Responses to cell injury 2 Flashcards
(17 cards)
What is ischemia
an inadequate blood supply to an organ or part of the body, especially the heart muscles.
Ischemia leads to what which in turn affects what?
Effects the mitochondria which in turn leads to a decrease in oxidative phosphorylation in turn decreasing amount of ATP produced
What 3 things can result from a decrease of ATP and how do these things further affect other areas
Decrease in ATP can lead to
1) Affecting the Na+ pump, and so an increase influx of Ca2+, H20, and Na+. Decrease efflux of K+. Overall there is ER swellin, cellular swelling and loss of microvili and blebs.
2) Increases anaerobic glycolysis (Fermentation). In turn leads to decrease in glycogen, increase in lactic acid, decrease in pH. Increase in lactic acid and decrease in pH leads to clumping of nuclear chromatin.
3) Detachment of ribosomes in turn leading to decrease of protein synthesis.
For an increase in anaerobic glycolysis as a result of decreased ATP, which cells are more affected and why?
Cells with limited capacity for glycolysis such as the brain will not survive as longer as cells with greater glycolytic capacity such as the liver
what does ROS stand fro
Reactive oxygen species. Hydroxyl radical
What can lead to mitochondrial injury?
Increased cytosolic Ca2+, reactive oxygen species and lipid peroxidation leads to mitochondrial injury or dysfunction.
What are the effects of the damage to mitochondria
Mitochondrial cytochrome C used in ETC and ATP formation survival goes through pro-apoptotic death
There is also loss of membrane potential due to loss of H+ which in turn affects the inability to generate ATP leading to necrosis
Effects of influx of calcium, specifically what organelles it affects
Increased extracellular Ca2+ as well as the ca2+ from mitochondria and smooth ER causes an increased cytosolic
ca2+.
This causes the activation of cellular enzymes
1) Phospholipase > decrease in phospholipids > membrane damage
2) Protease > disruption of membrane and cytoskeletal proteins > membrane damage
3) endonuclease > nuclear damage
4) ATPase> decrease in ATP
Overall: Apoptosis of the cell through increase of mictochonrial membrane permeability an activation of caspases
How are ROS formed?
Intake of O2 into mitochondria.
O2 undergoes incomplete reduction leading to a superoxide. Inflammation, radiation, chhemicals causes injury to the superoxide. Forming hydrogen peroxide which undergoes a fenton reaction leading to a hydroxyl radical.
What is the fenton reaction mediated by?
Mediated by transition metals, reduced by stroage and transport proteins
What are the pathological effects of ROS, what do they react with?
leads to Cell injury and death
Reacts with:
Fatty acids> oxidation > generation of lipid peroxidases> disruption of plasma membrane, organelles
Proteins > oxidation > loss of enzymatic acitvity, abnormal folding
DNA > oxidation > mutations, breaks
How can free radical be removed
Via antioxidant mechanisms.
SOD in mitochondria, converts O2 to H202
Glutathione peroxidase
Catalase in peroxisomes the conversion of h202 to h20 + ow
ROS are produced how?
Removed how
Byproduct of respiration
Produced by phagocytic leukocytes.
Removed by scavengers which always causes oxidative stress
Briefly describe membrane damage
Decrease in O2 leading to phospholipid loss due to decrease in ATP in mitochondria.
Increase of Ca2+ leading to lipid breakdown products and cytoskeletal damage
Hypoxia > decreased o2 leads to what to things and what are the effects?
decreased aerobic respiration
- Decreased ATP which means decreased ATP dependent transport and decreased ATP dependent macromolecule synthesis
Increased anaerobic respiration
- dcreased pH
- blood flow
- cell type
draw mini diagram for atp dependent transport include the following increased influx of ca2+ enzyme activation caspase activation attack of macromolecules influx of na+ and h20 cell swelling phospholipids cell membrane damage plasma loss of osmotic balance influx of ions mitochondria opening of ion channels lysosome leakage of enzymes
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Hypoxia of the heart
1) occurs how?
2) enzymes?
3) increase serum levels reflect tissue injury, what are the tissue injuries
1) intracellular proteins leak through damaged cell membrane
2) cardiac specific enzymes such as cardia isoform of creatine kinase. Ctronactile protein troponin
3) Increase serum levels reflect tissue injury
Myocardial infarction (irreversible injury)
Angina (reversible as plasma membrane intact)
