Cell Death Flashcards
Morphological differentiation in reversibly injured and irreversibly injured cells
Reversibly injured:
- Hydropic degeneration: cisternae of ER swell, Mitochondria swell and round up
- Ribosomes detach from ER
- Blebs of plasma membrane
Irreversibly injured:
- Severe swelling of mitochondria with large densities in mitochondrial matrix
- Injured lysosomal membranes - enzymes leak out and digest self
- Injured plasma membrane - proteins leak out
Do irreversibly injured cells have nuclei
No
How long after cell injury can light microscopic change be seen
Few mins/hours later
How long after cell injury can gross morphological changes be seen
Few days later
Appearance of cells dying by necrosis
Swelling - cell and internal organelles like mitochondria balloons and ruptures
Inflammation - circulating macrophages and polymorphs converge and phagocytose the necrotic cell
Occurs in large groups
Messy
Disorganised
Morphology of Necrosis
Increased eosinophilia - Loss of RNA (more pinkish)
Glassy homogenous cytoplasm - Loss of glycogen
Calcification (dystrophic) - dead cells
Nuclear changes
Describe the different types of Nuclear changes possible
Karyolysis: lysing of nucleus due to action of DNAse and RNAse causing fading of basophilia (loss of RNA hence less blue)
Karyorrhexis: fragmentation of nucleus
Pyknosis: condensation of the nucleus and clumping of chromatin (nuclear shrinkage and increased basophilia hence more blue)
Types of Necrosis + examples
- Coagulative - Myocardial/Renal Infarction
- Liquefactive - Stroke/Abscess (brain, renal)
- Fat - Pancreatitis/Injury to breast
- Caseous - Tuberculosis
- Fibrinoid - Hypertension (blood vessels)
What causes Fat Necrosis?
Action of digestive enzymes of adipose cells causing the release of fatty acid precipitates
What does Caseous Necrosis look like
Gray-white, soft, cheese like
What causes Fibrinoid necrosis?
Damage to blood vessels cause increased permeability to proteins, causing plasma proteins to accumulate in the wall making it highly eosinophilic
Which type of necrosis cause highly eosinophilic cells
Coagulative Necrosis, Fibrinoid Necrosis
Which type of necrosis causes cell outlines to not be retained/no residual tissue architecture
Liquefactive Necrosis, Caseous Necrosis
What are the main differences between Necrosis and Apoptosis
Necrosis:
- Messy and disorganised
- Inflammation
- Not cleared
- Occurs in a large group with neighbouring cells
Apoptosis:
- Tightly regulated intracellular program, Tidy
- No/Minimal inflammatory reaction
- Rapidly cleared
- Phagocytosed by neighbours
Positive results of apoptosis
- Destruction of cells during embryogenesis (eg. organogenesis) - prevent malformation
- Involution of hormone-dependent tissues (eg. endometrial cell breakdown)
- Cell loss in proliferating cell populations (eg. immature lymphocytes that fail to express useful antigens)
- Elimination of potentially harmful self-reactive lymphocytes
- Death of host cells that have served their useful purpose (eg. neutrophils)
- Deletion of activated mature ‘T’ cells at the end of immune response
- Killing of virus infected cells/cancer cells (by cytotoxic T cells/ NK cells)
- Killing of inflammatory cells (at immunoprivileged sites)
- Killing of DNA damaged cells - prevent mutations and cancer
Negative results of apoptosis
- DNA damage (eg. radiation)
- Accumulation of misfolded proteins (eg. degenerative diseases of CNS)
- Cell death (eg. viral infections)
- Pathologic atrophy in parenchymal organs (eg. duct obstruction in pancreas)
- Unscheduled apoptosis of neurons can cause disease (Parkinson’s or Lou Gherig)
What cellular observation can be found in apoptotic viral hepatitis cells
Councilman bodies
What is the sequential ultrastructural changes seen in apoptosis
- Cell shrinkage
- Chromatin condensation
- Cytoplasmic blebs and apoptotic bodies (split up)
- Phagocytosis of cell bodies by macrophages
Mechanism of Apoptosis
- Initiation Phase (Extrinsic + Intrinsic) - activates caspases
- Execution phase - proteolytic cascade
Explain the Extrinsic Initiation pathway of Apoptosis
- Ligand binding to death receptor on cell surface (TNF-a binding to the TNF-a receptor; Fas binding to CD95)
- Receptors cluster acitvating caspase 8
- Caspase 8 activates Caspase 3
- Caspase 8 and 3 cleave apoptotic substrates
Explain the Intrinsic Initiation pathway of Apoptosis
- DNA damage induces p53
- p53 induces Bax protein synthesis
- Bax promotes release of cytochrome C from the mitochondria
- Cytochrom C in the cytosol activates Caspase 9
- Caspase 9 activates Caspase 3
Explain the Execution pathway of Apoptosis
Caspases are cysteine proteases which selectively cleave target proteins (eg. Caspase-activated DNase (CAD) - cuts DNA between nucleosomes)
What is the difference in diffusion analysis of Apoptotic cells vs Necrotic cells
Apoptosis: Ladder pattern
Necrotic: Diffuse Smearing
How do apoptotic cells target themselves?
Phosphatidyl Serine moves from the inside to the outside leaflet of plasma membrane of apoptotic cells
Annexin I protein is released by the cell as a result of caspase activation to bind to PS on the cell surface as an “eat me” signal