The heavy metals discussed in this chapter—lead, arsenic, mercury, and iron—frequently cause toxicity in humans. The toxicity profiles of metals differ, but most of their effects appear to result from interaction with sulfhydryl groups of enzymes and regulatory proteins. Chelators are organic compounds with 2 or more electronegative groups that form stable bonds with cationic metal atoms. These stable complexes lack the toxicity of the free metals and often are excreted readily. Chelators, which function as chemical antagonists, are used as antidotes in the treatment of heavy metal poisoning.
TOXICOLOGY OF HEAVY METALS
Lead serves no useful purpose in the body and can damage the hematopoietic tissues, liver, nervous system, kidneys, gastrointestinal tract, and reproductive system (Table 57–1). Lead is a major environmental hazard because it is present in the air and water throughout the world.
TABLE 57–1Important characteristics of the toxicology of arsenic, iron, lead, and mercury. ||Download (.pdf) TABLE 57–1 Important characteristics of the toxicology of arsenic, iron, lead, and mercury.
|Metal ||Form Entering Body ||Route of Absorption ||Target Organs for Toxicity ||Treatmenta |
|Lead ||Inorganic lead oxides and salts ||Gastrointestinal, respiratory, skin (minor) ||Hematopoietic system, CNS, kidneys ||Dimercaprol, EDTA, succimer, unithiol |
| ||Tetraethyl lead ||Skin (major), gastrointestinal ||CNS ||Seizure control |
|Arsenic ||Inorganic arsenic salts ||All mucous surfaces ||Capillaries, gastrointestinal tract, hematopoietic system ||Dimercaprol, unithiol, succimer, penicillamine |
| ||Arsine gas ||Inhalation ||Erythrocytes ||Supportive |
|Mercury ||Elemental ||Inhalation ||CNS, kidneys ||Succimer, unithiol |
| ||Inorganic salts ||Gastrointestinal ||Kidneys, gastrointestinal tract ||Succimer, unithiol, penicillamine, dimercaprol |
| ||Organic mercurials ||Gastrointestinal ||CNS ||Supportive |
|Iron ||Ferrous sulfate ||Gastrointestinal ||Gastrointestinal, CNS, blood ||Deferoxamine, deferasirox |
Because of the ban on lead over 20 years ago in gasoline, and because of bans on other industrial products that previously contained lead, acute inorganic lead poisoning is no longer common in the United States. It can occur rarely from industrial exposures (usually via the inhalation of dust) and in children who have ingested large quantities of chips or flakes from surfaces in older houses covered with lead-containing paint. The primary signs of this syndrome are acute abdominal colic and central nervous system (CNS) changes, including, particularly in children, acute encephalopathy. The mortality rate is high in those with lead encephalopathy, and prompt chelation therapy is mandatory.
2. Chronic lead poisoning
Chronic inorganic lead poisoning (plumbism) is much more common than the acute form. Signs include peripheral neuropathy (wrist-drop is characteristic), anorexia, anemia, tremor, weight loss, and gastrointestinal symptoms. Treatment involves removal from the source of exposure, and chelation therapy, usually with oral succimer in outpatients and with parenteral agents (eg, EDTA with or without dimercaprol) in more severe ...