Hyperlipemia should be considered in the differential diagnosis for ponies or miniature horses with clinical signs of severe
depression, anorexia and icterus. The normal triglyceride level in horses and ponies should be less than 50 mg/dl, but may
be four-times higher in healthy donkeys and pregnant pony mares. A definitive diagnosis of hepatic lipidosis is confirmed
by the concurrent demonstration of increased blood concentrations of triglyceride (Figure 5), laboratory evidence of hepatic
disease and ultrasonographic or histopathologic findings of fatty infiltration in the liver.
Figure 5: Opalescent appearance of plasma with excessive triglycerides in a pony with hyperlipidemia.
There are numerous chemicals, drugs, mycotoxins and plant toxins that are hepatotoxic, but these rarely cause acute hepatic
failure in horses. Clinical signs and routine laboratory diagnostics will not distinguish between these toxins, so diagnosis
largely relies on exclusion of other causes, history of exposure and, in some cases, documentation of the toxin in the blood
Plants that have been reported to cause hepatic necrosis in horses in North America include: Kleingrass (Panicum), Lantana, Lechuguilla, Whitebrush, Sneezeweed (Helenium spp.), Lupine, bluegreen algae and ryegrass. Ingestion of pyrrolizidine alkaloid-containing plants is a common cause of chronic
liver disease in horses and is discussed separately below.
Horses rarely are exposed to hepato toxic chemicals in sufficient amounts to induce hepatic failure. Potential hepatotoxic
chemicals include arsenic, carbon tetrachloride, chlorinated hydrocarbons, carbon disulphide, pentachlorophenols, phenol,
phosphorus, polybrominated biphenyl and paraquat. All of these cause centrilobular necrosis, except phosphorus, which causes
primarily periportal changes.
Examples of intrinsically hepatotoxic drugs that cause zonal centri lobular necrosis include carbon disulfide and carbon
tetrachloride. Idiosyncratic hepatotoxicity has been reported following administration of erythromycin, rifampin, tetracycline,
halothane, phenothiazines, dantrolene, diazepam, sulfonamides, phenobarbital, phenytoin and aspirin. Excessive use of potent
corticosteroids (triamcinolone) has been reported to induce liver disease in the horse.
Chronic megalocytic hepatopathy
Megalocytic hepatopathy occurs worldwide and is the most common cause of chronic liver failure in horses in certain parts
of the United States. It is caused by the ingestion of pyrrolizidine alkaloid-containing plants. The development of clinical
signs of liver disease is usually delayed for weeks to months after consumption. The onset of obvious hepatic failure, characterized
by hepatic encephalopathy and photosensitization, is usually abrupt and occurs late in the disease. There are numerous species
of pyrrolizidine alkaloid-containing plants in the United States. Senecio spp. and Amsinckia are primarily found in western states and Crotolaria
spp. (Figure 6) and Heliotropium primarily in the Southeast.
Figure 6: Crotalaria, a pyrrolizadine alkaloid-containing plant.
Pyrrolizidine alkaloids are quite stable and intoxication may occur after ingestion of contaminated hay, pellets or grain.
Ingested pyrrolizidine alkaloids are metabolized by hepatic microsomal enzymes to toxic pyrrole derivatives that impair cellular
replication and protein synthesis, resulting in the formation of large hepatocytes (i.e. megalocytes). When the megalocytes
die, fibrosis ensues. When fibrosis becomes extensive, failure is inevitable.
A presumptive diagnosis of megalocytic hepatopathy can be made from history of exposure to pyrrolizidine alkaloids, clinical
signs and laboratory evidence of hepatic disease. Because fibrosis occurs periportally, GGT activity is persistently increased.
The histopathologic findings of megalocytosis, biliary hyperplasia and fibrosis are essentially pathognomonic.
Cholelithiasis and cholangiohepatitis
Cholelithiasis occurs most commonly in adult, middle-aged horses. The most frequently reported clinical signs include icterus,
abdominal pain, fever, depression and weight loss. Clinical signs often are intermittent unless the common bile duct is occluded,
whereupon persistent abdominal pain prevails.