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Chapter: Basic & Clinical Pharmacology : Heavy Metal Intoxication & Chelators

Major Forms of Mercury Intoxication

Mercury interacts with sulfhydryl groups in vivo, inhibiting enzymes and altering cell membranes.

Major Forms of Mercury Intoxication

Mercury interacts with sulfhydryl groups in vivo, inhibiting enzymes and altering cell membranes. The pattern of clinical intoxication from mercury depends to a great extent on the chem-ical form of the metal and the route and severity of exposure.

A. Acute

Acute inhalation of elemental mercury vapors may cause chemical pneumonitis and noncardiogenic pulmonary edema. Acute gingivo-stomatitis may occur, and neurologic sequelae (see following text) may also ensue. Acute ingestion of inorganic mercury salts, such as mercuric chloride, can result in a corrosive, potentially life-threatening hemorrhagic gastroenteritis followed within hours to days by acute tubular necrosis and oliguric renal failure.

B. Chronic

Chronic poisoning from inhalation of mercury vapor results in a classic triad of tremor, neuropsychiatric disturbance, and gingivo-stomatitis. The tremor usually begins as a fine intention tremor of the hands, but the face may also be involved, and progression to choreiform movements of the limbs may occur. Neuropsychiatric manifestations, including memory loss, fatigue, insomnia, and anorexia, are common. There may be an insidious change in mood to shyness, withdrawal, and depression along with explosive anger or blushing (a behavioral pattern referred to as erethism). Recent studies suggest that low-dose exposure may produce subclinical neurologic effects. Gingivostomatitis, sometimes accompanied by loosening of the teeth, may be reported after high-dose exposure. Evidence of peripheral nerve damage may be detected on elec-trodiagnostic testing, but overt peripheral neuropathy is rare. Acrodynia is an uncommon idiosyncratic reaction to subacute or chronic mercury exposure and occurs mainly in children. It is characterized by painful erythema of the extremities and may be associated with hypertension, diaphoresis, anorexia, insomnia, irritability or apathy, and a miliary rash. Chronic exposure to inorganic mercury salts, sometimes via topical application in cos-metic creams, has been associated with neurological symptoms and renal toxicity in case reports and case series.

Methylmercury intoxication affects mainly the central nervous system and results in paresthesias, ataxia, hearing impairment, dysarthria, and progressive constriction of the visual fields. Signs and symptoms of methylmercury intoxication may first appearseveral weeks or months after exposure begins. Methylmercury is a reproductive toxin. High-dose prenatal exposure to methylmer-cury may produce mental retardation and a cerebral palsy-like syndrome in the offspring. Low-level prenatal exposures to meth-ylmercury have been associated with a risk of subclinical neurode-velopmental deficits.

A 2004 report by the Institute of Medicine’s Immunization Safety Review Committee concluded that available evidence favored rejection of a causal relation between thimerosal-containing vac-cines and autism. In like manner, a recent retrospective cohort study conducted by the CDC did not support a causal association between early prenatal or postnatal exposure to mercury from thimerosal-containing vaccines and neuropsychological functioning later in childhood.

Dimethylmercury is a rarely encountered but extremely neurotoxic form of organomercury that may be lethal in small quantities.

The diagnosis of mercury intoxication involves integration of the history and physical findings with confirmatory laboratory testing or other evidence of exposure. In the absence of occu-pational exposure, the urine mercury concentration is usually less than 5 mcg/L, and whole blood mercury is less than 5 mcg/L. In 1990, the Biological Exposure Index (BEI) Committee of the American Conference of Governmental Industrial Hygienists (ACGIH) recommended that workplace exposures should result in urinary mercury concentrations less than 35 mcg per gram of creatinine and end-of-work-week whole blood mercury concen-trations less than 15 mcg/L. To minimize the risk of developmen-tal neurotoxicity from methylmercury, the US Environmental Protection Agency and the Food and Drug Administration (FDA) have advised pregnant women, women who might become preg-nant, nursing mothers, and young children to avoid consumption of fish with high mercury levels (eg, swordfish) and to limit con-sumption of fish with lower levels of mercury to no more than 12 ounces (340 g, or two average meals) per week.

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