COPPER TOXICOSIS/
CHRONIC ACTIVE HEPATITIS
W. Jean Dodds, DVM
Hemopet
310-828-4804; Fax 310-828-8251
Abnormal accumulation of copper in the
liver leads to chronic liver failure, and is an heritable
or familial trait recognized in an increasing number of dog breeds, including
the West Highland White Terrier, Bedlington Terrier, Skye Terrier, Doberman Pinscher, Labrador Retriever,
Keeshond, and American Cocker Spaniel. Other breeds may also be affected.
Certain diseases of the liver, especially those that cause blockage of the bile
duct or bile flow (cholestasis), also can result in
excessive hepatic copper accumulation.
While the level of copper and other
metals stored in the body generally tends to be higher in newborns, levels in
the dog remain fairly constant throughout life, and are higher than those
normally seen in humans. The mean
copper concentration in the liver of normal dogs of any breed is 200-400 ppm on a dry weight basis.
Dogs with copper toxicosis (also known as
chronic active hepatitis) may exhibit concentrations of copper up to 10,000 ppm, while levels of 2000 or greater ppm
are excepted to be toxic.
Copper toxicosis,
a copper storage disease, is known as Wilson's disease in people. A similar disease was first recognized in
the Bedlington Terrier
breed, and there is now a specific genetic DNA screening test for this
trait. Investigators at the
Clinical and Pathological Findings
In affected dog breeds, whether the
defect is an heritable trait involving the metabolism
of copper itself or is a copper storage disorder --- such as might be involved
with the Doberman pinscher --- does not affect the outcome. There are three progressive stages of copper
toxicosis. In
the first stage, the dog is young and not
clinically ill, copper levels are beginning to accumulate in the liver, and
values are reported to be as high as 1500 ppm.
Regardless of the breed, this accumulation begins very early in life, and the
rate of accumulation will vary among different breeds and also within
individual animals. Wedge biopsy of the
liver at this stage will look normal, although special copper stains of biopsy
tissue will reveal the excess copper. Stage
two of copper toxicosis occurs when the copper
level in the liver reaches 2000 ppm. The dog is typically not ill at this point
but wedge biopsy of the liver will show hepatitis and is the definitive test to
make a diagnosis. Laboratory findings
at that time may include an increase in ALT and alkaline phosphatase
enzyme levels, but these are nonspecific findings, not necessarily indicative
of copper toxicosis.
As an elevated ALT enzyme concentration reflects specific hepatocellular disease, it signifies a toxic or other form
of injury to the liver cell. There are
other pathological changes in blood profiles which can include: low platelet
counts, thyroid dysfunction, increase bilirubin in
the blood and/or urine, hypoalbuminemia, and
anemia. Finally, in stage three disease the dog becomes clinically ill, may have a poor
appetite (anorexia), depression, abdominal pain, vomiting, excessive drinking (polydipsia) and urination (polyuria),
icterus or jaundice, ascites,
high amylase and lipase concentrations, and weight loss, the latter is commonly
seen and may be the only clinical sign.
These clinical signs usually result from liver necrosis, which is
triggered by copper concentrations above 2000 ppm.
In the end stages of copper toxicosis, the concentration of copper in the liver may
actually decrease, as the cells that die during the necrotic process are those that
have accumulated copper. Because of the
progressive nature of the disease, most affected animals are not presented for
diagnosis and treatment until the late stages, when clinical symptoms are
present, or after some significant body stress event such as a pregnancy. In fact, most of the severely affected,
fatal cases in American Cocker Spaniels have occurred in females within a few
weeks to months after a pregnancy. An intriguing possibility is the potential relationship
between the high incidence of autoimmune hemolytic anemia in American Cocker
Spaniels [the breed with highest risk worldwide] and copper toxicosis
due to the free radicals produced by copper accumulation. Such a relationship
has been suggested in the Bedlington Terrier.
Management and Treatment
Treatment of copper toxicosis
can include dietary, medical, or a combination of these methods. Please see the accompanying two-page handout, which discuss dietary modification to reduce copper
accumulation. When copper accumulation is detected early on and the dog is asymptomatic, initiating treatment at that time may slow
down the accumulation of copper before irreversible damage to the liver has
occurred. In addition to the dietary
changes mentioned in the accompanying handout, chelating agents can be used which bind or chelate copper,
thereby enhancing its excretion in the urine or bile. The most commonly used chelating agent is d-penicillamine
given at 10-15 mg/kg. However, the use
of this copper-chelating drug is somewhat controversial because it also binds zinc, which made deplete tissue levels of zinc and
have undesirable side effects. Also, d-
penicillamine has other side effects such as
anorexia, nausea, and vomiting. In
treating some canine cases, the adverse effects of d-penicillamine were counteracted by using a homemade low
copper-low protein diet with additional zinc supplementation. Other drugs that have been used in chronic
active hepatitis are corticosteroids, such as prednisone, and colchicine. Of
the two drugs, prednisone would be preferred as it
helps the body excrete excess copper while fighting the inflammation and
fibrosis of the liver. Side effects of
both these drugs include inducing liver enzyme levels, and colchicine
often produces nausea.
Selected References
Dodds W J. Pet food
preservatives and other additives, Chapter 5. In: Complementary and Alternative
Veterinary Medicine. Mosby,
Dill-Mackey E. Chronic
hepatitis in dogs. Vet
Clinics
Dodds W J, Donoghue S.
Interactions of clinical nutrition with genetics, Chapter 8. In: The
Schilsky M L , Sternlieb I. Animal models of copper toxicosis. Adv Vet Sci Comp
Med, 37:357-373, 1993.
Thornburg L P. A study of canine hepatobiliary
diseases, Part 4: copper and liver disease.
Comp An Pract, 2(7):
3-6, 1988.
Hardy R M. Chronic Hepatitis in dogs: a
syndrome. Comp Cont Edu
Pract Vet, 8: 904-914, 1986.
Thornburg L P, Polley D, Dimmitt R.
The diagnosis and treatment of copper toxicosis
in dogs, Can Pract, 11(5): 36-39, 1984.