2 spectrum of toxic effects Flashcards
what is the spectrum categories of toxic effects?
- local vs systemic
- reversible vs irreversible
- immediate (acute) vs delayed (chronic)
- morphological, functional and biochemical effects
- allergic vs idiosyncratic reactions
- graded (continuous) vs quantal (all or none) responses
what are local effects?
-uncommon compared to systemic
-corrosive chemicals on skin (ex: strong acids and bases such as battery acid)
-irritating gases and vapours in respiratory tract (ammonia and chlorine gas cause build up of fluid in lungs)
what are systemic effects?
-xeno must be distributed into systemic circulation and distributed to organs/tissues
-many xenos preferentially cause toxic effect in one or few specific organs (target organs)
-target organ may not always have the highest xeno conc
what are reversible effects?
-effects disappear after exposure ends
-usually short-term and/or low dose exposures
-ex: drinking on a weekend, effects eventually go away
what are irreversible effects?
-effects persists or even worsen after exposure ends
-ex carcinomas, teratogenic effects, neuronal damage, liver cirrhosis
-usually long-term and/or high dose exposures
-ex: ethanol when decades of alcoholism cause liber cirrhosis)
what are immediate (acute) effects?
-timeframe minutes to days
-ex: cyanide (can’t produce ATP) and carbon monoxide poisoning (high affinity for Hb than O so can’t produce ATP)
what are delayed (chronic) effects?
-timeframe months to years
-ex: cancer develops 10-20 years after exposure, both in individuals and also potentially their offspring (recall diethylstilbestrol (DES) rare reproductive cancer in daughters)
-illustrates the need to conduct long-term toxicological studies and transgenerational toxicological studies
what are morphological effects?
-gross or microscopic effects on tissues; commonly irreversible
-ex: thalidomide teratogenicity (gross: missing limbs)
-ex: histopathological effects on liver cells (microscope view of cells differ with liver cirrhosis)
what are functional effects?
-ex: liver or kidney function, reproduction
-generally reversible effects
what are biochemical effects?
-virtually all toxic effects are initiated by an alteration in biochemical processes (ex: receptor binding, enzyme inhibition, interaction with DNA)
-such biochemical effects are often used as biochemical markers or “biomarkers” that serve as early indicators or “markers” of toxic effects
-note than such biochemical effects are reversible and do not necessarily indicate an adverse morphological or functional effect
what are allergic effects?
a) hypersensitivity reactions: require prior exposure; xeno can react with protein to produce antigen, antibodies are produced and illicit immune response
-ex: bee venoms and nuts can cause a severe allergic reaction
-ex: perfumes, multiple chemical allergy syndrome, “sick building syndrome”
b) autoimmune reactions: xenos can initiate autoimmune diseases such as systemic lupus erythematosus (fairly rare)
what are idiosyncratic effects?
-genetically based abnormal reactivity to a xeno with no known cause
-ex: certain drugs can produce rare, idiosyncratic reactions
what are graded effects?
-continuous (infinite number) responses
-ex: effects on body weight, food consumption, enzyme activity
what are quantal effects?
-all or none responses (yes or no)
-ex: mortality, cancer
why are certain organs targets of xenobiotics?
-generally due to greater susceptibility or higher xeno conc (depends on kinetics, dynamics and dose defines the poison), although the explanation is not always clear
what are the main reasons that certain organs are targets of xenobiotics?
PISBI
-increased susceptibility
-preferential distribution
-selective uptake
-bioactivation
-insufficient repair
what is an example of increased susceptibility?
ex: carbon monoxide (CO) poisoning in highly aerobic tissues (heart and brain) with little anaerobic capacity
what is an example of preferential distribution?
-higher blood flow to liver and kidney; MeHg able to cross BBB
what is an example of selective uptake?
-cadmium preferentially accumulates in kindey tubule cells due to high expression of Cd-binding protein (metallothionein; MT)
what is an example of bioactivation?
to reactive metabolites (ex: liver)
what is an example of insufficient repair?
ex: neuron damage in central and peripheral nervous system (limited ability to repair neurons)
