1. Heavy Metals- Poisoning

2. Background
Heavy metal toxicity represents an uncommon, yet clinically significant, medical condition.
If unrecognized or inappropriately treated, heavy metal toxicity can result in significant morbidity and mortality.
Many metals are essential to biochemical processes, and others have found therapeutic uses in medicine.

3. Background
Iatrogenic metal toxicity may occur with bismuth, gold, gallium, lithium, and aluminum species.
However, occupational exposure to heavy metals has accounted for the vast majority of poisonings throughout human history.
The classic acute occupational heavy metal toxicity is metal fume fever (MFF), a self-limiting inhalation syndrome seen in workers exposed to metal oxide fumes.

4. Background
Metal fume fever (MFF) - or "brass founders ague," "zinc shakes," "Monday morning fever" is characterized by fever, headache, fatigue, dyspnea, cough within 3-10 hours.
Occur with zinc oxide, magnesium, cobalt, and copper oxide fumes.
A neutrophil alveolitis ensues, with hypoxia, reduced vital capacity, and diffuse bilateral infiltrates seen on radiographs.

5. Background Appears to be a direct toxic irritation.
Treatment is supportive and effects generally resolve within 24 hours.
Must be clearly differentiated from the true chemical pneumonitis that occurs after exposure to metal fumes from cadmium, manganese, mercury, nickel and tend to progress to ARDS and cause significantly more morbidity and mortality.

6. Background
Toxic effects from chronic exposure to heavy metals are far more common than acute poisonings.
Chronic exposure may lead to a variety of conditions depending on the route of exposure and the metabolism and storage of the specific element in question.
Many of the heavy metals have been implicated as carcinogens in the setting of chronic exposure.

7. Background
The most common species implicated in acute and/or chronic heavy metal toxicity are lead, arsenic, and mercury.
Heavy metals bind to oxygen, nitrogen, and sulfhydryl groups in proteins, resulting in alterations of enzymatic activity.
Increased synthesis of metal binding proteins in response to elevated levels of a number of metals is the body's primary defense against poisoning.

8. Background
Thiol ligands - allow high-affinity binding with cadmium, copper, silver, and zinc among other elements.
Other ligands are ferritin, transferrin, albumin, and hemoglobin.
The most commonly involved organ systems include the CNS, PNS, GI, hematopoietic, renal, and cardiovascular.
Lead toxicity involves the musculoskeletal and reproductive systems.

9. Background
Generally, children are more susceptible to the toxic effects of the heavy metals and are more prone to accidental exposures.
Children and infants are prone to developmental delays secondary to lead toxicity. A history of ingestion or exposure is the most critical aspect of diagnosing heavy metal toxicity.
A complete history, including occupational, hobby, recreational, and environmental exposure is crucial in diagnosing heavy metal toxicity.

10. Lead Toxicity
Lead poisoning is probably the most important chronic environmental illness affecting modern children.
In children, virtually no organ system is immune to the effects of lead poisoning.
Significant insult to the brain occurs at very low levels and that medical intervention with chelation fails to reverse such effects.

11. Lead Toxicity Lead perturbs multiple enzyme systems.
Ligand with sulfhydryl groups is vulnerable.
The best-known effect is that on the production of heme.
Effects of lead poisoning on the brain are manifold and include delayed or reversed development, permanent learning disabilities, seizures, coma, and even death.

12. Lead Toxicity
Lead is renally excreted, but the elimination rate varies, depending on tissue that absorbed the lead.
Adults with lead poisoning have increased incidences of depression, aggressive behavior, and antisocial behavior. Men with lead poisoning tend to have lower sperm counts; women have an increase in miscarriages and smaller babies.
Lead-based paint, children are most likely to put things containing lead into their mouths

13. Lead Toxicity
Consider lead poisoning whenever a small child presents with peculiar symptoms that do not match any one particular disease entity.
Irritability
Sleeplessness or excess lethargy
Poor appetite
Headaches
Abdominal pain with or without vomiting (but usually without diarrhea)
Constipation

14. Lead Toxicity Changes in a child's activity level fever
Adults present with minor nonspecific findings.
sleep disorders
Gingival lead line

16. Lead Toxicity Sources:
occupations include lead workers, welders, glassmakers, and scrap metal workers.
making bullets, making fishing-weights, soldering, indoor firearm shooting, and remodeling older homes.
cosmetics and folk remedies
retained bullet or shrapnel fragments
lead-based foreign bodies
illicit liquor ingestion

17. Lead Toxicity Differential Diagnosis Acute and Chronic anemia
Guillain-Barre Syndrome
Depression
Sickle cell disease
Mercury toxicity
Neuropathies

18. Lead Toxicity Laboratory studies:
baseline hemogram – microcytic anemia, red cell fragility and acute hemolytic anemias.
low uric acids and uric aciduria – children
elevated uric acid levels and, possibly, clinical gout – adults
Subtle nephrogenic effects, which, if unappreciated, may lead to treatment failures or complications.

20. Lead Toxicity Imaging:
Radio-opaque foreign bodies throughout the GI tract
Radiodensity in the distal metaphyseal plate
Radiographs of the long bones in growing children may reveal the characteristic lead lines.
CT scan of the head or MRI to rule out cerebral edema or structural lesions.

22. Lead Toxicity Prehospital Care:
separating the child from the source of lead exposure.
Chelation is used only when the lead level is in the potentially encephalopathogenic level (>60 mcg/dL).
Protect airway if the patient is comatose or seizing.

23. Lead Toxicity Treatment:
In child with acute lead ingestion, an orogastric or nasogastric catheter may be needed to enable intestinal irrigation with polyethylene glycol.
Immediately institute chelation therapy if lead poisoning is seriously considered.
In whom the diagnosis is unclear can be treated symptomatically

24. Lead Toxicity Chelation:
All chelators have nonspecific effects, that is, they will chelate other metals as well as lead.
These agents bind lead in the vascular compartment and prevent it from reaching the end organs of toxicity.

25. Lead Toxicity Chelation:
Dimercaprol (British antilewisite; BAL): Rapidly crosses the blood-brain barrier Used in combination with calcium disodium edetate Adverse effects are fever, pain at the injection site, nausea, vomiting, headache, and sterile abscess formation mg/kg IM q4h

26. Lead Toxicity Chelation:
Edetate calcium disodium (Calcium Disodium Versenate)
-Nearly the perfect chelator.
-Allows lead to be renally eliminated
mg/kg/d IV continuous infusion over h for 5 days
mg/kg/d IM in 2-6 divided doses with lidocaine

27. Lead Toxicity Chelation: D-Penicillamine:
-Used as oral chelator of lead
mg/kg PO divided
Succimer (DMSA)
-10 mg/kg PO q8h, days 1-5; 10 mg/kg PO q12h days
Dimerval (DMPS)
250 mg q4h for 7 d, changing to 100 mg oral capsules q6h until levels drop, then shifting to q12h, and then weaning

28. Lead Toxicity Complications:
-Syndrome of inappropriate excretion of antidiuretic hormone (SIADH)
-Increased intracranial pressure (ICP)
-Renal impairment
-Hypertension

29. Arsenic Toxicity
In nature, arsenic exists in the metallic state in 3 allotropic forms (alpha or yellow, beta or black, gamma or grey) and several ionic forms.
Arsenic has been used as a medicinal agent, a pigment, a pesticide, an agent of criminal intent, production of glass and semiconductors.
Industrial exposure, herbal preparations, nutritional supplements, certain water supplies and seafood.

30. Arsenic Toxicity
Citric acid cycle activity is decreased, and production of cellular ATP is decreased
Inhibits cellular glucose uptake, gluconeogenesis, fatty acid oxidation, and further production of acetyl CoA
Uncoupling of oxidative phosphorylation
Carcinogenic

31. Arsenic Toxicity
Arsenic exposure is usually suicidal, malicious, homicidal, or occupational
Patients exposed to arsenic will have a garlic smell to their breath and tissue fluids.
Acute exposures generally manifest with the cholera-like gastrointestinal symptoms – bloody diarrhoea, vomiting, shock
Chronic toxicity - dermatitis, peripheral neuropathy (painful), whitish lines (Mees lines) on fingernails.

32. Arsenic Toxicity Toxicity: Cardiac arrhythmias
Chronic hepatic and renal damage
Gas exposure manifests with an acute hemolytic anemia
Hemoglobinuria
Shaking chills

33. Arsenic Toxicity Sources: -Rodenticide or herbicide
-Metal foundry, mining, glass production, or the semiconductor industry.
-Contaminate such common items as wine, glues, and pigments.

34. Arsenic Toxicity Lab Studies:
- Complete blood count – microcytic hypochromic anemia, reticulocytosis
- Plasma arsenic concentrations - should not exceed 50 mcg/L.
- Urine spot test & 24hr urine arsenic clearance.
- Metabolites include methylarsonic acid (MMA) and dimethylarsenic acid (DMA).
- Urine pregnancy test in women of childbearing age.

35. Arsenic Toxicity Lab Studies:
- abdominal radiograph may reveal the presence of radio-opaque densities
- Nerve conduction studies
- Cardiac arrhythmias - ECG

36. Arsenic Toxicity Treatment -airway, breathing, and circulation (ABC)
-Hemodynamic stabilization – crystalloids
-blood products
-gastrointestinal decontamination is controversial - orogastric lavage is recommended if the patient presents rapidly or plain radiography indicates that arsenic is present in the stomach.
-Whole bowel irrigation – polyethylene glycol
-chelation, hemodialysis, exchange transfusion.

37. Arsenic Toxicity Chelation:
Chelation therapy is imperative in all symptomatic patients
Dimercaprol (BAL in Oil) mg/kg IM q4h for 2 d, then qid on day 3, then bid for 10 days, cause hemolysis in G-6-PD deficient patients, nephrotoxic, hypertension.
Succimer (DMSA) - 10 mg/kg/dose PO q8h for 5 d; then q12h for 14 d
Dimerval (DMPS) mg q4h / 100 mg of active drug tid/qid

38. Mercury Toxicity
Mercury became known as the product that caused acrodynia, also known as pink disease
Manifestations of acrodynia include pain and erythema of the palms and soles, irritability, insomnia, anorexia, diaphoresis, photophobia, and rash.
Mercury poisoning is usually misdiagnosed because of the insidious onset, nonspecific signs and symptoms, and lack of knowledge within the medical profession.

39. Mercury Toxicity SOURCES:
Found in battery, thermometer, and barometer manufacturing.
Fungicides used in the agricultural industry.
Paints
Used in dental amalgams and various antiseptic agents.
Environmental pollution is a major concern because of increased usage of fossil fuels and agricultural products

40. Mercury Toxicity
Inorganic form can be divided into elemental mercury and mercuric salts
Organic mercury can be found in long and short alkyl and aryl compounds.
Mercury poisoning can result from vapor inhalation, ingestion, injection, or absorption through the skin.
Neurologic, gastrointestinal, and renal systems are worst affected.

41. Mercury Toxicity Short-chained (methylmercury) - Affects the CNS
Organic mercury- Most devastating to the CNS
Short-chained (methylmercury) - Affects the CNS
Long-chained - Subacute/chronic effects similar to that of inorganic mercury exposure
Elemental mercury - Primary neurologic toxicity
Inorganic mercury salts :
Acute - Severe corrosive gastroenteritis, acute tubular necrosis
Subacute or chronic - GI, neurologic, and renal dysfunction

42. Mercury Toxicity
The clinical presentation of mercury toxicity can manifest in a variety of ways, depending on the nature of the exposure, the intensity of the exposure, and the chemical form.
Acute exposure caused by inhaled elemental mercury can lead to pulmonary symptoms.
Fever, chills, shortness of breath, metallic taste, and pleuritic chest pain
Stomatitis, lethargy, confusion, and vomiting

43. Mercury Toxicity
Inhaled toxicity may induce interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, and interstitial fibrosis & fatal ARDS
Classic triad found in chronic toxicity is tremors, gingivitis, and erethism (ie, a constellation of neuropsychiatric findings that includes insomnia, shyness, memory loss, emotional instability, depression, anorexia, vasomotor disturbance, uncontrolled perspiration, and blushing).

44. Mercury Toxicity
Include headache, visual disturbance (eg, tunnel vision), peripheral neuropathy, salivation, insomnia, and ataxia.
Inorganic mercury or mercuric salt exposure - corrosive properties account for most of the acute signs and symptoms.
Hematochezia, vomiting, severe abdominal pain, and hypovolemic shock.
Metallic taste, stomatitis, gingival irritation, foul breath, loosening of teeth, and renal tubular necrosis leading to oliguria or anuria.

45. Palm of a patient showing discrete erythematous papules and papulovesicles. Note lack of oozing, crusts, or excoriations. Although there is some increased palmar erythema, it differs from pink disease of inorganic mercury poisoning of children by presence of papules and lack of pain.
Palm of a patient showing discrete erythematous papules and papulovesicles. Note lack of oozing, crusts, or excoriations. Although there is some increased palmar erythema, it differs from pink disease of inorganic mercury poisoning of children by presence of papules and lack of pain.

46. Arm of a patient showing discrete scattered (shotgun) 1- to 2-mm papules. Note lack of oozing, crusts, excoriations, or other signs of acute eczema.
Arm of a patient showing discrete scattered (shotgun) 1- to 2-mm papules. Note lack of oozing, crusts, excoriations, or other signs of acute eczema.

47. This is a one view, abdominal, upright radiograph in a male patient who intentionally ingested 8 ounces of elemental mercury. Notice how the mercury outlines the large intestine from ascending to descending.
This is a one view, abdominal, upright radiograph in a male patient who intentionally ingested 8 ounces of elemental mercury. Notice how the mercury outlines the large intestine from ascending to descending.

48. Patient with intentional ingestion of mercury from blood pressure instrument. Note how mercury beads can be seen deposited in lung fields.
Patient with intentional ingestion of mercury from blood pressure instrument. Note how mercury beads can be seen deposited in lung fields.

49. Mercury Toxicity
Organic mercury poisoning usually results from ingestion of contaminated food
Neurological - as visual disturbance (eg, scotomata, visual field constriction), ataxia, paresthesias (early signs), hearing loss, dysarthria, mental deterioration, muscle tremor, movement disorders, and, with severe exposure paralysis, and death.
Methylmercury most readily passes through the placenta. Even with an asymptomatic patient, maternal exposure can lead to spontaneous abortion or retardation.

50. Mercury Toxicity Differential Diagnosis: ARDS ALS
Exfoliative dermatitis
Gastroenteritis
Myasthenia Gravis
ARF
Fifth disease – erythema infectiosum

51. Mercury Toxicity Elemental mercury toxicity
Adverse effects of therapeutic medication (eg, lithium, theophylline, phenytoin) Alzheimer disease Cerebellar degenerative disease or tumor Delayed neuropsychiatric sequela of carbon monoxide Ethanol or sedative hypnotic drug withdrawal Lacunar infarction Metabolic encephalopathy Parkinson disease Senile dementia

52. Mercury Toxicity Inorganic mercury toxicity (mercury salts)
Acid ingestion Alkali ingestion Arsenic toxicity Iron toxicity Phosphorus toxicity Similar to the causes of acute gastroenteritis
Organic mercury toxicity
Cerebral palsy Intrauterine hypoxia Teratogenic effects in the embryo

53. Mercury Toxicity Lab Studies:
-Normal mercury levels are considered to be less than 10 mcg/L in the blood and less than 20 mcg/L in the urine
-Complete blood count and serum chemistries
-Consider pregnancy tests
-Flat plate radiograph of the abdomen to visualize ingested elemental mercury, which appears radiopaque.

54. Mercury Toxicity 1) ABCs
Treatment:
1) ABCs
2) Removal of contaminated clothing and copious irrigation of exposed skin
3) Aggressive hydration
4) Gastric lavage is recommended for organic ingestion
5) Activated charcoal is indicated for GI decontamination

55. Mercury Toxicity Treatment: 6) Whole bowel irrigation
7) Use chelating agents if the patient is symptomatic
8) Hemodialysis is used in severe cases of toxicity when renal function has declined.

56. Mercury Toxicity Chelation: Dimercaprol (BAL) –
3-5 mg/kg IM q4h for 2 d, followed by
2.5-3 mg/kg IM q6h for 2 d, followed by
2.5-3 mg/kg IM q12h for 7 d
Penicillamine (Cuprimine, Depen) –
15-40 mg/kg/d; not to exceed mg PO q6h
Succimer (DMSA) – dimercapto succinic acid
10 mg/kg PO tid for 5 d, followed by 10 mg/kg PO bid for 14 d

57. Iron Toxicity
Iron overdose has been one of the leading causes of death caused by toxicological agents in children younger than 6 years.
Iron is used as a pediatric or prenatal vitamin supplement and for treatment of anemia.
Patients with anemias that require frequent blood transfusions also are at risk for developing chronic iron toxicity.

58. Iron Toxicity Corrosive toxicity
Cellular toxicity - impaired oxidative phosphorylation and mitochondrial dysfunction
Liver, heart, kidneys, lungs, and the hematologic systems are impaired.
GI toxicity with ingestions of more than 20 mg/kg, but less than or equal to 40 mg/kg.
Moderate-to-severe intoxication occurs when ingestion of elemental iron exceeds 40 mg/kg.
Ingestions exceeding 60 mg/kg may be lethal.

59. Iron Toxicity
Iron ingestions with GI symptoms such as vomiting and diarrhea
Hemorrhagic gastroenteritis
Hyperglycemia with metabolic acidosis
Iron poisoning is often classified into 4 distinct stages. Understanding the course of poisoning is important

60. Iron Toxicity
Stage 1
Nausea and diarrhea, often accompanied by abdominal pain, characterize the gastrointestinal (GI) phase.
When the intoxication is severe, a hemorrhagic component is observed in conjunction with gastroenteritis.
The combination of fluid and blood loss, with additional third-spacing, may result in hypovolemia or shock.
Fatality occurs in a significant percentage of patients during this first phase.

61. Iron Toxicity
Stage 2
This stage is characterized by resolution of GI symptoms.
The patient appears to improve and recover.
This deceptive phase usually occurs 6-12 hours postingestion and may last as long as 24 hours.
Metabolic abnormalities during this phase may include hypotension, metabolic acidosis, and coagulopathy.
Some patients skip this phase and progress to stage 3.

62. Iron Toxicity Stage 3 is characterized by metabolic acidosis.
It is hypothesized that high iron concentrations produce venous pooling and third-spacing of fluids.
Elevated liver enzymes and bilirubin are commonly observed with coagulopathy, indicative of hepatic dysfunction.
Hypoglycemia may accompany liver dysfunction.
The acidosis may indicate failure of other organs, such as the heart and kidneys.

63. Iron Toxicity
Stage 4
This stage is characterized by scarring of the healing GI tract. The stomach and/or intestines may be affected, resulting in gastric outlet or intestinal obstruction.
This phase usually is experienced weeks after a severe poisoning.

64. Iron Toxicity Laboratory Studies:
Mild-to-moderate toxicity generally manifests at levels of mcg/dL.
Hepatotoxicity usually is observed at levels higher than 500 mcg/dL.
Levels higher than 800 mcg/dL are associated with severe toxicity.
Samples drawn too early or too late postingestion may be unreliable.

65. Iron Toxicity Hyperglycemia
CBC – counts > 15,000/cu.mm, anemia due to blood loss
Arterial blood gas (ABG)
Liver function tests
Electrolyte measurements, renal function tests
Lipase and amylase levels
Ferritin levels for chronic toxicity >1000 mcg/L
Blood grouping and cross matching
Pregnancy testing
Radiograph – KUB films

66. Iron Toxicity Treatment: -Assume all are hypovlemic, administer fluids
-Gastric lavage with large bore orogastric tube
-Perform whole-bowel irrigation
-Activated charcoal does not bind iron but should be utilized if co-ingestants are suspected
-Oxygen

67. Iron Toxicity
Chelation is the mainstay of therapy. It is indicated for serum iron levels >350 mcg/dL with evidence of toxicity or >500 mcg/dL regardless of signs or symptoms.
Deferoxamine (Desferal) : mg IM, followed by 500 mg q4h for 2 doses; not to exceed 6000 mg/24 h -Tachycardia, hypotension, shock, and GI toxi.

68. Iron Toxicity
Treat patients who are symptomatic with deferoxamine, regardless of iron level.
Admit patients who have been hemodynamically unstable to an intensive care unit.
Whole bowel irrigation may be of benefit.
Other modalities that may be essential include mechanical ventilation and blood product transfusions.
Aggressive hydration aids in eliminating chelated iron by maintaining an appropriate urine output.

69. Iron Toxicity Complications: Hepatic necrosis Myocardial dysfunction
Cardiogenic shock
CNS depression
Coma
Convulsion
Anemia
Coagulopathy
Sepsis (Yersinia infection)
Adult respiratory distress syndrome (ARDS)
Gastrointestinal perforation
Intestinal stricture formation

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