Toxicological Damage Flashcards
How can a cell be damaged?
When the limits of adaptation are exceeded
Loss of aerobic oxidative respiration
Hypoxia
Loss of blood supply and cut off of metabolic substrates
Ischemia
Common mechanisms of cell injury
ATP depletion
Mitochondrial damage and dysfunction
Influx of calcium
Accumulation of oxygen- derived free radicals (oxidative stress)
Defects in membrane permeability
Accumulation of damaged DNA and misfolded proteins
Chemical injury of cells
Mercuric chloride: bind sulfhydryl groups of proteins
Cyanide: poisons mitochondrial cytochrome oxidase
CCl4: conversion to free radical CCl3 –> causing lipid peroxidation
Acetaminophen: P450 catalyzed oxidation to toxic metabolites
Oxygen that has single (unpaired) electron
Reactive Oxygen Species (ROS)
How does cells deal with unwanted ROS?
enzymes: catalase, superoxide dismutase, glutathione peroxidase
cofactors: Glutathione, vitamin A, C, E
Mechanisms of cell injury caused by ROS
Lipid peroxidation of membranes
Cross-linking and other changes in proteins: causing breakdown or misfolding of proteins
DNA damage: cause mutations
Pathological process by which neurons are damaged and killed by over activation of receptors for excitatory neurotransmitter glutamate
Excitotoxicity
Excitotoxic mechanisms
Influx of Calcium
subsequent generation of ROS
Mitochondrial dysfunction
Reduced cerebral blood flow interrupts oxidative phosphorylation by mitochondria, reduces cellular ATP production
Stroke
Necrosis vs Apoptosis
Cell swelling or rupture
Necrosis
Necrosis vs Apoptosis
Denaturation or coagulation of cytoplasmic proteins
Necrosis
Necrosis vs Apoptosis
Breakdown of cell organelles for lethally injured cell
Necrosis
Necrosis vs Apoptosis
Programmed cell death
Apoptosis
