Page 1116 - Small Animal Clinical Nutrition 5th Edition

1162 Small Animal Clinical Nutrition

1995; Andersson and Sevelius, 1992; Thornburg, 1998). The
VetBooks.ir insidious onset contributes to the poor understanding of the
pathogenesis because most patients have an advanced stage of
the disease when it is recognized.
Hepatic fibrosis is an accumulation of extracellular collagen
and connective tissue within the liver (Center, 1996c) and is a
sequela to hepatic inflammation. Fibrosis not only results in
distortion of normal hepatic architecture, but also becomes a
barrier to movement of substances back and forth between
blood and hepatocytes. Cirrhosis is defined as fibrosis with loss
of normal acinar liver architecture and with regenerative nod-
ules (Figure 68-9) (Meyer, 1996). The architectural changes in
cirrhosis impair blood and bile flow and nutrient exchange,thus
perpetuating hepatocellular injury.

Canine Copper-Associated Hepatotoxicosis
Hepatic copper storage disease was first described in the
Bedlington terrier breed. The disease has some similarities to
Wilson’s disease in people (Hultgren et al, 1986). It is an inher-
Figure 68-7. An enlarged, pale yellow liver from a cat with hepatic ited autosomal recessive trait that impairs biliary excretion of
lipidosis.
copper (Su et al, 1982, 1982a). Affected dogs progressively
accumulate copper. Evidence of hepatic necrosis is observed
when copper concentrations exceed approximately 2,000 ppm
(µg/g) DW liver (normal copper concentrations are <400 µg/g
DW (Twedt et al, 1979; Twedt, 1990). As copper concentra-
tions increase, damage progresses to chronic hepatitis and ulti-
mately cirrhosis (Hultgren et al, 1986; Twedt et al, 1979;
Twedt, 1990). Rarely, massive widespread hepatic necrosis can
result in some dogs presenting with acute liver failure. Without
appropriate treatment with dietary management and copper
chelation,affected dogs usually succumb to their liver disease by
approximately seven to 10 years of age (Hultgren et al, 1986;
Twedt et al, 1979; Twedt, 1990). The gene responsible for this
defect has been identified (Van De Sluis et al, 2002) and it has
become possible to distinguish affected, homozygous normal
and carrier Bedlington terrier dogs using DNA markers
Figure 68-8. Photomicrograph of a liver specimen from a cat with (Yuzbasiyian-Gurkan et al, 1997). It was once estimated that
hepatic lipidosis. Hepatocytes containing lipid appear empty with an
inconspicuous nucleus when processed routinely with formalin fixa- about 25% of Bedlington terriers were affected with copper
tion and hematoxylin and eosin stain. toxicosis and another 50% were carriers. Now, through genetic
testing and responsible breeding programs, the incidence of this
disease is significantly lower.
Hepatic mitochondria are important intracellular targets of
Canine Chronic Hepatitis and Cirrhosis copper toxicosis. Functional abnormalities of mitochondria as-
Chronic hepatitis in dogs is a poorly defined group of clinico- sociated with oxidative injury (i.e., lipid peroxidation) have
pathologic entities characterized by parenchymal necrosis, par- been documented to occur in people, rats and Bedlington ter-
ticularly piecemeal and/or bridging necrosis, with associated riers with copper-induced hepatic injury (Sokol et al, 1993,
lymphoplasmacytic inflammation (Meyer, 1996; Thornburg, 1994). Oxidative injury and abnormal hepatic mitochondrial
1998; Speeti et al, 1998). Chronic hepatitis can result from respiration may be involved in the pathogenesis of copper tox-
many different causes including copper accumulation (See be- icosis. This theory forms the basis for using vitamin E and
low.), infectious diseases, drugs, breed-associated hepatitis and other antioxidants as potential therapeutic agents in addition to
possibly autoimmune disease. An etiology is never determined chelation therapy.
in most cases (Watson, 2004). The role of copper in hepatic diseases observed in other dog
Lymphoplasmacytic inflammation suggests an immune- breeds is less clear. Abnormal concentrations of copper in the
mediated mechanism. Autoantibodies have been recognized in liver can result secondary to cholestatic liver disease (Center,
dogs with chronic hepatitis but it is unknown if such an im- 1996c; Haywood et al, 1988; Johnson et al, 1982) or as a pri-
mune reaction is the cause or result of the disease (Weiss et al, mary defect in hepatic copper excretion resulting in hepatic