Toxicology – Mercury Poisoning

Sources

Mercury exists in several forms, and toxicity depends strongly on the form and route of exposure.

• Elemental mercury: thermometers, some older thermostats, dental amalgam, industrial processes, and gold extraction
• Inorganic mercury salts: some industrial chemicals, older disinfectants, pigments, and manufacturing processes
• Organic mercury compounds: especially methylmercury, which can accumulate in large predatory fish

Typical Presentation

A person with chronic occupational mercury exposure may develop:

• Tremor
• Irritability or personality change
• Memory problems
• Excessive sweating
• Gingivitis or inflammation of the mouth

Clinical Features

Elemental mercury vapor inhalation

• Cough
• Dyspnea
• Chemical pneumonitis
• Noncardiogenic pulmonary edema in severe exposure

Chronic vapor exposure can produce the classic combination of:

• Neuropsychiatric changes
• Tremor
• Gingivostomatitis

Neuropsychiatric symptoms may include irritability, insomnia, poor concentration, memory impairment, and emotional instability.

Inorganic mercury salts

Ingestion can cause:

• Severe nausea and vomiting
• Abdominal pain
• Hemorrhagic gastroenteritis
• Acute tubular injury
• Acute kidney failure

Chronic exposure can also produce neurologic abnormalities.

Organic mercury

Methylmercury primarily damages the nervous system and may cause:

• Paresthesias
• Ataxia
• Tremor or other movement abnormalities
• Visual impairment
• Hearing impairment
• Hyperreflexia
• Cognitive dysfunction

Developing fetuses and young children are particularly vulnerable to the neurologic effects of methylmercury.

Mechanism of Action

Mercury binds strongly to sulfhydryl groups in proteins.

This interferes with:

• Enzyme activity
• Cellular metabolism
• Membrane function
• Antioxidant defenses

The nervous system and kidneys are major targets of toxicity.

Management

Treatment includes:

• Immediate removal from the exposure source
• Supportive care
• Respiratory support for severe inhalational injury
• Renal monitoring after significant inorganic mercury exposure

Chelation may be considered in clinically significant poisoning, commonly with agents such as:

• Succimer (DMSA)
• DMPS

Choice of therapy depends on the mercury compound, exposure severity, symptoms, and specialist guidance.

Key Points

• Mercury toxicity differs markedly between elemental, inorganic, and organic forms.
• Swallowed liquid elemental mercury is poorly absorbed from an intact GI tract, whereas inhaled mercury vapor can be highly toxic.
• Chronic elemental mercury exposure classically causes tremor + neuropsychiatric changes + gingivostomatitis.
• Inorganic mercury mainly causes severe GI and renal toxicity.
• Methylmercury predominantly causes neurologic toxicity.
• Significant suspected mercury poisoning should be discussed with a medical toxicologist or poison center.

Toxicology – Lead Poisoning

Sources

Common sources of lead exposure include:

• Older lead-based paint and contaminated household dust
• Batteries
• Ceramics and pottery glazes
• Plumbing and contaminated water
• Certain toys, jewelry, figurines, and imported products
• Some traditional or nonstandard medicines
• Occupational or industrial exposure

Typical Presentation

A child living in an older home may present with:

• Developmental delay
• Learning difficulties
• Behavioral problems
• Fatigue
• Vague abdominal complaints

Chronic exposure is often subtle and may be discovered only after screening.

Clinical Features

Acute lead toxicity may cause:

• Nausea and vomiting
• Abdominal pain
• Diarrhea
• Hemolysis
• Acute kidney injury
• Severe neurologic toxicity in major exposures

Chronic lead toxicity may cause:

• Recurrent abdominal pain
• Constipation
• Fatigue
• Headache
• Cognitive and learning impairment
• Behavioral changes
• Anemia
• Peripheral neuropathy
• Motor weakness, including wrist drop

Children are particularly vulnerable to the neurodevelopmental effects of lead.

Mechanism of Action

Lead disrupts multiple cellular processes and can damage several organ systems, especially:

• Central and peripheral nervous systems
• Kidneys
• Bone and bone marrow
• Gastrointestinal tract
• Cardiovascular system

It also interferes with enzymes involved in heme synthesis, contributing to anemia.

Laboratory Findings

Diagnosis is based primarily on an elevated blood lead level.

Other possible findings include:

• Microcytic or normocytic anemia
• Basophilic stippling on peripheral blood smear
• Increased erythrocyte protoporphyrin in significant chronic exposure

These findings support the diagnosis but are not as specific as the blood lead concentration.

Characteristic Findings

Classic but less commonly seen findings include:

• Burton lines: blue-gray discoloration along the gingival margin
• Lead lines: dense metaphyseal bands seen on radiographs of growing bones in chronically exposed children

Management

The most important intervention is to identify and eliminate the source of exposure.

Chelation may be required for significant poisoning. Agents used include:

• Succimer (DMSA)
• Calcium disodium EDTA
• Dimercaprol in selected severe cases

The choice of chelator depends on the blood lead level, symptoms, and severity of toxicity. Severe neurologic toxicity requires urgent specialist management.

Key Points

• Children are especially susceptible to lead-related cognitive and developmental injury.
• Chronic poisoning may present with abdominal pain, constipation, anemia, and behavioral or learning problems.
• Basophilic stippling is a classic clue but is not diagnostic by itself.
• Treatment begins with removal of the exposure source.
• Chelation is reserved for sufficiently elevated blood lead levels or clinically significant poisoning.

Toxicology – Iron Poisoning

Source

Iron poisoning most commonly occurs from ingestion of iron-containing medications or supplements, such as ferrous sulfate or ferrous gluconate. Young children are particularly vulnerable because tablets may resemble candy.

Typical Presentation

A child with significant iron ingestion may develop:

• Repeated vomiting
• Abdominal pain
• Diarrhea
• GI bleeding
• Lethargy
• Metabolic acidosis

Severe poisoning can progress to shock, liver injury, coma, and death.

Clinical Features

Severity depends mainly on the amount of elemental iron absorbed.

Milder toxicity commonly causes:

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea

More severe toxicity may cause:

• Hematemesis or GI bleeding
• Dehydration and hypovolemia
• Hypotension and shock
• Metabolic acidosis
• Altered mental status
• Hepatic failure
• Coma

Marked acidosis and very high serum iron concentrations suggest more serious poisoning.

Stages of Toxicity

1. GI Phase – first several hours
2. Vomiting, diarrhea, abdominal pain, and possible GI bleeding.
3. Latent Phase – roughly 6–24 hours
4. GI symptoms may temporarily improve even though systemic toxicity continues. Tachycardia, lethargy, and metabolic acidosis may persist.
5. Shock Phase – about 12–24 hours
6. Hypotension, vasodilation, impaired cardiac output, and circulatory collapse may develop.
7. Hepatic Phase – approximately 2–3 days
8. Severe poisoning can produce acute hepatotoxicity and liver failure.
9. Late GI Scarring – weeks later
10. Healing gastrointestinal injury can produce strictures and, in some cases, gastric outlet obstruction.

Mechanism of Action

Normally, iron is carried in the blood bound to transferrin. In overdose, transferrin becomes saturated and excess free iron circulates.

Free iron:

• Directly damages the gastrointestinal mucosa
• Disrupts mitochondrial energy production
• Generates oxidative injury
• Damages blood vessels and solid organs

This contributes to acidosis, shock, and hepatic injury.

Management

Treatment is primarily supportive and may include:

• Airway and cardiovascular stabilization
• IV fluids for dehydration or shock
• Monitoring of serum iron, electrolytes, acid-base status, glucose, and liver function
• Abdominal imaging in selected cases because some iron tablets are radiopaque
• Whole bowel irrigation when substantial tablets remain in the GI tract and toxicology guidance supports it

Activated charcoal is ineffective because it does not meaningfully bind iron.

Deferoxamine is the specific iron chelator and may be used for patients with severe clinical toxicity or other findings suggesting substantial systemic iron poisoning.

Key Points

• Think of the classic progression: GI symptoms → temporary improvement → shock → liver injury → possible late GI stricture.
• A symptom-free interval does not guarantee recovery.
• Activated charcoal does not work for iron.
• Deferoxamine binds circulating free iron in severe poisoning.
• Some iron tablets may be visible on plain abdominal radiographs.

Toxicology – Cadmium Poisoning

Source

Cadmium exposure is usually occupational and may occur during:

• Welding
• Soldering
• Electroplating
• Mining and smelting of zinc, copper, or lead

Other possible sources include nickel–cadmium batteries, ceramic pigments and glazes, and some metal-containing consumer products.

Typical Presentation

A worker exposed to cadmium fumes may initially develop a flu-like illness several hours later, with fever, chills, muscle aches, and dry cough. Despite an initially mild examination, severe lung injury can develop later.

Clinical Features

Inhaled cadmium is particularly dangerous because it can cause delayed pulmonary toxicity.

Acute inhalation may lead to:

• Fever and chills
• Myalgia
• Dry cough
• Shortness of breath
• Chemical pneumonitis
• Pulmonary edema
• Acute respiratory distress syndrome (ARDS)
• Respiratory failure

The early flu-like syndrome is sometimes called the “cadmium blues.”

Acute ingestion may cause severe gastrointestinal irritation and injury.

Chronic Toxicity

Long-term exposure may cause:

• Renal tubular dysfunction
• Bone disease, including osteomalacia
• Neurologic abnormalities
• Increased cancer risk

Mechanism of Action

Cadmium is a toxic metal that binds to cellular proteins and interferes with normal enzyme and cellular functions. It also promotes oxidative injury.

The protein metallothionein can bind cadmium and reduce its immediate toxicity, but cadmium–metallothionein complexes can accumulate in the kidneys and contribute to chronic renal injury.

Management

Treatment is primarily supportive:

• Immediate removal from exposure
• Respiratory support as needed
• Monitoring for delayed pulmonary edema and ARDS
• Renal and electrolyte monitoring

There is no well-established chelation therapy for cadmium poisoning, and some chelators may worsen toxicity. Management should involve a medical toxicologist or poison center.

Key Points

• Inhalation of cadmium fumes can cause delayed, severe lung injury.
• Early symptoms may resemble metal fume fever but can progress to respiratory failure.
• Chronic exposure primarily damages the kidneys and bones.
• BAL (dimercaprol) is generally avoided because it may increase renal toxicity.
• Significant suspected exposure warrants careful observation because pulmonary deterioration may be delayed.

Here’s the paraphrased study-note version:

135. Toxicology – Metal Fume Fever

Source

Metal fume fever is an acute illness caused by inhalation of metal oxide fumes, classically zinc oxide. It is most often seen in welders, smelters, and others who work with heated metals.

Typical Presentation

A worker develops a flu-like illness several hours after welding or similar metal exposure. Symptoms may recur after time away from work, such as after a weekend, and then become less severe with repeated daily exposure.

This pattern is sometimes called “Monday fever.”

Mechanism of Action

The exact mechanism is not fully understood. It appears to involve an inflammatory response in the lungs rather than a true allergic reaction.

Repeated exposure can produce temporary tolerance, but this tolerance may fade after a period away from work.

Clinical Features

Symptoms usually begin within a few hours of exposure and may include:

• Fever
• Chills
• Malaise
• Headache
• Muscle aches
• Nausea
• Cough
• Shortness of breath
• Chest discomfort

Chest X-rays are often normal.

Management

Treatment is mainly supportive:

• Remove the patient from further exposure
• Rest and hydration
• Symptomatic treatment for fever and discomfort
• Evaluate for other causes if symptoms are severe, prolonged, or atypical

Most cases resolve spontaneously within a short period.

Key Points

• Classically associated with zinc oxide fumes from welding.
• Symptoms resemble an acute viral illness.
• Onset is usually several hours after exposure.
• Temporary tolerance can develop with repeated exposure and disappear after time away.
• Prevention depends on proper ventilation and occupational respiratory protection.

Toxicology – Extrapyramidal Side Effects (EPS)

Definition

Extrapyramidal side effects are drug-induced movement disorders caused mainly by dopamine-blocking medications. They can occur at normal therapeutic doses.

Common Causes

EPS can occur with many antipsychotic drugs, but they are more common with first-generation (typical) antipsychotics, especially:

• Butyrophenones
• Phenothiazines

They may also occur with other dopamine-blocking drugs.

Mechanism of Action

EPS result from dopamine D₂ receptor blockade in the basal ganglia, especially within the nigrostriatal pathway.

Reduced dopamine activity disrupts normal motor control and produces several characteristic movement disorders.

Clinical Features

The type of EPS often depends on how long the patient has been taking the medication.

• Acute dystonia: Usually occurs early. Causes sustained involuntary muscle contractions, abnormal posturing, neck or facial spasms, and sometimes tongue or jaw involvement.
• Akathisia: A feeling of intense inner restlessness with an inability to remain still.
• Drug-induced parkinsonism: May develop after weeks to months and can cause bradykinesia, shuffling gait, tremor, and cogwheel rigidity.
• Tardive dyskinesia: Usually appears after prolonged treatment and causes repetitive involuntary movements, especially of the mouth, lips, tongue, and face. It may persist even after the drug is stopped.

Management

Treatment depends on the specific movement disorder.

Common approaches include:

• Reducing or stopping the offending medication when appropriate
• Diphenhydramine or benztropine for acute dystonia and some parkinsonian symptoms
• Benzodiazepines in selected cases
• Beta-blockers such as propranolol for akathisia

Tardive dyskinesia requires a different long-term management approach and may be treated with medications that reduce abnormal dopamine signaling, such as VMAT2 inhibitors.

Key Points

• EPS are caused by dopamine blockade in the basal ganglia.
• Acute dystonia and akathisia tend to occur early.
• Parkinsonism usually develops later.
• Tardive dyskinesia is associated with long-term exposure and may be irreversible.
• EPS and neuroleptic malignant syndrome can both occur during therapeutic antipsychotic use, but NMS is distinguished by fever, autonomic instability, altered mental status, and severe rigidity.

Toxicology – Neuroleptic Malignant Syndrome (NMS)

Definition

Neuroleptic malignant syndrome is a life-threatening reaction associated with severe dopamine blockade. It is classically characterized by:

• Hyperthermia
• Altered mental status
• Autonomic instability
• Severe muscle rigidity

It can occur even at therapeutic antipsychotic doses and often evolves over 1–3 days.

Common Causes

NMS is most often associated with:

• Antipsychotic medications, especially potent dopamine antagonists
• Rapid dose escalation
• Parenteral antipsychotic use
• Abrupt withdrawal of dopaminergic therapy in patients with Parkinson disease

Mechanism of Action

The syndrome is thought to result from marked reduction in dopamine activity, particularly in the hypothalamus and basal ganglia.

This leads to:

• Impaired temperature regulation
• Severe muscle rigidity
• Autonomic dysfunction
• Altered mental status

Clinical Features

Typical findings include:

• High fever
• Tachycardia
• Hypertension or labile blood pressure
• Tachypnea
• Diaphoresis
• Confusion or decreased consciousness
• “Lead-pipe” muscular rigidity
• Bradykinesia
• Leukocytosis
• Elevated creatine kinase (CK)
• Rhabdomyolysis

Complications can include acute kidney injury, dysrhythmias, respiratory failure, and shock.

Differential Diagnosis

Important mimics include:

• Serotonin syndrome
• Malignant hyperthermia
• Anticholinergic toxicity
• Sympathomimetic toxicity
• Severe infection or encephalopathy

A useful distinction is:

• NMS: lead-pipe rigidity, bradykinesia, elevated CK, slower onset
• Serotonin syndrome: clonus, hyperreflexia, GI symptoms, faster onset
• Anticholinergic toxicity: dry skin and mucous membranes rather than diaphoresis

Management

Treatment is mainly supportive:

• Immediately stop the offending dopamine-blocking drug
• Airway and cardiovascular support as needed
• IV fluids
• Active cooling for hyperthermia
• Benzodiazepines for agitation

Additional therapies sometimes used in severe cases include:

• Dantrolene to reduce muscle rigidity and heat production
• Bromocriptine or another dopamine agonist to restore dopaminergic activity

Close monitoring is needed for rhabdomyolysis, renal injury, electrolyte disturbances, and cardiac complications.

Key Points

• Think of fever + rigidity + autonomic instability + altered mental status.
• Lead-pipe rigidity strongly favors NMS over serotonin syndrome.
• CK elevation and rhabdomyolysis are common.
• Early recognition and withdrawal of the causative drug are critical.
• Symptoms often develop over days rather than within a few hours.

Toxicology – Serotonin Syndrome

Definition

Serotonin syndrome is a potentially serious condition caused by excessive serotonergic activity in the central nervous system. It can occur after increasing the dose of a serotonergic medication, taking an overdose, or combining multiple drugs that increase serotonin.

Common Causes

Drugs associated with serotonin syndrome include:

• SSRIs
• SNRIs
• MAO inhibitors
• Tricyclic antidepressants
• Triptans
• Lithium
• Certain opioids such as meperidine or tramadol
• Cocaine and other stimulants
• Cyclobenzaprine
• Dextromethorphan
• Linezolid
• St. John’s wort

Combinations involving MAO inhibitors plus other serotonergic agents are particularly dangerous.

Clinical Features

The syndrome is classically recognized by a combination of:

• Mental-status changes: agitation, confusion, anxiety, lethargy, or coma
• Autonomic hyperactivity: hyperthermia, sweating, tachycardia, hypertension, nausea, vomiting, and dilated pupils
• Neuromuscular hyperactivity: tremor, hyperreflexia, clonus, myoclonus, and increased muscle tone

Clonus and hyperreflexia, especially in the lower extremities, are particularly helpful diagnostic clues.

Symptoms usually develop rapidly, often within hours of a medication change or interacting drug exposure.

Mechanism of Action

Excess serotonin overstimulates central and peripheral serotonin receptors, particularly 5-HT₁A and 5-HT₂A receptors.

This produces the characteristic combination of altered mental status, autonomic instability, and neuromuscular excitation.

Management

Treatment includes:

• Immediately stopping all serotonergic medications
• Airway and cardiovascular support when required
• IV fluids
• Benzodiazepines for agitation, tremor, and excessive sympathetic activity
• Active external cooling for significant hyperthermia

Severe cases with extreme hyperthermia may require sedation, paralysis, and mechanical ventilation.

Cyproheptadine, a serotonin receptor antagonist, may be considered when significant symptoms persist despite supportive treatment.

Differential Diagnosis

Important conditions that can resemble serotonin syndrome include:

• Neuroleptic malignant syndrome
• Anticholinergic toxicity
• Malignant hyperthermia
• Sympathomimetic poisoning

Compared with neuroleptic malignant syndrome, serotonin syndrome generally develops more rapidly and is more strongly associated with clonus and hyperreflexia.

Key Points

• Think of the triad: mental-status changes + autonomic instability + neuromuscular hyperactivity.
• Clonus is one of the most useful bedside findings.
• Symptoms often appear within hours rather than days.
• Stop serotonergic drugs promptly and provide supportive care.
• Severe hyperthermia is caused largely by excessive muscle activity and requires aggressive supportive management.

Toxicology – Methemoglobinemia

Definition

Methemoglobinemia occurs when an excessive amount of hemoglobin is oxidized into methemoglobin, a form that cannot effectively carry and release oxygen to tissues. This produces functional tissue hypoxia despite adequate oxygen being present in the lungs.

Common Causes

Oxidizing drugs and chemicals associated with methemoglobinemia include:

• Benzocaine and prilocaine
• Phenazopyridine
• Dapsone
• Nitrates and nitrites
• Nitroglycerin
• Nitroprusside
• Nitric oxide
• Aniline compounds
• Sulfonamides
• Naphthalene
• Certain other industrial or pharmaceutical oxidizing agents

Mechanism of Action

Oxidizing substances convert the iron in hemoglobin from the normal ferrous state (Fe²⁺) to the ferric state (Fe³⁺).

Ferric hemoglobin cannot bind oxygen normally. In addition, the remaining normal hemoglobin holds onto oxygen more tightly, further reducing oxygen delivery to tissues.

Clinical Features

Early manifestations may include:

• Cyanosis
• Headache
• Dizziness
• Fatigue
• Nausea
• Mild shortness of breath

More severe poisoning can cause:

• Increasing dyspnea
• Confusion
• Altered mental status
• Tachycardia
• Seizures
• Coma
• Cardiovascular collapse

Blood may have a characteristic dark or “chocolate-brown” appearance.

Diagnosis

A characteristic finding is a saturation gap, in which oxygen measurements do not fit the patient’s clinical appearance.

Standard pulse oximetry becomes unreliable and often trends toward readings around the mid-80% range despite supplemental oxygen.

The diagnosis is confirmed by co-oximetry, which directly measures the percentage of methemoglobin. A routine arterial blood gas may show a normal or relatively preserved PaO₂ because it measures dissolved oxygen rather than hemoglobin’s ability to carry it.

Management

Treatment includes:

• Immediately stopping the responsible oxidizing agent
• Supplemental oxygen
• Supportive care and cardiovascular monitoring

Mild, asymptomatic cases may improve spontaneously as normal red-cell reducing systems convert methemoglobin back to functional hemoglobin.

Methylene blue is the principal antidote for clinically significant methemoglobinemia because it accelerates reduction of methemoglobin back to normal hemoglobin.

Special Consideration – G6PD Deficiency

Methylene blue requires NADPH for its action. In patients with G6PD deficiency, it may be less effective and can provoke hemolysis, so treatment requires particular caution and specialist guidance.

Key Points

• Methemoglobinemia results from oxidation of hemoglobin iron from Fe²⁺ to Fe³⁺.
• Cyanosis that does not improve as expected with oxygen should raise suspicion.
• Co-oximetry, rather than a routine pulse oximeter or PaO₂ alone, confirms the diagnosis.
• Methylene blue is the standard antidote for significant symptomatic toxicity.
• G6PD deficiency is important because it can complicate methylene blue treatment.

Toxicology – Opioid Withdrawal

Definition

Opioid withdrawal is a hyperadrenergic syndrome that occurs after abrupt reduction or cessation of opioids in someone who has developed physical dependence.

Symptoms usually begin sooner with short-acting opioids and later with long-acting agents such as methadone.

Typical Presentation

Common findings include:

• Yawning
• Tearing
• Runny nose
• Goose bumps
• Dilated pupils
• Sweating
• Restlessness
• Muscle aches or cramps
• Nausea and vomiting
• Diarrhea
• Tachycardia
• Hypertension

Patients often feel extremely uncomfortable and may be unable to sit still.

Severity

Unlike alcohol or benzodiazepine withdrawal, opioid withdrawal is usually not directly life-threatening, but it can still cause significant dehydration, electrolyte abnormalities, and distress.

The duration depends on the opioid involved:

• Short-acting opioids generally produce a shorter withdrawal syndrome
• Long-acting opioids can cause more prolonged symptoms

Mechanism of Action

Chronic opioid exposure causes neuroadaptation within the central nervous system.

When opioids are suddenly removed, inhibitory opioid signaling disappears and there is a rebound increase in sympathetic and noradrenergic activity, producing the characteristic withdrawal symptoms.

Management

Treatment may include:

• Buprenorphine or methadone to control withdrawal and support ongoing treatment
• Clonidine or lofexidine to reduce autonomic symptoms
• Fluids and electrolyte replacement when needed
• Antiemetics for nausea and vomiting
• Antidiarrheal therapy
• Non-opioid analgesics for muscle aches

Long-term treatment for opioid use disorder commonly includes buprenorphine or methadone, with naltrexone used in selected patients after opioid abstinence has been established.

Key Points

• Opioid withdrawal causes mydriasis, sweating, piloerection, GI upset, muscle aches, and autonomic hyperactivity.
• It is generally very uncomfortable but less medically dangerous than alcohol or benzodiazepine withdrawal.
• Buprenorphine and methadone can both treat withdrawal and support longer-term recovery.
• Symptomatic treatment can reduce autonomic and gastrointestinal symptoms.