Cell Ageing and Death Flashcards
What are the two pathways of irreversible cell death?
Necrosis
Apoptosis
What is necrosis?
Death of cells with loss of membrane integrity and enzymatic destruction of cellular constituents. Require NO ENERGY
Always PATHOLOGICAL
How does necrosis stimulate an inflammatory response?
Cellular constituents leak into surrounding tissues and circulation.
Inflammatory response to these constituents and initiation of repair process
What is dystrophic calcification?
Calcium deposition into dead cells. Used to identify necrosis
What is the most common necrosis?
Coagulative Necrosis
How does coagulative necrosis occur?
Cells are consumed by various enzymatic processes and cells but the CELL OUTLINE is preserved (no nucleus can be seen)
Give an example of when coagulative necrosis would occur
Often in cardiac muscle after myocardial infarction (can be follow by restitution - scar formation and fibrosis - so no hole forms)
What is liquefactive necrosis?
Necrosis leaves no cell structure remaining leading to PUS formation
Example of where liquefactive necrosis can occur?
When cells die in brain a hole appears (no healing or scarring occurs)
Associated with localised bacterial/fungal infections
What is caseous necrosis?
Cheesy appearing necrosis due to granulomatous inflammation
Amorphous (no clear form) white centre to granulomas (epithelial cells and histiocytes) associated with chronic inflammation
When does caseous necrosis occur?
In TB
What is apoptosis?
Programmed cell death in response to a range of stimuli
Requires energy as the death is controlled
Can be PHYSIOLOGICAL/PATHOLGICAL
How does apoptosis occur?
Cells undergo shrinkage, with condensation/fragmentation of nuclear chromatin.
Cells are PACKAGED before being destroyed, resulting in “spotty” debris
Example of physiological apoptosis and what happens when this fails
Formation of fingers (apoptosis of cells between fingers)
Removal of self-reactive lymphocytes (antibodies constantly changing, so inevitably, some will attach to lymphocyte itself) - if this fails, autoimmune disease results
Inducing cancer cell death
Hormonal-dependent involution (endometrial lining proliferates during menstruation and these cells undergo apoptosis)
When does pathological apoptosis occur?
In response to injury by: Radiation (inc. UV light) Chemotherapy Viral infection, like Hepatitis Cancers Graft vs Host disease (rejection of transplanted tissue)
What are the mechanism by which apoptosis occurs and what is the objective?
Rely on activating CASPASES (essential in cells for apoptosis):
Extrinsic
Intrinsic
How does the extrinsic pathway stimulate apoptosis?
Relies on cell Fas receptor that is associated with the Fas associated death domain.
Activated all the caspases in a cascade reaction
What happens if the extrinsic pathway cannot stimulate apoptosis?
People with Fas mutations often get autoimmune disease
What indused apoptosis and an inflammatory response?
TNF (Tumour Necrosis Factor)
How does the intrinsic pathway occur?
AKA mitochondrial pathway
Normal cells have anti-apoptotic molecules in mitochondrial membranes (presence stimulated by growth factors)
Loss of anti-apoptotic molecules and replaced by pro-apoptotic molecules (Bax and Bak)
Mitochondrial membranes become leaky and the released proteins (Cytochrome C) stimulate caspases
What does p53 allow?
Senses DNA damage and halts cell cycle to allow repair
If DNA cannot be repaired, p53 stimulates caspases and induces apoptosis
What do apoptotic abnormalities cause?
Too little - cancers, autoimmune disease
Too much - neurodegerative disorders
Sometimes, necrosis and apoptosis are mixed in ischaemic injury (heart attacks) and viral infections (hepatitis)
How are apoptosis and homeostasis related?
Homeostatsis also involves maintaining balance of apoptosis
What is the order of events in apoptosis?
Pyknosis - cells shrink
Chromatin condensation - nucleus clumps and breaks up
Cytoplasmic blebs - cytoplasm breaks up
Macrophages - phagocytose debris
What causes cellular aging?
Oxidative stress due to free radical (produced by basic metabolic pathways) damage
Accumulation of metabolic by-products
What is a morphological sign of cellular aging?
Lipofuscin (brown pigment) - due to breakdown of lysosomes. Commonly seen in brain and heart
What is progeria?
Rare genetic disorder. Abnormal cell ageing leads to elderly appearance at young age
Why do cells die?
Cells can only divide a LIMITED no. of times.
What are telomeres? Function?
Chromosome are capped with TTAGGG repeats, which become smaller with every division
The caps provide protection and stop chromosome ends from degradation and fusion
Why do stem and germ cells not die while somatic cells die?
Continue dividing due to telomerase which keeps adding TTAGGG repeats, after they are lost
Telomerase not active in somatic cells
How do cancers become immortal?
Reactivate telomerase
What is the only proven way to extend life?
Calorie restriction reduces IGF (Insulin-like Growth Factor) signalling, silencing specific genes
