3 Cell injury and death Flashcards
What are the four types of cellular adaptation?
Hyperplasia
Hypertrophy
Atrophy
Metaplasia
What are the aetiologies of cell injury?
Oxygen availability Physical trauma Chemical agents Infectious organisms Irradiation Immunological Lack of nutrients/vitamins Genetic disorders Ageing
How does irradiation damage cells?
Generates free radicals which damages macromolecules. Apoptosis induced due to nucleic acid damage.
Which tissues have high/low sensitivity to radiation?
High: bone marrow, gonads, intestines
Low: uterus, pancreas, adrenal
How is mitochondrial function affected in cell injury? (3)
Less ATP leads to…
No Na pump, so Ca/H20 influx leads to cellular swelling.
Anaerobic glycolysis accumulates lactic acid, lowering pH.
Ribosomes detach from RER, reducing protein synthesis.
How does a membrane defect lead to cell injury?
Loss of metabolite gradients.
Increased Ca activates ATPases, phospholipases, proteases and endonuclease.
So… break down of ATP, membrane, proteins and DNA.
What is necrosis and what are the 5 types?
Passive process inciting inflammatory reaction.
Coagulative Caseous Colliquative Gangrene Fat, fibrinoid
What is coagulative necrosis?
Tissue becomes firm and swollen, retaining microscopic architecture. Typical of ischaemic injury.
What is colliquative necrosis?
Coagulative necrosis of the brain. No collagenous framework means tissue liquidises and forms a cyst.
What is caseous necrosis?
Cheese like. Cellular structure destroyed, surrounded by granulomatous inflammation. Found in TB.
What is gangrenous necrosis?
red cell breakdown leads to black colour.
Wet=bacterial co-infection.
When does physiological apoptosis occur?
Embryogenesis, involution, self-tolerance.
When does pathological apoptosis occur?
DNA/protein damage.
Viral infections.
Cytotoxic T-cells.
Chemo/radiotherapy.
How is apoptosis initiated?
intrinsically+extrinsically
Intrinsically: DNA damage activates p53 system, down regulating Bcl-2.
Extrinsically: FAS and TNF activate FasL/TNFR receptors.
What are caspases and how are they activated?
Effector molecules of apoptosis. Released by mitochondria.
Activated by apoptosis initiating factor (AIF) and cytochrome C.
