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. 1974 Feb;15(2):125–129. doi: 10.1136/gut.15.2.125

Defective biliary excretion of copper in Wilson's disease

D J Frommer
PMCID: PMC1412902  PMID: 4820637

Abstract

The biliary excretion of copper was measured in eight patients with Wilson's disease (three untreated, with hepatic dysfunction) and 10 control subjects (three with hepatic dysfunction). The duodenum was perfused with an amino-acid solution containing a non-absorbed marker, 51CrCl3, and juice was aspirated from the duodeno-jejunal junction. The mean concentration of copper in the duodenal aspirate in Wilson's disease was significantly lower than in the control group. The mean biliary copper excretion rate in Wilson's disease of 8·6 ± 0·8 μg/20 min (SEM) was also significantly below that of the control group (16·4 ± 0·8 μg/20 min). The presence of liver dysfunction made no significant difference to the excretion rates in either group of patients. These results suggest that the copper accumulation in Wilson's disease is due to the inability of the liver to excrete copper into bile in adequate amounts.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BICKEL H., NEALE F. C., HALL G. A clinical and biochemical study of hepatolenticular degeneration (Wilson's disease). Q J Med. 1957 Oct;26(104):527–558. [PubMed] [Google Scholar]
  2. BUSH J. A., MAHONEY J. P., MARKOWITZ H., GUBLER C. J., CARTWRIGHT G. E., WINTROBE M. M. Studies on copper metabolism. XIV. Radioactive copper studies in normal subjects and in patients with hepatolenticular degeneration. J Clin Invest. 1955 Dec;34(12):1766–1778. doi: 10.1172/JCI103232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CARTWRIGHT G. E., HODGES R. E., GUBLER C. J., MAHONEY J. P., DAUM K., WINTROBE M. M., BEAN W. B. Studies on copper metabolism. XIII. Hepatolenticular degeneration. J Clin Invest. 1954 Nov;33(11):1487–1501. doi: 10.1172/JCI103027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CARTWRIGHT G. E., WINTROBE M. M. COPPER METABOLISM IN NORMAL SUBJECTS. Am J Clin Nutr. 1964 Apr;14:224–232. doi: 10.1093/ajcn/14.4.224. [DOI] [PubMed] [Google Scholar]
  5. Canelas H. M., de Jorge F. B., Tognola W. A. Metabolic balances of copper in patients with hepatolenticular degeneration submitted to vegetarian and mixed diets. J Neurol Neurosurg Psychiatry. 1967 Aug;30(4):371–373. doi: 10.1136/jnnp.30.4.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carrico R. J., Deutsch H. F., Beinert H., Orme-Johnson W. H. Some properties of an apoceruloplasmin-like protein in human serum. J Biol Chem. 1969 Aug 10;244(15):4141–4146. [PubMed] [Google Scholar]
  7. DENNY-BROWN D., PORTER H. The effect of BAL (2,3-dimercaptopropanol) on hepatolenticular degeneration (Wilson's disease). N Engl J Med. 1951 Dec 13;245(24):917–925. doi: 10.1056/NEJM195112132452401. [DOI] [PubMed] [Google Scholar]
  8. Ertan A., Brooks F. P., Ostrow J. D., Arvan D. A., Williams C. N., Cerda J. J. Effect of jejunal amino acid perfusion and exogenous cholecystokinin on the exocrine pancreatic and biliary secretions in man. Gastroenterology. 1971 Nov;61(5):686–692. [PubMed] [Google Scholar]
  9. Frommer D. The binding of copper by bile and serum. Clin Sci. 1971 Dec;41(6):485–493. doi: 10.1042/cs0410485. [DOI] [PubMed] [Google Scholar]
  10. GOLDSTEIN N. P., RANDALL R. V., GROSS J. B., MCGUCKIN W. F. COPPER BALANCE STUDIES IN WILSON'S DISEASE; OBSERVATIONS ON THE EFFECT OF PENICILLAMINE, CARBACRYLAMINE RESINS, AND POTASSIUM SULFIDE. Arch Neurol. 1965 May;12:456–462. doi: 10.1001/archneur.1965.00460290012002. [DOI] [PubMed] [Google Scholar]
  11. Go V. L., Hofmann A. F., Summerskill W. H. Simultaneous measurements of total pancreatic, biliary, and gastric outputs in man using a perfusion technique. Gastroenterology. 1970 Mar;58(3):321–328. [PubMed] [Google Scholar]
  12. Lewis K. O. The nature of the copper complexes in bile and their relationship to the absorption and excretion of copper in normal subjects and in Wilson's disease. Gut. 1973 Mar;14(3):221–232. doi: 10.1136/gut.14.3.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mistilis S. P., Farrer P. A. The absorption of biliary and non-biliary radiocopper in the rat. Scand J Gastroenterol. 1968;3(6):586–592. [PubMed] [Google Scholar]
  14. Murphy G. M., Billing B. H., Baron D. N. A fluorimetric and enzymatic method for the estimation of serum total bile acids. J Clin Pathol. 1970 Oct;23(7):594–598. doi: 10.1136/jcp.23.7.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. O'Reilly S., Weber P. M., Oswald M., Shipley L. Abnormalities of the physiology of copper in Wilson's disease. 3. The excretion of copper. Arch Neurol. 1971 Jul;25(1):28–32. doi: 10.1001/archneur.1971.00490010038005. [DOI] [PubMed] [Google Scholar]
  16. PLAYOUST M. R., DALE N. E. Metabolic balance studies in a patient with Wilson's disease and hypercalcuria. Metabolism. 1961 Apr;10:304–314. [PubMed] [Google Scholar]
  17. SCHEINBERG I. H., STERNLIEB I. Copper metabolism. Pharmacol Rev. 1960 Sep;12:355–381. [PubMed] [Google Scholar]
  18. SCHEINBERG I. H., STERNLIEB I. WILSON'S DISEASE. Annu Rev Med. 1965;16:119–134. doi: 10.1146/annurev.me.16.020165.001003. [DOI] [PubMed] [Google Scholar]
  19. SUNDERMAN F. W., Jr, WHITE J. C., SUNDERMAN F. W. Metabolic balance studies in hepatolenticular degeneration treated with diethyldithiocarbamate. Am J Med. 1963 Jun;34:875–888. doi: 10.1016/0002-9343(63)90094-9. [DOI] [PubMed] [Google Scholar]
  20. Sass-Kortsak A. Copper metabolism. Adv Clin Chem. 1965;8:1–67. doi: 10.1016/s0065-2423(08)60412-6. [DOI] [PubMed] [Google Scholar]
  21. Sternlieb I., Van den Hamer C. J., Morell A. G., Alpert S., Gregoriadis G., Scheinberg I. H. Lysosomal defect of hepatic copper excretion in Wilson's disease (hepatolenticular degeneration). Gastroenterology. 1973 Jan;64(1):99–105. [PubMed] [Google Scholar]
  22. Strickland G. T., Beckner W. M., Leu M. L., O'Reilly S. Turnover studies of copper in homozygotes and heterozygotes for Wilson's disease and controls: isotope tracer studies with 67 Cu. Clin Sci. 1972 Nov;43(5):605–615. doi: 10.1042/cs0430605. [DOI] [PubMed] [Google Scholar]
  23. Strickland G. T., Blackwell R. Q., Watten R. H. Metabolic studies in Wilson's disease. Evaluation of efficacy of chelation therapy in respect to copper balance. Am J Med. 1971 Jul;51(1):31–40. doi: 10.1016/0002-9343(71)90321-4. [DOI] [PubMed] [Google Scholar]
  24. UZMAN L. L., IBER F. L., CHALMERS T. C. The mechanism of copper deposition in the liver in hepatolenticular degeneration (Wilson's disease). Am J Med Sci. 1956 May;231(5):511–518. doi: 10.1097/00000441-195605000-00004. [DOI] [PubMed] [Google Scholar]
  25. Weber P. M., O'Reilly S., Pollycove M., Shipley L. Gastrointestinal absorption of copper: studies with 64Cu, 95Zr, a whole-body counter and the scintillation camera. J Nucl Med. 1969 Sep;10(9):591–596. [PubMed] [Google Scholar]
  26. ZIMDAHL W. T., HYMAN I., COOK E. D. Metabolism of copper in hepatolenticular degeneration. Neurology. 1953 Aug;3(8):569–576. doi: 10.1212/wnl.3.8.569. [DOI] [PubMed] [Google Scholar]

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