By Joseph D. Roder, D.V.M., Ph.D., D.A.B.V.T. (Auth.)
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Rumbeiha WK, Lin YS, Oehme FW. Comparison of N-acetylcysteine and methylene blue, alone or in combination, for treatment of acetaminophen toxicosis in cats. Am J Vet Res. 1995;56:1529–1533. Wilkie DA, Kirby R. Methemoglobinemia associated with dermal application of benzocaine cream in a cat. J Am Vet Med Assoc. 1988; 192:85–86. Yeruham I, Shlosberg A, Hanji V, et al. Nitrate toxicosis in beef and dairy cattle herds due to contamination of drinking water and whey. Vet Hum Toxicol. 1997;39:296–298.
Most of the hepatic blood supply is portal blood. • The liver detoxifies most xenobiotics before they enter the systemic circulation. • first-pass effect • greatest concentration of cytochrome P450 is in the liver The liver is exposed to reactive intermediate metabolites. • Xenobiotics are metabolized to more water-soluble compounds. • Some toxins are excreted in the bile. • The liver has an immense reserve capacity and regenerative ability. • decreased liver function not noted until 75% of hepatic mass is diminished Mechanisms of Hepatic Intoxication HEPATIC FAILURE • Cytotoxic effect Clinical Presentation and Diagnosis of Common Veterinary Toxicants 47 • Examples • Amanita mushrooms • phenolics • copper intoxication • Damage associated with reactive metabolite • Examples • acetaminophen in dogs • pyrrolizidine alkaloid–containing plants CHOLESTASIS • Damage to the bile canaliculi or epithelial cells of the bile ducts • Decrease in production and secretion of bile • Increase in bilirubin and bile acids • Examples • aflatoxin • lantana Tests of Hepatic Function CLINICAL LABORATORY • Liver function tests • alanine aminotransferase (ALT) • alkaline phosphatase (ALP or AP) • aspartate aminotransferase (AST) • ␥-glutamyl-transferase (GGT) • sorbitol dehydrogenase (SDH) • Serum bilirubin • Bile acids • Other tests of hepatic function • serum albumin generally performed for chronic conditions • coagulation coagulation factors are produced in the liver 48 Clinical Presentation and Diagnosis of Common Veterinary Toxicants CLINICAL PRESENTATION • By time of onset of clinical signs • acute hepatic failure • chronic hepatic failure • Clinical signs • anorexia • depression • coma • vomiting • icterus, jaundice Common Veterinary Respiratory Toxins Respiratory Irritants • Ammonia • Hydrogen sulfide Ventilatory Muscle Paralysis • • • • • • Botulism Neuromuscular junction blockers Organophosphorus insecticides Snake envenomation Strychnine Tetanus Respiratory Center Depression • • • • • • Barbiturates Ethylene glycol Hypnotics Opiates and opioids Sedatives Tricyclic antidepressants Clinical Presentation and Diagnosis of Common Veterinary Toxicants 49 Pneumonia • Crude oil • 3-Methyl indole • Paraquat Cellular Hypoxia • • • • • Carbon monoxide Cyanide Hydrogen sulfide Methemoglobinemia Sulfhemoglobin References Blodget DJ.
Figure 3–11 Production of hydrogen peroxide reactive oxygen species. The hydroperoxyl radical is a short-lived radical that forms hydrogen peroxide and oxygen. Pathophysiology of Selected Mechanisms 63 Figure 3–12 Reaction catalyzed by superoxide dismutase (SOD). This enzyme reduces the reactivity of the superoxide anion by forming hydrogen peroxide and oxygen. Figure 3–13 Fenton reaction. Interaction of hydrogen peroxide and ferrous iron mediates production of ferric iron and reactive ions. Figure 3–14 Reactive oxygen species damage to cells.
Veterinary Toxicology by Joseph D. Roder, D.V.M., Ph.D., D.A.B.V.T. (Auth.)