Ingestion of pyrrolizidine alkaloid containing plants is the most common cause of chronic liver injury worldwide.
Australian species include cotton fireweed (Senecio quadrientatus), common heliotrope, ragwort (Senecio species), rattlepod (Crotalaria species), and Paterson’s curse (Echium plantagineum). Kimberley walkabout disease (see hepatoencehpalopathy), is due to chronic ingestion of Crotalaria species, such as Crotalaria retusa (wedge-leaf rattlepod), Crotalaria montana (rattlepod), Crotalaria juncea (sunn hemp), and Crotalaria goreensis (Gambia pea).
Paterson’s curse (Echium plantagineum) is in the family Boraginaceae that includes other toxic weeds such as yellow burr weed (Amsinckia spp.), viper’s bugloss (E. vulgare) and common heliotrope (Heliotropium europaeum). Paterson’s curse is commonly associated with poisoning of livestock in Western Australia. In other parts of Australia it is sometimes called Salvation Jane, blueweed, Lady Campbell weed, or Riverina bluebell. Paterson’s curse is a declared plant (noxious weed) and is a target for biological control.
Most alkaloid-containing plants are unpalatable to horses, but may be ingested when forage is sparse. The typical lethal dose of pyrrolizidine alkaloids is around 200mg/kg bodyweight, but this varies between alkaloids (plants). The effects are cumulative, such that signs may not become apparent until months or years after the major exposure period. Acute toxicity may result in signs of disease as little as 4 weeks after ingestion.
After ingestion pyrrolizidine alkaloids are metabolized in the liver to the more toxic pyrroles. These toxic metabolites crosslink double-stranded DNA producing an anti-mitotic effect; consequently affected hepatocytes enlarge (megalocytes) as the cytoplasm increases without nuclear division. As cells die they are replaced by connective tissue. The pyrroles also inhibit enzymes within the hepatocyte and block protein synthesis leading to faster cell death.
Signs of toxicity
The most common signs of pyrrolizidine toxicity are weight loss, icterus, and hepatic encephalopathy. Photosensitization may also occur.
Diagnosis
The diagnosis of pyrrolizidine alkaloid toxicosis is based on signs, a history of exposure to toxic plants, and laboratory data. Liver-based enzymes are elevated during acute damage; these commonly include GGT and alkaline phosphatase as lesions are commonly periportal. Hepatocellular enzymes, SDH and GLDH, are also increased acutely. Enzyme levels may be normal and decreased chronically due to an overall reduction in hepatic mass.
Liver function can be assessed through the measurement of bile acids.
A liver biopsy is required to differentiate pyrrolizidine alkaloid toxicity from other hepatic diseases. The classification histological changes are megalocytosis, biliary hyperplasia, and peri-portal fibrosis. Megalocytosis is also seen with aflatoxicosis and therefore cannot be considered to be pathognomonic for pyrrolizidine alkaloid toxicity.
Treatment and Prognosis
Improvement is unlikely in cases with substantial fibrosis. A biopsy is required in order to classify and stage the disease and determine prognosis. Diet is also helpful, with the ideal diet being high in carbohydrates, low in protein, and rich in branched-chain amino acids. Frequent feeding is also recommended to prevent fluctuations in blood glucose. Beet pulp, sorghum, bran and milo are feedstuffs that are rich in the beneficial branched-chain amino acids. Mixing molasses into the diet is also helpful. Avoid high protein feeds, such as lucerne or alfalfa. Corn may be a good feed for provision of calories, without a high level of protein.
Tags: Liver; Toxicities