POTD: Heavy Metals (LLFTP #8)

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Today's POTD will be based on the continuation of one of the cases I mentioned in my previous email. 

Spoilers?

I originally wanted to talk about Latrodectus (Black Widow) envenomation (a patient with Crohn's disease presented with isolated severe abdominal cramping, without any fever or other GI symptoms), but Dr. Ervin already wrote a nice POTD about it back in August. 

Instead, we'll follow the conclusion of Dr. Mohan's case with the altered beauty influencer. The heavy metal panel comes back at the beginning of the episode (seriously impressive turnaround time), and the patient has a mercury level > 90 mcg/L. The ordered treatment is "chelation TID, 10 mL/kg of DMSO" (which is actually a small scripting error, as you'll see below). Done and done, and Dr. Robby gracefully takes his lumps and acknowledges that "Slo-Mo" had handled the case appropriately. 

Let's learn about mercury toxicity as well as some of the other heavy metals that love to appear in test questions! 

Mercury (Hg/Hydrargyrum)

  • 3 common forms — elemental mercury, mercury salts, and organic mercury

    • Elemental — found in devices such as thermometers; volatile and easily aerosolizes, inhalation --> pulmonary, CNS, and renal symptoms

    • Salts — found in batteries, skin cream, dental products; absorbed by GI tract and across skin --> GI and renal symptoms

    • Organic — found in paint, skin cream, fish; absorbed by GI tract and across skin --> neurological symptoms

  • Hg bonds to various functional groups on proteins, leading to widespread dysfunction

  • Hg can cause direct oxidative damage to lung/GI membranes and renal tubules

  • CNS deposition of mercury (more common in elemental and organic mercury exposure) leads to posterior encephalopathy/atrophy --> sensory neuropathies, vision changes/deficits, ataxia

  • Neurological deficits likely longstanding or permanent, especially if chronic/subacute

  • Above symptoms are fairly nonspecific, diagnosis relies on thorough history

  • Supportive care is key, chelation (compounds that bind heavy metal ions, allow excretion) can help lower Hg levels

    • Elemental/salts —  IM dimercaprol 5 mg/kg q4h x 48 hours, then 2.5 mg/kg q6h x 48 hours, then 2.5 mg/kg q12h x 7 days; PLUS PO succimer (DMSA) 10 mg/kg q8h x 5 days, then q12h x 14 days

    • Organic — only succimer (DMSA), as dimercaprol has been shown to increase neurotoxicity

    • For acute ingestions, consider GI decontamination

    • HD can be considered as part of supportive care regimen if there is significant renal impairment, but does not effectively lower Hg levels

    • Exchange transfusions trialed in past with no proven benefit

Lead (Pb/Plumbum)

  • Previously had widespread presence in paint, gasoline (and exhaust), pipes; paint and pipes in older homes continue to be a source today, despite being banned in 1978 and 1986, respectively

    • Leaded gasoline banned in the US in 1996, but fumes could still cause agricultural contamination in imports; worldwide ban achieved in 2021

    • Childhood exposure through exhaust fumes reduced the intelligence (and worsened the health) of many Americans born between the 60's and 90's; i.e. petrol company lobbying and obfuscation (lead toxicity has never been unexpected, it has an older historiography than some modern religions) robbed multiple generations

    • Other exposure sources include industrial occupations, contaminated pewter/ceramics, contaminated spices, contaminated cosmetics, alternative pseudomedical practices, lead bullets

    • Children are at higher risk — they absorb more Pb for their body weight in both ingestion and inhalation, store more Pb in metabolically-active tissue, and excrete less Pb in their urine 

  • Like mercury, lead binds many proteins and inhibits their function, especially calcium and zinc related proteins

    • High blood Pb levels can lead to acute syndrome of lead-induced encephalopathy from cerebral edema --> AMS, seizures, coma, death

    • Chronic toxicity harms neurocognitive development, inhibits RBC production and maintenance ("basophilic stippling" on smear), dysregulates proximal renal tubule function, and impairs sex, growth, and thyroid hormones

  •  Nonspecific multisystemic symptoms, usually at Pb > 10mcg/dL

    • "Asymptomatic" children at risk for IQ loss (highest rate of IQ decrease is at 1 to 10mcg/dL)

    • Children may display irritability, constipation, and/or anorexia 

    • Adults may also have cardiovascular disease, peripheral neuropathy, gout, infertility

    • Levels >70mcg/dL have high risk for lead encephalopathy

  • Careful history is once again key to the path to diagnosis

  • Care is centered around screening and decontamination

    • All children with Medicaid are screened at 12 and 24 months (5mcg/dL is threshold for further testing)

    • All children recommended to be screened by age 3-5 

    • Supportive care (including supplementation with iron, zinc, and calcium)

    • Chelation indicated for levels of >45mcg/dL in children, >70mcg/dL in adults, or any patient with encephalopathy

      • BAL (dimercaprol) + calcium disodium EDTA is most common regimen, +/- succimer

      • Chelation may increase release of Pb from bones, leading to temporary exacerbation of symptoms

    • Developmental deficits from chronic toxicity likely to remain permanent

    • Permanent neurological sequelae from lead encephalopathy also likely 

Iron (Fe/Ferrum)

  • Easily available as an OTC dietary supplement, ingestion of such is the primary exposure

    • 325mg ferrous sulfate contains 65mg elemental iron

    • 300mg ferrous gluconate contains 36mg elemental iron

    • 100mg ferrous fumarate contains 33mg elemental iron

    • For prenatal vitamins and children's vitamins, check label/manufacturer's site

    • Ingestion of >20 mg/kg associated with moderate toxicity

    • Ingestion of >60 mg/kg associated with severe toxicity

  • Less commonly, iron toxicity can result from multiple transfusions for leukemia, thalassemia, etc.

  • Toxicity divided into two mechanisms

    • Caustic/corrosive effect results in direct injury to GI mucosa, can lead to perforation, peritonitis --> hemorrhage, death

      • Typically occurs during the first 6 hours

      • Iron tablets are visible on XR

    • Cellular toxicity is due to disruption of oxidative phosphorylation in the mitochondria, free radical formation and oxidative damage

      • GI symptoms may resolve prior to appearance of systemic symptoms

      • Nephropathy, cardiomyopathy, hepatopathy, and coagulopathy follow

      • Serum Fe levels >350μg/dL associated with moderate symptoms, >500μg/dL associated with severe symptoms

  • Treatment indicated for those a) with symptoms, or b) who have ingested potentially toxic quantities

    • Patients with resolved GI symptoms should continue observation/care for emergence of systemic symptoms

    • Decontamination with WBI indicated if large amount of pills are visible on XR

    • Patients with severe symptoms (acidosis, hemodynamic compromise) or high serum Fe level should receive deferoxamine chelation at 15 mg/kg/hr (max 35 mg/kg/hr) for up to 24 hours (or up to 6g)

    • Can give VitK and FFP to treat coagulopathy

    • Otherwise, supportive care as appropriate

Copper (Cu/Cuprum)

  • Exposure is most commonly from copper-containing cookware, contaminated water, or copper-containing pesticides or creams

  • Wilson's disease is also associated with high bioaccumulation of copper

  • Ingestions, like with iron, cause a direct gastropathy resulting in abdominal pain, vomiting, GI bleeding, et al. w/ potential for blue-green emesis (think how copper-containing surfaces like the Statue of Liberty develop verdigris)

  • High serum levels of copper can lead to:

    • Neuro — cognitive changes, encephalopathy

    • Cardiac — cardiomyopathy

    • Hepatic — necrosis

    • Heme — coagulopathy, hemolysis, methemoglobinemia 

    • Renal — rhabdomyolysis, AKI

  • Treatment, again, is mostly supportive + decon/chelation

    • High-dose zinc can help lower GI absorption 

    • Classically, D-penicillamine is the chelating agent of choice, given at a starting dose of 750mg QID

    • Can also use "single pass albumin dialysis" vs other extracorporeal cupriuresis

    • Symptoms generally reversible with successful elimination of copper

Other little lessons from episode #8:

  • If you have a backyard pool, invest in locked rigid covers and alarms, because otherwise the kids will find a way to get in

  • You're not dead until you're warm and dead — unless you're in rigor mortis, have obvious traumatic injuries incompatible with life, have snow in your airway after being buried by snow, or have a K > 12

  • If you lose any part of your body, to maximize the chances of replantation, you or someone else (if you're unstable) should retrieve it, wrap it in a moist towel/napkin/cloth, place it in a plastic bag, then put that plastic bag on ice

  • Peter Safar, the University of Pittsburgh, and the Freedom House Ambulance Service are the progenitors of the modern EMS model — a public service staffed by trained personnel tthat can provide care en route to the hospital, as opposed to a taxi service

  • Have a high index of suspicion for human trafficking (and/or other forms of abuse) when the patient is accompanied by someone who answers questions for them and refuses to allow a private history/exam; do your best to finagle a private conversation and assess safety, and consult social work to help provide resources if needed

References:
https://www.ncbi.nlm.nih.gov/books/NBK560920/
https://www.ncbi.nlm.nih.gov/books/NBK499935/
https://www.ncbi.nlm.nih.gov/books/NBK541097/
https://www.ncbi.nlm.nih.gov/books/NBK459224/
https://www.ncbi.nlm.nih.gov/books/NBK557456/

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