L1-4: Cell Pathology & Healing Flashcards
RMolecular and cellular triggers for apoptosis
- Reduced ATP synthesis/mitochondrial damage
- Loss of Ca2+ homeostasis
- Disrupted membrane permeability
- Free radicals
Hypoxia Triggers
- Ischaemia — loss of blood flow due to local thrombus or embolus or systemic (cardiac failure)
- Hypoxaemia — abnormally low oxygen level in blood due to altitude sickness or haemoglobin problems (anaemia)
- Oxidative phosphorylation inhibition e.g. cyanide poisoning
Define: reperfusion
Restoration of blood flow
Pathological effects of free radicals
- Lipid peroxidation which leads to membrane damage
- Protein modifications that lead to breakdown, misfolding
- DNA damage that leads to mutations
Pathological effects of mitochondrial damage
Decreased oxidative phosphorylation leads to decreased ATP which causes:
- Impaired function/activity of Na+ pump - influx of Ca2+, H2O, Na+, efflux of K+ causes ER and cellular swelling and loss of microvilli
- Increased anaerobic glycolysis causes decrease in glycogen and pH. The latter combined with increased lactic acid causes clumping of nuclear chromatin
- Detachment of ribosomes leads to disfunctional protein synthesis
Membrane components affected
Membrane damage can be attributed to:
- Loss of phospholipids
- Lipid breakdown products
- Cytoskeletal damage
Differences between apoptosis and necrosis
- Cell size shrinks during apoptosis, and swells during necrosis
- Nucleus undergoes fragmentation during apoptosis and undergoes pyknosis, karyorrhexis and karyolysis during necrosis
- Plasma membrane is altered but intact during apoptosis, and disrupted in necrosis
- Adjacent inflammation only occurs during necrosis
Role of heat shock proteins in cell injury
- Expression is upregulated in response to cell stressors.
- Serve to protect proteins from stress-related damage
- Clean up damaged proteins from the cell
True or false: many many tissues and organs can survive significant injury if they are “pre-stressed”
TRUE.
Coagulative necrosis
Cells have died but the basic shape and architecture of the tissue remains - tissue maintains solid consistency.
Most common manifestation of ischaemic necrosis in tissues.
In most cases necrotic cells are ultimately removed by inflammatory cells.
Which type of necrosis is most commonly associated with ischaemic injury?
Coagulative necrosis, except for in the case of ischaemic brain injury where liquefaction most commonly occurs.
Type of necrosis where basic architecture of tissue remains
Coagulative necrosis
Liquefactive necrosis occurs due to
infiltration by neutrophils which causes abscess formation - ROS and proteases are released
Which type of necrosis is associated with granulomatous inflammation of tuberculosis?
Caseous necrosis
Difference between red and white infarct
White - arterial occlusion.
Red/haemorrhagic - venous occlusion
Apoptosis triggers
- Withdrawal of growth stimuli
- Death signals - TNF and Fas
- DNA damage - p53
Peter Medawar’s mutation accumulation theory
Mutation accumulation theory predicts that genetic diseases should increase in frequency with age and that there could be a large heterogeneity in deleterious genes between different individuals.
The delayed disease response in Peter Medawar’s mutation accumulation theory is due to
The delayed disease response is due to cell repair mechanisms which gradually lose their activity
What is the DNA “end-replication problem”?
The shortening of the ends of chromosomes by about 20bp during replication.
Werner’s syndrome is characterised by
premature ageing
The WRN gene encodes a DNA helicase
Which cytokines contribute to maintaining the senescent phenotype?
IL-6 and IL-8
