Lecture 1: Cell Death Mechanisms Flashcards
Define adaptation, reversible injury, and irreversible injury.
Adaptation: A response to stress or increased demand that maintains the steady state of the cell without compromising cellular function.
Reversible/ sublethal injury: stage at which deranged function and morphology of the injured cells can return to normal if the damaging stimulus is removed
Irreversible injury: A response to stress/ stimuli that compromises cellular function to the point that it cannot recover (leads to necrosis or apoptosis)
Draw a diagram describing cell responses due to stress or injury-inducing stimulus.
____________ expression is up-regulates when a cell is physiologically stressed. Mentioned the function of this molecule.
Heat shock response proteins (“chaperone” proteins) protects proteins from stress-related damage as well as assisting in eliminating damaged proteins.
Mention the morphological features of reversible injury.
Macroscopic changes:
- Cellular swelling: associated with increases permeability of plasma membrane
- Fatty change: appearange of lipid vacuoles in cytoplasm
Ultrastructural:
- plasma membrane blebbing
- ER (detachment of ribosomes) and mitochondrial swellin
- Nuclear alterations (clumping of chromatin)
- “myelin figures” - collection of damaged phospholipids
Mention the morphological features of necrosis.
-
Cytoplasmic changes:
- Increased eosinophilic staining-denatured protein and loss of RNA
- Vacuolation-digested cytoplasmic organelles
- Swelling of ER and mitochondria
- Myelin figures - whorls of phospholipid from damaged membranes
- Nuclear change: due to the breakdown of DNA and chromatin: Karyolysis, Pyknosis, Karyorrhexis
- Discontinuous plasma and organelle membranes
Mention the triggers of hypoxia.
- Ischaemia
- Local (embolus)
- Systemic (cardiac failure)
- Hypoxaemia
- Oxygen problems
- Haemoglobin problem
- Oxidative phosphorylation inhibition
- e.g. cyanide poisoning
Explain how the reduction of ATP leads to cell injury.
- Reduced activity of ATP-dependent Na+ pumps -> influx of sodium and efflux of potassium -> isoosmotic gain of water -> cell swelling and dilation of the ER.
- Reduced activity of ATP-dependent Ca2+ pumps -> influx of calcium -> apoptosis, membrane damage, nuclear damage
- Increase in anaerobic glycolysis -> lactic acid accumulation -> decreased intracellular pH -> decreased activity of many cellular enzymes & chromatin clumping
- Detachment of ribosome -> protein misfolding -> apoptosis
Explain how hypoxia may lead to cell structural damage.
Explain how free radicals affect the cell.
Explain how the reduction of ATP leads to cell injury.
- Reduced activity of ATP-dependent Na+ pumps -> influx of sodium and efflux of potassium -> isoosmotic gain of water -> cell swelling and dilation of the ER.
- Reduced activity of ATP-dependent Ca2+ pumps -> influx of calcium -> apoptosis, membrane damage, nuclear damage
- Increase in anaerobic glycolysis -> lactic acid accumulation -> decreased intracellular pH -> decreased activity of many cellular enzymes & chromatin clumping
- Detachment of ribosome -> protein misfolding -> apoptosis
Define necrosis.
Necrosis refers to cell death that happens without the participation of the cell. It is always associated with a pathological process (disease)
Mention the types of necrosis.
- Coagulative Necrosis
- Liquefactive Necrosis
- Caseous Necrosis
- Infarction:
- Red/haemorrhagic
- White
Differ between coagulative and liquefactive necrosis.
Coagulative necrosis:
- arises due to denaturation of proteins leading to dead cells (but tissue architecture preserved).
- firm texture
- characteristic of infarcts (necrosis due to ischemia) in all solid organs except brain
- dead cell region may be regenerated or replaced by scar (fibrosis)
Liquefactive necrosis:
- arises due to enzymatic digestion of all macromolecules, leading to loss of tissue structure.
- Mostly due to massive infiltration by neutrophils
- baterial or fungal infections stimulate rapid accumulation of inflammatory cells
Describe caseous necrosis.
It involves the accumulation of amorphous (unstructured) debris within an area of necrosis. Tissue architecture is losr and viable cells are no longer recognisable. It is also associated with granulomatous inflammation of tuberculosis and some fungal infections.
What is an infarction?
Infarction refers to an area of ischaemic necrosis in a tissue or organ. If it’s red/haemorrhagic, it involves venous occlusion, with features such as loose/floppy tissue and fluid buildup. If it’s white, it’s most likely due to arterial occlusion.
Define apoptosis.
Apoptosis is a mechanism of programmed cell death (physiological). It can be triggered by death signals (TNF, Fas), lack of growth stimuli, or DNA damage (triggered by p53).
Briefly describe spinal muscular atrophy.
It is a progressive denervating process, where there is a continued loss of spinal motor neurons (SMN) after the normal death of surplus embryonic neuroblast.
_________ is overexpressed in follicular lymphoma (B-cell bone marrow tumour).
Bcl-2
Due to GF deprivation, mitochondrial injury usually leads to ___________.
apoptosis
Mention the morphological features of apoptosis.
- Intensely eosinophillic cytoplasm (H&E stain)
- Nuclear chromatin condensation and fragmentation (Karryorhexis)
- Cells shrink -> Formation of apoptotic bodies (nuclei and cytoplasm)
- Quickly phagocytosed
- No inflammatory response
Recall the 2 major pathways of apoptosis.
__________ pathways is receptor-dependent.
Extrinsic
Recall that apoptosis is a matter of the balance between apoptotic and anti-apoptotic signals.
How does the cell adapt to ER stress?
In the case of excess misfolded proteins (due to various insults), the cell reduces protein synthesis and increases the production of chaperones.
Differ between necrosis and apoptosis.
