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Scottish Trace Element and Micronutrient Reference Laboratory

Scotland's specialised laboratory for trace elements and vitamins in health and disease

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Copper (Cu)

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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. Caeruloplasmin is a positive acute phase reactant and so a detectable increase in plasma copper (by up to 30%) would be expected after infection, injury, or inflammation. Failure to sustain such an increase could reflect copper depletion.

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 last trimester of pregnancy and with the use of oral contraceptives. In neonates copper is low (3-5µmol/L) but increases gradually to adult values by one to two years of age. Results below 5 µmol/L over several weeks in the developing child suggest a need for copper supplementation.

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. A detailed protocol is given through this link.

Metabolism of copper

Disorders of copper metabolism (Wilson's disease)

Sample Requirements and Reference Values

Sample Type

Plasma, serum, urine, liver biopsy

Container

Plasma/serum: lithium heparin, plain, or 'Trace Element' (plain or heparin). Gel tube unsuitable
Urine/biopsy: Universal container.

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.

Volume

Plasma/serum: 500 µL (minimum)
Urine: 25 mL
Liver biopsy: 1 to 5 mg

Reference ranges

- copper

10 to 22 µmol/L

- caeruloplasmin

0.2 to 0.6 g/L

- urine

< 1.0 µmol/24 h

- liver

8 to 40 µg/g dry weight
> 250 µg/g dry weight (suggestive of Wilson's Disease)

Turnaround time

1 week

Method

Plasma: Inductively coupled plasma/emission spectrometry
Urine/biopsy: Graphite furnace/atomic absorption spectrometry

  1. The sample tube should be free of rubber rings or other contaminating sealing materials in the cap. For Vacutainers, special dark blue-topped Trace Metal tubes (Code No: 36 7735 LiHep or 6526 12054 Plain) are preferable.
  2. 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 despatched at room temperature.
  3. Plasma or serum Cu results of less than 10 µmol/l are abnormal and should be repeated. In neonates, adult levels are not fully reached till 1-2 years. Results remaining below 5 µmol Cu/l over a period of some weeks in the developing child suggest a need for copper supplementation. Values for plasma Cu above 30 µmol/l are abnormal but may be encountered in severe inflammatory disease, and in active liver disease. Measurement of caeruloplasmin on the sample is useful to distinguish cases of suspected copper toxicity.

 

Wilson's Disease

Food Standards Agency