S1) Cell Injury Flashcards
How do cells respond to environmental changes?
- Cells can maintain homeostasis during mild environmental changes
- During severe changes, cells undergo physiological and morphological adaptations to remain viable
What happens when cells reach the limits of their adaptive response?
- Reversible cell injury
- Irreversible cell injury and death
Identify 4 factors which affect the extent of cell damage
- Type of injury
- Duration of injury
- Severity of injury
- Type of tissue
Identify 7 agents by which cells can be damaged
- Hypoxia
- Physical agents
- Chemical agents and drugs
- Micro-organisms
- Immune mechanisms
- Dietary imbalances
- Genetic abnormalities
What is hypoxia and how does it cause cell injury?
- Hypoxia is oxygen deprivation and if persistent causes cell adaptation, injury or death
- Very common
Identify 5 physical agents which can cause cell injury
- Direct trauma
- Extremes of temperature (burns and severe cold)
- Sudden changes in atmospheric pressure
- Electric currents
- Radiation
Identify 5 chemical agents/drugs which can cause cell injury
- Oxygen in high concentrations
- Poisons
- Alcohol
- Illicit drugs
- Therapeutic drugs
Identify 4 micro-organisms which can cause cell injury
- Viruses
- Bacteria
- Fungi
- Parasites
Identify 3 types dietary imbalances which can cause cell damage
- Dietary insufficiency
- Dietary deficiencies
- Dietary excess
Provide and example of a genetic abnormality which can cause cell damage
Inborn errors of metabolism
Identify 4 types of hypoxia
- Hypoxaemic
- Anaemic
- Ischaemic
- Histiocytic
What are the targets of cell injury?
- Cell membranes
- Nucleus
- Proteins (structural proteins & enzymes)
- Mitochondria
Provide a 10-point summary of reversible hypoxic cell injury
- Cell is deprived of oxygen
- Mitochondria stops ATP production & membrane ionic pumps stop
- Na+ and H20 seep into the cell
- Cell swells and initiates a heat-shock response (stress)
- Glycolysis keeps cell alive but pH drops as lactic acid accumulates
- Calcium enters the cell & activates: phospholipases, proteases, ATPase and endonucleases
- ER and other organelles swell
- Enzymes leak out of lysosomes and attack cell contents
- Cell membrane is damaged (show blebbing)
- Cell dies – burst of a bleb
Describe the effect of the following enzymes in causing cell injury:
- Phospholipases
- Protease
- ATPases
- Endonucleases
- Phospholipases – cause cell membranes to lose phospholipids
- Proteases – damage cytoskeletal structures and attack membrane proteins
- ATPases – cause more loss of ATP
- Endonucleases – cause nuclear chromatin to clump
What is Ischaemia-Reperfusion Injury?
Ischaemia-reperfusion injury is the injury that occurs when blood flow is returned to a tissue that has undergone ischaemia but not necrosis
What causes Ischamia-Reperfusion injury?
- Increased production of oxygen free radicals with reoxygenation
- Delivery of complement proteins activates the complement pathway
- Increased neutrophils with returned blood flow results in inflammation and increased tissue injury
What are free radicals and what do they do?
- Free radicals are reactive oxygen species and have a single unpaired electron in an outer orbit
- This is an unstable configuration and hence, they react with other molecules often producing more free radicals
What do free radicals do in Ischaemic reperfusion injury?
- Attack lipids in cell membranes and cause lipid peroxidation
- Damage proteins, carbohydrates and nucleic acids
Identify 3 free radicals of particular biological significance in cells
- OH• (hydroxyl)
- 02- (superoxide)
- H202 (hydrogen peroxide)
What causes cell injury, in terms of free radicals?
- Cell injury is caused by an imbalance between free radical production and free radical scavenging
- Free radicals accumulate and the cell / tissue is said to be in oxidative stress
What is the anti-oxidant system?
The anti-oxidant system is the body’s defence system to prevent injury caused by free radicals
Identify and describe the components of the antioxidant system
- Superoxide dismutase catalyse the reaction production of H2O2 (less toxic) from O2-
- Catalases and peroxidases catalyse the production of H2O and O2 from H2O2
- Free radical scavengers neutralise free radicals
- Storage proteins that sequester transition metals in the extracellular matrix
Identify some free radical scavengers
- Vitamin A
- Vitamin C
- Vitamin E
- Glutathione
Identify two storage proteins involved in the antioxidant system
- Transferrin
- Ceruloplasmin
What are heat shock proteins?
Heat shock proteins are proteins triggered by any form of cell injury to protect the body in the stress response
Provide 3 examples of heat shock proteins
- Stress proteins
- Unfoldases
- Chaperonins
How do cells respond to the heat shock response?
- Decrease usual protein synthesis
- Increase synthesis of HSPs
What are the main cell alterations that can be seen under a light microscope?
- Cytoplasmic changes
- Nuclear changes
- Abnormal intracellular accumulations
Identify 4 reversible changes involved in cell injury as seen in electron microscopy
- Swelling of cell & organelles
- Cytoplasmic blebs
- Clumped chromatin
- Ribosome separation from the rER
Identify 5 irreversible changes involved in cell injury as seen in electron microscopy.
- Nuclear changes
- Swelling and rupture of lysosomes
- Membrane defects
- The appearance of myelin figures
- Lysis of the ER
Identify and describe the three types of nuclear changes that can occur in cell injury
Define apoptosis
Apoptosis is cell death with shrinkage, induced by a regulated intracellular program where a cell activates enzymes that degrade its own nuclear DNA and proteins
Define oncosis
Oncosis is cell death with swelling and the spectrum of changes that occur prior to death in injured cells
Define necrosis
- Necrosis is the morphologic changes that occur after a cell has been dead some time e.g. 4-24 hours
- It is not a type of cell death, i.e. it is an appearance and not a process