apoptosis and necrosis Flashcards
define apoptosis
programmed cell death
nothing has killed them they are kind of just killing themselves
whats a trigger to apoptosis
dna damage
a signalling messanger causes this
give an example of apoptosis during foetal depelopment
our fingers grow all stuck together, apoptosis allows us to have individual fingers
give an example of apoptosis in disease
- B53 gene faulty - lack of apoptosis - cancer development
- too much B53 gene is what HIV used to kill T-cells
define necrosis and give some examples
- death of a large number of cells all at once
- traumatic cell death
- frostbite
- toxic spider venom
- cerebral infarction
what is the gene P53?
detects DNA damage and can then trigger apoptosis
how does a cell apoptose?
- the cell triggers a series of proteins which lead to the release of enzymes
- these digest the cell
why is apoptosis beneficial in health?
development - removal of cells during development
cell turnover - removal of cells during normal turnover
outline the differences between apoptosis and necrosis.
apoptosis:
- programmed, controlled
- caused by signals, dna damage and cell stress
- orderly and systematic process
- maintained membrane until final stages
- no inflammation or affect on surrounding tissues
necrosis:
- uncontrolled, accidental
- caused by external injury, infections, toxins, ischemia
- unregulated and chaotic
- membrane is lost early, cellular contents spill
- inflammation occurs due to the release of cellular contents
- examples are trauma, infection and ischemia
when cells die by necrosis, they exhibit 2 major types of microscopic or macroscopic appearances, what are these?
- liquefactive / colliquative
- coagulative
what catagorises liquefactive / colliquative necrosis?
- partial or complete destruction of dead tissue and transformation into a liquid, viscous mass
- The loss of tissue and cellular profile occurs within hours - short amount of time
what catagorises coagulative necrosis?
maintenance of normal architecture of necrotic tissue for several days after cell death
Q: What is the main microscopic or macroscopic appearance of liquefactive necrosis?
A: Tissues undergoing liquefactive necrosis appear slimy and liquid-like due to tissue dissolution.
Q: What causes the dissolution of tissue in liquefactive necrosis?
A: Hydrolytic enzymes break down cellular organelles, leading to liquefaction.
Q: Where do the hydrolytic enzymes in liquefactive necrosis come from?
A: They are derived from bacterial enzymes or the cell’s own lysosomal enzymes.
Q: How does coagulative necrosis differ from liquefactive necrosis in terms of tissue structure?
A: In coagulative necrosis, the tissue structure is maintained temporarily, unlike in liquefactive necrosis, where tissue is quickly dissolved.
Q: Which type of necrosis is commonly seen in ischemic events like myocardial infarction?
A: Coagulative necrosis is typically associated with ischemic injury, such as myocardial infarction.
Q: In what conditions is liquefactive necrosis most commonly observed?
A: Liquefactive necrosis is commonly seen in brain infarcts and abscesses due to bacterial or fungal infections.
Q: What role do lysosomes play in liquefactive necrosis?
A: Lysosomes release hydrolytic enzymes that break down cell components, leading to liquefaction.
Q: What is the key difference in enzyme activity between liquefactive and coagulative necrosis?
A: Liquefactive necrosis involves active hydrolytic enzyme activity that digests tissue, while coagulative necrosis maintains tissue architecture due to less enzymatic breakdown.
in addition to the main types of necrosis: coagulative and liquefaction, what are the other types of necrosis?
Caseous Necrosis
Fat Necrosis
Gangrenous Necrosis
Fibrinoid necrosis
Q: What is the default pattern of necrosis associated with ischemia or hypoxia in most organs?
A: Coagulative necrosis is the default pattern of necrosis associated with ischemia or hypoxia in every organ in the body except the brain.
Q: What is the gross appearance of tissue undergoing coagulative necrosis?
A: The tissue appears firm, and its architecture is maintained for days after cell death.
Q: What is the microscopic appearance of cells in coagulative necrosis?
A: Cell outlines are preserved, but the cells lack nuclei.
Q: In what conditions is liquefactive necrosis typically seen?
A: Liquefactive necrosis is commonly seen with infections and following ischemic injury in the brain.
Q: Why does liquefactive necrosis occur in infections?
A: In infections, liquefactive necrosis is caused by the release of digestive enzymes and contents from neutrophils, leading to tissue liquefaction.
Q: What is the gross appearance of tissue undergoing liquefactive necrosis?
A: The tissue is in a liquid form and may appear creamy yellow due to pus formation.
Q: What is the microscopic appearance of liquefactive necrosis?
A: inflammatory cells with numerous neutrophils.
when does caseous necrosis occur?
a unique case
only tuberculosis
what is the microscopic appearance of cells undergoing caseous necrosis?
- eosinophilic center surrounded lymphocytes and activated macrophages
- known as a granuloma.
when does fat necrosis occur?
- occurs from acute inflammation
- affects tissues with numerous adipocytes
- damaged cells release enzymes which break down lipids into fatty acids
what is the gross appearance of cells being broken down during fat necrosis?
Whitish deposits as a result of the formation of calcium soaps.
what is the microscopic appearance of cells being broken down during fat necrosis?
Anucleated adipocytes with deposits of calcium
when does fibrinoid necrosis occur?
vascular damage (autoimmunity, immune-complex deposition, infections (viruses, spirochetes, rickettsiae)).
what is the gross appearance of cells broken down by fibrinoid necrosis?
Usually not grossly discernible.
what is the microscopic appearance of cells broken down by fibrinoid necrosis?
Deposition of fibrin within blood vessels.
what does gangrenous necrosis describe?
- used in clinic to describe the necrosis of the lower limbs
whats the gross appearance of cells affected by gengrenous necrosis?
Black skin with varying degree of decay.
whats the microscopic appearance of cells affected by gengrenous necrosis?
Combination of coagulative necrosis, due to ischemia (dry gangrene); and liquefactive necrosis (wet gangrene) if a bacterial infection is superimposed.
in what tissues does liquefactive necrosis occur and under what circumstances?
- solid organs - infections
- brain - hypoxia/ischemia
what 3 main factors drive liquefactive necrosis?
- enzymatic digestion of cellular debris
- enzymatic digestion of surrounding tissues
- denaturation of proteins
infections are a major cause of this because it produces these enzymes and causes for an immune response causing immune cells to further release enzymes
what are the main digestive enzymes leading to liquefaction?
- proteases
- DNases
- lysosomal enzymes
outline the difference in enzymatic digestion of coagulative vs liquefactive necrosis and why this is.
- liquefactive - both autolysis and heterolysis
- coagulative - only heterolysis because ishemia would have damaged the enzymes in the tissue effected - only the inflammatory cells have enzymes - also explains the late onset of digestion and removal of dead tissue
explain how fat necrosis occurs
- pancreatitis causes pancreatic cells to release lipases and amylases
- in breast tissue, the trigger is usually trauma
explain the occurance of fibrinoid necrosis
- endothelial damage and exudate lasma proteins
what triggers apoptosis?
intracellular and extracellular signals
intracellular:
- dna damage
- failure to conduct cell devision properly
extracellular:
- detachment ffrom the extracellular matrix
- withdrawal of growth factors
- specific signals from other cells
name a few inhibitors for apoptosis
- growth factor
- sex steroid
name some inducers of apoptosis
- growth factor withdrawal
- free radicals
- dna damage
- loss of matrix attachment
- viruses
- glucocorticoids
describe what occurs in the intrinsic pathway of undergoing apoptosis
- proteins from the Bcl-2 family decide
- both pro and anti apoptosis proteins in ratio to each other - whichever is higher is the decider
- Bcl-2 - prevents apoptosis - blocks cell death signals
- bax - promotes apoptosis - forms bax-bax dimers that enhance cell death signals
What is the extrinsic pathway of apoptosis, and how does it function?
A: - “death receptors” on the cell surface (e.g., TNFR1 and Fas/CD95) bind to ligands
- receptors cluster together
- This activates caspases, enzymes that initiate cell death
Q: What happens during the execution phase of apoptosis?
A: - Initiator caspases (like caspase-8) activate executioner caspases (like caspase-3).
- These degrade the cytoskeleton and nuclear proteins, causing DNA fragmentation
- The nucleus shrinks (pyknosis) and breaks apart (karyorrhexis).
- The cell shrinks but keeps its membrane intact, signaling phagocytosis.
- Dead cells form apoptotic bodies and are cleared without causing inflammation.
describe briefly a couple of the abnormal apoptotic responses detailing the cells involved
- neurons - neurodegenerative disease
- t lymphocytes - autoimmune disease
what actually is liquefactive necrosis and when is it likely to happen?
- type of tissue death
- cells rapidly digested by enzymes
- forms soft liquid mass
- commonly occurs in tissues with high enzymatic content eg brain after ischemic injury and infections
- this is the type of necrosis which results in pus or fluid accumulation due to cellular destruction
Why does liquefactive necrosis occur in the brain after ischemia, while coagulative necrosis occurs in other solid organs?
Liquefactive necrosis occurs in the brain because its lipid-rich neurons and glial cells contain high concentrations of enzymes that quickly digest tissue into a liquid form after ischemia. In solid organs like the heart or kidneys, structural proteins denature and coagulate after ischemia, preserving tissue architecture temporarily, leading to coagulative necrosis instead.
thinking about immunity and haematapoesis, when would apoptosis occur?
- if the MHC molecules weren’t there or working
- if they didn’t bind to TCR
- if they bound to readily to self-antigens
