At a Glance
Heavy metal toxicity should be considered in any patient presenting with renal disease of unexplained origin, bilateral neuropathy, acute changes in mental function, or a history of exposure, such as occupational exposure.
Patients with mercury toxicity can present with signs and/or symptoms suggestive of either acute or chronic exposure. In acute toxicity, paresthesias, incoordination, dyspnea, metallic taste, lethargy, and confusion can be seen. In chronic toxicity, tremors, gingivitis, and erethism (neuropsychiatric) are more common.
Humans are generally exposed to mercury through the diet. Elemental mercury, Hg0 (which is nontoxic to humans), in our environment is chemically converted to the ionized inorganic species, Hg2+, which is further converted to organic methylmercury by microorganisms in sediment of lakes and rivers. Both Hg2+ and methylmercury are highly toxic.
Methylmercury accumulates in fish and reaches its highest level in predatory fish. Therefore, most human exposure to methylmercury is through eating contaminated fish. Methylmercury is highly selective for lipid-rich tissue, such as neurons, explaining the numerous neurological and psychiatric symptoms in patients. In addition, it can pass through the placenta, causing irreversible neurological damage in the developing fetus.
Dental amalgams are no longer considered a significant source of mercury exposure.
Heavy metal toxicity is not common (prevalence is similar to inborn errors of metabolism), and diagnosis can be difficult, because the signs and symptoms are similar to many other diseases. Despite these facts, screening for heavy metal toxicity is indicated in all patients with symptoms suggestive of toxicity, as screening is relatively simple and treatment is available that reduces long-term morbidity.
Analysis of blood, urine, and hair can be used to determine exposure. The quantity of mercury found in blood and urine correlates with the degree of toxicity, whereas hair analysis can document remote exposure to mercury.
Normal whole blood mercury concentrations are less than 10 mcg/L. Levels greater than or equal to 50 mcg/L are considered significant for methylmercury exposure, whereas levels greater than or equal to 200 mcg/L are considered significant for ionized inorganic mercury, Hg2+. In urine, most people have less than 10 mcg of mercury/24-hour specimen with levels exceeding 50 mcg/day, indicating significant exposure. Anything greater than 1 mcg/g in hair indicates exposure to more than normal amounts of mercury.
Patients exposed to high levels of mercury can develop nephrotic syndrome and membranous nephropathy, which is associated with elevated urinary excretion of albumin and transferrin. Urinary excretion of the tubular enzyme, N-acetyl-beta-D-glucosaminidase, may prove to be an early marker of mercury toxicity.
Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?
Appropriate specimen collection is critical for all heavy metal testing. Tubes with metal caps or glued inserts affect test results. Most commonly, a plastic royal blue top trace element collection tube containing EDTA anticoagulant is required for accurate analysis. In addition, when collecting hair specimens, it is important to avoid contamination.
Diet, medication, and nutritional supplements may introduce interfering substances and affect mercury analysis. After consultation with a physician, patients should be encouraged to discontinue nutritional supplements, vitamins, minerals, and nonessential over-the-counter medications and avoid shellfish and seafood for 48-72 hours.
What Lab Results Are Absolutely Confirmatory?
Heavy metal toxicity can be confirmed if three factors are present:
a source of metal exposure is evident
the patient demonstrates signs and symptoms of toxicity with that metal
an abnormal concentration of that metal is present in blood, urine, or tissue
Because of its relatively long half-life, whole blood mercury levels are the most accurate at assessing mercury exposure. Urine can be helpful in following the effectiveness of chelation therapy and is also thought to better indicate the mercury burden of the kidneys.
The most sensitive and specific methods for measuring total mercury levels in biological fluids are atomic absorption spectrometry (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS). These methods can accurately detect mercury as low as 1 ppb. In addition, these methods can be utilized to perform mercury speciation to differentiate inorganic from methylmercury.
The diagnosis of membranous nephropathy, which can be associated with mercury toxicity, can be confirmed by granular staining for IgG on immunofluorescence microscopy and subepithelial immune deposits on electron microscopy.
Additional Issues of Clinical Importance
Small children exposed to high concentrations of mercury vapor develop acrodynia or pink disease, which cause a body rash, swelling and irritation of palms and feet, followed by skin desquamation, irritability, photophobia, fever, insomnia, and profuse sweating. This used to be more common when exposure was through teething powders.
Mercury toxicity is expressed three ways:
Mercury avidly reacts with sulfhydryl groups of proteins, causing a change in the tertiary structure of proteins and a loss of biological activity.
Mercury causes some proteins to become more immunogenic, eliciting B-cells to produce immunoglobulin against new antigens, particularly collagen.
Mercury is very lipophilic and binds to proteins in lipid-rich tissues, such as neurons. Ionized inorganic mercury, Hg2+, concentrates in the kidney, where it produces the greatest toxicity, whereas methylmercury, because of its lipophilic nature, targets myelin in neurons.
Mercury toxicity is treated by removing the source of exposure, supportive care, and chelation therapy, such as 2,3-dimercapto-1-propanesulfonic acid (DMPS) or penicillamine.
Errors in Test Selection and Interpretation
Measurement of plasma mercury levels is not recommended, because mercury concentrations in plasma are one-twentieth of that in erythrocytes.
High concentrations of gadolinium and iodine are known to interfere with most testing for heavy metals. If either gadolinium- or iodine-containing contrast media have been administered within 96 hours of specimen collection, results are not valid and should be repeated more than 96 hours after administration of a contrast media containing gadolinium or iodine.
Because of possible contamination issues, elevated levels should be confirmed by obtaining a follow-up specimen.
Mercury is volatile, and concentrations may reduce after 7 or more days of storage.
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- At a Glance
- Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?
- What Lab Results Are Absolutely Confirmatory?
- Additional Issues of Clinical Importance
- Errors in Test Selection and Interpretation