ABSTRACT
Metabolism/Excretion ◾ Rapid hepatic methylation to methylarsonic acid (MAA) and dimethylarsinic acid
(DMA)—methylation requires glutathione ◾ Glutathione depletion is common in alcoholics and malnourished, will ↓ methylation
and ↑ toxicity of arsenicals ◾ Renal excretion (90%) > GI-fecal > dermal-hair and nails
Arsenic: Pathophysiology 1. Reduced glucose production from impaired gluconeogenesis from pyruvate 2. Reduced glucose uptake and utilization 3. Reduced production of high-energy ATP by oxidative phosphorylation 4. Rapid glucose depletion with severe hypoglycemia, especially in the CNS and PNS
◾ GI: Initial sx-metallic taste, garlic breath, nausea (N), vomiting (V), cramps, ricewater (cholera-like) diarrhea
Chronic Toxicity ◾ PNS: Stocking (feet) > glove peripheral sensory neuropathy, ↓ pain-touch-position-
temp-vibration sensation, ↓ DTRs → ascending flaccid paralysis; partial sensorimotor recovery only, even after chelation
Bowen’s disease), Mees’ lines on nails ◾ Pulm: Lung cancer ◾ Arsenic: Dermal effects-skin cancers and grooved ngernails (Mees’ lines) ◾ Arsenical hyperkeratosis (premalignant) ◾ Arsenical epidermoid (squamous) cancer ◾ Arsenical hyperkeratoses ◾ Arsenical Bowen’s disease ◾ Arsenical Mees’ lines (keratin destruction of nails)
Denition: Accelerated peripheral vascular disease of the lower extremities causing dry gangrene and auto-amputation caused by high arsenic levels in drinking well water (endemic in Taiwan, India, Bangladesh) and also associated with As-induced skin, liver (hepatic angiosarcoma), and lung cancers.
