Necrosis / Cell death Flashcards
How do cells respond to damage?
- Change in cellular activity
- Alteration of cell morphology
What does inability to successfully adapt to damaging stimuli lead to?
- Sublethal cell injury
or - Cell death
Do cell types show different suceptibility to damage?
Yes - e.g. neurons far more sensitive to ischaemia than fibroblasts
Give examples of cell damage
- Trauma: physical damage
- Carbon monoxide inhalation: prevents O2 transport
- Contact with strong acid: coagulated tissue proteins
- Paracetamol overdose: metabolites bind to liver cell proteins and lipoproteins
- Bacterial infection: toxins and enzymes
- Ionising radiation: Damage to DNA
What cellular components are affected in cell damage/death?
- Mitochondria
- Ionic channels within cell membranes
- Cell membrane
- Cytoskeleton
- DNA
- Proteins
What can happen during ischaemia?
- Reduced energy production
- Metabolism changes, changing pH
- No energy to drive ion channels e.g. Na/K pump leading to osmotic swelling and rupture of organelles
- Ca2+ pump fails, causing activation of phopholipase, protease and endonuclease leading to membrane disruption, proteolysis of cytoskeleton and cell disintegration
What are 6 types of necrosis?
- Coagulative: due to severe ischaemia. Occurs in solid organs
- Liquefactive: occurs in brain due to hydrolytic enzyme release
- Caseous: seen in tuberculosis
- Fat: in breast and pancreas
- Fibrinoid: Occurs in arteries e.g. vasculitis
- Haemorrhagic: dead tissue with extravasated RBC - due to blocked venous drainage leading to congestion and arterial perfusion failure
What is gangrene and the 2 types?
Macroscopic term used to describe dead black tissue
* Dry: coagulative type necrosis with little/no infection (rare)
* Wet: tissue infected with gram -ve bacteria
Describe apoptosis
- Programmed cell death
- Collateral injury to surroinding tissue is minimised (cytoplasmic contents not released)
- Cell components recycled
How does apoptosis differ from necrosis?
Apoptosis is cell death under a physiological/genetic control
What settings does apoptosis occur in?
- During development (formation of digits in embryo)
- Homeostatic mechanism to maintain cell populations
- Defence mechanisms (neutrophil death in acute inflammation)
- Cell damage
- Ageing (involutoin of thymus)
What signals activate apoptosis?
- Lack of growth factors (GFs/hormones)
- Ligand-receptor interaction (Fas or TNF-a)
- Injurious agents e.g. DNA damage p53
- T and NK cells
What are the 3 stages of apoptosis?
- Initiation: apoptosis stimulated by Bax protein and pores form in mitochondrial membrane
- Execution: activation of initiator and executioner caspases which lead to endonuclease activation, breakdown of cytoskeleton and apoptotic body formation
- Disposal: phagocytosis by macrophages and/or adjacent epithelial cells
What is ischaemia
The lack og oxygen and blood flow due to an obstruction in an artery/vessel
What is infarction?
- Necrosis due to ischaemia
What is hypoxia?
- Inadequate amount of oxygen in tissues
- Usually due to obstruction of blood flow
Whats the pathway for hypoxic cell injury
- Lack of oxygen
- Decreased oxidative phosphorylation
- Decreased ATP
- Membrane damage and rupture of lysosomes and endoplasmic reticulum
What is the temperature where irreversible changes accumulate in human cells?
Above 43 degrees celcius
What mechanisms can microorganisms cause cell damage?
- Toxins affecting cell metabolism
- Enzymes breaking down tissue
- Intracellular replication (viruses)
- Inflammatory response
- Immune response
*
How are death cap mushrooms poisonous?
Contain Amatoxin which inhibits RNA polymerase
What is autolysis and when does it occur
- Death of cells due to release of digestive enzymes from inside the cells (lysosomes)
- After death of the whole organism or from removal of the organism
What do histo specimens have to be fixed in?
Neutral buffered formalin
What happens as duration of injury increases?
