heavy metal toxicity

heavy metals

elements having atomic weights between 63.546 and 200.590 and a specific gravity greater than 4.0

essential trace heavy metals

• cobalt

• copper

• iron

• zinc

non-essential heavy metals

• mercury

• lead

• arsenic

• cadmium

• chromium VI

moa of heavy metals

• form complexes or ligands with organic molecules

• modified molecules lose function

  • inactivation of enzymes

  • altered protein structures

• leads to abnormal cell function and/or cell death

symptoms of heavy metals

• mental confusion

• GI upset

• vision problems

• chronic fatigue

• variety of neuropathies

conditions that suggest heavy metal toxicity

• Parkinson’s, Alzheimer’s disease

• depression, hypoglycemia

• neuritis/ neuropathy

diagnosing heavy metal toxicity

• identify toxic element

  • hair or blood analysis

• specific lab tests/ clinical findings

• lead - microcytic red cells; ALAD

• high serum iron

• Mees’ lines

• metal gum lines

lewisite

arsenic war gas in WWI

acute exposure of lewisite

• blistering

• GI irritation

• central and peripheral neuropathies

chronic exposure of lewisite

• dermatitis and keratitis

• skin cancer

• liver

• kidney damage

1st lewisite antidote

British Anti-Lewisite (BAL)

acute lead toxicity

• high doses

  • direct tissue interaction

    • mucosal damage in GI

    • kidney convulsions

    • death

most sensitive to acute lead toxicity

• hematopoietic system

  • hypochromic

  • microcytic anemia

chronic lead toxicity

• ataxia

• vertigo

• irritability

• insomnia

• delirium

• learning problems in children

kind of mercury that is nephrotoxic

inorganic

population sensitive to neurotoxic methylmercury

• fetuses

• small children

manganese moa

known to block calcium channels and deplete dopamine in CNS

replicates symptoms of Parkinson’s disease

manganese

iron and drug overdose

leading cause of death in children

iron corrosiveness

• corrosive to GI

  • hematemesis

  • diarrhea

  • hypovolemic

iron moa

• impairs oxidative phosphorylation and mitochondrial dysfunction

  • cellular death

organs affected by liver

• liver

• heart

• kidneys

• lungs

• hematologic system

BAL (dimercaprol) value or no value on heavy metals

• value

  • As

  • Hg

  • Pb

• no value

  • Se

  • Fe

  • Cd

BAL (dimercaprol) risks

• hypertension

• tachycardia

• convulsions

dimercaprol dissociation

rapidly in acidic urine

most widely used chelator

Ca-EDTA

prevent dissociation from Ca-EDTA

IV bicarbonate

Ca-EDTA metal usage

• primarily for Pb

• eliminate

  • Zn

  • Mn

  • Fe

  • Cu

  • heavy radioisotopes

Ca-EDTA administration

• IM or IV

• not oral

  • increases GI absorption

penicillamine metal chelation

• Pb

• Hg

• As

• Cu

• Zn

penicillamine major toxicity relation

related to inhibition of pyridoxal-dependent enzymes

penicillamine therapy

adjunctive therapy after EDTA or BAL

DMSA

water soluble analog of BAL

DMSA metal usage

• Pb

• Hg

DMSA limited excretion

• Ca

• Fe

• Mg

deferoxamine synthesis

synthesized by a streptomyces organism

deferoxamine metal usage

• specific for Fe

  • IM or IV

when deferoxamine used

iron toxicity is severe

signs of severe iron toxicity

• shock 

• acidosis

• severe gastroenteritis

deferoxamine GI decontaminants

polyethylene glycol bowel prep

• GoLYTELY

• colyte