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Pyrrolizidine Alkaloid Toxicity in a mature brangus cow

August 28, 2020 by Mallory Pfeifer

Pyrrolizidine Alkaloid Toxicity in a mature brangus cow
David A. Sher, B.S, Catherine Barr, PhD, Dipl ABT, Gabriel Gomez, DVM, PhD, Dipl ACVP

An adult, female, 800 lb., Brangus cow in poor body condition was submitted to the Texas A&M Veterinary Medical Diagnostic Laboratory (TVMDL) for necropsy. The animal was part of a herd that reported multiple losses in the previous weeks and days. The clinical signs exhibited by other animals was not reported by the owner or the submitting veterinarian; however, the submitted animal exhibited neurological deficits, including aggression.

On necropsy, the carcass exhibited advanced autolytic changes and the skin had excoriations over the shoulders. The skeletal muscles were diffusely atrophied and the subcutis had multifocal pockets of edema and hemorrhage. The thoracic and peritoneal cavities had moderate amounts of serosanguineous fluid. The liver had an irregular capsular surface and appeared slightly enlarged, firm and mottled dark-brown to tan. The epicardial surface of the heart contained coalescing areas of hemorrhage. The mesentery and the submucosa of the abomasum were expanded with pockets of edema. The major microscopic finding was the dissecting fibrosis of the liver (Figure 1). Areas of fibrosis in the liver contain many hyperplastic bile ductules and often entrapped islands of viable and variably degenerate hepatocytes. Multifocally, the hepatocytes were enlarged and contained enlarged nuclei (karyomegaly). Additional microscopic findings included: 1. neutrophilic alveolitis in the lung (aspiration) accompanied with mixed bacterial colonies and keratin squames; 2. moderate intraneuronal lipofuscin in the brain.

In this animal, testing for rabies was negative and microscopic analysis of the rumen content failed to reveal any toxic plants. The changes observed in the liver were chronic and consistent with prior ingestion of pyrrolizidine alkaloid-containing plants. The neurological deficits observed clinically in this animal were likely secondary to the lesion observed in the liver (hepatic encephalopathy). The edema observed in multiple organs was likely due to hypoproteinemia produced by a combination of liver disease and negative energy balance.

Pyrrolizidine alkaloids (PA) are found in various unrelated species of plants, particularly of the families Compositae (Senecio spp.), Leguminosae (Crotalaria spp., Tephrosia spp.), and Boranginaceae (Heliotropium, Cynoglossum, Amsinckia, Echium, Trichodesma and Symphytum spp.), that produce different configurations of the alkaloids. Pyrrolizidine alkaloids are produced as a defense mechanism against herbivorous pests and have been found to result in hepatotoxicity. Ingestion of large amounts of the toxins may bring about constipation or diarrhea, bloody stool, or rectal prolapse. At lower levels of consumption, it is the metabolism of pyrrolizidine alkaloids into reactive aromatic pyrroles that causes progressive liver damage, eventually leading to hepatic failure and excess ammonia in the blood. Susceptibility from highest to lowest in veterinary species is as follows: pig > horse> cattle> sheep and goats. Clinically, cattle may also demonstrate aimlessness wandering, head pressing, aggression, or other signs of encephalopathy. During the acute phase of the disease, the liver will exhibit an enlarged and jaundiced appearance with variable hemorrhage. In chronic cases, the liver will shift to a more pale appearance due to replacement of functional liver with dissecting fibrous connective tissue. The fibrosis may be so extensive as to cause portal hypertension resulting in veno-occlusive disease, ascites, severe mesenteric edema, diarrhea, jaundice and photosensitization (type III). The presence of bile duct hyperplasia and karyomegaly are changes that aid in the microscopic diagnosis of pyrrolizidine alkaloid toxicity. Swelling of the gallbladder – with thickened bile – as well as edema of the abomasum and portions of the intestine may also be expected.

As stated, a wide range of plants produce pyrrolizidine alkaloids. Within the state of Texas, the most prevalent threats are of the Senecio species. Butterweed (Senecio glabellus) is present in eastern Texas and along the Gulf Coast, while threadleaf groundsel (S. douglasii) and Riddell’s groundsel (S. riddellii) are found in the Trans Pecos, in South Texas and on the plains. Texas grounsel (S. ampullaceus) overlaps both of these zones and inhabits most of the state.

Butterweed and Texas grounsel are both annuals, coming up in late December/January as winter rosettes – they are sometimes the greenest plants available during this time, making them attractive forage but with only a small volume available. Because of this, animals in eastern parts of Texas tend more toward to delayed onset of clinical signs associated with hepatoencephalopathy rather than the more acute presentation of gastrointestinal signs allowed by overconsumption of larger perennial plants like threadleaf and Riddell’s groundsels in the more western part of the state. Plants belonging to other species including Crolataria or Cynoglossum must be avoided as well. With over 300 known variations of pyrrolizidine alkaloids, being fully aware of their prevalence is a challenge. Unfortunately, the only appropriate response to pyrrolizidine alkaloid toxicity is to prevent further ingestion of plants containing these alkaloids.

References:
Bildfell, Rob. “Overview of Pyrrolizidine Alkaloidosis.” Merck Manual, Merck & Co., Inc., October 2013, merckvetmanual.com/en-ca/toxicology/pyrrolizidine-alkaloidosis/overview-of-pyrrolizidine-alkaloidosis.

Joaquín Tamariz, et al. The Alkaloids: Chemistry and Biology, Volume 80; Hans-Joachim Knölker, editor. 2018. Pgs. 1-314.

Cullen, J.M., & Stalker, M.J. (2016). Liver and Biliary system. In M.G. Maxie (Ed.), Jubb, Kennedy and Palmer’s pathology of domestic animals (6th ed., pp. 336-338). St. Louis, MO: Elsevier.

Filed Under: Case Study Tagged With: bovine, cattle, cow, histopathology, pathology, toxicology

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