Typically, pyrrolizidine alkaloidosis is a chronic poisoning
that results in hepatic failure. It is caused by many toxic plants, most commonly of
the genera Senecio, Crotalaria, Heliotropium,
Amsinckia, Echium, Cynoglossum,
and Trichodesma. These
plants grow mainly in temperate climates, but some (eg, Crotalaria
spp) require tropical or subtropical climates. The plants most often implicated
include ragwort (S jacobea),
groundsel (S riddellii,
S longilobus), rattleweed (Crotalaria retusa), and
seeds of yellow tarweed (A
Cattle, horses, farmed deer, and pigs are most susceptible;
sheep and goats require ~20 times more plant material than cattle. Individual
susceptibility varies greatly within species; young growing animals are most
Etiology and Pathogenesis
More than 300 toxic factors (alkaloids with a
pyrrolizidine base) have been found in plants, with some plants containing a
mixture of several different pyrrolizidine alkaloid toxins. S
jacobea contains jacobine; retrorsine, seneciphylline, and
monocrotaline are other pyrrolizidine alkaloids frequently incriminated in
These plants, which under normal conditions are avoided by
grazing animals, may be eaten during drought conditions. Some animals may eat
these plants preferentially as roughage when they are available on extremely
lush pasture. Animals are also poisoned by eating the plant material in hay,
silage, or pellets. Seeds from Crotalaria,
Amsinckia, and Heliotropium spp, which
have been harvested with grain, have caused disease in horses, cattle, pigs, and
The alkaloids are metabolized in the liver to highly
reactive pyrroles, which produce cytotoxic effects on target sites, most
commonly the nuclei of hepatocytes. Other target sites may include the
epithelial and vascular tissues of the kidneys and lungs. These toxic pyrroles
cross-link DNA strands and also unite DNA with nucleoproteins such as actin.
These molecular alterations are presumed to create the cytotoxic, antimitotic,
and megalocytic effects characteristic of pyrrolizidine alkalosis.
Hepatic pathology with associated clinical signs is the
most common manifestation of pyrrolizidine alkalosis in domestic animal species.
Acute intoxication is characterized by sudden death from hemorrhagic hepatic
necrosis and visceral hemorrhages. This is a rare event, because the poor
palatability of these plants makes rapid ingestion of large quantities of the
toxins uncommon. More chronic exposure is typical, and the liver reflects the
cumulative and progressive effects of repeated ingestion of small doses of
toxin. Clinical signs may not be seen for several weeks or months after initial
exposure. Consumption of the offending plant may even have ceased months
earlier. The ongoing hepatic damage in these instances is suspected to be due to
the recycling of toxic pyrroles as they are released from one dying cell and
taken up by another. Clinical progression may also be altered by concurrent
hepatic pathology; a hemolytic crisis may be precipitated in sheep with
excessive hepatic copper stores (see Copper Poisoning).
In horses and cattle, signs include loss of condition,
anorexia, dullness, and constipation or diarrhea. Tenesmus and passing of
bloodstained feces may be followed by rectal prolapse, especially in cattle.
Ascites and icterus may be present, and cattle and sheep sometimes show
intermittent photosensitization (see Photosensitization).
Some animals become progressively weaker and reluctant to move. Others exhibit
signs of hepatic encephalopathy such as head-pressing, yawning, aimless
wandering, or even frenzied and aggressive behavior. Pica may be seen. Death may
occur suddenly or after prolonged recumbency with hepatic coma and high levels
of ammonia in the blood.
Less common clinical signs that have been described with
pyrrolizidine toxicoses include inspiratory dyspnea in ponies due to laryngeal
and pharyngeal paralysis, dyspnea due to interstitial pneumonia in horses, and
renal disease in pigs.
In acute cases, the liver may be enlarged,
hemorrhagic, and icteric. In chronic cases, it is atrophied, fibrous, finely
nodular, and usually pale with a glistening surface due to fibrous
thickening of the capsule. Other livers are markedly icteric. The
gallbladder is often edematous and grossly distended with thick, mucoid
bile. Edema of the abomasum and segments of the bowel, mesentery, and
associated lymph nodes is common, and there may be ascites. In some cases,
numerous small hemorrhages are present in the abdominal serous membranes.
The lungs of some severely affected horses may be emphysematous and fail to
collapse (often due to ingestion of Crotalaria spp).
Characteristic histologic changes occur in the liver.
Irreversible enlargement of individual hepatocytes (megalocytosis) is often
seen; it is conspicuous in horses and sheep but less pronounced in cattle.
In cattle, marked perivenous fibrosis of sublobular veins is usually
present, but this is not a consistent finding in horses and sheep. In all
species, increases in connective tissue, both within and around the lobules,
are marked. Bile duct hyperplasia is variable but may be the most striking
microscopic change seen in some livers. Pulmonary changes seen in horses
exposed to some Crotalaria spp may include hyperplasia of
bronchioalveolar epithelium, congestion, septal fibrosis, and emphysema.
Renal tubular lining cells and glomerular epithelial cells also may be
individually enlarged in pigs.
Chemical analysis of whole blood for toxic metabolites can
confirm recent exposure but depends on the half-life of RBCs to which these
pyrroles are bound. An ELISA that recognizes riddelliine and closely related
pyrrolizidine alkaloids present in whole blood has also been described but is
not widely available. More commonly, a presumptive diagnosis is made based on
clinical signs, compatible changes in biochemical parameters, and a history of
exposure. When hepatic cirrhosis is extensive, hypoalbuminemia and
hyperglobulinemia develop. Serum levels of fibrinogen, bilirubin,
γ-glutamyltransferase, and glutamate dehydrogenase may be increased, but it
should be recognized that the insidious nature of this disease can result in
surprisingly mild serum biochemical changes. Hepatic biopsy is often useful,
especially if megalocytic change is seen. Other hepatotoxins, such as copper or
aflatoxin, as well as infections such as chronic fascioliasis, must be
considered before making the diagnosis. At necropsy the diagnosis can often be
made based on gross findings, together with characteristic histologic changes in
hepatic, pulmonary, and/or renal tissues. Hepatic assay for pyrrolic metabolites
can also be performed.
Treatment and Control
Further intake of toxic plant material must be prevented.
Animals showing signs rarely recover, and lesions present in asymptomatic
animals may progress and result in further losses over several months. Because
high protein intake may precipitate clinical signs, rations high in
carbohydrates are indicated. Supportive treatment for dehydration and
photosensitization may be needed.
Preventing further outbreaks by reducing exposure should
Sheep are commonly used for grazing control of these
plants, but this practice carries risks unless sheep destined for early
slaughter are used. Biologic control of plants with predator moths, flea
beetles, and seed flies has met with variable success. Senecio
and related toxic species in pastures have been controlled satisfactorily by
annual herbicide applications, preferably in spring before hay or silage
Last full review/revision October 2013 by Rob Bildfell, DVM, MSc, DACVP