Page 714 - Clinical Small Animal Internal Medicine

682 Section 7 Diseases of the Liver, Gallbladder, and Bile Ducts

centrilobular liver necrosis as a result of hypoxic dam- Therapy
VetBooks.ir age. In dogs surviving the hemolytic crisis, cirrhosis or those of an acute hemolytic crisis have developed,
Once signs of chronic hepatitis or cirrhosis are present,
occurs much more often than in other animals.
specific therapy is usually not possible. Symptomatic
History and Clinical Signs and supportive care is therefore important. In chronic
With chronic copper accumulation, the clinical signs are hepatitis or cirrhosis, management of hepatic encepha-
those of chronic hepatitis or cirrhosis. The reader is lopathy, portal hypertension, and ascites is vital.
therefore referred to the relevant sections for further Readers are referred to Chapter 65 for further details
details. In the acute form there is acute hemolysis, ane- regarding therapy.
mia, severe icterus, and sometimes uremia. The acute Hemolytic crisis is a very serious event. Administration
form is often lethal within a few days. of penicillamine, which is a chelating drug that binds
metals, preferentially copper, is indicated. The penicil-
Diagnosis lamine–copper complex is excreted from the kidneys
Laboratory examination may reveal any of the changes into urine, resulting in free copper being removed from
seen in chronic hepatitis and cirrhosis, such as increased the circulation. Intravenous infusion of fluids with diure-
ALT, ALP, GGT, bile acids, and bilirubin. Hypoalbuminemia sis may also be helpful to enhance urinary copper
and hepatic encephalopathy with increased ammonia con- excretion.
centrations occur only in late stages. There are no specific It is important to try to prevent the development of
laboratory parameters that are specific for copper accumu- clinical signs in dogs at risk for copper storage disease.
lation. Ceruloplasmin and free copper concentrations are Hence, asymptomatic dogs should be examined at a
not different from healthy dogs, whereas Wilson disease in young age, and if there is copper accumulation, life‐long
humans is associated with decreased ceruloplasmin levels. medication with drugs that prevent further accumula-
On the basis of the clinical examination and result of tion of copper is essential. There are two drugs available,
blood tests, it is not possible to differentiate copper stor- and both are given orally in a capsulated form.
age disease from chronic hepatitis or cirrhosis. The diag- Penicillamine may be given 30 minutes before each meal
nosis can only be made by demonstrating increased at a total daily dose of 25 mg/kg. Penicillamine binds
copper accumulation in a liver biopsy in animals older copper in the circulation and the bound complex is
than 1 year. Histologically, copper in a liver biopsy may be excreted in the urine. Another drug is zinc, which may be
detected with specific stains such as rubeanic acid. The given as zinc gluconate at a dosage of 30 mg/kg/day in
same staining may be used on cytologic preparations col- divided doses immediately before each meal. The action
lected by fine needle aspiration. Copper accumulation of zinc is at the level of the intestinal mucosa, as it induces
begins in hepatocytes around the central veins (zone 3) the formation of copper‐binding metallothionein, thus
and gradually spreads outwards toward the portal areas. preventing the absorption of copper. The two drugs
The copper is stored in the hepatic lysosomes. The cop- should not be combined since they form complexes and
per‐induced liver cell damage only occurs when a certain inactivate each other. These medications are unable to
level is exceeded. The damage leads to ongoing liver cell reduce hepatic copper levels in most cases, but they pre-
necrosis and secondary inflammation that can eventually vent further accumulation and development of the
result in fibrosis and cirrhosis. The normal concentration symptomatic stage. Another measure to prevent further
of copper in the canine liver is between 50 and 300 μg/g accumulation is to reduce the copper content of the food.
dry weight. Dogs with copper accumulation have levels Commercial foods have been developed to treat and pre-
exceeding 1000 μg/g dry weight at 1 year of age, but most vent copper storage diseases, and have been proven to be
cases have higher concentrations. With time, levels of very effective. These are veterinary‐formulated liver
12 000 μg/g dry weight may be reached. At 1 year of age, a diets containing low copper and high zinc.
few dogs have concentrations between 300 and 1000 μg/g
dry weight, and most of them appear not to accumulate Copper Storage‐Associated Hepatitis and Cirrhosis
when reexamined later. in Labrador Retrievers
A genetic test for the mutated COMMD1 gene is avail- Since 2006, Labrador retrievers have been reported to
able, although not all dogs with the disease have this have a form of copper storage disease causing hepatitis,
defect. However, heterozygote carriers cannot be distin- which if untreated results in cirrhosis. Much of the
guished from homozygote healthy animals. A few decades description pertaining to the Bedlington terrier applies to
ago, the incidence of the disease in Bedlington terriers was the disease in Labradors. Like all forms of copper storage,
about 30–50%. However, with the availability of a reliable the disease develops gradually due to the slow accumula-
genetic test, the incidence of the disease has dramatically tion of copper in the centrilobular area of the liver.
declined, with clinical cases becoming quite rare. Therefore, the typical age of onset of clinical signs in this