- Definition
- Pathophysiology
- Systems Affected
- Genetics
- Incidence/Prevalence
- Signalment
- Signs
- Causes
- Risk Factors
BASICS
- Caused by the chronic ingestion of PA-containing plants; PAs are a distinct group of structurally similar molecules found in approximately 6000 plant species worldwide
- Hundreds of different alkaloids exist
- Alkaloid composition and concentration, as well as toxicity, vary tremendously among plants, within different parts of the plant, and with stage of plant maturity
- 3 plant families (Compositae, Leguminosae, and Boraginaceae) account for most PA-containing plants. Clinical disease in the USA most common with Senecio, Amsinckia, Cynoglossum, and Crotalaria. Symphytum, Echium, and Heliotropium also contain PAs
- Economic losses have decreased owing to widespread recognition of the problem and effective livestock management and biologic control measures (particularly with Senecio jacobaea)
- Intoxications usually occur when horses graze paddocks or pastures heavily contaminated with these plants or consume contaminated hay during a period of several weeks to months
- Acute intoxications are rare, primarily because of the large amount of plant material a horse would need to ingest at any 1 feeding or several feedings
- PAs are rapidly absorbed from the gastrointestinal tract and undergo extensive hepatic metabolism by mixed-function oxidases
- Some are detoxified to harmless metabolites, which then are eliminated via the urine or bile. Others are activated by conversion to toxic metabolites, primarily by dehydrogenation, yielding highly toxic pyrrole derivatives
- Pyrroles alkylate double-stranded DNA, thus inhibiting cell mitosis. Nuclear and cytoplasmic cell masses expand because of the impaired ability to divide, thus forming megalocytes. As megalocytes die, they are replaced by fibrous connective tissue
- Pyrroles also bind to cellular constituents in lung and kidney tissues
- Hepatobiliary—interference with cell replication leads to hepatocytomegaly and necrosis with bile duct proliferation and fibrosis; endothelial proliferation in centrilobular and hepatic veins occurs
- Renal/urologic—pyrrole-bound molecules can lead to megalocytosis of the proximal convoluted tubules, atrophy of glomeruli, and tubular necrosis; this has not been described in horses
- Respiratory—pyrrole-bound molecules can lead to alveolar hemorrhage and edema, progressive proliferation of alveolar walls, pulmonary arteritis, and hypertension; this is not commonly reported in horses
- Cardiovascular—right ventricular hypertrophy and cor pulmonale have been documented experimentally, most likely secondary to PA-induced lung damage
Most intoxications occur during the plant growing season; however, intoxications can occur at any time because of the persistent toxicity of these alkaloids in baled hay.
- Most affected horses suffer chronic weight loss and debilitation associated with hepatic insufficiency, which can be subtle in nature; this is referred to as the chronic-delayed form
- In the chronic-delayed form, clinical signs can appear quite suddenly, despite exposure and liver lesions having been chronic and progressive
- The extent of hepatic damage depends greatly on the daily amount of alkaloid consumption, degree of pyrrole conversion, age of the animal, and metabolic and mitotic status of the target cells
- Food intake and nutritional status also can modify the effects of PAs
- Most affected patients, particularly those with the chronic-delayed form, exhibit neurologic signs
- Loss of appetite
- Weight loss
- Weakness and sluggishness
- Photodermatitis
- Icterus
- Behavioral abnormalities—mania, derangement, yawning, aimless walking, head pressing, drowsiness, blindness, and ataxia
- Inspiratory dyspnea—related to paralysis of the pharynx and larynx
- Gastric impaction
- Ascites
- Diarrhea with tenesmus
- Plants commonly incriminated in the USA—S. jacobaea (tansy ragwort), Senecio vulgaris (common groundsel), Senecio douglasii var. longiilobus (threadleaf groundsel), Senecio riddellii (Riddell's groundsel), and Cynoglossum officinale (hound's tongue)
- Most animals must ingest 1–5% of body weight in plant material daily before effects are observed. Sometimes as much as 50% is required before clinical signs become apparent
- With tansy ragwort, the chronic lethal dose for horses is 0.05–0.20 kg/kg (equivalent to 1 dried hound's tongue plant per day for 2 weeks)
- Amsinckia and Crotalaria spp. rarely cause problems, because the highest percentage of alkaloid is present in the seed. Intoxication can result from ingestion of contaminated grain, cakes, or rarely after chronic ingestion of Amsinckia-contaminated hay
DIAGNOSIS
TREATMENT
MEDICATIONS
FOLLOW-UP
MISCELLANEOUS