Pyrollizidine alkaloids are compounds found in many plants. Some are quite strongly hepatotoxic, and are a major cause of economic loss in the Riverina as well as in most of southern Australia .
Pyrollizidine alkaloids are found in many plants in many families. The plants producing them which are of major economic importance in the Riverina are the heliotropes (Heliotropium spp., especially H. europeum) and Paterson's Curse Echium lycopsis (E. plantagineum). These are native to Europe but are now naturalised and widespread in the Riverina and most of southern Australia. Senecio spp. are important elsewhere in N.S.W., but are relatively uncommon in the Riverina.
Paterson's Curse is an erect winter/spring growing annual. It first forms flat rosettes with broad, hairy leaves, it then grows 1 - 2 m high with smaller leaves and purple or occasionally pink or white, flowers. It grows rapidly in mild, wet winters and can quickly become the dominant feature of the countryside. It is readily grazed by sheep, which appear to be relatively tolerant of its toxin, but cattle, which are much more susceptible to poisoning avoid grazing it when possible.
Heliotrope, also called Barooga weed and Caterpillar weed, is a downy covered spring/summer growing annual. It has grey/green oval leaves, 1 - 5 cm long and small, white flowers in rows at the end of stems, the appearance of which leads to the name 'caterpillar weed'. It grows prolifically after summer rain, especially on disturbed ground. It is a poor competitor, and grows best on fairly bare ground particularly fallowed paddocks. It is not highly palatable, but with pasture improvement concentrating on winter/spring growth, it is often the only green feed available. British breeds of sheep and their crosses are most likely to eat it, but merinos will eat it - especially if they have had access to it all their lives. Cattle do not like it, but will eat it under duress.
The alkaloids of Echium & Heliotropium are toxic. The mechanism of action is unknown, but the main, or at least most striking pathological change appears to be megalocytosis. This is enlargement of cells, which can be quite marked. Megalocytosis is marked in the liver, but can occur to a lesser extent in the kidney and lungs. The megalocytosis is believed to be due to the inhibition of mitosis. The cells continue to grow but without division may reach 20 times normal size. At the same time there is liver fibrosis and bile duct proliferation. The fibrosis is marked in cattle and minimal in sheep, although on rare occasions marked fibrosis may be seen in sheep. The changes are usually slow to develop - there is a three week latent period before any changes are visible histopathologically.
Affected livers show changes in copper metabolism. In sheep there is an increased affinity for copper resulting in quite high liver copper levels. Under certain conditions - usually mild stress - there can be mobilisation of these excess reserves of copper leading to a haemolytic crisis. This syndrome, known as Toxaemic Jaundice or The Yellows is the most obvious economic loss due to pyrollizidine alkaloids, and is the major killing disease of sheep in much of the Riverina.
Pyrollizidine alkaloids produce a range of clinical syndromes. In cattle, the most common picture seen is death, following a relatively short period (usually 2 - 12 hours) of nervous signs - excitement, blindness, twitching and finally convulsions These signs can be seen within three weeks of cattle being introduced onto paddocks where green pyrollizidine alkaloid bearing plants are the only green feed. Usually only occasional incidents are seen - one or two beasts on any one property - but occasionally severe mortalities are seen - 10% or more of a mob dying. These heavy mortalities are usually seen in cattle recently introduced into the area - presumably local cattle learn to avoid poisonous plant species.
On autopsy, affected cattle have enlarged, fibrotic livers with or without jaundice. In some cases there is mesenteric oedema which can be quite marked, and include the gastrointestinal organs - the abomasal oedema mimicking extreme Type II Ostertagiasis. This oedema is due to hepatic portal occlusion. There is also sometimes renal petechiation. The brain has congestion of the blood vessels, and histologically shows diffuse vacuolation of the white matter (status spongiosus) - this is considered to be a direct result of liver dysfunction (hepatogenous encephalopathy). No evidence of chronic disease has been demonstrated, but it is probably that a certain amount of liver damage is present in most cattle in the Riverina, and that this causes some production loss.
Sheep show a wider range of clinical syndromes, but by far the most common one is toxaemic jaundice or secondary copper poisoning. Hepatogenous chronic copper poisoning is usually associated with heliotrope rather than Paterson's Curse, but the ubiquitous nature of both these plants makes it difficult to be certain that that is the case. The alkaloid damaged liver accumulates excessive amounts of copper. Mild stress results in the release of this copper which then causes intravascular haemolysis. Pastures in which subterranean clover Trifolium subterraneum dominates can also cause excessive liver copper levels, even though the pasture has low copper levels, in the absence of liver damage. A combination of the two is especially dangerous. Affected sheep usually die suddenly with extreme jaundice, although some may linger for 24 hours. Post-mortem decomposition is extremely rapid, and autopsies done more than 24 hours after death usually only reveal a sticky mess. On autopsy all fat is bright yellow, the liver is enlarged and discoloured - yellow or brown - and the kidneys enlarged and dark blue/black. Liver copper levels are in excess of 500 p.p.m. and kidney levels greater than 80 p.p.m.
Other syndromes seen in affected properties are hepatogenous photosensitisation, and toxic hepatitis. These are rare in the Riverina. It is especially unusual for sheep to avoid toxaemic jaundice long enough to develop hepatitis. When sheep have had several years on alkaloids without developing toxaemic jaundice, the liver becomes irreparably damaged and sheep become unthrifty. On necropsy the liver is a classic 'hob-nail' liver shrunken and very fibrous.
For many years methods for the control or cure of pyrollizidine alkaloidosis have been tried and discarded. In recent years, the direct administration of molybdenum and sulphates have been effective in controlling outbreaks of toxaemic jaundice. They increase the excretion and reduce the retention of copper. A suitable preparation is 5oz Sodium molybdate and 5lb Glaubers salt (hydrous sodium sulphate) with water to 2 gallons. An oral drench of 4oz per head is given. It is recommended that this be given daily for some time, but often one dose is sufficient. Regular treatment with this preparation may allow sheep to survive until they develop toxic hepatitis. The standard preventive measure adopted by most graziers in those areas where toxaemic jaundice is a severe problem is not to keep sheep for more than a few years.
Biological control of the offending weeds in the area, which offers the most promise in the prevention of pyrollizidine alkaloidosis. The sowing of dryland lucerne appears to control the growth of heliotrope quite well. Once established, lucerne competes successfully with heliotrope for available moisture, to the extent that very little heliotrope grows in even quite light lucerne stands. The lucerne also provides a palatable alternative to that heliotrope which does grow. Heliotrope control in fallow and stubble paddocks is more difficult, but normal good agricultural practice in working fallow immediately after rain will keep growth to a minimum and avoid the temptation to graze the paddock. Heliotrope growth in stubble will probably remain a problem, but with more use of weedicides in farming, there is a tendency for stubble paddocks to have less growth following summer rains, and subsequently less grazing
The release of beetles to control Paterson's Curse promises to be useful in the reduction of pyrollizidine alkaloidosis. Whether this promise is well founded or not remains to be seen, but it is a pity that sectional pressure has hindered the release program.
Pyrollizidine alkaloids are the toxic principals in the most important poison plants in the Riverina. They are important causes of economic loss to the sheep and cattle industries of the region. Advances are being made in the control of the weeds, but it seems that the problem will remain economically important for some time.