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/