Background: Throughout the centuries, several incidents of mercury toxicity have been reported. Mercury has been found in Egyptian tombs, indicating it was used as early as 1500 BC. In the late 18th century, antisyphilitic agents contained mercury. It was during the 1800s that the phrase "mad as a hatter" was coined because of the chronic mercury exposure that the felters faced because mercury was used in hat making.

In the 1940s and 1950s, mercury became known as the product that caused acrodynia, also known as pink disease. Manifestations of acrodynia include pain and erythema of the palms and soles, irritability, insomnia, anorexia, diaphoresis, photophobia, and rash.

Some of the more recent occurrences include exposures in Minamata Bay in Japan (1960); mercury contaminated fish in Canada; methylmercury-treated grain in Iraq (1960, 1970); and, in the United States (1996), a beauty cream product from Mexico called "Crèma de Belleza-Manning."

For centuries, mercury was an essential part of many different medicines, such as diuretics, antibacterial agents, antiseptics, and laxatives. More recently, these drugs have been substituted and drug-induced signs of mercury toxicity are rare. Mercury toxicity in environmental pollution is a major concern because of increased usage of fossil fuels and agricultural products, both of which contain mercury.

Mercury poisoning is usually misdiagnosed because of the insidious onset, nonspecific signs and symptoms, and lack of knowledge within the medical profession.

Mercury is found in many industries, such as battery, thermometer, and barometer manufacturing. Mercury can be found in fungicides used in the agricultural industry. Before 1990, paints contained mercury as an antimildew agent. In medicine, mercury is used in dental amalgams and various antiseptic agents.

On July 7, 1999, a joint statement by the American Academy of Pediatrics (AAP) and the US Public Health Service (USPHS) was issued alerting clinicians and the public of thimerosal, a mercury-containing preservative used in some vaccines. Subsequent investigation has not proven any definite link between this small amount of mercury and any known disease.

Most recently, 2 areas have caused public concern regarding mercury toxicity: (1) the potential risk associated with eating fish, especially when dealing with pregnancy and (2) the use of dental amalgams, or fillings, by dentists. In May 2001, one of Canada's largest newspapers, the National Post, featured an exposé on the pros and cons of eating fish titled, ”One fish, two fish, good fish, bad fish” in its “Health and Medicine” section.

Pathophysiology: Mercury is the only metal that is liquid at room temperature. Its elemental symbol is Hg, which is derived from the Greek word hydrargyrias, meaning "water silver." Mercury is found in organic and inorganic forms. The inorganic form can be further divided into elemental mercury and mercuric salts. Organic mercury can be found in long and short alkyl and aryl compounds.

Mercury in any form is toxic. The difference lies in how it is absorbed, the clinical signs and symptoms, and the response to treatment modalities. Mercury poisoning can result from vapor inhalation, ingestion, injection, or absorption through the skin.

Neurologic, gastrointestinal, and renal systems are the most commonly affected organ systems in mercury exposure.
• Organic mercury - Most devastating to the CNS
o Short-chained (methylmercury) - Affects the CNS
o Long-chained - Subacute/chronic effects similar to that of inorganic mercury exposure
• Elemental mercury - Primary neurologic toxicity
• Inorganic mercury salts
o Acute - Severe corrosive gastroenteritis, acute tubular necrosis
o Subacute or chronic - GI, neurologic, and renal dysfunction

Elemental mercury (Hg) is found in liquid form, which easily vaporizes at room temperature and is well absorbed (80%) through inhalation. Its lipid-soluble property allows for easy passage through the alveoli into the bloodstream and red blood cells (RBCs). Once inhaled, elemental mercury is mostly converted to an inorganic divalent or mercuric form by catalase in the erythrocytes. This inorganic form has similar properties to inorganic mercury (eg, poor lipid solubility, limited permeability to the blood brain barrier, and excretion in feces). Small amounts of nonoxidized elemental mercury continue to persist and account for central nervous system toxicity.

Elemental mercury as a vapor has the ability to penetrate the CNS, where it is ionized and trapped, attributing to its significant toxic effects. Elemental mercury is not well absorbed by the GI tract and, therefore, when ingested (eg, thermometers), is only mildly toxic.

Inorganic mercury, found mostly in the mercuric salt form (eg, batteries), is highly toxic and corrosive. It gains access to the body orally or dermally and is absorbed at a rate of 10% of that ingested. It has a nonuniform mode of distribution secondary to poor lipid solubility and accumulates mostly in the kidney, causing significant renal damage. Although poor lipid solubility characteristics limit CNS penetration, slow elimination and chronic exposure allow for significant CNS accumulation of mercuric ions and subsequent toxicity. Long-term dermal exposure to inorganic mercury may also lead to toxicity.

Excretion of inorganic mercury, as with organic mercury, is mostly through feces. Renal excretion of mercury is considered insufficient and attributes to its chronic exposure and accumulation within the brain, causing CNS effects.

Organic mercury can be found in 3 forms, aryl and short and long chain alkyl compounds. Organic mercurials are absorbed more completely from the GI tract than inorganic salts are; this is because of intrinsic properties, such as lipid solubility and mild corrosiveness (although much less corrosive than inorganic mercury). Once absorbed, the aryl and long chain alkyl compounds are converted to their inorganic forms and possess similar toxic properties to inorganic mercury. The short chain alkyl mercurials are readily absorbed in the GI tract (90-95%) and remain stable in their initial forms. Alkyl organic mercury has high lipid solubility and is distributed uniformly throughout the body, accumulating in the brain, kidney, liver, hair, and skin. Organic mercurials also cross the blood brain barrier and placenta and penetrate erythrocytes, attributing to neurological symptoms, teratogenic effects, and high blood to plasma ratio, respectively.

Methylmercury has a high affinity for sulfhydryl groups, which attributes to its effect on enzyme dysfunction. One enzyme that is inhibited is choline acetyl transferase, which is involved in the final step of acetylcholine production. This inhibition may lead to acetylcholine deficiency, contributing to the signs and symptoms of motor dysfunction.

Excretion of alkyl mercury occurs mostly in the form of feces (90%), secondary to significant enterohepatic circulation. The biological half-life of methylmercury is approximately 65 days. Organic mercury is found most commonly in antiseptics, fungicides, and industrial run-off.

Frequency:
• In the US: The 2003 annual report of the American Association of Poison Control Centers' Toxic Exposure Surveillance System documented 3362 exposures to mercury or compounds containing mercury. Of these, 569 were in children younger than 6 years and 1705 were in persons older than 19 years. Overall, 44 individuals were reported to have moderate effects, 6 had major effects, and none died as a result of mercury exposure.

Mortality/Morbidity: Long-term neurologic effects are a major concern with chronic mercury exposure. Two widely publicized topics of concern to the general population are dental fillings, or amalgams, and fish consumption, especially in children and pregnant women.

• After an exhaustive investigation and review of the evidence, including the form of mercury in question, the route of exposure, and the dose, the Public Health Service concluded that dental amalgams do not pose a serious health risk (Public Health Service, 1993).

• The primary source of environmental exposure to mercury in the general population is through the consumption of contaminated fish. (Agency for Toxic Substances and Disease Registry, 1997). Fish consumption has clear health benefits, and the risk posed by mercury exposure is currently speculative. The fetal brain is more susceptible to mercury-induced damage than that of an adult. As a result of this data, the Environmental Protection Agency (EPA) reduced the allowable intake of methylmercury from 0.5 mcg to 0.1 mcg of mercury per kilogram per day, which is lower than the amount allowable according to other regulatory agencies (EPA, 2001). The EPA guideline is derived from reports of subtle and small neuropsychologic changes in children in the Faeroe Islands study, whose exposure was mainly from whale consumption (CDC, 2001). A similar study in the Seychelles found no adverse effects from fish consumption alone (Myers, 2003).

The Food and Drug Administration (FDA) has recommended that pregnant women, breastfeeding mothers, and young children avoid eating fish with a high mercury content (>1 ppm), such as shark, swordfish, tilefish, and king mackerel. This also includes fresh and frozen tuna (mercury content between 0.5 ppm and 1.5 ppm) but not canned tuna, which consists of smaller, shorter-lived species with lower mercury levels. From a nonprofessional perspective, this translates into a weekly consumption of one can (198 g or 7 oz) of tuna for an adult (Canadian Food Inspection Agency, 2002). Rather than ban the sale of these species, Health Canada recommends that they be consumed no more than once per week or once per month by children and by women of childbearing age (Health Canada, 2002). Mercury levels in freshwater fish vary, but, in general, bass, pike, muskellunge, and walleye have high levels of mercury and should be eaten in moderation. Provincial guidelines for sport fish often mirror federal seafood recommendations (Ontario Ministry of the Environment, 2001).

Race: No scientific evidence has demonstrated any difference in the outcome of mercury exposure that is attributable to race.

Sex: No scientific evidence has demonstrated any difference in the outcome of mercury exposure that is attributable to sex.

To read the entire article: http://www.emedicine.com/EMERG/topic813.htm

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