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”
What does liquefactive necrosis look like?
Enzymatic digestion of tissues
What is caseous necrosis?
Contains amorphous (structureless) debris
What is caseous necrosis commonly associated with?
Tuberculosis
What does caseous necrosis look like?
Cottage cheese ew
Define gangrene
Necrosis visible to the naked eye
Define infarction
Necrosis caused by reduction in arterial blood flow, can result in gangrene
Define infarct
Area of necrotic tissue which is the result of loss of arterial blood supply
What is dry gangrene?
Necrosis modified by exposure to air (coagulative necrosis)
What is wet gangrene?
Necrosis modified by infection (liquefactive necrosis)
What is gas gangrene?
Wet gangrene where infection is with anaerobic bacteria that produce gas
What are the commonest causes of infarction? (2)
Thrombosis
Embolism
Why are some infarcts white?
In solid organs when the end artery is occluded so there is no blood supply
Why are some infarcts red?
Infarct complicated by haemorrhage - mainly in loose tissue with dual blood supply
What do the consequences of infarction depend on?
Alternative blood supply
Speed of ischaemia
Tissue involved
O2 content of blood
What is ischaemia-reperfusion injury?
If blood flow is returned to a damaged but not yet necrotic tissue, damage sustained can be worse than if blood flow hadn’t been returned
What can cause ischaemia-reperfusion injury?
1) increased production of oxygen free radicals with reoxygenation
2) increased number of neutrophils resulting in more inflammation
3) delivery of complement proteins and activation of complement pathway
True or false: when membranes are leaky, molecules can leak out as well as in
TRUE
Which important things can leak out of membranes? (3)
1) potassium-can lead to cardiac arrest
2) enzymes
3) myoglobin-blocks glomerulae in kidney and can cause renal failure
What is rhabdomyolysis?
Lots of skeletal muscle breakdown
What is apoptosis?
Cell death with shrinkage
True or false: apoptosis is the equal and opposite force to mitosis
TRUE
True or false: lysosomal enzymes are involved in apoptosis
FALSE
When does apoptosis occur physiologically?
In order to maintain steady state
Hormone-controlled involution
Embryogenesis
When does apoptosis occur pathologically? (3)
1) Cytotoxic T cell killing of virus-infected or neoplastic cells
2) When cells are damaged, particularly with damaged DNA
3) Graft vs host disease
What is graft vs host disease?
Occurs after bone marrow transplant for leukaemia-sometimes new WBCs recognise the host as foreign therefore graft vs host disease
What is budding in apoptosis?
Contains parts of organelles and become apoptotic bodies
What are the three phases of apoptosis?
1) Initiation
2) Execution
3) Degradation and phagocytosis
Which two mechanisms trigger initiation and execution of apoptosis and what do both of these result in?
Intrinsic and extrinsic
Result in activation of caspases
What are caspases?
Enzymes that control and mediate apoptosis and cause the cleavage of DNA and proteins of cytoskeleton
How is the intrinsic pathway of apoptosis initiated?
Triggered most commonly be irreparable DNA damage and withdrawal of growth factors or hormones
How is the intrinsic pathway of apoptosis carried out?
P53 protein is activated, resulting in outer mitochondrial membrane becoming leaky. Cytochrome C is released from mitochondria and this causes activation of caspases
How is the extrinsic pathway of apoptosis initiated?
Triggered by cells that are a danger eg. Tumour cells, virus-infected cells
How is the extrinsic pathway of apoptosis carried out?
One of the signals is TNF-alpha, secreted by T killer cells. This binds to cell membrane receptor (“death receptor”), resulting in activation of caspases
Why are apoptotic bodies phagocytosed?
Express proteins on their surface which are recognised by phagocytes or neighbouring cells and degradation takes place
True or false: the plasma membrane is intact in apoptosis
TRUE
Where do abnormal cellular accumulations come from? (3)
1) Cell’s own metabolism
2) Extracellular space
3) Outer environment
What kind of things can accumulate in cells?
- water and electrolytes
- lipids
- carbs
- proteins
- ‘pigments’
When does fluid accumulate in cells?
Hydropic swelling when energy supplies are cut off (hypoxia), Na+ and water flood into cells
Where is hydropic swelling a particular problem?
Brain-compresses and pressure in the skull increases
When do lipids accumulate in cells?
Steatosis (accumulation of triglycerides)
Where is steatosis most common?
Liver
What are the causes of lipid accumulation in cells? (4)
1) Alcohol
2) Diabetes mellitus
3) Obesity
4) Toxins
Which is the only organ that can eliminate cholesterol?
Liver
Complete the sentence:
Cholesterol accumulates in _______ muscle cells and macrophages in _______________ plaques called _____ cells.
Smooth
Atherosclerotic
Foam
In which conditions do proteins accumulate in cells? (2)
1) Alcoholic liver disease (Mallory’s hyaline)
2) alpha-1-antitrypsin deficiency
When do pigments accumulate in cells? (2)
1) carbon/coal dust/soot (air pollutant)
2) tattoos
Give an example of an endogenous pigment
Haemosiderin (iron storage molecule)
When does haemosiderin form?
Systemic or local excess of iron (eg bruise)
What is the systemic overload of iron in organs called?
Haemosiderosis
What is hereditary haemochromatosis?
Genetically inherited disorder resulting in increased intestinal absorption of dietary iron
What are the symptoms of hereditary haemochromatosis? (3)
1) Liver damage
2) Heart dysfunction
3) Multiple endocrine failures, including pancreas
What is the treatment for hereditary haemochromatosis?
Repeated bleeding
What accumulates in jaundice?
Bilirubin (breakdown product of heme)
What is localised calcification called?
Dystrophic
What is generalised calcification called?
Metastatic
True or false: metastatic calcification is more common than dystrophic
FALSE - other way round
Why does metastatic calcification occur?
Hypercalcaemia secondary to disturbances in calcium metabolism
What causes hypercalcaemia? (2)
1) increased secretion of parathyroid hormone (PTH) resulting in bone resorption
2) destruction of bone tissue
Why can germ cells and stem cells continue to replicate?
Contain telomerase which maintains the length of telomeres
Why can cancer cells replicate multiple times?
Produce telomerase
