Ver el código de «Heavy metal toxicity»

Heavy metal toxicity results from exposure to metals like lead, mercury, arsenic, or cadmium, which interfere with cellular function. Exposure may occur occupationally, environmentally, through ingestion, or from alternative medicines. Chronic toxicity can present insidiously, while acute toxicity may mimic [[sepsis]] or [[encephalopathy]]. Diagnosis is often delayed due to nonspecific symptoms.

==Background==
*Heavy metals exert toxicity by binding sulfhydryl groups on enzymes and proteins, generating reactive oxygen species, and displacing essential metals from metalloenzymes<ref name="Goldfrank">Nelson LS, et al. ''Goldfrank's Toxicologic Emergencies''. 11th ed. McGraw-Hill; 2019.</ref>
*Pathophysiology is a combination of type III (immune complex) and direct cellular toxicity depending on the specific metal
*Routes of exposure:
**Occupational: Mining, smelting, battery manufacturing/recycling, painting, welding, electronics, jewelry making, plumbing, agriculture (pesticides)
**Environmental: Contaminated water (arsenic, lead), soil, air pollution, proximity to industrial sites
**Ingestion: Ayurvedic and traditional/herbal medicines (up to 20% of Ayurvedic preparations contain detectable lead, mercury, or arsenic),<ref name="Saper">Saper RB, et al. Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the internet. ''JAMA''. 2008;300(8):915-923.</ref> folk remedies (azarcon, greta, surma, kohl), contaminated food, retained bullet/shrapnel fragments
**Inhalation: Metal fumes (welding, smelting), dust, volatile compounds (organic mercury)
**Iatrogenic: Gadolinium (MRI contrast), cisplatin, gold (chrysotherapy), bismuth subsalicylate overuse
*Most common heavy metal poisonings seen in the ED:
**[[Lead toxicity]] — most common chronic heavy metal poisoning worldwide; children disproportionately affected (lead paint, contaminated water, soil)
**[[Iron toxicity]] — most common cause of pediatric poisoning death from metals (accidental supplement ingestion)
**[[Arsenic toxicity]] — groundwater contamination, pesticides, homicidal/suicidal ingestion
**[[Mercury toxicity]] — occupational (thermometers, dental amalgam), dietary (methylmercury in fish), folk remedies
*Cigarette smoking increases cadmium and lead body burden<ref name="Goldfrank"/>
*Multiple metals may be present simultaneously (e.g., Ayurvedic preparations, environmental contamination, e-waste recycling workers)

==Clinical Features==
Symptoms depend on the metal, dose, route, and duration of exposure but may include:

*Neurologic: Peripheral neuropathy (classically motor in lead; sensory in arsenic and thallium), confusion, tremor, [[encephalopathy]], [[seizures]], ataxia, cognitive decline, irritability, psychosis
*GI: Abdominal pain (often colicky), nausea, vomiting, diarrhea (rice-water diarrhea in arsenic; bloody diarrhea in iron), anorexia, metallic taste, gingival lead lines (Burton lines)
*Heme: Anemia (microcytic sideroblastic in lead; hemolytic in arsenic, copper), basophilic stippling (lead — impaired RNA degradation), coagulopathy
*Renal: Acute tubular necrosis, proximal tubular dysfunction, [[Fanconi syndrome]] (cadmium, lead, mercury), proteinuria, chronic kidney disease
*Dermatologic: Mees' lines on nails (arsenic, thallium), hyperpigmentation (arsenic — "raindrop" pattern), diffuse alopecia (thallium — hallmark; also arsenic), contact dermatitis (nickel, chromium), argyria (silver — blue-gray skin)
*Cardiovascular: [[Hypertension]] (lead, cadmium), [[QT prolongation]] (arsenic, thallium, cesium), cardiomyopathy (cobalt — "beer drinker's cardiomyopathy"), dysrhythmias
*Pulmonary: Chemical pneumonitis (metal fume inhalation — zinc, cadmium, mercury vapor, beryllium), [[ARDS]], pulmonary fibrosis (beryllium, cobalt)
*Hepatic: Hepatotoxicity (iron, copper, arsenic, phosphorus)
*Other: Fatigue, weight loss, immunosuppression, developmental delay and IQ loss in children (lead), garlic breath odor (arsenic, organophosphates, selenium, thallium, phosphorus)

{| class="wikitable"
|-
! Metal !! Classic/Distinguishing Features
|-
| '''[[Lead toxicity|Lead]]''' || Basophilic stippling, lead lines on gingiva, wrist/foot drop, abdominal colic, microcytic anemia, encephalopathy in children, radiopaque material on AXR
|-
| '''[[Arsenic toxicity|Arsenic]]''' || Rice-water diarrhea, Mees' lines, garlic breath, raindrop hyperpigmentation, painful sensory neuropathy, QT prolongation, pancytopenia
|-
| '''[[Mercury toxicity|Mercury]]''' || Erethism (irritability, insomnia, shyness), intention tremor, gingivostomatitis, acrodynia (pink disease — children), nephrotic syndrome (inorganic), Minamata disease (organic)
|-
| '''[[Thallium toxicity|Thallium]]''' || '''Alopecia''' (hallmark — appears 2–3 weeks), painful ascending neuropathy, GI symptoms, combined sensory-motor neuropathy, tachycardia
|-
| '''[[Iron toxicity|Iron]]''' || Five stages: (1) GI hemorrhage, (2) latent/quiescent, (3) shock/metabolic acidosis, (4) hepatotoxicity, (5) GI scarring/obstruction
|-
| '''[[Cadmium toxicity|Cadmium]]''' || Itai-itai disease (osteomalacia + renal failure), chemical pneumonitis from fume inhalation, renal tubular dysfunction, '''no effective chelation'''
|-
| '''[[Cobalt toxicity|Cobalt]]''' || Cardiomyopathy, polycythemia, thyroid dysfunction, hip prosthesis failure ("arthroprosthetic cobaltism")
|}

==Differential Diagnosis==
*[[Sepsis]] or systemic inflammatory response
*Drug toxicity or overdose (especially organophosphates, which share garlic breath and cholinergic symptoms)
*Metabolic disorders (e.g., [[porphyria]], [[uremia]], [[Wilson disease]])
*Psychiatric illness (if symptoms are vague or bizarre)
*Neurologic diseases (e.g., [[Guillain-Barré syndrome]], [[multiple sclerosis]], [[Parkinson's disease]], [[amyotrophic lateral sclerosis]])
*[[Vitamin deficiencies]] (e.g., B12, thiamine, folate)
*Autoimmune conditions (vasculitis, [[sarcoidosis]])
*Malignancy (paraneoplastic syndromes may mimic neuropathy and constitutional symptoms)
*[[Alcohol withdrawal]] or [[Wernicke encephalopathy]]
*Organic dust toxic syndrome or [[hypersensitivity pneumonitis]] (for inhalational exposures)

==Evaluation==
===Workup===
History (the most important diagnostic tool):
*Occupation and workplace exposures (current and past)
*Hobbies (ceramics/pottery glazing, stained glass, target shooting, fishing sinker casting, jewelry making, painting)
*Home environment (age of house, peeling paint, renovation, water source, nearby industry)
*Diet (game meat from lead shot, imported spices, rice from arsenic-contaminated regions, high-mercury fish)
*Medications and supplements: Specifically ask about herbal/traditional/Ayurvedic remedies, imported cosmetics (kohl, surma), folk remedies (azarcon, greta, litargirio, pay-loo-ah)<ref name="Saper"/>
*Pica or geophagia (especially in children and pregnant women)
*Retained bullet or shrapnel fragments
*Multiple household members or coworkers with similar symptoms (cluster exposure)

Laboratory:
*CBC with differential and peripheral smear (basophilic stippling, microcytic anemia, hemolysis)
*CMP (renal function, hepatic function, electrolytes, glucose)
*Urinalysis (proteinuria, glycosuria — Fanconi syndrome)
*Specific metal levels based on clinical suspicion:
**Blood lead level (venous, not capillary for confirmation) — CDC reference value: 3.5 µg/dL in children; clinical action varies by level
**'''Spot urine arsenic''' (24-hour urine preferred; must avoid seafood for 48 hours prior to testing as organic arsenicals in seafood cause false elevations)
**Whole blood mercury (organic/methylmercury) and/or urine mercury (inorganic/elemental mercury)
**Urine cadmium and blood cadmium
**Urine thallium
*Serum iron and TIBC for [[iron toxicity]]
*Free erythrocyte protoporphyrin (FEP) or zinc protoporphyrin (ZPP) — elevated in chronic lead exposure (screening tool, not diagnostic)
*Reticulocyte count
*Coagulation studies (PT/INR if hepatotoxicity suspected)
*Lactate, VBG/ABG (metabolic acidosis in iron, arsenic)
*Type and screen if significant GI bleeding or hemolysis anticipated
*'''Urine heavy metal panel:''' available but has significant limitations — interpretation requires creatinine correction; "provoked" or post-chelation urine testing is '''unreliable and not recommended'''<ref name="ACMT">American College of Medical Toxicology. Position statement on post-chelator challenge urinary metal testing. ''J Med Toxicol''. 2010;6(1):74-75.</ref>

Imaging:
*Abdominal X-ray: May show radiopaque material in the GI tract (lead, arsenic, iron, mercury, thallium) — obtain in acute ingestion or pediatric lead exposure<ref name="Goldfrank"/>
*Long bone radiographs (pediatric): "Lead lines" (dense metaphyseal bands) indicate chronic lead exposure in growing children (not diagnostic but supportive)
*Chest X-ray: pulmonary infiltrates in metal fume inhalation (cadmium, mercury vapor, zinc)

EKG:
*[[QT prolongation]]: Arsenic, thallium, cesium — risk of [[torsades de pointes]]
*Dysrhythmias (cobalt → cardiomyopathy; iron → shock with widened QRS)
*Obtain in all symptomatic patients and all suspected acute ingestions

===Diagnosis===
*Confirmed by elevated blood or urine levels of the specific metal in the context of compatible clinical findings<ref name="Goldfrank"/>
*Hair and nail testing are unreliable for acute toxicity and not recommended for clinical decision-making (subject to external contamination, no standardized reference ranges)
*Interpret results with '''toxicologist or Poison Control input''' whenever possible — reference ranges and clinical significance vary by metal, specimen type, and laboratory
*Provoked (post-chelation challenge) urine testing is NOT recommended by ACMT and should not be used to diagnose heavy metal toxicity<ref name="ACMT"/>
*Consider the diagnosis in any patient with unexplained multisystem disease — particularly the combination of neuropathy + anemia + abdominal pain + renal dysfunction

==Management==
*Remove the source of exposure — this is the single most important intervention (occupational controls, GI decontamination if recent ingestion, removal from contaminated environment, discontinue offending supplement/remedy)
*GI decontamination (acute ingestions):
**Whole bowel irrigation (GoLYTELY) is the preferred method for ingested metals seen on AXR (lead, iron, arsenic) — activated charcoal does NOT bind metals effectively<ref name="Goldfrank"/>
**Consider gastric lavage only if very early presentation with large ingestion
**Endoscopic or surgical removal for retained lead foreign bodies (fishing sinkers, bullets in stomach/intestine)
*Supportive care: IV fluids (aggressive hydration for renal protection), seizure control ([[benzodiazepines]]), electrolyte repletion, blood transfusion for severe anemia or GI hemorrhage
*Chelation therapy (in consultation with toxicology or Poison Control — 1-800-222-1222):

{| class="wikitable"
|-
! Metal !! Chelation Agent(s) !! Key Notes
|-
| '''[[Lead toxicity|Lead]]''' (adults BLL ≥45 µg/dL symptomatic; children ≥45 µg/dL) || Succimer (DMSA) PO; CaNa2-EDTA IV; Dimercaprol (BAL) IM || Encephalopathy or BLL >70 (children) / >100 (adults): start BAL IM first, then add CaNa2-EDTA 4 hours later; '''never give EDTA before BAL''' in encephalopathy (may worsen CNS lead levels)
|-
| '''[[Arsenic toxicity|Arsenic]]''' || Dimercaprol (BAL) IM; Succimer (DMSA) PO || BAL for acute symptomatic; DMSA for chronic or mild-moderate; '''unithiol (DMPS)''' is an alternative (not FDA-approved)
|-
| '''[[Mercury toxicity|Mercury]]''' (inorganic/elemental) || Succimer (DMSA) PO; Dimercaprol (BAL) IM || BAL is '''contraindicated in organic/methylmercury''' (increases CNS mercury deposition); use DMSA instead
|-
| '''[[Gold toxicity|Gold]]''' || Dimercaprol (BAL) IM || Used for gold-induced cytopenia or severe mucocutaneous reactions
|-
| '''[[Iron toxicity|Iron]]''' || '''Deferoxamine''' IV || Not a traditional chelator; specific iron chelation; indicated for significant iron poisoning with metabolic acidosis, shock, or serum iron >500 µg/dL
|-
| '''[[Copper toxicity|Copper]]''' / [[Wilson disease]] || Penicillamine PO; Trientine PO || Dimercaprol for acute severe cases
|-
| '''[[Thallium toxicity|Thallium]]''' || '''Prussian blue''' (ferric hexacyanoferrate) PO || Traps thallium in the GI tract preventing enterohepatic recirculation; '''not a traditional chelator'''; also use multidose activated charcoal
|-
| '''[[Cadmium toxicity|Cadmium]]''' || '''No effective chelation''' || Supportive care only; BAL is '''contraindicated''' (dimercaprol-cadmium complex is more nephrotoxic than cadmium alone)
|}

*Key chelation cautions:
**'''Dimercaprol (BAL):''' Formulated in '''peanut oil''' — contraindicated in peanut allergy; causes hypertension, tachycardia, painful IM injections, fever in ~30% of children; contraindicated in hepatic insufficiency and G6PD deficiency (hemolysis risk)<ref name="BAL">Dimercaprol. ''StatPearls''. NCBI Bookshelf. Updated August 2023.</ref>
**'''CaNa2-EDTA:''' Must use '''calcium disodium''' salt — disodium EDTA (Endrate) causes fatal [[hypocalcemia]] and cardiac arrest; always verify the correct formulation<ref name="EDTA">Ethylenediaminetetraacetic Acid (EDTA). ''StatPearls''. NCBI Bookshelf. Updated June 2023.</ref>
**Succimer (DMSA): Oral, generally well tolerated; may cause transaminase elevation and neutropenia; FDA-approved only for pediatric lead poisoning but used off-label for other metals
**All chelators can redistribute metals — treatment protocols involve scheduled courses with rest periods between courses
*'''Notify local/state public health authorities''' if exposure source is environmental or occupational (reportable in most jurisdictions)
*Contact Poison Control (1-800-222-1222) early — even before lab confirmation — for chelation guidance, dosing, and disposition planning

==Disposition==
*Admit if:
**Symptomatic (encephalopathy, seizures, hemodynamic instability, significant GI hemorrhage, acute renal failure)
**Requiring parenteral chelation therapy (BAL, CaNa2-EDTA, deferoxamine)
**Suspected acute intentional ingestion (suicidal, homicidal)
**Radiopaque material on AXR requiring whole bowel irrigation
**Pediatric lead level ≥45 µg/dL or any level with symptoms
**[[QT prolongation]] or dysrhythmia
*Discharge may be appropriate for:
**Asymptomatic patients with low-level chronic exposure and confirmed outpatient follow-up
**Mildly symptomatic patients started on oral chelation (succimer) with reliable follow-up within 24–48 hours
*Arrange:
**Toxicology or occupational/environmental medicine follow-up for source identification, remediation, and serial metal level testing
**Public health notification for environmental or occupational exposures
**Developmental assessment referral for children with elevated lead levels
**Household/workplace contact screening when environmental source identified

==See Also==
{{Heavy metals list}}

==External Links==
*[https://www.ncbi.nlm.nih.gov/books/NBK560920/ Heavy Metal Toxicity — StatPearls]
*[https://www.poison.org/articles/chelation-therapy Chelation Therapy — Poison Control]
*[https://www.cdc.gov/lead-prevention/about/index.html Lead Poisoning Prevention — CDC]
*[https://www.atsdr.cdc.gov/toxprofiles/ Toxicological Profiles — ATSDR]
*[https://emedicine.medscape.com/article/814960-overview Heavy Metal Toxicity — Medscape]

==References==
<references/>

[[Category:Toxicology]]