Lecture Seven: Cell Injury And Irreversible Effects: Death Flashcards
What does oncosis result from
Massive trauma
What is the term given to regulated cell death?
Programmed cell death
What is oncosis/necrosis?
Cell death due to massive trauma
List the morphological changes that occurs with oncosis
Cell and organelle swelling
Membrane permeabilisation and lysis
Leakage of intracellular components -> inflammation
Repair of tissue by scarring
What is necroptosis
Programmed cell death
Which is initiated in a regulated way
Shows morphological features of necrosis
Describe necroptosis
- Death ligands (e.g. TNF and FasL) signal through their receptors (TNFR1, Fas) and the RIP1/3 protein kinases
- leads to mitochondrial dysfunction, generation of ROS, lipase activation
What is TNF
Tumour necrosis factir
What are Necrostatins
Compounds which inhibit RIP1 kinase activity
Suppress cell death, inflammation and loss of function after ischaemia or traumatic brains injury
What is Pyrpotosis
Pro inflammatory suicide mechanism leading to cell lysis
Occurs to
- prevent replication if intracellular bacteria
- alert others of immune system to the presence of pathogens
Describe the pyroptosis process
Products from pathogenic bacteria in macrophages activat inflammasomes.
These activate inflammatory capase1 protease leading to cell lysis
What type of suicide mechanism is pyroptosis?
Pro-inflammatory
Why does pyroptosis occur?
- prevents replication of intracellular bacteria
- alerts other cells of immune system to the presence of pathogens
What is apoptosis
Cell suicide
What does apoptosis do?
Removes cells that are excess to requirements,
old and due to be turned over or
damaged
How does apoptosis proceed?
Via Cell rounding, shrinkage, fragmentation
Maintenance of membrane and organelle integrity
Either engulfment of apoptotic bodies by resident phagocytes with no tissue damage or inflammation OR
If the phagocytes are overwhelmed, apoptosis proceeds by membrane disintegration and release of cellular contents and inflammation
What is autophagic cell death
Cells that kill themselves by ingesting themselves
How does autophagic cell death work?
Vacuoles with double membranes enclose the cytoplasm or organelles in the cytoplasm
These fuse with lysosomes to generate autolysosomes in which the acidic hydroplanes degrade the contents (incl. inner membrane)
What is the function of autophagic cell death?
Remove mis folded and potentially toxic proteins and damaged organelles
Degrading disposable components to generate energy and metabolises for essential protein synthesis (in deprived cells)
Sustains cell viability
What does massive autophagic vacuolisation lead to?
Cell death
Injury to, or occlusion of an artery may cause what?
Ischaemia, hypoxia or anoxia
What is ischaemia
Loss of blood flow
What is hypoxia
Reduced tissue oxygen concentrations
What is anoxia
Effective lack of oxygen
What happens after ischaemia/hypoxia/anoxia?
Oxidative phosphorylation ceases and cell relies in anaerobic glycolysis for its ATP requirements
Describe the cascade of events that may lead to cell death
- Reduced ATP –> reduced Na+/K+ ion exchanger —> increased intracellular Na+ concentration
- glycolysis activated, generates lactic acid & decreases cytoplasmic pH
- activates Na+/H+ exchanger –> Na+ enters cell
- Elevated [Na+] activates Na+/Ca2+ exchanger –> Ca2+ accumulates
- Redcued [ATP] –> Reduced Ca2+ efflux pump activity –> [Ca2+] not adequately controlled
- Ca2+ dependent phospholipases are activated –> Fatty acids & lisophospholipids released –> Damage membranes
- Ca2+ dependent proteases cleave cytoskeletal components –> further damaging membranes
- Cell lyses
- Spilled cellular contents –> induce inflammation
what are lipophospholipids also known as?
detergents
name some Ca2+ dependent proteases
calpain,
cathespin
What can apoptotic death be induced by?
- Engagement of death ligands with their receptors (TNF with TNFR1 & Fas with Fas)
- Damage to DNA
- Absence of growth survival factors
- Loss of cell adhesion to ECM which activates anoikis (an apoptotic process)
- Stresses that activate P53
What does anoikis mean
homelessness
What stresses activate p53?
DNA damage, hypoxia, oxidative stress