Session 1-Cell Injury Flashcards
What does the degree of injury depend on?
Type of injury
Severity of injury
Type of tissue
What kind of things can cause cell injury?
- Hypoxia
- Toxins
- Physical agents
- Radiation
- Microorganisms
- Immune mechanisms
- Dietary insufficiency and deficiencies, dietary excess
What is the difference between hypoxia and ischaemia?
Hypoxia=decreased O2 supply
Ischaemia=decreased blood supply
What is hypoxaemic hypoxia?
Arterial content of O2 is low
What is anaemic hypoxia?
Decreased ability of haemoglobin to carry O2
What is ischaemic hypoxia?
Interruption to blood supply
What is histiocytic hypoxia?
Inability to utilise O2 in cells due to disabled oxidative phosphorylation enzymes
How does the immune system damage the body’s cells? (2)
1) Hypersensitivity reactions-host tissue is injured secondary to overly vigorous immune reaction
2) Autoimmune reactions-immune system fails to distinguish self from non-self
What is an example of a hypersensitivity reaction?
Urticaria=hives
What is an example of an autoimmune reaction?
Grave’s disease of thyroid
Which cell components are most susceptible to injury? (4)
1) Cell membranes
2) Nucleus
3) Proteins
4) Mitochondria
In hypoxia, what is happening at a molecular level to the Na/K pump?
Stops working so influx of Ca2+, water and Na+ and an efflux of K+ and this can lead to swelling, blebs, ER swelling
Why do ribosomes detach from RER in hypoxia?
Ribosomes are attached to RER using energy from ATP, hypoxia leads to less ATP so ribosomes detach and there is less protein synthesis
What can prolonged hypoxia lead to?
Increased cytosolic Ca2+ and consequent activation of ATPase, phospholipase, protease and endonuclease
True or false: prolonged hypoxia is reversible
FALSE - irreversible
What are free radicals?
Reactive oxygen species with a single unpaired electron in an outer orbit-unstable configuration so can react with other molecules, producing more free radicals
What are the three free radicals of particular biological significance in cells?
OH (big dot) - hydroxyl, most dangerous
O2- (superoxide)
H2O2
How are free radicals produced? (5)
1) normal metabolic reactions
2) inflammation
3) radiation
4) contact with unbound metals within body: iron and copper
5) drugs and chemicals
How does the body control free radicals? (3)
1) Anti-oxidant system (donate electrons to free radical)
2) metal carrier and storage proteins sequester iron and copper
3) enzymes neutralise free radicals
Give two examples of metal carrier and storage proteins used to control free radicals
Transferrin
Ceruloplasmin
What is it called if the number of free radicals overwhelms the anti-oxidant system?
Oxidative imbalance
What is the main target of free radicals and what does this cause?
Lipids in cell membranes
Cause lipid peroxidation, leading to autocatalytic chain reaction
What other molecules can free radicals oxidise?
Proteins, carbs and DNA-bend out of shape, break or become cross-linked
Which type of proteins can be used to protect the cell against injury?
Heat shock proteins - mend mis-folded proteins and maintain cell viability
What do injured cells look like under a microscope in hypoxia?
Pale and swollen
What does a dead cell look like under a microscope in pyknosis?
Very pink as proteins denature and coagulate
What does a cell look like under a microscope in karyorrhexis?
Nucleus breaks into pieces
What is a characteristic of a karyolytic cell?
No nucleus
What are blebs?
Cytoskeleton is broken down by proteases, the membrane is looser and not held in place
How can cell death be diagnosed?
By testing its function-add dye/fluorescence and if the membrane is defected, the dye will enter. Only dead cells will look coloured
Define oncosis
Cell death with swelling, changes that occur in injured cells prior to death
What is necrosis?
Morphologic changes that occur after a cell has been dead some time (12-24 hours)
What are the two main types of necrosis?
Coagulative
Liquefactive (colliquitive)
What are the two other special types of necrosis?
Caseous
Fat necrosis
What happens in coagulative necrosis?
Ischaemia of solid organs in which proteins denature and become clotted and clump together
Give an example of an organ that may suffer from coagulative necrosis
Kidney
What is a solid organ?
Organ with lots of CT support
What happens in liquefactive necrosis?
Ischaemia in loose tissues, presence of many neutrophils and enzymes are released
Give an example of an organ likely to suffer from liquefactive necrosis
Brain
What does coagulative necrosis look like?
Cellular architecture is preserved and the cells have a “ghost outline”