Clinical Information

Arsenic is perhaps the best known of the metal toxins, having gained notoriety from its extensive use by Renaissance nobility as an antisyphilitic agent and, paradoxically, as an antidote against acute arsenic poisoning. Even today, arsenic is still 1 of the more common toxicants found in insecticides, and leaching from bedrock to contaminate groundwater.

The toxicity of arsenic is due to 3 different mechanisms, 2 of them related to energy transfer. Arsenic covalently and avidly binds to dihydrolipoic acid, a necessary cofactor for pyruvate dehydrogenase. Absence of the cofactor inhibits the conversion of pyruvate to acetyl coenzyme A, the first step in gluconeogenesis. This results in loss of energy supply to anaerobic cells, the predominant mechanism of action of arsenic on neural cells that rely on anaerobic respiration for energy. Neuron cell destruction that occurs after long-term energy loss results in bilateral peripheral neuropathy.

Arsenic also competes with phosphate for binding to adenosine triphosphate during its synthesis by mitochondria via oxidative phosphorylation, causing formation of the lower energy adenosine diphosphate monoarsine. This results in loss of energy supply to aerobic cells. Cardiac cells are particularly sensitive to this form of energy loss; fatigue due to poor cardiac output is a common symptom of arsenic exposure.

Arsenic furthermore binds avidly with any hydrated sulfhydryl group on protein, distorting the 3-dimensional configuration of that protein, causing it to lose activity. Interaction of arsenic with epithelial cell protein at the sites of highest physiologic concentration, the small intestine and proximal tubule of the kidney, results in cellular degeneration. Epithelial cell erosion in the gastrointestinal tract and proximal tubule are characteristic of arsenic toxicity. Arsenic is also a know carcinogen, but the mechanism of this effect is not definitively known.

A wide range of signs and symptoms may be seen in acute arsenic poisoning including headache, nausea, vomiting, diarrhea, abdominal pain, hypotension, fever, hemolysis, seizures, and mental status changes. Symptoms of chronic poisoning, also called arseniasis, are mostly insidious and nonspecific. The gastrointestinal tract, skin, and central nervous system are usually involved. Nausea, epigastric pain, colic abdominal pain, diarrhea, and paresthesias of the hands and feet can occur.

Arsenic exists in a number of different forms; organic forms are nontoxic, inorganic forms are toxic. See ASFRU / Arsenic Fractionation, Random, Urine for details about arsenic forms.

Because arsenic is excreted predominantly by glomerular filtration, analysis for arsenic in urine is the best screening test to detect arsenic exposure.