Understanding Metal Ion Reactions in Biological Systems

A classic example of essential metal deficiency resulting from nonessential metal exposure is Itai itai disease. Cadmium pollution in the Jinzu River basin in Japan resulted in severe nephrotoxicity in approximately 184 people. Renal tubule damage caused excessive loss of electrolytes and small proteins from the urine. In severe cases, urinary Ca loss was so severe that bone Ca was mobilized, resulting in osteomalacia. Renal tubular defects persisted for life and induced hypophosphatemia, hyperuricemia, and hyperchloremia, which are characteristic biochemical features of Itai-itai disease (see Section 21.6.1). 

Iron is another essential metal that can overload the body as a result of genetic disorders. Hereditary hemochromatosis and sub-Saharan African hemochromatosis are two examples. These two disorders differ in that hereditary hemochromatosis results in excessive iron when iron intake levels are normal, while sub-Saharan African hemochromatosis requires excessive intake of Fe coupled with a genetic predisposition to poorly regulate iron. Generally speaking, toxicity associated with excess essential metals tends to be rare, and it most frequently occurs in people who inappropriately consume dietary supplements. 

The majority of this chapter focuses on the toxicology of nonessential metals. Cadmium, lead, and mercury are three nonessential metals that have been investigated in great detail over the years, and they will be highlighted below. Other nonessential metals such as aluminum, beryllium, and nickel have not received as much attention but can pose toxicity issues. Arsenic and selenium are technically not metals, but are often included in discussions of metal toxicology. These elements will not be discussed here. 

Metals tend to be highly reactive in biological systems. Unfortunately, the behavior of metals usually cannot be predicted based on their ionic chemistry alone. 

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