Mercury(Hg) Poisoning

อ.นพ. วรพ�นธ์� เกร�ยงสุ�นทรก�จAmbulatory Pediatrics

Department of Pediatrics

คณะแพทยศาสตร์ ศ�ร์�ร์าชพยาบาล มหาวิ�ทยาล�ยมห�ดล

Minamata disease

Kumamoto Prefecture, 1956

http://www.fda.gov/food/foodborneillnesscontaminants/metals/ucm115644.htm

Top 15 Fish – Mercury Levels

PPM / Oz.

3 forms of mercury Organic: Elemental / inorganic salts organic Hg Inorganic: Hg + other elements compound or salts

used in industry, cosmetic skin creams Elemental Hg inorganic Hg in the body Elemental: quick silver, thermometer, fluorescent light

bulb, electrical switch, dental amalgam

Microorganism in water/ soil

How people are exposed to Hg ? Elemental Hg: breath elemental Hg vapors (dental

office, smelting operation, Hg spilled or released ) Inorganic Hg: Hg salts are used Organic Hg: seafood consumption (fish, shellfish

contaminated with methylmercury), pass through the placenta , breast milk

Elemental (metallic) mercury (Hg0)

Inorganic mercury Mercurous ionCalomel, mercurous chlorideMercuric ionMercuric chloride

Organic mercury MethylmercuryEthylmercuryDimethylmercuryMethoxyethylmercuryPhenylmercury

Pathophysiology Binding to sulfur Replacing hydrogen ion in sulfhydryl groups React with phosphoryl, carboxyl and amide group widespread enzymes dysfunction

Pathophysiology Mercury salt poisoning: necrosis of GI mucosa and

proximal renal tubules (shortly after exposure)Mercurial ointments use: membranous

glomerulonephritis, acrodynia Methyl mercury poisoning:

– fetal Minamata disease: atrophy of the cerebellar hemispheres, postcentral gyri, calcarine area ataxia, sensory neuropathy, visual field constriction

– Less severe in adult

Clinical manifestations Elemental mercury

– Respiratory system: cough, chills, fever, shortness of breath

CXR: interstitial pneumonitis, atelectasis, emphysema, interstitial fibrosis, restrictive lung disease

– GI: N/V, dysphagia, weakness– Headache, visual disturbance– Sub-acute inorganic mercury poisoning: tremor, renal

dysfunction, gingivostomatitis

Elemental mercury Common in occupational setting Max. limit of ambient air concentration 0.9 mg/m3

(0.1 mg/m3) Children is more sensitive to mercury vapor:

minute ventilation to body size Direct aspiration of metallic mercury: massive

endotracheal hemorrhage Vacuuming spilled mercury

Dental amalgamsOccupational exposure: acceptable low Vaporized mercury from chewing: clinically

insignificant Immunologic hypersensitivity: very rare cases

Amalgam (elemental Hg)

"Amalgam is not a true alloy. It is made up of 50% mercury, which is not locked into a set filling but escapes continuously during the entire life of the filling in the form of vapor, ions and abraded particles“

Australasian Society Of Medicine And Toxicology

Amalgam: advantages vs disadvantages

Patient

Durable and cheap Low rate of local side effect No conclusive evidence for

systemic adverse effect

Environmental & health care provider

Decreased exposure due to good conduct and Hg hygiene protocols

Environmental impact of dental amalgam is almost insignificant

J Ir Dent Assoc. 2013 Dec-2014 Jan;59(6):311-7.

Inorganic mercury Ingestion: caustic gastroenteritis, grayish

discoloration of mucous membrane, metallic tasteRenal: oliguria (within 3 days) from proximal

tubular necrosis No report of Hg poisoning form button battery

ingestion

Pediatrics. 1992;89:747–757

Inorganic mercury Chronic toxicity GI: metallic taste, burning sensation in the mouth,

loose teeth, gingivostomatitis NS: tremor, neuroanesthesia, erethism (mad

hatter disease), emotional lability, tunnel vision, insomnia

Renal: reversible proteinuria, nephrotic syndrome Skin: acrodynia or pink disease

Pink disease (acrodynia)

Symptom complex associated with excessive sweating, tachycardia, irritability, anorexia, photophobia, insomnia, tremors, paresthesias, decreased deep-tendon reflexes, and weakness.

Thimerosal (inorganic Hg) 0.1% thimerosal or 600 mcg/mL Hg A preservative in multi-dose vials in areas with in

adequate refrigeration No longer use in the US for routine childhood

vaccines since 2001

Global Alliance for Vaccines and Immunisation.Report to the GAVI Alliance Board Report of the Chief Executive Officer. 2012.Immunol Allergy Clin North Am.2003;23:589–603.

Organic Hg compound Almost purely permanent neurologic diseaseAssociated with methylmercury Lipophilic property Delayed neurotoxicity (weeks to months)Detected in breast milk (30% of blood conc.)

Source and route of organic Hg exposure Seafood FDA limit: 1 ppm for methyl mercury in fish EPA limit: 0.1 mcg/kg/day High blood concentration group in self-reported

high consumers of seafood High risk groups:

– pregnant women or who may become pregnant – nursing mother – young children

Minamata

Decreased wt. and muscle tone Profound developmental delay Seizure Deafness and blindness Severe spasticity

Elemental Inorganic Organic

Primary route of exposure

Inhalation Oral Oral

Primary tissue distribution

CNS, kidney Blood (transient, acute) CNS, kidney, liver, blood, hair

KidneyCNS (delayed)

Clearance Renal, GI Renal, GI Methyl: GIAryl: renal, GI

Clinical effectsCNS Tremor Tremor, erethism Paresthesias, ataxia,

tremor, tunnel vision, dysarthria

Pulmonary +++ – –Gastrointestinal + +++ (caustic) +Renal + +++ (ATN) +Acrodynia + ++ –Therapy BAL, DMSA BAL, DMSA DMSA (early)

Differential characteristics of Hg exposure

Diagnostic testing for Mercury Whole Blood 24-hour Urine Hair Clinical

Elemental/Inorganic (+) (++) (+) (+)

Acute, transient Confirm exposure Reflects past exposure and external adsorption

Poor correlation to total body burden (TBB)

Monitor chelation Early detection

Poor correlation to TBB

Organic (++) (–) (+) (+)Best reflects TBB(N-acetyl-β-D-glucosaminidase, β2-microglobulin)

Fecal elimination Reflects past exposure and external adsorption

Poor correlation to TBB

Reflects irreversible CNS toxicity

Early detection

Hg concentration Overlap of Hg concentration found in the normal

population, asymptomatic exposed individualsNo correlation between either whole blood or

urine mercury concentration and mercury toxicity1.0 μg/L or less for whole blood and 0.5 μg/L for

urine are generally considered to exposure in non-poisoned individuals

Centers for Disease Control and Prevention. Fourth National Report on Human Exposure to Environmental Chemicals. July 26, 2012. 2009.

General management for elemental Hg

Aspiration: postural drainage, ETT suction Localized injection: surgical excision Sweep spilled Hg into tightly sealed container No vacuum for spilled Hg Broken CFL bulb: EPA guideline / local

requirements www.pcd.go.th/info_serv/haz_lamp.htm

Opening window to release vaporAdhesive tape to pick up fragments

General management for inorganic Hg Activated charcoal (AC): substantial adsorption

(800 mcg mercuric chloride: 1 g AC)Whole bowl irrigation with PEG Severe gastroenteritis

– Removal over endoscopic evaluation in suspected penetrating GI mucosal injury

General management for organic Hg Chronic ingestion of contaminated foodAggressive decontamination: acute ingestion,

dermal exposure

Chelation (BAL, DMSA) Thiol groups in chelators compete with

endogenous sulfhydryl groups for the binding of mercury

Preventing inactivation of sulfhydryl-containing enzymes and other essential proteins

Indication: – history of significant mercury exposure with– Presence of typical symptoms of mercury poisoning

Urine or blood concentration: unclear cases, guide the duration of therapy

Summary 3 major forms: elemental, inorganic and organicLarge variety of clinical presentation Neurologic sequelae esp. from organic Hg

exposures : largely irreversible Promotion of public education and awareness

regarding – Danger of Hg – Avoidance – Proper disposal