CASE NOTES
Challenges Faced in Diagnosing Toxic Hepatopathy in Cattle
Dr. Melinda Gabor, Veterinary Pathologist, Industry and Investment NSW, Elizabeth Macarthur Agricultural Institute
Posted Flock & Herd August 2010
Introduction
The liver is a common site of toxic injury and a great variety of plant toxins can cause hepatic injury in cattle. Diagnosing toxic hepatopathy and identifying the most probable cause can be a diagnostic challenge and relies on the identification of specific hepatic responses to injury. The presentation examines common hepatic responses to toxic plants with an emphasis on a case study with combined lantana and heliotrope intoxication.
Discussion
Pyrrolizidine alkaloids have been identified in over 6000 plants of 3 families with the most common plant genera encountered by domestic animals including species from the Senecio, Crotalaria, Heliotropium, Cynoglossum, Amsinckia, Echium and Trichodesma genera.
More than 600 pyrrolizide alkaloids have been identified chemically and individual plants may contain more than one toxic alkaloid. Most pyrrolizidine alkaloids are hepatotoxic once converted to reactive pyrrolic esters in the liver. This occurs predominantly in the periacinar (zone 3) hepatocytes causing acute periacinar necrosis.
Pyrrolizidine alkaloids inhibit DNA synthesis, arresting mitosis while in some cases allowing ongoing replication, resulting in megalocytosis of hepatocytes. Regenerative, chronic responses by the liver include oval cell proliferation, bile duct proliferation, fibrosis, and nodular regeneration of hepatocytes.
Lantana camara is an attractive ornamental shrub that produces toxic pentacyclic triterpenes of which a number of toxic constituents have been identified. At high doses it causes severe acute zonal necrosis, however in grazing animals the more usual effect is subacute to chronic cholestasis characterised by severe icterus and photosensitisation. Again one of the more consistent findings in the liver is hepatocyte enlargement or megalocytosis.
Fine cytoplasmic vacuolation of periportal hepatocytes, bile accumulation in canaliculi, hepatocyte cytoplasm and kupffer cells, bile duct proliferation, periportal hepatocyte apoptosis and hepatocyte dissociation are present in dose-dependent degrees.
The challenge to accurate diagnosis is recognition and interpretation of the effects of individual animal variation, quantity of plant ingested, frequency of ingestion, nature and concentration of the toxic principles present in the plant and the ingestion of multiple plants. Using a case study of known exposure to both Heliotropium and Lantana camara, the microscopic hepatotoxic effects of each of these plants is demonstrated and discussed using histological images.