Lect 3 - Cell Injury Flashcards
What is Atrophy?
a decease in cell number
What is Hypertrophy?
individual cells getting bigger
What is Hyperplasia?
more cells develop to try to keep up demand
what is Metaplasia?
a change in cell morphology
What types of cell death are there?
Necrosis/Apoptosis
what mechanisms can cause cell injury?
lack of Oxygen availability Physical Trauma Chemical agents Infectious organisms Irradiation (Also can be Immunological, Lack of essential nutrients/vitamins or Genetic disorders)
what is cell injury due to lack of oxygen known as?
Hypoxia and anoxia (Reduction or loss respectively of oxygen delivered to cells, often caused by ischaemia)
how can reoxygenation of a hypoxic cell further injure it?
re-perfusion injury - can cause generation of oxygen free radicals which can kill cells.
How can Physical trauma damage cells?
- Disruption of cell structure
- Thrombosis leading to ischaemia is often a secondary effect.
- Extremes of temperature leading to Frostbite or heat denaturation.
Give some examples of Chemical agents that can cause cell injury
– Alcohol – Tobacco smoke – Drugs – Poisons – Environmental – Occupational
How does irradiation damage cells?
• e.g. X-rays, radioactive particles
• Generation of free radicals and direct damage to macromolecules
• different organs have different sensitivity
• v.high in bone marrow, gonads, intestines
• v.low in uterus, pancreas, adrenal
• e.g. UV-light
• can induce inflammatory response several
hours after exposure
What happens when mitochondria are damaged in a cell?
cell gets less ATP, therefore has to try to pick up its rate of glycolysis. in addition, Na Pumps fail, so Ca H20 and Na come flowing in. this causes swelling and other problems.
Ribosomes become detached, meaning protein synthesis slows.
YOU GET LIPID DEPOSITION,
what patient group has tissues which show signs of mitochondrial damage well?
Alcoholics.
Alcohol damages mitochondria. this causes swelling and fatty change which is easily seen histologically.
give examples of agents that could compromise a cell’s membrane.
bacterial toxins, viral proteins, complement, cytolytic lymphocytes, and various physical and chemical agents
why is a compromised cell membrane bad?
• Loss of membrane barriers leads to breakdown in metabolite gradients
• Increased Ca2+ in turn activates a number of enzymes, with potential deleterious cellular effects.
– ATPases (thereby hastening ATP depletion),
– phospholipases (which cause membrane damage),
– proteases (break down membrane and cytoskeletal proteins)
– endonucleases (responsible for DNA fragmentation)
what is necrosis?
• Cell death as result of lethal cell injury
what types of necrosis are there?
– Coagulative
– Caseous
– Colliquative
– Gangrene
also fibrinoid (fat)
Describe Coagulative necrosis
- Dead tissue becomes firm and slightly swollen
- Tissue shows retention of microscopic architecture
- Typical of ischaemic injury (except in brain)
- Cellular proteins may leak into blood
(Note, this is the most common type)
Describe Caseous necrosis and in what disease it is associated?
- Characteristic of tuberculosis
- Cheese like
- Cellular detail destroyed in this area, which is surrounded by granulomatous inflammation.
- Dead tissue lacks any structure
Describe Colliquative necrosis and what tissue does it tend to happen in?
• Necrotic neural tissue is liable to total liquefaction and site is eventually marked by a cyst
what types of gangrene are there?
wet and dry
What is apoptosis?
programmed cell death
In what processes does Physiological Apoptosis happen?
Embryogenesis
Involution
Elimination of self reacting lymphocytes
what what processes does pathological apoptosis occur?
Pathological DNA/protein damage Viral infections Cell killing by cytotoxic T-cells (Chemo/radiotherapy?)
describe apoptosis
Apoptosis initiating factor (AIF) and cytochrome C are normally sequestered in mitochondria, but when released into the cytosol activate caspases, which are the effector molecules of apoptosis.
what two molecules cause lack of apoptosis in cancer?
P53 (the ‘guardian of the genome’) is activated by DNA damage and causes the elimination of damaged cells by apoptosis. Mutations to p53 are very common in malignant tumours, thus allowing cells to accumulate genetic abnormalities
Bcl-2 sequesters cytochrome C and thus inhibits apoptosis. Activating mutations leading to bcl-2 overexpression are another way that some tumours gain the ability to proliferate in an uncontrolled way.
describe what a cell undergoing apoptosis would look like
reduced size, fragmented nucleus forming apoptotic bodies. other parts intact until phagocytosed.
