Page 272 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

VetBooks.ir Chapter 15

Liver Toxicity

Karyn Bischoff, Motoko Mukai and Shashi K. Ramaiah

INTRODUCTION Liver injury by xenobiotics is encountered in a variety
of circumstances. Some natural toxins such as the cyclic
The liver is a remarkable organ that usually protects the
peptides of Amanita phalloides, pyrrolizidine alkaloids,
individual against injury from xenobiotic compounds.
cycasin from cycad palms and other phytotoxins are exam-
However, this organ is often the site of metabolism and it
ples of environmental hazards. They may be ingested by
is where some chemicals concentrate and become
the curious or very hungry veterinary patient. Others, such
bioactivated, leading to hepatic injury. Although its
as mycotoxins, are ingested unknowingly because of feed
capacity for repair and regeneration (Ramaiah et al.,
contamination due to climatic conditions favorable to fun-
2004; Mehendale, 2005) makes it a quite robust organ, if
gal growth. A striking example of this phenomenon was
the ability to regenerate is not adequate, or if injury to the
the aflatoxin contamination of dog food, which resulted in
liver is very severe, liver damage can progress to liver
dozens of canine deaths in late 2005 and early 2006
failure and death.
(Stenske et al., 2006; Newman et al., 2007; Dereszynski
There is continued interest concerning the higher
et al., 2008). Other circumstances of exposure to hepato-
incidence of liver damage caused by prescription/
toxins in the home or farm have included accidental food
injectable drugs, over-the-counter medications, dietary
or feed contamination with industrial chemicals or pesti-
supplements, and special diets, in addition to environmental
cides. For example, in 1955, a human outbreak of hepatic
chemicals/xenobiotics (Watkins, 1999). Though alcohol
porphyria in Turkey was caused by ingestion of wheat to
consumption is not a major risk factor in most veterinary
which hexachlorobenzene, a fungistatic agent, had been
patients, other factors such as toxic pasture or house plants,
added (Can and Nigogosyan, 1963).
cyanobacterial toxins, pollutants, pesticides, fungal toxins,
The goal of this chapter is to provide a basic under-
and toxicants in household waste can cause hepatic injury.
standing of the liver physiology and pathophysiology, and
An incomplete list of hepatotoxins is found in Table 15.1.
to expand on the common toxicosis inducing liver injury
Complicating matters is the increasing population of geriat-
in veterinary medicine.
ric veterinary patients. Preexisting liver disease must be
considered in patients exposed to liver toxicants.
In humans, drug-induced liver injury (DILI) has
become the most frequent cause of acute liver failure in STRUCTURAL AND FUNCTIONAL
the United States and around the world, exceeding all ORGANIZATION OF THE LIVER
other causes combined. Although the incidence of idio- Lobule and Acinus
syncratic DILI with approved drugs at therapeutic doses
is relatively low and estimated at 1 10 per 100,000 trea- The structural and functional organization of the liver
ted patients, the outcome is potentially a very grave one. has been described by two concepts: the hepatic lobule
Approximately 10% of those human patients will die or and hepatic acinus models. The hepatic lobule, the
require liver transplantation, making idiosyncratic DILI classic model, is defined histologically as a hexagonal
the leading causes for urgent liver transplantation region of parenchyma surrounding the central vein. Six
(Stirnimann et al., 2010). Toxic liver disease also remains portal triads, composed of branches from the portal
the single major cause for regulatory actions concerning vein, hepatic artery and bile ductules, border the edge
drugs. Such actions may include failure of approval, of the lobule. One-cell thick plates or cords of hepato-
withdrawal from the market, restrictions on use and cytes are arranged radially around the central vein,
warnings to physicians. forming the blood sinusoids between them. The hepatic
Veterinary Toxicology. DOI: http://dx.doi.org/10.1016/B978-0-12-811410-0.00015-5
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