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Heavy Metal Toxicity

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Heavy Metal Toxicity Scott Phillips, MD, FACP, FACMT, FAACT Marci Balge, RN, MSN, COHN-S Arsenic Mercury Lead This educational module was produced by Scott Phillips ... – PowerPoint PPT presentation

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Title: Heavy Metal Toxicity


1
Heavy Metal Toxicity
  • Scott Phillips, MD, FACP, FACMT, FAACT
  • Marci Balge, RN, MSN, COHN-S

Arsenic
Mercury
Lead
2
This educational module was produced by Scott
Phillips MD, FACP, FACMT, FAACT and Marci Balge,
RN, MSN, COHN-S for The University of Texas
Health Science Center at San Antonio (UTHSCSA)
Environmental Medicine Education Program and
South Texas Environmental Education and Research
Program (STEER-San Antonio/Laredo/Harlingen,Texas)
Administrative support was provided by the
Association of Occupational and Environmental
Clinics through funding to UTHSCSA by the Agency
forToxic Substances and Disease Registry
(ATSDR), U.S. Department of Health and Human
Services.Use of this program must include
acknowledgement of the authors,UTHSCSA and the
funding support.For information about other
educational modules contact the UTHSCSA STEER
office, Mail Code 7796, 7703 Floyd Curl Drive,
San Antonio,Texas 78229-3900,(210)567-7407.
3
Definitions
  • Metals originally included only gold, silver,
    copper, iron, lead, and tin.
  • Dense, malleable, lustrous
  • Conduct heat and electricity, cations
  • Many other elements since added to the list with
    some of these characteristics
  • Metalloids are elements with features
    intermediate between metals and non-metals.
    Example arsenic

4
Periodic Table
5
Heavy metal
  • A metal having an atomic weight greater than
    sodium, a density greater than 5 g/cm3
  • Some notion of toxicity
  • Usually includes lead, cadmium and mercury
  • Many others may variably be added to list

6
  • Acute single exposures

urine
blood
Metal levels
time
exposure
7
Case Presentation
  • 15-month old boy was treated with ampicillin for
    abdominal pain and diarrhea. The problem
    continued and the parent gave the child multiple
    doses of a Central American home remedy called
    azarcon. The child developed seizures. PE BP
    103/68, P 94, RR 22, Tmax 98 F. Exam listless,
    with poor motor tone. No neck stiffness, the
    heart, lungs and abdomen were unremarkable. Sz
    re-occurred. WBC 9.6 no anemia, Plts Nl, Lytes
    nl, UA nl Spinal tap was nl, with elevated
    opening pressure, cerebral edema was found on Cat
    Scan of the Head.

8
Case (cont)
  • The child was intubated, given lorazepam,
    fosphenatoin and phenobarbital without control of
    the Sz. An x-ray reveled a radiopaque image in
    the GI tract.
  • The child expired, despite aggressive supportive
    care.
  • What is azarcon?

9
Azarcon
  • Azarcon is a folk remedy that contains 85-96
    lead tetroxide
  • Other lead containing remedies include Greta.

10
Case (cont.)
  • The child was found to have a blood lead level of
    124 ug/dl., and died from lead encephalopathy.

11
Lead
12
Lead Paint
  • The use of lead in residential paint was banned
    in 1977
  • Lead-containing pigments still are used for
    outdoor paint products because of their bright
    colors and weather resistant properties
  • Tetraethyl and tetramethyl lead are still used as
    additives in gasoline in several countries

13
Sources of Exposure
  • Soil and dust
  • Paint chips
  • Contaminated water
  • Parents lead-related occupation
  • Folk remedies
  • Congenital exposure
  • Pica
  • Developmental delay

14
Toxicocokinetics and Toxicoynamics
  • Absorption
  • Lungs depends on size particle
  • GI
  • Adults 20-30
  • Children as much as 50 of dietary lead
  • Inadequate intake of iron, calcium, and total
    calories are associated with higher lead levels
  • Skin
  • Inorganic lead is not absorbed
  • Organic lead is well absorbed
  • Lead is carried bound to the RBC

15
Pharmacokinetics and Pharmacoynamics
  • Distributed extensively throughout tissues bone,
    teeth, liver, lung, kidney, brain, and spleen

16
  • Body lead storage bones- can constitute a source
    of remobilization and continued toxicity after
    the exposure has ceased
  • Lead crosses the BBB and concentrates in the gray
    matter
  • Lead crosses the placenta
  • Excretion
  • Kidneys. The excretion increases with increasing
    body stores (30?g-200 ?g/day)
  • Feces

17
Clinical Manifestation
  • Acute toxicity
  • Acute encephalopathy, renal failure and severe GI
    symptoms

18
Chronic and Long Term Toxicity- Pathophysiology
  • Lead has affinity for SH groups and is toxic to
    zinc-dependent enzyme systems
  • Heme synthesis hemoglobin, cytochromes
  • Steroid metabolism and membrane integrity
  • Interference in vitamin D synthesis in renal
    tubular cells (conversion of 1-hydroxyvitamin D
    to 1,25-hydroxyvitamin D)

19
ALA- aminolevulinic acid ? in plasma and urine
COPRO- coprorphyrinogen ? in urine
Protoporphyrin ? accumulates in the RBC
20
General Signs and Symptoms of Lead Toxicity
  • Fatigue
  • Irritability
  • Lethargy
  • Paresthesis
  • Myalgias
  • Abdominal pain
  • Tremor
  • Headache
  • Vomiting
  • Weight loss
  • Constipation
  • Loss of libido
  • Motor neuropathy
  • Encephalopathy
  • Cerebral edema
  • Seizures
  • Coma
  • Severe abdominal cramping
  • Epiphyseal lead lines in children (growth arrest)
  • Renal failure

21
Range of Lead-induced Health Effects in Adults
and Children
22
Childhood Lead Poisoning
  • Childhood lead poisoning is now defined as a
    blood lead level of 10 ?g/dl

23
  • The average lead level of American children is 2
    ?g/dl
  • 8.9 of American children have lead poisoning
  • Lead intoxication is more prevalent in minority
    groups and among those living in the northeast

24
Neurotoxicity of Lead in Childhood
  • Mental retardation in severe lead intoxication
  • ? 5 points in IQ for every 10 ?g/dl ? in blood
    lead level- population based studies
  • Other adverse developmental outcomes
  • Aggression
  • Hyperactivity
  • Antisocial behaviors
  • Learning disability- impairment in memory,
    auditory processing, and visual-motor
    integration. The IQ is normal. These effects has
    been demonstrated with blood lead levels as low
    as 6 ?g/dl

25
Diagnosis
  • Evaluation of clinical symptoms and signs
  • CBC
  • Serum iron levels, TIBC, ferritin
  • Abdominal radiographs (for recent ingestion of
    lead-containing material)
  • Whole blood lead level
  • X-ray fluorescence (XRF)- to asses body burden

26
Treatment
  • Environmental inspection/hazard reduction
  • Nutritional supplementation
  • Chelation therapy

27
Nutritional Supplementation
  • Iron supplementation
  • Calcium supplementation calcium rich foods
  • Phosphorus supplementation
  • Frequent food consumption- regular meals snacks

28
Chelation Therapy
  • BLL gt 70 ?g/dl or encephalopathy
  • Hospital admission
  • Administration of a parenteral chelator
  • BLL gt 45 ?g/dl- oral chelator
  • BLL 25-45 ?g/dl- if these levels persist despite
    environmental intervention

29
Arsenic
30
Introduction
  • Arsenic is common in the environment
  • Sources
  • Groundwater
  • Arsenic containing mineral ores
  • Industrial processes
  • Semiconductor manufacturing (gallium arsenide)
  • Fossil fuels
  • Wood treated with arsenic preservatives
  • Metallurgy
  • Smelting (copper, zinc, lead) and refining of
    metals and ores
  • Glass manufacturing

31
Introduction
  • Commercial products
  • Wood preservatives
  • Pesticides
  • Herbicides
  • Fungicides
  • Food
  • Seafood and fish
  • Others
  • Antiparasitic drugs
  • Folk remedies

32
Soil Pica
  • Soil pica behavior when children ingest large
    amounts of soil at a time (e.g. up to 1 teaspoon
    or 5,000mg)
  • Children 1 to 2 years old have strongest soil
    pica behavior, which may occur as part of their
    normal exploratory behavior
  • Preschool children also purposely eat soil for
    unknown reasons
  • Some cultures promote eating soil, specifically
    clay, as part of a cultural practice

33
Toxicokinetics
  • T1/2 of inorganic arsenic in the blood is 10 hrs
    and of organic arsenic is around 30 hours
  • 2-4 weeks after the exposure ceases, most of the
    remaining arsenic in the body is found in
    keratin-rich tissues (nails, hair, skin)

34
Toxicokinetics
  • Inorganic arsenic is converted to organic arsenic
    (biomethylation to monomethyl arsonic- MMA or
    DMA) in the liver. This may represent a process
    of detoxification
  • Renally excreted (30-50 of inorganic arsenic is
    excreted in about 3 days). Both forms are
    excreted depend on the acuteness of the exposure
    and dose

35
Pathophysiology
  • Trivalent forms
  • bind to sulfhydryl groups leading to inhibition
    of enzymatic systems
  • inhibit the Krebs cycle and oxidative
    phosporylation. These lead to inhibition of ATP
    production
  • Pentavalent forms
  • can replace the stable phosphate ester bond in
    ATP and produce an arsenic ester stable bond
    which is not a high energy bond
  • Endothelial damage, loss of capillary integrity,
    capillary leakage, volume loss, shock

36
Manifestations of acute arsenic poisoning
37
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38
Palmer Keratosis
39
Biological Monitoring
  • Urinary arsenic measurement
  • Spot sample (mcg/L)
  • Timed urine collection (mcg/24 hours)
  • Normal values
  • Spot urine 10 mcg/L (10-150 mcg/L)
  • 24 hours urine collectionlt25 mcg/24 hours
  • Whole blood lt1mcg/L (usually is elevated in
    acute intoxication)

40
Biological Monitoring
  • Ingestion of seafood may elevate urinary arsenic
    levels
  • If urinary arsenic levels are high
  • Ask the patient whether he ingested seafood in
    the last 72 hours
  • Speciation can be performed in several
    laboratories
  • Methylated derivatives determination in the
    urine. These levels are not influenced by the
    presence of organic arsenic from marine origin

41
Treatment of acute poisoning
  • Gastric lavage
  • Activated charcoal does not bind well inorganic
    arsenic
  • Whole bowel irrigation with polyethylene glycol
  • Skin decontamination in dermal exposure

42
Treatment of acute poisoning
  • Supportive care
  • Chelation therapy should be instituted promptly
    (minutes to hours)
  • BAL (British anti-Lewisite)- IM
  • Succimer (DMSA)- PO
  • DMPS PO, IV
  • D-Penicillamine- less effective

43
Cadmium
44
What is Cadmium?
  • A metal most often encountered in earths crust
    combined with chlorine (cadmium chloride), oxygen
    (cadmium oxide), or sulfur (cadmium sulfide)
  • Exists as small particles in air, result of
    smelting, soldering or other high temp.
    industrial processes
  • By-product of smelting of zinc, lead, copper ores
  • Used mainly in metal plating, producing
  • pigments, batteries, plastics and as a
  • neutron absorbent in nuclear reactors

Cadmium is used in batteries
45
Cadmium and Smelters/Mine Sites
  • Cadmium is a by-product of smelters
  • Has been a concern at the Summitville mine site
    in Colorado

Photo of Smelter
46
Exposure Sources - Tobacco
  • Tobacco smoke (a one pack a day smoker absorbs
    roughly 5 to 10 times the amount absorbed from
    the average daily diet)

Tobacco smoke is an important source of cadmium
exposure
47
Exposure Sources By Mouth
  • Foods (only a small amount is absorbed)
  • Itai Itai disease (cadmium contamination diet
    low in calcium vitamin D)
  • Cadmium a component of chuifong tokwan, sold
    illegally as a miracle herb

Low levels are found in grains, cereals, leafy
vegetables, and other basic foodstuffs
48
Biologic Fate
  • Cadmium has no known beneficial function in the
    human body
  • Is transported in the blood bound to
    metallothionein
  • Greatest concentrations found in kidneys liver
  • Urinary excretion is slow
  • Biologic half-life may be up to 30 yrs.

49
Why Is Cadmium a Health Hazard?
  • Affects lungs kidneys
  • 2o effects on skeletal system
  • Binds to sulfhydryl groups, displacing other
    metals from metalloenzymes, disrupting those
    enzymes
  • Competes with calcium for binding sites on
    regulatory proteins
  • Lipid peroxidation has been demonstrated

50
Respiratory Effects
  • Acute inhalation may mimic metal fume fever
  • Fever, chills decreases in FVC and FEV1
  • Initial symptoms flu-like symptoms
  • Later chest pain, cough, dyspnea
  • Bronchospasm and hemoptysis may occur
  • Chronic inhalation MAY result in impairment of
    pulmonary function with reduction in ventilatory
    capacity

51
Renal Effects
  • May cause tubular and glomerular damage with
    resultant proteinuria
  • May follow chronic inhalation or ingestion
  • Latency period of 10 yrs
  • Nephropathy is progressive irreversible

52
Renal Effects
  • Chronic exposure progressive renal tubular
    dysfunction
  • Toxic effects are dose related
  • Critical renal concentration
  • Decreased GFR
  • Chronic renal failure
  • Kidney stones more common

53
Skeletal Effects
  • Bone lesions occur late in severe chronic
    poisoning
  • Pseudofractures
  • Other effects of osteomalacia and osteoporosis
  • Appear to be secondary to increased urinary
    calcium and phosphorus losses

54
Signs and Symptoms - Acute
  • Food poisoning (ingestion)
  • Bronchitis (inhalation)
  • Interstitial pneumonitis (inhalation)
  • Pulmonary edema (inhalation)
  • A condition that mimics metal fume fever

Children who eat dirt (pica behavior) are at risk
55
Signs Symptoms - Chronic
  • Chronic exposure may result in renal dysfunction
    and bone disease
  • Mild anemia, anosmia yellow discoloration of
    the teeth may occur

Chronic exposure may effect the sense of smell
56
Evaluation
  • Inhalation
  • Chest radiograph
  • Chronic exposure
  • Renal tests
  • Serum electrolytes, BUN, serum and urinary
    creatinine, serum creatinine, cadmium in blood
    urine, urinary protein
  • Other tests CBC LFTs

57
Direct Biologic Indicators
  • 24 hour urine cadmium reflects exposure over
    time an total body burden
  • Blood cadmium
  • Cadmium in hair not reliable

No quantitative relationship between hair cadmium
levels and body burden
58
Indirect Biologic Indicators
  • Urinary ß2-microglobulin evaluate urine levels
    gt 300 ?g/g creatinine
  • Urinary RBP
  • Urinary metallothionein (MT)

59
Treatment Management
  • Acute Exposure
  • No proven treatment
  • Supportive treatment includes fluid replacement,
    oxygen, mechanical ventilation. With ingestion,
    gastric decontamination by emesis or gastric
    lavage soon after exposure. Activated charcoal
    not proven effective
  • Chronic Prevent further exposure

60
Mercury
61
Mercury
  • Occurs in three forms (elemental, inorganic
    salts, and organic compounds)
  • Contamination results from mining, smelting, and
    industrial discharges. Mercury in water can be
    converted by bacteria to organic mercury (more
    toxic) in fish.
  • Can also be found in thermometers, dental
    amalgams, fluorescent light bulbs, disc
    batteries, electrical switches, folk remedies,
    chemistry sets and vaccines.

62
Mercury - Exposure
  • Elemental
  • liquid at room temperature that volatizes readily
  • rapid distribution in body by vapor, poor in GI
    tract
  • Inorganic
  • poorly absorbed in GI tract, but can be caustic
  • dermal exposure has resulted in toxicity
  • Organic
  • lipid soluble and well absorbed via GI, lungs and
    skin
  • can cross placenta and into breast milk

63
Elemental Mercury
  • At high concentrations, vapor inhalation produces
    acute necrotizing bronchitis, pneumonitis, and
    death.
  • Long term exposure affects CNS.
  • Early insomnia, forgetfulness, anorexia, mild
    tremor
  • Late progressive tremor and erethism (red
    palms, emotional lability, and memory impairment)
  • Salivation, excessive sweating, renal toxicity
    (proteinuria, or nephrotic syndrome)
  • Dental amalgams do not pose a health risk.

64
Inorganic Mercury
  • Gastrointestinal ulceration or perforation and
    hemorrhage are rapidly produced, followed by
    circulatory collapse.
  • Breakdown of mucosal barriers leads to increased
    absorption and distribution to kidneys (proximal
    tubular necrosis and anuria).
  • Acrodynia (Pink disease) usually from dermal
    exposure
  • maculopapular rash, swollen and painful
    extremities, peripheral neuropathy, hypertension,
    and renal tubular dysfunction.

65
Organic Mercury
  • Toxicity occurs with long term exposure and
    effects the CNS.
  • Signs progress from paresthesias to ataxia,
    followed by generalized weakness, visual and
    hearing impairment, tremor and muscle spasticity,
    and then coma and death.
  • Teratogen with large chronic exposure
  • Asymptomatic mothers with severely affected
    infants
  • Infants appeared normal at birth, but psychomotor
    retardation, blindness, deafness, and seizures
    developed over time.

66
Diagnosis and Treatment
  • Dx made by history and physical and lab analysis.
    Inorganic mercury can be measured in 24 hour
    urine collection organic mercury is measured in
    whole blood.
  • The most important and effective treatment is to
    identify the source and end the exposure
  • Chelating agents (DMSA) may enhance inorganic
    mercury elimination. Dimercaprol may increase
    mercury concentration in the brain.

67
Mercury - Prevention
  • Many mercury compounds are no longer sold in the
    United States.
  • Elemental mercury spills
  • Roll onto a sheet of paper and place in airtight
    container
  • Use of a vacuum cleaner should be avoided
    because it causes mercury to vaporize (unless it
    is a Hg Vac)
  • Consultation with environmental cleaning company
    is advised with large spills.
  • State advisories on public limit or avoid
    consumption of certain fish from specific bodies
    of water.

68
Questions?
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