The 2010 Breeders' Cup and 2010 Juvenile Champion, Uncle Mo, came into his 3-year-old season the overwhelming favorite for
the 2011 Kentucky Derby. But several weeks before he was set to run, he became ill, and only two days before the race, May
5, 2011, he was scratched.
(WILLIAM R. SALLAZ/GETTY IMAGES)
The illness took the potential Triple Crown contender to the sidelines for extensive testing. After several weeks, Bill Bernard,
DVM, Lexington, Ky.; Doug Byars, DVM, Dipl. AVCIM, Dipl. AVECC, Byars Equine Advisory, Georgetown, Ky.; and Tom Divers, DVM,
professor of clinical sciences, Cornell University College of Veterinary Medicine, diagnosed cholangiohepatitis, an inflammation
of the bile passages and liver, based on a biopsy of his liver and nearby lymph nodes. In a statement issued June 3, 2011,
the internists reported that they did not know how he contracted the disease.
"Uncle Mo was placed on medications prior to the Derby, though he did not get antibiotics or a liver biopsy prior to scratching
from the race," says Byars. "We just didn't have enough time for this horse to recover before the race."
According to The Merck Veterinary Manual, the etiology of cholangiohepatitis is likely related to bacteremia that is due to an organism eliminated in the bile, an
ascending infection of the biliary tract after an intestinal disturbance or ileus.1 Horses may have an initiating ascending gram-negative infection, but gram-positive aerobic or anaerobic infection is possible,
If present, the ascending infection is "thought to initiate a cholangitis, which may extend to the periportal region of the
liver," says Divers.
Jennifer Davis, DVM, PhD, assistant professor of equine internal medicine and clinical pharmacology at North Carolina State
University College of Veterinary Medicine, reports that although bacteria via ascending proximal small intestinal infection
or inflammation may occur, bacteria or bacterial products (such as endotoxins) or inflammatory mediators in the portal circulation
might also cause periportal neutrophilic inflammation.
However, not all cases are caused by bacterial infection. "There are many causes of cholangiohepatitis—bacterial, viral, toxic
and immunologic," says Divers.
Davis describes two possible pathogenic mechanisms: The first is due to an ascending infection from the proximal small intestine
characterized by acute inflammation of the wall of the bile ducts (cholangitis) and entry of large numbers of neutrophils
directly into the lumen of the biliary ducts. The inflammatory response can extend into the periportal hepatic parenchyma,
causing cholangiohepatitis. Fluid accumulation in the small intestine secondary to ileus and increased luminal pressure could
increase the chances of an ascending infection by forcing bacteria into the bile duct. Increased luminal pressure may also
reduce bile flow.
The second mechanism involves induction of neutrophilic infiltration by bacteria, bacterial products, inflammatory mediators
or a combination of causes in the portal circulation. "Injury to the intestine from a variety of causes can increase the permeability
of the mucosal barrier," says Davis. "Absorption of bacteria or their products [particularly endotoxins] promotes intestinal
The inflammatory response in the intestine might be associated with the appearance of mediators such as interleukin-8, tumor
necrosis factor alpha and interleukin-1-beta in the portal blood. "The effects of these mediators on endothelial cells and
neutrophils in portal circulation could induce periportal inflammation and, eventually, suppurative cholangiohepatitis," Davis