Toxicology Intro Flashcards
Xenobiotic definition
foreign substance introduced to body
Toxic agent
chemical/physical compounds toxic at high doses
Poison
chemical/physical compound toxic at a low dose
Toxin
a toxic agent produced by biological systems
Toxidrome
constellation of toxic effects comprising of a series of clinical fingerprints for a group of toxic chemicals
6 ways of classifying in toxicology
- use in public domain
- target organ
- physical state
- effects
- source
- biochemical properties
Route of exposure in toxicology
oral
intravenous
inhalation
parenteral
how to define duration of use of substances
acute (single use)
subacute (repeated <1 month)
subchronic (repeated 1-3 months)
chronic (>3 months)
graded dose response
relationship of test subject’s response to increasing dosage of a chemical
quantal dose response
relationship of a population of test subjects against an increasing dosage of chemical agent
Cell signalling dysfunction is caused by
- changes in genetic expression
- changes in the excitability of the cell
reversible cell damage/injury
trauma to cell that heals, continuous or increased injury can lead to irreversible injury
irreversible injury
leads to apoptosis or necrosis
Cell injury or damage
occurs when injury exceeds to limits of an adapted cell
Adaptation
cellular response to stress in the environment to maintain homeostasis in the body. It can be physiological or pathological.
7 causes of cell injury
hypoxia
physical/chemical agents
immunologic agents
infectious agents
genetic derangement
nutritional imbalance
ageing
ATP role in cellular injury
- depletion of ATP leads to failure energy-dependent functions
- causes dysfunction in mitochondria, leading to leakage of mitochondrial proteins, which is a signal for apoptosis
Reactive oxygen species production
- phagocytic leukocytes produce ROS (respiratory burst)
- mitochondria when O2 is reduced to oxygen radical
- mitochondria when hydrogen peroxide is reduced to hydroxyl radical
Cell injury by ROS
- lipid peroxidation
- cross linking and protein changes
- DNA mutation/damage
signs of necrosis
- severe cell swelling and rupture
- denaturation and coagulation of cellular proteins
- breakdown of cell organelles for lethally injured cell
signs of apoptosis
cell shrinkage, chromatin condensation, cytoplasmic blebs, apoptotic bodies
phagocytosis
intrinsic caspase activation via mitochondria
- loss of survival signal caused by DNA damage + accumulation of misfolded protein
- Inhibit Bcl-2 and Bcl x, leading to the release of apoptogenic molecules by destroying membrane
- pro apoptotic proteins released to cytoplasm
extrinsic caspase activation via death receptor
- FasL of lymphocytes and cytotoxic T cells bind to FAS receptor on target cell
- engage FAD receptor by ligands on adjacent cells
- activate caspase
- self phosphorylation -> activation
- activate endonucleases and breakdown cytoskeleton