Clinical Information

Copper (Cu) is an important trace element that is associated with a number of metalloproteins. Copper in biological material is complexed with proteins, peptides, and other organic ligands. Up to 90% of copper exported from the liver into peripheral blood is protein bound to ceruloplasmin, transcuprein, or metallothionein. A smaller amount of copper in plasma (<10%) is bound to albumin by specific peptide sequences, and this copper is in equilibrium with plasma amino acids. The ceruloplasmin molecule contains 6 to 8 atoms of Cu per molecule with 6 atoms of Cu involved in the protein's ferroxidase and free radical scavenging activities. The other 1 to 2 atoms of Cu are termed "labile" and may allow ceruloplasmin to act as a copper transporter, with a pool of copper being exchanged between albumin, transcuprein, and the labile sites of ceruloplasmin.

Low serum copper, most often due to excess iron or zinc ingestion and infrequently due to dietary copper deficit, results in severe derangement in growth and impaired erythropoiesis. Low serum copper is also observed in hepatolenticular degeneration (Wilson disease) due to a decrease in the synthesis of ceruloplasmin and allelic variances in cellular metal ion transporters. In Wilson disease, the albumin-bound copper may actually be increased, but ceruloplasmin-bound copper is low, resulting in low serum copper. However, during the acute phase of Wilson disease (fulminant hepatic failure), ceruloplasmin and copper levels may be normal; in this circumstance, hepatic inflammation causes increased release of ceruloplasmin. It is useful to relate the degree of liver inflammation to the ceruloplasmin and copper-see discussion on hypercupremia below. Significant hepatic inflammation with normal ceruloplasmin and copper suggest acute Wilson disease.

Other disorders associated with decreased serum copper concentrations include malnutrition, hypoproteinemia, malabsorption, nephrotic syndrome, Menkes disease, copper toxicity, and megadosing of zinc-containing vitamins (zinc interferes with normal copper absorption from the gastrointestinal [GI] tract).

Hypercupremia is found in primary biliary cholangitis (formerly primary biliary cirrhosis), primary sclerosing cholangitis, hemochromatosis, malignant diseases (including leukemia), thyrotoxicosis, and various infections. Serum copper concentrations are also elevated in patients taking contraceptives or estrogens and during pregnancy.

Since the GI tract effectively excludes excess copper, it is the GI tract that is most affected by copper ingestion. Increased serum concentration does not, by itself, indicate copper toxicity.