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HEAVY METALS POISONING

Ma. Esel Jalandoni-Bermejo, MD, FPPS, DPSAMS, MsGC


USLS College of Medicine
16 April 2018
Learning Objectives
1. Know the most common heavy metals relevant to the
practice of Medicine
2. Know what form of health hazards these
chemicals pose to men
3. Know how to identify the different signs and symptoms
caused by the toxic effects of the same
4. Know the basic treatment and preventive measures
for these heavy metals
God’s Wonderful Creation for Mankind

Air Water
(atmosphere) (hydrosphere)

Soil
(lithosphere)

All living forms, including man


(biosphere)
Heavy Metals

Arsenic- As
Mercury
Lead
ARSENIC (As)
▪ Commonly encountered in mining areas
▪ Three forms: solid, liquid and gas
▪ Trivalent (arsenite) > toxic than pentavalent (arsenate)
▪ Absorption: oral, inhalation and parenteral routes
▪ Dermal absorption via mucous membranes and
abraded skin
▪ Toxicity depends on form, valence, state and solubility
▪ Arsine gas causes hemolysis

Navarro, et. al. Fundamentals of Pediatrics, 2014


ARSENIC
▪ Trivalent compounds bind to sulfhydryl groups and
inhibit several enzymatic pathways, glycolysis and
Kreb’s cycle uncoupled phosphorylation
▪ Sources of natural arsenic: volcanoes, mountains,
forests and grass fires, coal, oil, minerals, run-off soil,
wind
▪ Sources of man-made arsenic: pesticides, fertilizers,
litter
▪ Sources of arsenic in groundwater: mining and industrial
wastes and pesticides
Navarro, et. al. Fundamentals of Pediatrics, 2014

ARSENIC
Elemental Arsine gas Organic Inorganic
Sources seafoods & pesticides, dyes,
pesticides homeopathic meds
, contaminated
artesian wells, rice
cooked in
contaminated water

Characteristics insoluble in water & most toxic form, non-toxic


bodily fluids thus is used in mass
insignificantly poisoning
absorbed and
nontoxic
Absorption lungs GIT GIT, lungs & skin
ARSENIC
ARSENIC
Acute inhalation - no immediate symptoms
Latent (2 to 24H) - hemolysis, malaise, headache, weakness, dyspnea, N/V, jaundice, renal
failure
Acute ingestion (minutes to hours)
- GI toxicity- nausea, vomiting, diarrhea, hemorrhagic gastroenteritis, hypovolemic shock
- cardiovascular toxicity, cardiogenic shock
Sequelae - neurologic toxicity, delirium, seizure, encephalopathy, coma
Late sequelae
-hematuria, proteinuria and ATN
-delayed sensorimotor peripheral neuropathy, diminished pain, touch and temp sensation
-ascending paralysis
Subacute Toxicity
-prolonged fatigue, malaise, weight loss, chronic encephalopathy, leukopenia, anemia,
thrombocytopenia, chronic cough, gastroenteritis
-dermatologic findings: alopecia, oral ulcerations, desquamation, peripheral edema,
pruritic macular rash
Chronic Exposure
-hyper/hypopigmentation, hyperkeratoses (palms and soles), squamous and basal cell CA
-encephalopathy, peripheral neuropathy
-hepatomegaly, hypersplenism, non-cirrhotic portal fibrosis, portal hypertension,
”Blackfoot” disease - obliterative arterial disease of the lower ext.
Blackfoot disease

Basal cell carcinoma


ARSENIC
Clinical Manifestations
▪ Hallmarks of acute ingestion: abrupt onset of abdominal
pain, vomiting, bloody diarrhea, followed by weakness,
CV instability, hypovolemia & dehydration
▪ Dermal effects: facial edema, desquamation of palms and
soles, and Mee’s lines
▪ Severe toxicity: acute respiratory distress, pulmonary
edema, acute tubular necrosis & encephalopathy

Navarro, et. al. Fundamentals of Pediatrics, 2014


ARSENIC
▪ Triad of arsine gas exposure: abdominal pain, dark
urine and jaundice
▪ Chronic poisoning develops after low dose exposure:
skin lesions, neuropathy and carcinoma
Skin: alopecia, melanosis “raindrops on a dusty road”
pigmentation of trunk, legs & arms, “blackfoot
disease” characterized as distal numbness,
intermittent claudication, gangrene &
spontaneous amputation

Navarro, et. al. Fundamentals of Pediatrics, 2014


ARSENIC
▪ Neuropathy
headache, confusion, dementia, ataxia, numbness,
tingling sensation of fingers & toes, muscle weakness &
atrophy

▪ Definite carcinogen
skin, lungs, colon, liver, urinary bladder & kidneys

Navarro, et. al. Fundamentals of Pediatrics, 2014


ARSENIC
Diagnosis
▪ History of exposure, clinical findings and Arsenic levels
in the blood & urine
normal blood level <5 ug/L
normal 24-hour urine <50 ug/L
▪ Other lab tests:
CBC- anemia Urine hemoglobin
PBS- basophilic stippling Electrolytes
Liver & renal function tests

Navarro, et. al. Fundamentals of Pediatrics, 2014


ARSENIC
▪ Plain abdominal xray: radio opacity
▪ ECG: ventricular tachycardia & fibrillation, abnormal
T waves & prolonged QT interval
▪ Chronic exposure: 24-hour urine, hair and nail arsenic
determination, EMG-NCV studies, skin biopsy

Navarro, et. al. Fundamentals of Pediatrics, 2014


ARSENIC
Treatment
1. Prompt removal from source & decontamination
2. Aggressive stabilization and supportive care
3. Correction of fluids and electrolyte imbalance
4. Antidote therapy (chelation)
5. Hemodialysis if renal failure is present

Navarro, et. al. Fundamentals of Pediatrics, 2014


ARSENIC
6. Chelation therapy
▪ effective when administered right after exposure
▪ effective chelating agents in children:
DMPS (dimercaptopropane)
DMSA (dimercaptosuccinic acid)
▪ Dimercaprol- chelator of choice for patients not able
to tolerate oral therapy; side effect of hypertension

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY (Hg)
Epidemiology
▪ Used to be pervasive but its use was restricted due to
its environmental and health hazards
▪ Global initiative of phasing out in 2008- removal of Hg
containing devices in healthcare facilities
▪ Phasing out spearheaded by DOH thru AO 21
▪ NPMCC reported 50/1,927 children (2.6%) in 2008 were
secondary to accidental Hg ingestion
▪ Ranks 7th among top poisons in pediatric age group

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY
Elemental Inorganic Organic
(methyl mercury)
thermometers, pesticides, disinfectants, fish containing methyl
Sources spygmomanometer, antiseptics, dry batteries, mercury
batteries, latex paints explosives (Minamata disease)
(before 1991)
insoluble in water & 10% absorbed from the 90% absorbed in GIT,
Absorption bodily fluids thus is GIT and cross the BBB crosses the BBB and
insignificantly absorbed placenta
and nontoxic
▫vacuuming of carpets contaminated with mercury & breaking of mercury
Comments fluoresent light bulb may result in elemental mercury vapor exposure
▫dental amalgams containing elemental mercury release trace amounts
but do not pose a risk
▫Thimerosal mercury-containing preservative used in some vaccines
MERCURY
MERCURY
Pathophysiology

Mercury is absorbed thru inhalation, ingestion, dermal


contact and thru parenteral route

Distributed to tissues (kidney and brain) ➔ Disruption of


enzymes, transport mechs, membranes and
structural proteins ➔ Cellular necrosis or dysfunction
➔ Multi-organ failure

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY
Clinical Manifestations
1. Acute inhalation of elemental mercury vapor
▫ acts as direct airway irritant and cellular poison-
exudative alveolar & interstitial edema, erosive bronchitis &
bronchiolitis with interstitial pneumonitis & epithelial
desquamation pulmonary dysfunction: alveolar distention,
interstitial pneumonitis & emphysema, non-cardiogenic,
pulmonary edema, pneumatocele, pneumothorax, mediastinal
emphysema, restrictive lung disease
▫ fever, chills, headache, cough, tachypnea, dyspnea, chest pain
& tightness, N&V, metallic taste, abdominal cramps & diarrhea
Acute ingestion- leads to systemic poisoning
Injection- leads to abscess formation, granuloma, embolization & systemic absorption
MERCURY
2. Acute ingestion of elemental mercury
▫ signs and symptoms of systemic mercury poisoning

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY
3. Acute ingestion of inorganic mercury salts
▫ causes damage throughout the GIT
▫ usually secondary to ingestion of button battery
▫ corrosive gastroenteritis
(metallic taste, oropharyngeal burns, hematemesis)
▫ corrosive stomatitis
▫ necrotizing esophagitis
▫ gastritis
▫ ulcerative colitis
▫ acute tubular necrosis

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY
4. Chronic inorganic mercury intoxication
▫ Classic triad: 1. tremor
2. fine choreoathetosis
3. spasmodic ballismus
▫ neuropsychiatric disturbances, delirium, headaches, memory
loss & insomnia
▫ anorexia & fatigue
▫ gingivostomatitis

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY
5. Acrodynia or Pink disease
▫ rare idiosyncratic hypersensitivity reaction 2* to
exposure to mercurous powders
▫ symptoms of generalized pain, paresthesia &
acral rash that spreads to face
(red-pink, papular, pruritic and painful, desquamation and ulceration of the skin)

▫ anorexia, apathy, photophobia and hypotonia


▫ headache, irritability, tremors, hypertension
▫ emotional changes, insomnia, performance deficits, cognitive
dysfunction

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY
6. Minamata disease
▫ widespread mercury poisoning
▫ due to ingestion of contaminated fish delayed neurotoxicity:
ataxia, paresthesias, tremors, visual impairment, memory loss,
progressive dementia and death
▫ infants exposed in utero: LBW, microcephaly, developmental
delay, CP, deafness, blindness, seizure

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY
▫ neuromuscular changes: weakness, muscle atrophy,
twitching
▫ ingestion of organic mercury local GI injury: nausea and
vomiting, hematochezia, renal injury
▫ classic triad: dysarthria, ataxia and constricted vision
▫ prognosis is good after removal of source

Navarro, et. al. Fundamentals of Pediatrics, 2014


“MINAMATA DISEASE”
Minamata disease was first discovered in Minamata City in Kumamoto prefecture in
1956. It was caused by the release of methylmercury in the industrial wastewater from
the Chisso Corporation's chemical factory, which continued from 1932 to 1968. This
highly toxic chemical bioaccumulated in shellfish and fish in Minamata Bay and the
Shiranui Sea, which when eaten by the local populace resulted in mercury poisoning.
While cat, dog, pig, and human deaths continued over more than 30 years, the
government and company did little to prevent the pollution.
MERCURY
Diagnosis
1. History of exposure
2. Clinical findings
3. Mercury levels in the blood and urine
normal blood level: <2 ug/dL
normal urine level: <10 ug/dL
4. Plain abdominal xray
5. CBC, blood gas, liver function test, urinalysis
6. Chest xray- pulmonary edema and/or pneumonitis
7. Endoscopy recommended for corrosive ingestion
8. EMG with NCV- detect neurologic effects
Navarro, et. al. Fundamentals of Pediatrics, 2014
MERCURY
Treatment
1. Prompt removal of patient from the source of exposure
2. Treat pulmonary effects
3. Identification and elimination of the source
4. Dermal and gastric decontamination
5. Bronchoscopy to remove mercury beads

Navarro, et. al. Fundamentals of Pediatrics, 2014


MERCURY
6. Nebulization with Acetylcysteine
7. Prompt irrigation, excision and suctioning to remove injected
mercury droplets
8. Chelation therapy
▪ DMSA- fewer side effects & more effective
▪ Dimercaprol- chelator of choice for pxs unable to tolerate oral therapy
▪ D-penicillamine - oral chelator for less severe cases

Prevention
Avoiding use of devices containing mercury
▪ thermometers
▪ dental amalgam
▪ cosmetics

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD (Pb)
▪ Continues to be a problem in the Philippines despite
phasing out of lead in gasoline
▪ Sources
1. paint chips 8. art materials
2. dust 9. plastics
3. soil 10. toys
4. batteries 11. school & office supplies
5. cable sheath 12. plumbing materials
6. water pipes 13. cosmetics
7. cosmetics
Navarro, et. al. Fundamentals of Pediatrics, 2014
LEAD
Occupational sites
1. auto repair 6. smelting
2. battery recycling 7. refining
3. construction 8. paint manufacturing
4. printing
5. mining

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
Pathophysiology
▫ absorbed thru inhalation, ingestion & dermal contact (organic Pb)
▫ extensively distributed in the blood, bones and soft tissues
▫ absorbed 4-5 times more in children than adults
▫ fetus and infants highly susceptible to its toxic effects
▫ targets & affects motor neurons- axonal degeneration &
demyelination

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
▫ interferes with enzyme systems important in heme synthesis,
eg. ∆ aminolevulinic acid dehydratase & ferrochelatase
▫ interferes with calcium-dependent protein kinase that regulates
cell growth, learning and memory
▫ interferes with heme-containing hydroxylase that converts
25-hydroxyvitamin D into 1,25 hydroxyvitamin D
▫ impairs enzymes important in maintaining cell membrane
integrity & affects steroid metabolism

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
Effects on Cells
1. Binds to enzyme ferrochelatase ➔ changes the contour
and diminishes cell function ➔ decreased heme & increased
protoporphyrin level (toxic)

Ferrochelatase catalyzes the insertion of ferrous iron into


protoporphyrin IX, yielding heme
LEAD
2. Competes with calcium
Many calcium-binding proteins, eg. calmodulin, calbindin,
calsequestrin & calretinin, have higher affinity
to lead abnormal intra and intercellular signalling

Neurotransmitter release is a calcium dependent


process.

3. Prevents normal development of brain structures

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
Clinical Manifestations
▫ Clinical signs and symptoms develop after repeated exposure
▫ Acute poisoning is unusual
▫ Acute ingestion of 15 g lead acetate leads to death
▫ Suspected in children with exposure to lead plus high grade
fever, CNS manifestations, eg. seizures, sensorial change,
headache, irritability

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
Signs & symptoms
▫ decreased IQ
▫ learning disability
▫ irritability, hyperactivity, aggressiveness & inattentiveness
▫ impaired growth & hearing
▫ lack of fine- motor coordination
▫ delayed puberty
▫ Fanconi-like aminoaciduria
▫ gingival lines, pica

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
Clinical Manifestations
Gastrointestinal anorexia
abdominal pain
vomiting
constipation
CNS cerebral edema
increased ICP
headache, lethargy & papilledema
seizure, coma & death
Kidney renal tubular dysfunction
Blood hemolytic anemia
Nerves peripheral neuropathy
LEAD
Diagnosis
1. Whole blood lead level (BLL)- gold standard for diagnosis
▫ Lead poisoned children are identified by screening
▫ BLL 10ug/dL is a cause for concern
▫ BLL > 45 ug/dL requires chelation
2. CBC- anemia
3. Abdominal xray- shows ingested lead dust
4. Xray of long bones (9 mos- 5 years old)- shows growth
arrest lines, especially in children of chronic exposure
5. Peripheral blood smear- basophilic stippling

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
Other Tools for Assessment
1. Xray fluorescence – to assess bone lead stores
2. 24-hour urine sample
3.▫Lead in hair
4. KUB US- shows (+) radiopaque flecks in the intestinal tract
- doesn’t rule out lead toxicity if negative
5. Erythrocyte protoporphyrin (EP) levels - increased

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
Treatment
Acute poisoning
1. Decontamination by whole bowel irrigation/ gastric lavage if lead
is seen on abdominal xray
2. Gastric contents & contaminated objects are double-bagged,
sealed and properly disposed

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
Chronic poisoning
1. Identify sources of exposure, including family members and
neighbors
2. Exposed individuals must be removed from the area of
exposure, clinically evaluated, worked up and chelated, if
necessary
3. Micronutrient supplementation to reduce the bioavailability of
lead, eg. calcium, iron, ascorbic acid, zinc, vit B complex

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
▫ Calcium- inhibits GI absorption of lead by displacing it from the
mucosal carriers
▫ Ascorbic acid- reduces BLL
▫ Iron- improves BDS (Bayley Development Scale)

AAP Recommendation
Chelating agents
- Should not be routine given for BLL 25-45 ug/L unless such
levels persist despite environmental intervention
- Given for BLL > 45 ug/L

Navarro, et. al. Fundamentals of Pediatrics, 2014


LEAD
▫ Oral DMSA is effective in short- term reduction of moderately
elevated BLL at 10 mkd in 3 DD x 5 days then 20 mkd in 2 DD
x 14 days
▫ Two week rest period is used to assess rebound of the BLL

Prevention
1. Avoid use of leaded paints, especially indoors
2. Properly remove paints in old houses
3. Plant shrubs and grasses around to reduce soil lead exposure
4. Avoid storing of food in open cans and imported ceramic containers
5. Reduce hand-to-mouth activity
6. Frequent washing of hands and toys
Navarro, et. al. Fundamentals of Pediatrics, 2014
ASBESTOS
▫ A naturally occurring fibrous mineral that has the ability to resist
heat, fire and electricity.
▫ Its fibers are microscopic in nature, they are extremely durable
and resistant to fire and most chemical reactions and breakdowns.