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QUESTIONS

1. Besides Bedlington terriers, what is the other dog breed affected by copper associated hepatitis?
    
2. In Bedlingtons, this disease is inherited as autosomal recessive.  How is it believed to be inherited in the other breed?
    
3. A new client with a Bedlington terrier has records send from her previous DVM.  This dog had a quantitative copper measure done on a liver biopsy at age 6 months and another at age 16 months.  This dog is well and has never been sick in any way.  Why do you suppose the other DVM did these biopsies? (Hint: the dog is a champion show Bedlington.)
    
4. The human disease most similar to Copper Associated Hepatitis of Bedlington terriers is called _______________.
    
5. Normally, copper is absorbed from the GI tract, bound to albumin, and transferred to _______________, a special carrier protein for copper.  In the human version of this disease, there is a deficiency of this protein leaving excess copper loose in the circulation to be taken up by tissues. The organs that take up the most copper are the liver, the brain (humans only - dog brains don't seem to have a problem with copper) and _______________.  The liver cannot excrete all this copper and fails.
    
6. Why is quantitative copper analysis needed on liver tissue to diagnose this disease (in other words, why can't you just stain for copper and note that there is an excess?)
    
7. What is a Kayser-Fleisher ring?
    
8. In humans, 4 findings are sought in the consideration of this disease. Using your extra sensory perception & what you know about this disease, can you figure out what these four findings are?
    
9. D-Penicillamine (Cupramine) and/or Trientine HCl (Cuprid) are used in treatment. What do they do?
    
10. Some recommend zinc supplementation in the diet as a specific treatment for this disease.  Why?
     
11. A Bedlington's quantitative analysis of Copper is 300 micrograms per gram.  Is this high?
    
    
    
    
     

ANSWERS

1. The other breed is the West Highland White terrier.
   
   
   
   
    
2. In the Westy, the mode of inheritance is thought to be Autosomal dominant (my impression is that this is not known for sure).
   
   
   
   
    
3. If you owned a valuable Bedlington & wanted to use him for stud, you should evaluate him for heterozygosity for Copper Associated Hepatitis.  One way to do this is the do a copper analysis in puppyhood and another in adulthood.  In a heterozygote, the copper level will be high in puppyhood & normalize later. This is not a 100% test because some adults normalize relatively later than age one or two but heterozygotes never actually get the disease.  For breeding one should know if one's dog is a carrier.
   
   
   
   
    
4. The human disease is Wilson's disease.
   
   
   
   
    
5. The storage protein is Ceruloplasmin.  The other organ that collects copper is the kidney. The kidney is, however, better at excreting copper than is the liver so you wouldn't usually see kidney disease (just liver disease).
   
   
   
   
    
6. In cholestasis of any cause, copper accumulates in the biliary system. This is separate from Copper associated hepatitis and unless you do a quantitative analysis you won't find the much higher levels of copper associated with copper associated hepatitis.
   
   
   
   
    
7. In humans with Wilson's disease, a brown circumferential ring of pigment on the cornea (called a Kayser-Fleisher ring)  is seen on the patient's eyes. According to Strombeck's book, dogs with copper associated hepatitis may have these rings also.
   
   
   
   
    
8. The 4 findings sought out in people suspected of having Wilson's disease are:
   
   a) liver biopsy showing high copper levels
   
   b) reduced serum level of ceruloplasmin (this test is not available for dogs)
   
   c) increased urine copper levels
   
   d) Kayser-Fleisher rings
   
   
   
   
    
9. Cupramine and cuprid are heavy metal chelators.  They chelate divalent cations in the circulation and the chelated metals are excreted in urine. Cuprid is newer & is supposed to have fewer nausea type side effects than cupramine.
   
   
   
   
    
10. There is a substance called metallothionein which is produced by the intestinal mucosa. It inhibits the absorption of both zinc and copper.  It is stimulated by the presence of excess zinc in the GI tract.
    
    
    
    
     
11. A copper level of 300 micrograms per gram of liver is normal.  Normal range (from Ettinger) is 91-377 micrograms per gram.