mechanism of cell injury Flashcards
(21 cards)
what are the major causes of ATP depletion
reduced supply of oxygen and nutrients, mitochondrial damage
consequences of mitochondrial damage
formation of mitochondrial permeability transition pore
> loss of membrane potential
> failure of phosphorylation and ATP production
>necrosis
> release of Cyc C into cytosol and activation of apoptosis
consequences of Ca influx after cell injury
opening of mitochondrial permeability transition pore
an influx of Ca in cytosol leads to the activation of some enzymes such as:
phospholipases: X phospholipids → CM damage.
Proteases: X cytoskeletal proteins→ CM damage (connection)
Endonucleases: nuclear damage.
ATPases: X ATP
free radicals
chemical species that have a single unpaired electron in the outer orbital
characteristics of free radicals
- unstable atoms
-react with inorganic and organic chemicals - initiate autocatalytic reactions
- the creation of more radicals (propagation_
oxidative stress
the increase ROS (reactive oxygen species) - oxygen-derived free radicals
oxidative stress may cause
cell injury, cancer, aging, and some degenerative diseases like Alzheimer
by-products of mitochondrial respiration (free radicals compounds)
superoxide anion (O2-), hydrogen peroxide (H2O2), and hydroxyl group (OH)
generation of free radicals through absorption of radiant energy
UV light and X-rays > hydrolyze water into OH and H free radicals
how are free radicals generated in the production of leukocytes
from NADPH oxidase and xanthine oxidase generate superoxide anion
CCL4 and CCL3
not ROS but similar
Fenton reaction
generate free radicals from the reaction of H2O2 with ferric ion
can nitric oxide (NO) act as a free radical
yes
how are free radicals removed
> Decay spontaneously
Antioxidants: Vitamin E and A, ascorbic acid and glutathione in the cytosol.
binding proteins
what enzymes help in the removal of free radicals
- Catalase: H2O2 → O2 + H2O
Superoxide dismutase (SOD): superoxide anion → H2O2,
Glutathione Peroxidase: H2O2 → H2O or OH → H2O.
Reduced Glutathione level is important in cell safety.
pathological effects o free radicals
Lipid peroxidation in membranes
Oxidative modification of proteins.
Lesions in DNA.
degrading enzymes in the lysosome
RNases, DNases, and proteases.
how to detect tissue damage in the liver
through LFT (liver function test)
ALT (Alanine aminotransferase)
AST (Aspartate aminotransferase)
ALK (ALP)
which is more rapidly damaging ischemia or hypoxia
ischemia
Ischemia-reperfusion injury
reversible: Restoration of blood flow to ischemic tissues can promote recovery if they are reversibly injured.
Irreversible: reperfusion paradoxically exacerbates injury (more dead cells)