2b. Cell Death Flashcards
What is oncosis?
Cell death with swelling, the spectrum changes that occur in injured cells prior to death
What is necrosis?
In a living organism the morphological changes that occur after a cell has been dead some time
Seen after 12-24 hrs
What are the types of necrosis?
Main: coagulative, liquefactive
Other: caseous, fat necrosis
Why are there 2 types of necrosis?
Coagulative necrosis is protein denaturation (e.g. ischaemia of solid organs)
Liquefaction necrosis is enzyme release (e.g. ischaemia in loose tissues, presence of many neutrophils)
What does coagulative necrosis look like?
Denaturation of proteins dominates over release of active proteases
Cellular architecture is somewhat preserved
What does liquefactive necrosis look like?
Enzyme degradation is substantially greater than denaturation
Leads to enzymatic digestion of tissues
No outline of cells
What is caseous necrosis?
Contain amorphous (structureless) debris
Particularly associated with infections, especially TB
Looks like cottage cheese
What is gangrene?
Necrosis visible to the naked eye
An appearance of necrosis
What is infarction?
Necrosis caused by reduction in arterial blood flow
Cause of necrosis
Can result in gangrene
What is infarct?
An area of necrotic tissue which is the result of loss of arterial blood supply
An area of ischaemic necrosis
What is the difference between dry gangrene and wet gangrene?
Dry - necrosis modified by exposure to air (coagulative necrosis)
Wet - necrosis modified by infection (liquefactive necrosis)
What is gas gangrene?
Wet gangrene where the infection is with anaerobic bacteria that produce gas
What are the commonest causes of infarction?
Thrombosis
Embolism (thrombus that has detached)
Why are some infarcts white?
Also called anaemic infarcts
Solid organs, occlusion of an end artery
Often wedge shaped
Coagulative necrosis
Why are some infarcts red?
Also called haemorrhagic infarct Loose tissue Dual blood supply Raised venous pressure Re-perfusion
What do the consequences of infarction depend upon?
Alternative blood supply
Speed of ischaemia
Tissue involved
Oxygen content of blood
What is ischaemic-reperfusion injury?
If blood flow is returned to a damaged but not yet necrotic tissue, damage sustained can be worse than I’d blood flow hasn’t been returned
What are the causes of ischaemic-reperfusion injury?
Increased production of oxygen free radicals with reoxygenation
Increased number of neutrophils resulting in more inflammation and increased tissue injury
Delivery of complement proteins and activation of the complement pathway
What is apoptosis?
Cell death with shrinkage induced by a regulated intracellular program where a cell activates enzymes that degrade own nuclear DNA and proteins
Why does physiological apoptosis occur?
In order to maintain a steady state
Hormone controlled involution - shrinking of organ
Embryogenesis
Why does pathological apoptosis occur?
Cytotoxic T cell killing of virus-infected or neoplastic cells
When cells are damaged, particularly with damaged DNA
Graft versus host disease
What are the 3 phases of apoptosis?
Initiation
Execution
Degradation and phagocytosis
What are initiation and execution triggered by?
2 mechanisms: intrinsic and extrinsic
Both result in activation of caspases
- enzymes that control and mediate apoptosis
- cause cleavage of DNA and proteins of the cytoskeleton
What happens in the intrinsic pathway?
Initiating signal comes from within cell
Triggers most commonly irreparable DNA damage and withdrawal of growth factors or hormones
p53 protein activated, results in outer mitochondrial membrane becoming leaky
Cytochrome C released form mitochondria and causes activation of caspases