragmentation into smaller bodies
necrosis - complete lysis
apoptosis vs necrosis regulation
apoptosis - tightly controlled
necrosis - loss of homeostatic regulation
energy requirement apoptosis vs necrosis?
apoptosis - energy dependant
necrosis - passive
DNA differences apoptosis vs necrosis?
apoptosis - non-random fragmentation prior to apoptotic body formation
necrosis - random fragmentation after cell lysis