Cell Injury, Death and Degeneration Flashcards
List the 7 main causes of cell injury.
Physical agents Chemical agents Infections Hypoxia/ischaemia Genetic defects Immunological reactions Nutritional imbalance
Outline the 5 main mechanisms of cell injury.
Damage to mitochondria
-Disrupted ATP synthesis
Damage to cell membranes
- Disrupted ion concentrations
- Disrupted osmotic imbalance
- This causes cell oedema and bursting
Damage to cytoplasm (including ribosomes)
- Disrupted protein/enzyme synthesis (includes architectural proteins)
- Therefore abnormal function and structure
Damage to nucleus
- DNA damage and disrupted DNA repair
- Gene expression is altered
Oxidative stress
- Caused by ROS/free radicals
- Formed due to hypoxia, toxic substances, radiation
List 5 types of reversible cell damage.
“Cloudy swelling” - i.e. osmotic imbalance leads to high ion concentrations and influx of water
Cytoplasmic blebs
Disrupted microvilli
Swollen mitochondria
“Fatty change” - formation of lipid vacuoles due to faulty lipid metabolism
Give 2 examples of irreversible cell damage.
Cell membrane rupture
Pyknotic nucleus
What is the difference between necrosis and infarction?
Necrosis - un programmed, pathological cell death
Infarction - necrosis due to loss of blood supply
List 3 cellular features of necrosis.
Disruption of cell membranes (including organelle membranes)
- Cell swelling
- Vacuolation
Cell lysis and release of cell contents
- Damage to adjacent cells
- Acute inflammation
DNA disruption
-DNA hydrolysis
What are the 4 different types of necrosis?
Coagulation (haemorrhagic or gangrenous)
Colliquitive
Caseous
Fat
What are the features of coagulative necrosis?
Firm
Retains tissue shape
What are the features of colliquitive necrosis?
Tissue becomes liquid
Tissue structure is lost
What are the features of caseous necrosis?
Combination of coagulative and colliquitive necrosis
Cheese-like appearance
Give 5 examples of physiological apoptosis.
Hormone dependent involution of uterus/breasts/ovaries
Embryological development
Self-reactive T cells in the thymus
Deletion of cells in proliferating populations
Deletion of inflammatory cells after an inflammatory response
Draw a simple diagram outlining what causes cell injury and eventual cell death.
(See diagram in notes)
What are the 4 cellular features of apoptosis?
Cell shrinkage
Chromatin condensation
Cell membranes remain intact
Cytoplasmic blebs and apoptotic bodies
Define depositions.
“Abnormal intra- or extracellular accumulation of substances.”
What are the 4 different types of deposition?
Intracellular
Extracellular
Endogenous substances
Exogenous substances
Give 5 examples of intracellular depositions of endogenous substances.
Melanin Haemosiderin Bile Lipid Degeneration products (e.g. lipofuscin)
Give 3 examples of extracellular depositions of endogenous substances.
Amyloid
Fibrosis
Calcium
Give 3 examples of depositions of exogenous substances.
Tattoo pigment
Carbon
Asbestos
What are the 2 causes of amyloid depositions?
Abnormal folding of soluble protein fibrils creating abnormal insoluble aggregates
Many different proteins can do this
Describe the pathogenesis of amyloid depositions.
Excessive production/accumulation of normal protein
Production/accumulation of abnormal protein
Tendency of protein to misfold
What are the 2 types of amyloid deposition occurring due to excessive production of normal protein?
AL amyloid
AA amyloid
What does AL amyloid deposition consist of?
Give an example of a disease which might cause this.
Consists of: immunoglobulin light chain
Example: B lymphocyte neoplasms, e.g. multiple myeloma
What does AA amyloid deposition consist of?
Give an example of a disease which might cause this.
Consists of: serum amyloid associated protein (normal; produced in liver)
Example: chronic inflammation, e.g. RA
Give 5 examples (other than amyloid) of pathological depositions.
Steatosis (liver) Lipofuscin (liver) Iron (liver) Iron (macrophages) Carbon (lungs)