HEAVY METALS (continued)
Cadmium:
* Used in alloys, pigments, and batteries
* Concentrates in tobacco and rice -- so smokers have a
higher Cd burden than others
* Less than 5% is absorbed from GI, however 10-40% is
absorbed after inhalation
* t1/2 is about 10-30 years in the body
Symptoms of Cd poisoning:
Acute:
oral exposure causes local irritation and vomiting
inhalational exposure can cause respiratory problems
Chronic:
Cd is conjugated in the liver and is either excreted in
the bile or bound to metallothionein (MT)
Kidney is the main target–the CdMT complex can
escape an hepatocyte and get to the kidney
In the lumg, Cd causes emphysema and pulmonary
fibrosis
Cd effects on the bone result in osteomalacia
Can cause cancer of the lung, prostate, and kidney
Treatment of Cd poisoning:
No chelators are available
Chelators may actually increase the availability of Cd to
the rest of the body!
Other metals:
Aluminum:
Shaver’s disease – inhalational Al exposure
Antimony:
Similar to that seen in Arsenic
Barium:
Soluble salts (BaCl) produce cardiocascular and CNS effects
Insoluble salts (BaSO3) display minimal toxicity, if any
Beryllium:
Skin lesions, dermatitis, and granulomas; it’s also a
carcinogen in lab animals
Fluoride:
Higher concentrations discolor the teeth, and can lead
to brittle bones
Nickel:
Dermatitis – from nickel jewelry
Nickel carbonyl can cause: pneumonia, hyperthermia,
and delerium
Nickel subsulfate is a human carcinogen
The chelator is dithiocarbamate
Thallium:
Used as a rodenticide
Distributes in the body similar to potassium
Acute exposure causes GI and cardiovascular effects
Overview of Chelators:
Edetate calcium disodium (EDTA) is used for:
Lead
* Usually given IV
Dimercaprol (BAL) is used for:
Arsenic, Gold, Lead, and Mercury
Succimer is used for:
Lead, and possibly arsenic & mercury
* Its advantage is that it can be given orally
Penicillamine is used for:
Mercury, Lead, and Arsenic
Deferoxamine is used for:
Iron
AIR POLLUTION, SOLVENTS, & VAPORS
Air Pollutants
Five main pollutants:
Carbon monoxide (52%)
Sulfur dioxide (18%) – mucous membrane irritation and
bronchoconstriction
Hydrocarbons (12%)
Particulate matter (10%)
Nitrogen oxides (6%)
Two kinds of pollution:
Reducing – caused by sulfur dioxide
Oxidizing – caused by the other four
Carbon Monoxide:
* Most common cause of accidental and suicidal
poisoning
* Heavy smokers may have CoHb levels of 6% (Norm is .4-.7%)
* CO toxicity is due to its affects on Hb affinity for oxygen;
CO will cause a left-shift in the dissociation curve
* t1/2 for CO is 320 minutes, being eliminated thru the lungs
* Brain and Heart are the sites for the most toxic effects
* Symptoms of CO poisoning, therefore, resemble hypoxia
* Treatment of CO poisoning is O2; hyperbaric oxygen is the
preferred treatment (100% O2 reduces the t1/2 to 80 min.)
Particulate Matter:
* Silicosis is the most common example
* Silica dusts result in fibrotic nodules in the lung
* Asbestosis results from long-term inhalation of its dust
* Asbestosis is associated w/ increased risk of mesothelioma
of the lung
Solvents and Vapors
Aliphatic hydrocarbons:
Gasoline and kerosine – are CNS depressants; death from
hemorrhagic pulmonary edema can occur w/in 24 hrs
of aspiration! Also contain benzene, which is a known
carcinogen in humans.
Methane and Ethane -- in natural gas and propane
* Higher-molecular weight hydrocarbons also act as CNS
depressants
Halogenated hydrocarbons:
Carbon tetrachloride (CCl 4) – CNS depression, kidney
injury, liver injury, liver cancer, and sensitizes the heart
to catecholamines; it is metabolized by a P-450 to
a hazardous free-radical (akin to a Montana militiaman)
the free radicals cause membrane lipid peroxidation
* Other HHs also produce CNS depression at high doses
* Vinyl chloride is a carcinogen
* Trichloroethylene and tetrachloroethylene are fairly safe
* Tetrachloroethylene is used in the dry-cleaning industry
Aliphatic Alcohols:
Ethanol:
Oxidized to acetaldehyde in the liver
Acute EtOH inhibits microsomal enzymes
Chronic EtOH increases microsomal enzyme activity
Methanol:
Found in canned fuels, paint removers, and some
antifreeze solutions
Causes CNS depression
Upon metabolism, formaldehyde and formic acid are
formed;
acidosis and blindness can result from this accumulation
of formic acid and formaldehyde!
The best therapy for Methanol poisoning is EtOH by IV;
EtOH
has a much higher affinity for the dehydrogenase
Isopropanol:
Found in ‘rubbing alcohol’, hand lotions, and de-icing
compounds
Produces CNS depression and severe gastritis
Glycols:
Ethylene glycol:
Is a CNS depressant; target organ of toxicity is the kidney
The toxicity is due to its metabolite – oxalic acid
Antifreeze toxicity is also treated with EtOH, IV
Diethylene glycol: same as for ethylene glycol
Propylene glycol: does NOT produce kidney injury
Glycol ethers:
Used in films, wire insulation, paints, fingernail polish, inks, etc..
(see the book for the LONG names) these are teratogenic,
and produce testicular atrophy (ouch!)
The exception to this is Propylene glycol monomethyl ether,
which is neither a teratogen nor a reproductive toxin
Aromatic hydrocarbons:
Benzene:
Found in gasoline; acute exposure causes CNS depression
Its chronic toxicity results in aplastic anemia and leukemia
Toluene:
Only produces CNS depressant effects; NO other toxicities
This is ‘supposedly’ why there was this ‘glue sniffing’ craze(?)