Signalment:  

Adult female Boer goat, Capra circusGoats on a small holding with fair nutrition, Drenched with Q-drench 2 weeks ago. 25 goats, 2 sick, one found dead.

Gross Description:  

Generalised jaundice, liver swollen and finely mottled. Kidney swollen and moist with small (<1mm) white lesions scattered across surface. Lung, red with emphysema and foam in airways.

Histopathologic Description:

Liver: The periportal areas are moderately expanded by fibrosis that is sometimes bridging, along with biliary hyperplasia and infiltration of occasional lymphocytes. Disrupting and effacing bile duct epithelium, obliterating bile ducts and extending into surrounding fibrous tissue are abundant negatively stained outlines of acicular crystals, shrunken, individualized, hypereosinophilic and sloughed epithelial cells, cellular debris and occasional neutrophils. Within occasional remaining intact bile ducts are non-viable neutrophils and cellular debris. Crystals are occasionally present in adjacent hepatocytes and Kupffer cells and there is hyperplasia of Kupffer cells. Occasional hepatocytes are lost, shrunken and hypereosinophilic and replaced by neutrophils and cellular debris (necrosis). Remaining hepatocytes contain granular cytoplasm, often contain feathery vacuolation or occasionally contain variably sized, well defined cytoplasmic vacuoles (lipid), yellow-brown granular pigment (bilirubin) (cholestasis) and rare cytosegresomes. 

Morphologic Diagnosis:  

Liver; Cholangiohepatitis, necrotizing, moderate, chronic with biliary crystals and bridging portal fibrosis

Lab Results:  

Gall bladder- profuse predominant growth of Escherichia coli (haemolytic).

Condition:  

Cholangiohepatitis with crystal depostion

Contributor Comment:  

This is a spectacular case of crystal-associated cholangiohepatopathy, and although crystals are not seen, their outlines are readily apparent. Crystal-associated cholangiohepatopathy is a progressive disease seen with ingestion of plants containing steroidal saponins that form crystals in bile ducts and less commonly hepatocytes, Kupffer cells and renal tubules.(1,4) Larger crystals are found with prolonged ingestion. This is a disease that primarily affects ruminants with sheep and goats being more commonly affected than cattle.(1)

The crystals are composed principally of calcium salts of the steroidal saponins that are metabolised in the rumen and liver to form episapogenin glucuronides. In the presence of calcium they can precipitate and form crystals.(5) Crystals can obstruct bile ducts and lead to icterus and secondary photosensitization.(2) It is still unclear whether the biliary crystals alone cause liver damage or whether other toxins in the plants play a role.(1,5)

Levels of saponins vary greatly with age of plant, location and size and the plants are thus not always toxic. Outbreaks commonly occur in summer when young plants become wilted, especially if rain is followed by hot dry weather.(4)

Plants that are known to cause crystal-associated cholangiohepatopathy include:

Scientific name	Distribution	Common name
Tribulus terrestris	South Africa, Australia, North America	Puncture Vine
Narthecium ossifragum	Norway, UK	Bog asphodel
Agave lecheguilla	North America	Lecheguilla
Nolina texana	North America	Texan bear grass
Brachiaria decumbens	Brazil, Australia, Malaysia	Signal grass
Panicum coloratum	Australia, North America, Africa	Kleingrass
Phytolacca octandra	NZ, South America	Inkweed

Many plants contain steroidal saponins, but have not yet been documented as causing biliary crystals. Solanales, Primulales, Ranunculales, Fabales, Sapindales, Poales and Liliales are all orders of plants that contain steroidal saponins(1), so should not be ignored when investigating the etiology of crystal assosicated- cholangiohepatopathy.

In this case the significance of the E.coli is unclear. It may have been a post mortem contaminant, or a retrograde opportunist making use of the disrupted biliary epithelium.

JPC Diagnosis:  

Liver: Biliary hyperplasia, portal, diffuse, moderate, with intraductal crystal formation and periportal bridging fibrosis

Conference Comment:  

Steroidal saponins are a type of glycoside, which, like alkaloids, are bitter and usually not readily consumed by domestic animals. Their metabolism to glucuronide conjugates result in the crystal formation evident in this case and subsequent hepatic disease secondary to biliary obstruction. Plants in early, rapid growth stages are most hazardous with the highest levels of saponins while mature plants can be grazed without incidence.(3)

Conference participants contrasted this entity with that of sporidesmin, the mycotoxin that causes biliary epithelial necrosis. Biliary hyperplasia with minimal inflammation is present in both entities and photosensitization is a common sequela, albeit through slightly different mechanisms. Saponins lead to biliary obstruction rather than necrosis, but both result in accumulation of phylloerythrin due to cholestasis inciting the characteristic skin manifestation of facial eczema when the affected animal is exposed to sunlight. (2)

The contributor outlined the most well-known steroidal saponin-producing plants, of which Tribulus terrestris may be most readily recognized since it has caused enormous loss of sheep in South Africa, where it is known as yellow bighead due to icterus and marked facial edema.(5)

References:

1. Collett MG, Thompson KG & Christie RJ. Photosensitisation, crystal-associated cholangiohepatopathy, and acute tubular necrosis in calves following ingesion of Phytolacca octandra (inkweed). New Zealand Vet J 2011;59:3

2. Cullen J, Brown D. Hepatobiliary System and Exocrine pancreas. In Zachary JF, McGavin MD, ed Pathologic basics of Veterinary Disease 5th ed. Missouri, Elsevier Mosby pp440

3. Galey FD. Disorders caused by toxicants. In: Smith BP, ed. Large Animal Internal Medicine. 4th ed. St. Louis, MO: Mosby Elsevier; 2009:1697-1698.

4. McDonough SP, Woodbury AH, et al. Hepatogenous photosensitization of sheep in California associated with ingestion of Tribulus terrestris (puncture vine) J Vet Diagn Invest 1994 6:392

5. Stalker MJ, Hayes MA. Liver and biliary system. In Maxie MG, ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed., vol 2, Philadelphia, PA; Elsevier Saunders 2007: pp 376-378

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4-1. Liver

4-2. Liver

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