Laboratory Studies
Testing for arsenic
Inorganic arsenic exists in various forms. The most toxic are As-III and As-V. Detoxification occurs as As-III is oxidized in the liver to As-V and then methylated to dimethylarsine and monomethylarsine over the course of 24 hours. As-III and As-V levels in the urine peak at about 10 hours and return to normal 20-30 hours after acute ingestion; the methylated compounds peak at 40-50 hours and can be measured as long as 20 days after ingestion. Blood levels are not useful. The biological half-life of inorganic arsenic is only 2 hours so blood or serum arsenic is unlikely to be detected after 2-4 hours.
Organic arsenic of a nontoxic variety is present in shellfish and saltwater fish, such as haddock or cod. The arsenobetaine and arsenocholine in seafood are excreted completely in the urine within 1-2 days. The urine of a person consuming seafood within 1-2 days of testing is likely to contain 50-2000 mcg of arsenic. Actual arsenic toxicity is characterized by the excretion of 500-50,000 mcg/day. In 41 cases of arsenic-induced peripheral neuropathy, most patients had total 24-hour urine concentrations of 100-400 mcg. A method has been developed to fractionate the inorganic and organic species using a cation-exchange cartridge and then analyzing the fractions using spectrophotometry. [21] Of historical interest, the earliest test for arsenic was developed by the English chemist James Marsh (1794-1846).
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CBC with indices and reticulocyte count: In acute arsine exposure, patients have acute hemolytic anemia; with regular, long-term exposure, patients develop microcytic, hypochromic anemia. Eosinophilia and neutropenia also may be noted. [19]
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Urinalysis: A 24-hour urine collection for total arsenic may be done if the diagnosis is subtle. A urine spot test is helpful in acute intoxication.
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Hair analysis or fingernail analysis may be indicated in regular, long-term exposure.
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In acute exposures, renal and liver function studies should be done. Levels of potassium, magnesium, and calcium must be monitored.
Imaging Studies
Upper GI radiography after acute ingestion may show radiopaque material in the upper GI tract, as it does in pica (ie, ingestion of inappropriate materials) involving other heavy metals. Maximal absorption of arsenic occurs in the small intestine.
CT scans and MRIs of the brain may show the cerebral edema and hemorrhagic or ischemic changes associated with acute toxicity.
Other Tests
Electrodiagnostic testing
Motor and sensory nerve conduction velocities, visual evoked potentials, and somatosensory evoked potentials may be helpful in monitoring the progress of treatment. The neuropathy is axonal in nature with some demyelination.
Electromyography shows denervation potentials and reduction in motor unit activity. High-amplitude, polyphasic motor units are seen. A myelopathy may develop and anterior horn cell abnormalities may suggest amyotrophic lateral sclerosis.
Following acute exposure, axonal degeneration and progressive slowing of sensory and motor conduction velocities plateaus and begins to improve after treatment. In chronic, low-level exposure, a distal, axonal, primarily sensory neuropathy develops. This is a duration-dependent sensorimotor neuropathy that affects all sensory modalities but includes severe loss of large-fiber sensation (ie, position and vibration sense).
Cranial nerves are spared.
Electroencephalography
Electroencephalography may be useful in monitoring any encephalopathy or seizures associated with acute toxicity. No EEG finding is pathognomonic for arsenic toxicity.
Histologic Findings
Nerve biopsies of people who have arsenical neuropathy show degenerated fibers and reduction of myelinated fibers in particular, but axons of all sizes are absent or markedly fragmented. Spinal cord pathways and anterior horn cells may be affected. In chronic toxicity, varying degrees of nerve fiber regeneration may be observed. Acute encephalopathic changes seen in the brain include perivascular hemorrhage. The chief mechanism is cerebral edema and vascular occlusion.
