What are routes of exposure for heavy metals?
Inhalation, ingestion, dermal absorption
What is LD50 and problems associated with it?
= median lethal dose, given all at once which causes the death of 50% of a test group.
- a way to measure short-term acute poisoning
- The LOWER the LD50, the MORE TOXIC the substance
Problems: wide variability between species (e.g. chocolate safe in humans, toxic to many species), animal rights concerns re: testing
What are some mechanisms of heavy metal toxicity?
- Enzyme/cofactor inhibition or potentiation
- Disruption of membrane and other transport processes
- Disrupt mitochondrial function→fatigue
- Decreased neuronal function and nerve conduction
- Bind sulfhydryl groups on proteins and amino acids
Who is most at risk for lead toxicity?
Children living in older housing
Pregnant women and the developing fetus
What are some sxs of lead toxicity?
May appear Asx
Impaired abilities may include: Decreased learning and memory, Lowered IQ, Decreased verbal ability, Impaired speech and hearing functions, Early signs of hyperactivity or ADHD
What are sxs of low lead toxicity?
Myalgia and parasthesia Mild fatigue Irritability Lethargy Occasional abdominal discomfort
What are sxs of moderate lead toxicity?
Arthlagia General fatigue Difficulty concentrating Muscular exhaustibility Tremor Headache Diffuse abdominal pain Vomiting Weight loss constipation
What are sxs of severe lead toxicity?
Paresis or paralysis Encephalopathy: may abruptly lead to seizures, changes in consciousness, coma, and death Lead line (blue-black) on gingival tissue Colic (intermittient, severe abdominal cramps)
What is the best test to screen for lead exposure?
blood test; lead present in circulation
What are the blood lead levels needed to report to CDC?
Adult <20mcg/dL
Child <5mcg/dl
What are some potential imaging findings associated with lead toxicity?
Abdomen: May reveal lead items swallowed by small children
Long bones: May reveal “lead lines” w/ significant exposure
What is the health concern associated with elemental mercury? (metallic, shiny, silver-white liquid)
- Metabolism of elemental mercury by microorganisms in sediment creates Methylmercury which bioaccumulates in aquatic and terrestrial food chains
- Main dietary exposure is methylmercury from fish, it’s highly absorbable through GI tract (95%)
- Gut flora may also methylate elemental Hg to make it into methylmercury
How are we exposed to elemental mercury?
- Thermostats, thermometers, sphygmanometers, barometers, dental amalgams
- Inhalation of it volatilized from dental amalgams is a major source of exposure for the gen. population, it’s vapor is highly lipid soluble
- Released into air by combustion of fossil fuels, solid waste incineration, mining, and smelting; this then can deposited on land and in water
What is the health concern associated with Methylmercury? (its organic form)
- Large amounts of fish eaten over wks to mons can cz damage to nervous system, cerebral palsy
- Binds tightly to muscle of fish (not as much in oil of fish)
- In humans, crosses BBB and placental barriers; ½ life of 50-70 days in adult human serum, ½ life of 90 days in human children, ½ life of 46 days in lactating humans, ½ life of 20+ years in human brain
- High uptake in the brain: potent neurotoxin and teratogen
- Not fat soluble: has to be transported into the brain: methylmercury binds to cysteine→ molecule looks similar enough to methionine to take its place in the membrane transport system
What is the role of ethylmercury in humans?
It’s formed when the body breaks down thimerosal (vaccine preservative since 1930s). Excreted from the blood more quickly than methylmercury.
What is inorganic mercury?
A category of mercury compounds including mercuric chloride, mercuric sulfide. Found in batteries, some disinfectants, some health remedies and skin lightening creams
bioaccumulation vs. biomagnification?
Bioaccumulation = accumulation of substances in an organism. Biomagnification = as you move up the food chain, concentration increases.
Notable characteristics of cadmium?
Predominant use = battery manufacturing
Other sources = pigment production, coatings, plastic stabilizers
Absorption may be increased in iron deficiency
Where does cadmium accumulated in the body is why is this concerning?
Liver and kidneys where it is bound to metallothionein.
- 1/3-1/2 of total body burden accumulates in kidney tissues, czing renal tubular + glomerular damage: irreversible proteinuria and progressive reduction in GFR
Concern: If chelating a person with elevated cadmium and mobilizing it for excretion, one key routes thru urine and thus risking further damage to kidneys.
How does cadmium contribute to osteomalacia and/or osteoporosis?
Increased urinary excretion of calcium + phosphorus and decreased hydroxylation of Vit. D metabolites.
How does cadmium effect the lungs?
- Acute / heavy exposure to welding dust and fumes →severe pneumonitis
- Chronic inhalation→changes in lung function consistent with emphysema
- Associated with lung CA
Notable characteristics of arsenic?
- Found/uses: Medicines, cosmetic lighteners, paint pigments, industrial wood preservation
- Well absorbed from GI tract, less so through inhalation, poorly absorbed through skin
What source is best for testing acute exposure of heavy metals?
Blood: Metals are cleared rapidly + accumulate in storage depots
What are the pros to testing hair for heavy metal exposure?
- Good for evaluating methylmercury
- Cheap and easy to perform
- When performed properly, can provide a qualitative screening test for exposure to heavy metals (but cannot dx metal toxicity)
- CDC, EPA, and ATSDR all recognize the validity of hair mercury levels as an indicator of maternal and fetal exposure to methylmercury
