Cell Injury Flashcards
List possible causes of cell injury
Hypoxia Toxins Immune mechanisms Physical agents Microorganisms Radiation Free radicals
Define disease
A consequence of failed homeostasis with morphological and functional disturbances
What is hypoxia?
O2 deprivation
What are 4 forms of hypoxia?
Hypoxaemic hypoxia
Anaemic hypoxia
Ischaemic hypoxia
Histiocytic hypoxia
Describe hypoxaemic hypoxia and its causes
Low arterial content of O2
Caused by a reduced inspired PO2 at high altitude/ reduced O2 absorption in lung disease
Describe anaemic hypoxia and its causes
Decreased ability of Haemoglobin to carry O2
Caused by anaemia or CO poisoning
Describe ischaemic hypoxia and its causes
Interruption to the blood supply
Caused by blockage of a vessel/ heart failure
Describe hystiocytic hypoxia and its causes
Inability to utilise O2
Caused by defective oxidative phosphorylation enzymes/ organophosphate poisoning
What toxins can cause cell injury?
Glucose and salt in hypertonic solutions High O2 conc. Poisons Pollutants Insecticides Herbicides Asbestos Alcohol Narcotic drugs Medicines
How can immune mechanisms damage cells?
Hypersensitivity reactions: overly vigorous immune reaction damages host tissue
Autoimmune reactions: immune system fails to distinguish self from non-self
Give an example of how a hypersensitivity reaction can damage cells
Urticaria (hives)
Give an example of how autoimmune reactions damage cells
Graves’ disease
What physical agents can damage cells?
Direct trauma
Extreme temps
Changes in pressure
Electric currents
When does cell injury due to hypoxia go from reversible to irreversible?
If O2 is not restored
What reversible injury can be caused by hypoxia?
Decreased O2 -> decreased oxidative phosphorylation -> decreased ATP:
Influx of Ca, H2O, Na, efflux of K, cellular swelling (oncosis), loss of microvilli, bless, ER swelling
Detachment of ribosomes from ER, decreased protein synthesis, decreased metabolism-> lipid deposition
Increased anaerobic resp-> low pH->reduced enzyme activity
What irreversible injury can be caused by hypoxia?
Increased membrane permeability, influx of Ca so increased Cytosolic Ca:
Activates ATPases, phospholipases, proteases, endonucleases
-> damage to membrane, cytoskeletal proteins and nuclear chromatin
What reversible structural changes occur in hypoxia cells?
Swelling Chromatin clumping Autophagy Ribosome dispersal Blebs (bumps on membrane where cytoskeleton has detached)
What irreversible structural changes occur in hypoxic cells?
Nuclear changes
Lysosomes rupture
Membrane defects
ER lysis
What are free radicals and how do they cause cell injury?
They are reactive oxygen species that are produced in high oxygen concentrations.
Can cause an imbalance in antioxidants leading to oxidative stress. Attack proteins and carbohydrates and mutate DNA.
Why does Ischaemic-reperfusion injury occur?
If blood flow is returned to damaged (but not necrotic) tissue, damage can worsen. This is because of:
Increased free radical production with reoxygenation.
Increased neutrophils leading to inflammation and tissue injury.
Activation of complement pathway.
What are heat shock proteins?
They protect against cell injury by mending misfolded proteins and maintain cell viability to maximise cell survival.
Eg. Unfoldases, chaperonins, ubiquitin
Define oncosis
Changes that occur in injured cells prior to cell death
Define necrosis
The morphological changes that occur after cell death in living tissue
What is coagulative necrosis and when does it occur?
More protein denaturation than enzyme release.
Cellular architecture is preserved creating a ‘ghost outline’.
More likely in hard tissues, tends to be due to infarcts (but not infarct in the brain).
What is liquefactive necrosis and when does it occur?
More enzyme release than protein denaturation.
Tissue is lysed and disappears.
Occurs in soft tissues, tends to be due to infection (or infarction in the brain).
Name 4 types of necrosis
Coagulative
Liquefactive
Caseous
Fat
What is caseous necrosis and when does it occur?
Halfway between coagulative and liquefactive.
Tissue appears amorphous, no ghost outline.
Associated with infections, especially TB.
What is fat necrosis and when does it occur?
Destruction of adipose tissue leads to release of fatty acids which form soapy deposits.
Occurs when cell death occurs in adipose tissue eg. after direct trauma to fatty tissues.
What is gangrene?
Grossly visible necrosis
What are the differences between dry and wet gangrene?
Dry = coagulative, modified by exposure to air, bacteria cannot grow
Wet = liquefactive, infection with bacteria, causes increased neutrophils and proteolytic enzymes, can leak into blood vessels and cause septicaemia.
What is gas gangrene?
A type of wet gangrene where bacteria respired anaerobically, causing bubbles under the skin.
What is infarction?
Necrosis due to ischaemia
When does a White infarct occur?
When there is occlusion of an end artery with no peripheral vessels, meaning the area is not reperfused and left entirely without blood.
In what tissues does white infarct occur?
Kidney
Spleen
When does a red infarct occur?
Occlusion of an artery to a tissue with a dual blood supply. The tissue is reperfused leading to a build up of blood, which haemorrhages at once.
Increased pressure decreases the blood flow leading to ischaemia and infarct.
In what tissues does red infarct occur?
Bowel
Brain
Define apoptosis
Programmed cell death
Give a physiological example of apoptosis
During embryonic development.
Cytotoxic T cells killing virally infected cells.
Give a pathological example of apoptosis
Toxic injury/ Tumours causing DNA damage.
Foreign cells attacking host cells eg. after bone marrow transplant.
What are the three phases of apoptosis?
Initiation
Execution
Degradation and phagocytosis
What structural changes occur during apoptosis?
DNA damage leads to activation of mitochondrial caspases.
Chromatin condenses, fragmentation of nucleus, binds to form apoptic bodies, removed by phagocytes/nearby cells.
List differences between oncosis/necrosis and apoptosis
Oncosis/necrosis:
Continuous group of cells
Cells are enlarged (swelling)
Nucleus undergoes pyknosis, karyorrhexis & karyolysis
Plasma membrane is disrupted and lysed early
Cellular content undergoes enzymatic digestion
Adjacent inflammation is frequent
Always pathological.
Apoptosis:
Single cells
Cell size is reduced (shrinkage)
Nucleus fragments into nucleosome size
Plasma membrane remains intact but with altered structure
Cellular content remains intact, may be released in apoptotic bodies
No adjacent inflammation
Often physiological (can be pathological)
