Toxicology Part 2

gastrointestinal, respiratory (all mucosal surfaces)

major route of absorption: ARSENIC

ARSENIC

this heavy metal is avidly bound to the skin, hair, and nails

renal (major); sweat and feces (minor)

metabolism and elimination: ARSENIC (methylation)

INORGANIC LEAD

metabolism and elimination of this form of LEAD is via renal (major); feces and breast milk (minor)

ORGANIC LEAD

form of LEAD absorbed in the skin, respiratory, and gastrointestinal

ORGANIC LEAD

metabolism and elimination of this form of LEAD is via urine and feces (major); sweat (minor)

ORGANIC LEAD

this form of LEAD is more toxic, readily absorbable

ELEMENTAL MERCURY

form of MERCURY absorbed via the respiratory tract; associated with CNS tremors

ELEMENTAL MERCURY

metabolism and elimination of this form of MERCURY is via urine (major), feces (minor)

INORGANIC MERCURY (Hg2+, Hg+)

form of MERCURY absorbed via the gastrointestinal tract, skin (minor); associated with acute renal tubular necrosis

ORGANIC MERCURY (alkyl, aryl)

form of MERCURY absorbed via gastrointestinal, skin, respiratory (minor); associated with CNS effects

ARSENIC

heavy metal associated with GI symptoms + garlic breath + QT
prolongation + skin cancers

LEAD

heavy metal with bone as the major reservoir

LEAD

heavy metal that causes microcytic anemia, wrist/foot drop, cognitive deficits, nephropathy

ORGANIC LEAD

heavy metal form that is more lipid-soluble, crosses the blood-brain barrier, and causes encephalopathy

ELEMENTAL MERCURY

heavy metal form with inhalation exposure; primarily affects the brain and kidneys

INORGANIC MERCURY

heavy metal form that mainly causes renal toxicity

ORGANIC MERCURY (METHYLMERCURY)

heavy metal form that is most neurotoxic; readily crosses the placenta, causing severe fetal CNS injury

LEAD

heavy metal with no physiologic role in the human body

LEAD

heavy metal commonly found in storage batteries, plumbing in older buildings, aviation gasoline (piston-engine aircraft), folk medicines such as Azarcon and Greta (Mexican remedies), and cosmetics (Kohl)

1. leaded gasoline

2. lead-based paints

3. lead solder in food cans

LEAD is previously widespread due to (3)

T

T/F: Children are more vulnerable to LEAD poisoning than adults because the developing central nervous system is highly sensitive to lead toxicity

F: hypertension, increased cardiovascular disease risk, occupational lead poisoning

T/F: health effects of LEAD toxicity in adults are related to the CNS

INORGANIC LEAD

form of lead absorbed through the respiratory and gastrointestinal

(GI) tracts; poorly absorbed through intact skin

inhalation; ingestion

with LEAD, occupational exposure is via ______; non-occupational exposure is via _______

50%

children absorb up to ___% of LEAD, making them more susceptible than adults

LEAD

Absorption of this heavy metal increases with low dietary calcium, iron deficiency, and ingestion on an empty stomach

LEAD

heavy metal distribution: 99% bound to erythrocytes; 1% in plasma; crosses the placenta

bone

heavy metal storage: __________ is the major reservoir, containing >90% of total body lead in adults

F: LEAD

T/F: ARSENIC stored in bone can continue to elevate blood lead levels for years after exposure stops

LEAD

heavy metal pharmacodynamics: inhibits enzymes; interferes

with Ca²⁺, Fe²⁺, Zn²⁺; causes oxidative stress leading to multisystem toxicity

LEAD

heavy metal pharmacodynamics: associated with neurotoxicity, especially in developing CNS

LEAD

heavy metal pharmacodynamics: irreversible ↓IQ, learning and behavioral deficits in children

encephalopathy

1. increase intracranial pressure

2. ataxia

3. seizures

4. coma

5. death

blood lead levels >100 mcg/dL leads to (5)

LEAD

this heavy metal inhibits ALA dehydratase and ferrochelatase → impaired heme synthesis; increases RBC fragility

LEAD

heavy metal associated with microcytic hypochromic or normocytic anemia, ↑ free erythrocyte protoporphyrin (FEP)/zinc protoporphyrin (ZPP), basophilic stippling, hemolysis (severe exposure)

LEAD

heavy metal associayed with chronic tubular/interstitial injury; saturnine gout

lead colic, gingival lead line (Burton line)

in heavily exposed individuals to LEAD, these gastrointestinal symptoms may manifest (2)

LEAD

heavy metal pharmacodynamics: hypertension, prolonged QTc, increased risk of cardiovascular mortality with chronic exposure

acute inorganic LEAD poisoning

form of inorganic LEAD intoxication: rare today, caused by industrial inhalation, and requires days to weeks of repeated exposure

acute inorganic LEAD poisoning

form of inorganic LEAD intoxication: with clinical features of lead encephalopathy, lead colic, hemolytic anemia or anemia with basophilic stippling, and elevated liver aminotransferases

acute inorganic LEAD poisoning

form of inorganic LEAD intoxication: diagnosed through history of exposure and abdominal x-ray

chronic inorganic LEAD poisoning

form of inorganic LEAD intoxication: more common, produces multisystem disease, wrist drop, and saturnine gout

whole blood lead level (BLL)

gold standard for detecting LEAD poisoning that reflects current circulating LEAD; does not accurately measure cumulative body burden

bone lead measurement (K x-ray fluorescence)

diagnostic tool that estimates long-term cumulative LEAD exposure

chelation challenge test

diagnostic tool that reflects soft tissue LEAD only; rarely indicated in clinical practice

ORGANOLEAD poisoning

form of LEAD intoxication: very rare today due to the worldwide phase-out of tetraethyl and tetramethyl lead

ORGANOLEAD poisoning

form of LEAD intoxication: well absorbed because of their volatility and lipid solubility via the skin and respiratory tract

LEAD encephalopathy

complication of LEAD that is treated as a medical emergency and requires intensive care

mannitol or hypertonic saline and corticosteroids

cerebral edema associated with LEAD encephalopathy should be managed with (2)

1. CaNa2EDTA (edetate calcium disodium) - IV

2. dimercaprol (BAL) - IM

3. succimer (DMSA) - oral

chelation therapy for inorganic LEAD poisoning (3)

IM dimercaprol (BAL), IV CaNa2EDTA

for severe encephalopathy due to inorganic LEAD poisoning, chelation therapy begins with _________ and addition of __________ after approximately 4 hours is done

oral succimer (DMSA)

after ≤5 days of parenteral therapy, chelation therapy for inorganic LEAD poisoning may switch to ________

T

T/F: in treatment of inorganic LEAD poisoning, succimer (DMSA) may also be started via nasogastric tube if EDTA is unavailable

F: children

T/F: chelation therapy is recommended for symptomatic patients with elevated BLL; adult with BLL ≥45 mcg/dL

succimer (DMSA)

T/F: dimercaprol (BAL) does not improve long-term neurocognitive outcomes in children with BLL 25–44 mcg/dL

T

T/F: BLL may rebound after chelation because of release of lead from bone stores

F: organic

T/F: in inorganic LEAD poisoning, empiric (asymptomatic) chelation therapy in patients with markedly elevated blood lead levels should be considered

ARSENIC

naturally occurring heavy metal found in the earth's crust

ARSENIC

heavy metal used in semiconductor manufacturing, wood preservatives, nonferrous metal alloys, glass manufacturing, and turf herbicide

ARSENIC

environmental source of this heavy metal is through groundwater contamination from coal ash in unlined landfills and groundwater contaminated by natural mineral deposits

ARSENIC

heavy metal that is a major public health problem in the Ganges Delta (India and Bangladesh)

ARSENIC

heavy metal found via dietary exposure through contaminated foods such as apple juice (10 pbb) and rice cereals (100 pbb)

ARSINE GAS (AsH3)

highly toxic arsenic-containing gas used in the semiconductor industry and causes severe hemolysis

ARSENIC

heqavy metal historically used as Fowler’s solution

ARSENIC

heavy metal developed as a chemical warfare agent; lewisite (dichloro[2-chlorovinyl]arsine)

ARSENIC (arsenic trioxide)

heavy metal approved to be used therapeutically for relapsed acute promyelocytic leukemia (APL)

ARSENIC (melarsoprol)

heavy metal used to treat advanced African trypanosomiasis (sleeping sickness)

ARSENIC

aside from respiratory and gastrointestinal absorbtion, percutaneous absorption of this heavy metal is limited but may become clinically significant after heavy exposure

liver

most absorbed inorganic arsenic is methylated in the ________

monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)

major metabolite of ARSENIC

T

T/F: with chronic daily exposure <1000 mcg, about two-thirds of absorbed ARSENIC is excreted in the urine within 2–3 days

F: prolong

T/F: massive ARSENIC ingestion hastens the elimination half-life

T

T/F: ARSENIC detected in hair or nails may represent either internal absorption or external contamination, making interpretation difficult

trivalent ARSENIC (As3+, arsenite)

form of ARSENIC that is 2–10 times more acutely toxic than pentavalent ARSENIC (As⁵⁺, arsenate)

pentavalent ARSENIC (As⁵⁺, arsenate)

trivalent ARSENIC (As3+, arsenite) is a form of ARSENIC that is 2–10 times more acutely toxic than

T

T/F: both trivalent and pentavalent forms can cause the full spectrum of arsenic toxicity because they undergo in vivo interconversion

ARSINE GAS (AsH3)

form of ARSENIC that causes massive intravascular hemolysis by altering erythrocyte membrane ion transport

ARSENIC

heavy metal that is a known human carcinogen; associated with lung, skin, and bladder cancer

ARSENOBETAINE

form of arsenic found in seafood, is nontoxic and is excreted unchanged in urine

acute inorganic ARSENIC poisoning

inorganic arsenic poisoning with symptoms beggining within minutes to hours after ingestion of high doses; associated with severe GI fluid loss leading to hypotension, shock, and death

acute inorganic ARSENIC poisoning

inorganic arsenic poisoning associated with QTc prolongation. pancytopenia, and Aldrich-Mees lines

urinary ARSENIC

diagnosis of acute inorganic ARSENIC poisoning is via _________ since blood arsenic is not useful because it is rapidly cleared from the blood stream

1. unithiol (DMPS) - IV

2. dimercaprol (BAL) - IM

chelation therapy for acute inorganic ARSENIC poisoning (2)

succimer (DMSA) - oral

in acute inorganic ARSENIC poisoning, this chelation therapy is effective but not preferred initially because severe gastroenteritis may impair oral absorption

ARSENIC

chronic absorption of >0.01 mg/kg/day (approximately 500–1000 mcg/day in adults) of this heavy metal leads to chronic inorganic poisoning

chronic inorganic ARSENIC poisoning

inorganic ARSENIC poisoning with time to symptom onset varying depending on dose and individual susceptibility

ARSENIC (chronic inorganic poisoning)

tobacco smoking may synergistically increase toxicity and cancer risk of this heavy metal

ARSENIC (arsenic trioxide)

heavy metal associated with QT prolongation and Torsades de pointes

ARSENIC

heavy metal associated with raindrop hyperpigmentation; hyperkeratosis of the palms and soles

F; chronic inorganic ARSENIC poisoning

T/F: in acute inorganic ARSENIC poisoning, urine arsenic may normalize within days to weeks after exposure ends

F: arsenobetaine

T/F: avoid seafood for atleast 3 days before urine testing to prevent false elevation from arsenic trioxide

F: past exposure

T/F: hair and nail arsenic may indicate recent exposure but must be interpreted cautiously because of possible external contamination

oral unithiol (DMPS) or succimer (DMSA)

chelation treatment for chronic inorganic ARSENIC poisoning

T

T/F: folate supplementation may improve ARSENIC methylation, especially in folate-deficient individuals

ARSINE GAS poisoning

ARSENIC poisoning characterized by massive intravascular hemolysis and has a latent period of 2–24 hours

ARSINE GAS poisoning

ARSENIC poisoning where oliguric acute renal failure develops within 1–3 days due to hemoglobin deposition in the renal tubules

T

T/F: massive exposure may cause fatal cellular respiratory failure before renal failure develops

ARSINE GAS poisoning

ARSENIC poisoning where chelation therapy has no proven clinical benefit

elemental MERCURY

the only heavy metal that is liquid at room temperature