Copper is an essential trace element that plays a key role in the formation of red blood cells and maintenance of normal brain function. It is a constituent of numerous metallo-enzymes required in cytochrome oxidation, free radical detoxification and catecholamine production, and in the crosslinking of collagen, elastin and keratin (1).
Copper is mainly absorbed through the GI tract. Copper can be a very toxic ion and must be transported efficiently after absorption. Approximately 90% plasma Cu is bound firmly to ceruloplasmin and the rest is bound loosely to albumin. The primary route of Cu excretion is through the bile, with a small proportion excreted in the urine (1).
In patients with Wilson's disease, biliary excretion of Cu and incorporation into ceruloplasmin are both severely impaired. Copper accumulates in the liver, causing progressive liver damage and subsequently overflows to the brain, causing involuntary movements and loss of co-ordination. Deposition of Cu in the cornea produces Kayser Fleischer rings (2, 3).

Menkes disease (kinky hair syndrome) is a rare Cu deficiency disease caused by a genetically determined X-chromosomal defect in Cu absorption from the intestinal mucosa to the blood. The defect prevents Cu transport across most other body cells, making correction by parenterally administered Cu impossible. It is characterized by subnormal Cu levels in blood, liver and hair, progressive mental deterioration, hypothermia, defective keratinization of hair and degenerative changes in aortic elastin. Death usually occurs before 2 years of age (4).

Copper ores are mined, smelted and refined to produce many industrial and commercial products. Copper is widely used in cooking utensils and water distribution systems, as well as fertilizers, bactericides, fungicides and antifouling paints. Copper is also used in production of wood preservatives, electroplating, azo-dye manufacture, as a mordant for textile dyes, in petroleum refining and the manufacture of Cu compounds.

For non-occupationally exposed population the major route of exposure to Cu is oral. The average daily oral intakes of Cu (food plus drinking water) are between 1 and 2 mg. Women using Cu IUDs are exposed to only 80 µg or less of Cu per day from this source (5).

1. Deficiency
2. Wilson's disease and other hepato-biliary disorders
3. Toxicity

Copper levels are monitored in subjects on prolonged TPN to ensure adequate nutritional intake. Plasma Cu levels are useful measures of moderate to severe deficiency but less sensitive measures of marginal deficiency.

In Wilson's disease, plasma levels of Cu and ceruloplasmin may be decreased, but the body's burden of Cu as found in the liver is elevated. Urine levels of Cu are usually increased.

In cases of acute ingestion of Cu salts, such as Cu sulfate solutions, plasma Cu will be high and ceruloplasmin levels will be normal.

Ceruloplasmin is an acute phase reactant, increasing in response to infection, inflammation, and trauma, so plasma Cu levels are expected to rise in these conditions. Steroid hormones stimulate ceruloplasmin synthesis. Plasma Cu levels can be two to three-fold higher in pregnancy and with the use of oral contraceptives because of estrogen action (6, 7). Raised Cu levels are also seen in lymphoma and Hodgkin's disease, where an early response to treatment can be judged by the fall in serum Cu to normal levels.

Plasma/serum: copper deficiency, Wilson's disease and other hepato-biliary disorders, and toxicity.

Urine: 24 hour urine is required for investigating Wilson's disease. Random urine is acceptable for investigating occupational exposure and acute poisoning.

Liver biopsy: Measuring copper in liver tissue has been used in the diagnosis of Wilson's disease in which concentrations of over 250 µg/g dry weight are usually found. However, values below this level do not exclude the diagnosis and high levels may also be found in obstructive liver disease.

Toxicity: The mainstay of treatment for Wilson disease is removal of Cu from the body with chelating agents. Zinc, which can block Cu absorption in the stomach, has been used to treat patients with Wilson's disease (2).