MECHANISM OF CELL INJURY Flashcards
- the cellular response to injurious stimuli is dependant on the type of injury,
its duration and its severity.
GENERAL CONSIDERATION
- consequences of an injurious stimulus are dependent on the?
- type of cell injured
- current status,
4 intracellular systems are particularly vulnerable to injury.
CELL MEMBRANE
MITOCHONDRIA
PROTEIN SYNTHESIS
GENETIC APPARATUS
3 Mecahanism of cell injury
1.GENERAL CONSIDERATIONS
2.BIOCHEMICAL MECHANISM
3.CHEMICAL INJURY
cell injury occurs when the free radical generation overwhelms
antioxidant defense mechanisms.
FREE RADICAL INDUCED INJURY
ATP depletion and ↓ ATP synthesis are common consequences of
both ischemic and toxic injury.
ATP DEPLETION
4 Generation of free radicals
CELLULAR METABOLISM
IONIZING RADIATION
DEVALENT METALS
hydrolyzes water into hydroxyl (OH) and
hydrogen (H)free radicals.
IONIZING RADIATION
the transition metals (copper and iron), accept or donate free electrons during certain intracellular reactions,
DEVALENT METALS
small amount produce from cell redox reactions, intracellular oxidase, excess of O2, altered metabolism
CELLULAR METABOLISM
Important reactants
SUPEROXIDE ANION-O2
HYDROXL RADICAL-OH
HYDROGEN PEROXIDE- H202
PEROXYNITTE- ONOO
Main site of damage
DAMAGE OF MEMEBRANE
DAMAGE OF PROTEIN
DAMAGE TO DNA
Protective mechanism of cell
- STORGAE & TRANSPORT PROTEINS
- ANTIOXIDANTS
- ENZYME NEUTRALIZING FREE RADICALS
- SUPEROXIDE DISMUTASE
- CATALASE
can catalyze formation of reactive oxygen
forms; they are minimized by being bound to storage and transport proteins
IRON AND COPPER
either block the formation of free radicals or inactivate/ scavenge them:
ANTIOXIDANTS
a selenium-containing enzyme
which catalyzes GSH to GSSG.
- this enzyme also catalyzes the reduction of lipid peroxides by glutathione, preventing propagation of lipid
peroxidation reactions.
GLUTATHIONE PEROXIDASE
catalyzes the conversion of
O2-.to H2O2.
Superoxide dismutase (SOD)
In humans and dogs this toxicity is detoxified in the liver to glucurunide & sulfate conjugates then excreted in the urine
ACETAMINOPHEN TOXICTY
this animal are deficient in glucuronyl transferase & large portion of acetaminophen toxicity.
CAT
CCL4
Carbon tetrachloride toxicity
is highly reactive and causes lipid peroxidation (autocatyzing) →see severe and rapid membrane destruction → ↓protein synthesis (30
min); ER swelling & ribosomal dissociation (2 hrs.).
CCL3
this animals (compared to humans) produce relatively more of the metabolite “para-aminophenol”, which is released from the liver cells and results in oxidative damage to hemoglobin
CAT AND DOGS
