Copper is an essential component of numerous copper metalloenzymes that are required for normal oxidative metabolism, iron metabolism, free radical detoxification, and synthesis of haemoglobin, elastin, and collagen.
The liver stores significant amounts of copper, so clinical deficiency is unlikely without a prolonged inadequate dietary intake. Most plasma copper is in the form of caeruloplasmin which is a positive acute phase reactant and so a detectable increase in plasma copper (by up to 30%) may be seen after infection, injury, or inflammation. Deficiency may result as a result of high oral zinc intake, stomach/duodenal disease and renal insufficiency.
Copper is normally excreted in bile and so an increase in urinary copper occurs in Wilson’s Disease and to a lesser degree in cholestatic liver disease. Oestrogens increase copper by increasing caeruloplasmin synthesis so it can be two to three-fold higher in the last trimester of pregnancy and with the use of oral contraceptives.
In neonates, copper is low (3-5 µmol/L) but increases gradually to adult values by one to two years of age.
The measurement of 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. A more reliable and safer test is the measurement of copper uptake using the stable isotope 65Cu.
Sample Requirements and Reference Ranges for Copper
| Sample Type | Plasma, serum, urine, liver biopsy |
|---|---|
| Container | Plasma/serum: lithium heparin, plain, or ‘Trace Metal’ (plain or heparin). SST and EDTA unsuitable. Urine: 24 h sample. Acid-washed container not necessary. |
| Precautions | Liver biopsy: Samples should be without preservative and transferred directly to the wall of a Universal container; please do not put onto lint. They should be stored frozen. They may be dispatched at room temperature.
Please mix 24 hour urine well before taking an aliquot. |
| Minimum volume* | Plasma: 250 µL; urine: 1 mL Liver biopsy: 0.5 mg |
| Reference ranges | |
| - plasma/serum copper | 10 to 22 µmol/L (men) 11 to 25 µmol/L (women) 27 to 49 µmol/L (pregnancy) 1.5 to 7.0 (0 to 3 months) 4.0 to 17.0 (4 to 6 months) 8.0 to 20.5 (7 to 12 months) 12.5 to 23.5 (1 to 5 years) 13.0 to 21.5 (6 to 9 years) 12.5 to 19.0 (10 to 13 years) |
| - caeruloplasmin | 0.2 to 0.6 g/L |
| - urine | < 0.6 µmol/24h |
| - liver | 8 to 40 µg/g dry weight > 250 µg/g dry weight (possible Wilson’s Disease) |
| Turnaround time | 1 week |
| Method | Inductively coupled plasma mass spectrometry |
* This is the absolute minimum volume; these volumes are insufficient to carry out a repeat analysis in the event of an analytical problem.