Researching the Cause of Gallbladder Mucocele in Dogs

Veterinarians are diagnosing an increasing number of dogs with a disease known as gallbladder mucocele. Is this because ultrasonography – the tool required for diagnosis - is more commonly available and they are more adept at recognizing the disease? Or is the incidence truly on the rise? What causes a gallbladder mucocele? And how can we better diagnose, treat, and prevent it? With so many questions surrounding gallbladder mucocele formation, the AKC Canine Health Foundation (CHF) is dedicated to finding answers.

The canine gallbladder sits between liver lobes in the abdomen. It serves as a reservoir for bile, an important liquid made by the liver that aids in lipid (fat) digestion. The gallbladder lining has an important and complex role in maintaining water and electrolyte balance; managing cholesterol, lipid, amino acid, and bile acid levels; and processing bodily and foreign compounds. A mucocele forms when the gallbladder lining relentlessly secretes abnormally thick mucus. This mucus accumulates, becomes increasingly thick or sludge-like, and obstructs the normal flow of bile from the gallbladder into the small intestine. The gallbladder may even rupture secondary to overdistention by this sludge, requiring emergency surgery to save the dog’s life.

Veterinary scientists do know that gallbladder mucocele is more common in Shetland Sheepdogs, Miniature Schnauzers, and Cocker Spaniels, but can also be seen in other breeds like Pomeranians and Chihuahuas, as well as mixed breeds. Affected dogs are likely to have concurrent hypothyroidism, Cushing’s disease (hyperadrenocorticism), and/or hyperlipidemia. Do these diseases predispose a dog to gallbladder mucocele formation? Or are they all caused by the same underlying metabolic or hormonal syndrome?

With funding from CHF Grant 01986: Profiling the Metabolic and Lipid Imbalances that are Causative of Gallbladder Disease in Dogs, investigators at North Carolina State University are exploring the complexities of these apparently related diseases. Research is ongoing, but initial results have already been presented at the American College of Veterinary Internal Medicine Forum and published in peer-reviewed journals. To refine the list of potential metabolic disruptions that contribute to gallbladder mucocele formation, investigators used metabolomics to study the serum and hepatic bile duct of affected dogs. Metabolomics is the study of small molecules (metabolites) and their interactions within a biological system. They found abnormalities in the metabolic pathways involving amino acids, glutathione, RNA, adenosine, bile acids, cholesterol, lipids, and energy. While this does not pinpoint the cause of gallbladder mucocele formation, it provides a starting point to construct theories about the pathways and compounds that ultimately affect the gallbladder lining.

The research team also documented that dogs with gallbladder mucocele are likely to have alterations in their serum thyroid hormone concentrations, even though they lack clinical signs of hypothyroidism at the time. Examination of thyroid biopsies from these dogs showed no inflammation, indicating that the mechanism causing hypothyroidism is different from primary lymphocytic thyroiditis. Additional study is needed to describe this thyroid dysfunction associated with gallbladder mucocele and rule out false thyroid dysfunction (known as non-thyroidal illness) due to the mucocele itself. Researchers suggest testing thyroid function at the time of gallbladder mucocele diagnosis and treating accordingly.

With funding from recently awarded CHF Grant 02644-A: Evaluation of Gallbladder Motility in Dogs with Hyperlipidemia, researchers at the Virginia-Maryland College of Veterinary Medicine will explore the impact that hyperlipidemia may have on gallbladder mucocele formation. Hyperlipidemia is defined as a persistent elevation in serum triglycerides and/or cholesterol and has been associated with decreased gallbladder motility in humans and rodents. To test the hypothesis that hyperlipidemia impairs gallbladder motility and therefore predisposes dogs to gallbladder mucocele formation, investigators will use ultrasonography to compare gallbladder motility in healthy dogs and those with hyperlipidemia. If the association is proven, owners and veterinarians can be more proactive about diagnosing and managing lipid levels in order to prevent or decrease the severity of gallbladder mucoceles.

Gallbladder mucocele formation in dogs is an emerging and deadly disease. Current knowledge suggests that genetic and metabolic factors are involved in altering the gallbladder lining function and facilitating the underlying or concurrent hormonal abnormalities. CHF and its donors remain committed to finding answers about this disease to inform better treatment and prevention strategies. Support canine health research at akcchf.org/donate so that all dogs can live longer, healthier lives.