Brief review of the anatomy and physiology of the biliary tree and bile
Bile is produced in the liver to aid in the digestion of food in the small intestine. Liver cells excrete bile into a tree-like system of branched ducts (bile ducts) within the liver. These ducts gradually coalesce into a large duct that extends between the liver and the small intestine.
The gallbladder is an oval shaped sack-like structure that extends from the large bile duct. The gallbladder acts as a reservoir to store and concentrate bile between meals as some bile exiting the liver via the large bile duct enters the gallbladder. When food enters the intestine, the gallbladder is stimulated to contract, thus depositing bile into the intestine.
Gallbladder mucoceles (GBM) are characterized by distention of the gallbladder by a thick mass of sludge and mucus (rather than liquid bile) and may result in obstruction and rupture of the gallbladder. Clinical signs of affected dogs include vomiting, loss of appetite, and abdominal pain. Without surgical removal of the gallbladder (cholecystectomy), the dog may die if rupture occurs. Many other diseases cause similar clinical signs, and because GBM are relatively uncommon, the diagnosis can be missed or delayed. The diagnosis is usually made via ultrasound examination (Figure 1), exploratory surgery, or at necropsy. In general, this appears to be a disease of older dogs. The average age of onset of clinical signs in Shelties in one study was 9 years (range 5 – 12 years) . It has been diagnosed in a 3-year-old Sheltie.
Gallbladder mucoceles have been diagnosed with increasing frequency in dogs since the late 1990’s [1-4]. Whether or not this was the result of a true increase in disease prevalence or simply the result of increased detection is unclear. Some have suggested that incorporation of abdominal ultrasound examination of dogs as a routine diagnostic tool has resulted in increased detection of gallbladder disease . Several articles describing GBM in dogs suggest a breed predilection for the problem in Shetland Sheepdogs as well as Cocker Spaniels and Miniature Schnauzers; however, mucoceles have been diagnosed in many other breeds and mixes. [4, 5-8].
The cause of GBM formation is unknown. Several predisposing factors have been considered such as breed (mentioned above), endocrine disease (hypothyroidism or hyperadrenocorticism (Cushing’s Disease)), [7, 9] hyperlipidemia (too much fat in the blood)  and hypercholesterolemia (high blood cholesterol levels) . Some have argued that these factors are unlikely to be direct causes as “the breeds of dog affected and endocrinopathies commonly associated with GBM formation have existed long before emergence of the disease as a clinical entity and are not found in all dogs diagnosed with the disease.” . It has been speculated that hyperlipidemia might decrease gallbladder contractility thus predisposing dogs to GBM formation. However, a 2021 study found that, although gallbladder volume was greater in dogs with hyperlipidemia than in healthy control dogs, there was no difference in gallbladder contractility between the two groups. The authors suggested that gallbladder distention could contribute to retention of bile and GB disease .
In 2010, a study was published linking a genetic defect to the formation of GBM in Shetland Sheepdogs , but the finding was later disproven in an expanded study done by two of the original investigators and others .
A 2015 study of 76 dogs with GBM and additional matched controls found that dogs with GBM were 2.2 times as likely to have been treated with thyroxine (probably for hypothyroidism) as control dogs, 3.6 times as likely to have been treated for Cushing's disease, and 2.3 times as likely to have had reported use of products containing imidacloprid (a topical flea and tick control insecticide) . Twenty-nine different breeds of dogs were diagnosed with GBM. Shetland Sheepdogs, Cocker Spaniels, and Chihuahuas were significantly overrepresented. Analysis of Shetland Sheepdog data only found that Shelties with GBM were 9.3 times as likely to have had reported use of imidacloprid as were control Shelties.
A 2019 study of dogs with GBM and no clinical signs of hypothyroidism or Cushing’s disease found thyroid dysfunction without autoimmune thyroiditis in many dogs . The authors considered it “unlikely that primary hypothyroidism or autoimmune thyroiditis was a major cause for abnormal thyroid hormone homeostasis in these dogs or somehow contributed to their gallbladder mucocele formation". Thyroid dysfunction could have been due to concurrent non-thyroidal illness, and because it was identified in many dogs, the authors recommended that comprehensive thyroid testing be done in dogs with GBM. The study did not support justification for routine testing for Cushing’s disease in dogs with GBM unless clinical signs were present. It was recommended that dogs at risk for GBM and recognized to have high serum cholesterol undergo ultrasonography to rule out mucoceles and have comprehensive thyroid hormone testing. Some support exists for a therapeutic effect of thyroid hormone supplementation in dogs with GBM and thyroid dysfunction .
Recommendations for Shetland Sheepdog Owners
- Since Shelties are one of the breeds considered to be at risk for GBM, inform your veterinarian of the possibility of GBM formation if your dog develops any of the above-mentioned clinical signs.
- Consider avoiding the use of topical insecticides containing imidacloprid since that may be a risk factor for GBM formation in Shetland Sheepdogs .
- Although dogs with GBM often have increased liver enzymes and other bloodwork abnormalities , normal liver function tests results may not rule out the presence of a GBM or gallbladder rupture .
- In Shelties at least 5 years of age with high serum cholesterol, consider periodic ultrasound examination of the gallbladder and comprehensive thyroid function testing . Ultrasound examination must be performed by a veterinarian experienced in recognizing GBM. In general, board certified radiologists and internal medicine veterinarians are competent at making the diagnosis. Some general practitioners are also very experienced and capable of making the correct diagnosis. Mobile sludge (gravity dependent matter) within the gallbladder is a common finding in “normal” dogs and should not be confused with mucocele formation. One study of client owned dogs found that biliary sludge was common, dogs remained asymptomatic, and the sludge rarely resolved in healthy dogs over a period of 1 year. Gallbladder content became less mobile with time suggesting that a change in consistency occurred over time .
- If the gallbladder ruptures, mortality is high even with surgical intervention. If your asymptomatic Sheltie is diagnosed with a GBM, discuss the options with your veterinarian. Considerations include: 1) prophylactic gallbladder removal (cholecystectomy), 2) no action unless clinical signs develop, and 3) medical therapy.
One study of gallbladder disease in 38 Shelties found that GBM could be subclinical, but could quickly result in acute illness . The authors recommended gallbladder removal in asymptomatic dogs with mucoceles because of low survival rate of clinically affected dogs. Another study comparing elective vs. nonelective gallbladder removal in dogs with GBM had similar findings . The mortality rate was 2 (6%) out of 31 for dogs undergoing an elective cholecystectomy and 21 (23%) out of 90 for dogs undergoing a nonelective cholecystectomy. A 3rd study comparing long-term survival of dogs with GBM treated by cholecystectomy, medical management, or both found that cholecystectomy resulted in the best long-term survival in dogs surviving the immediate postoperative period compared to medical management  †. Although medical management was associated with significantly shorter median survival time (1340 days) compared to surgical treatment (1802 days), it was considered a reasonable alternative when surgery could not be pursued.
- Few reports of medical resolution of GBM and no completed prospective studies on medical therapy exist. In one dog, a mucocele resolved 6 months after medical treatment (with ursodeoxycholic acid) and a fat-restricted diet; there was no change in mucoceles of 2 other dogs treated similarly . In another article, medical resolution of GBM in 2 dogs 3-4 months after treatment was reported . Despite resolution of GBM in those dogs, the authors still recommended cholecystectomy for treatment of dogs with GBM. Currently, there is a prospective treatment study in progress that hopefully will provide more definitive recommendations.
- How to treat a dog that does not have a confirmed mucocele, but has non-gravity dependent, organized sludge? The options are the same as for dogs with confirmed mucoceles. Perhaps medical therapy should be given a higher priority than surgery at least initially? One report of prophylactic gallbladder removal in dogs with non-gravity dependent sludge resulted in resolution of clinical signs of morning anorexia and exercise intolerance in 13 of 16 dogs .
- Medical treatments vary, but generally consist of ursodeoxycholic acid (ursodiol) to increase bile flow, liver protectants - S-adenosylmethionine (SAMe) and silymarin (milk thistle), a low fat (4% - 8.5%) diet and treatment of any concurrent Cushing’s disease, hypothyroidism, and hyperlipidemia [13,14, 18, 20-22]. Patients should be monitored periodically with ultrasound and blood work. Since GBM formation is significantly associated with proteinuria, treating the proteinuria may minimize long-term kidney morbidity in such patients .
- Even though a genetic mutation was initially thought to be a cause of GBM in Shelties , a more extensive study, done by two of the original investigators and others, found no statistically significant association between the mutation and the presence of GBM . Because of this, the authors declined to offer a DNA test for breeders as the test was not considered accurate enough to be used to make breeding decisions. At least one genetic testing laboratory is offering the DNA test, so be aware of the above studies when considering whether or not to use that test.
- Be knowledgeable as possible about the presence or absence of dogs with GBM in your dog’s pedigree, and use that knowledge in making breeding decisions just as you would with any other abnormality.
Figures 1 and 2 are ultrasound and gross images of a gallbladder and mucocele removed from an asymptomatic 8-year-old Sheltie. The owner had 2 full siblings sired by an affected dog. Both siblings were clinically normal, but received ultrasound scans as a screening measure since they were at an age where mucocele formation might occur. One was normal, the other had a mucocele. Even though the affected dog was clinically normal and the blood work was also normal, the owner elected to have the gallbladder removed. The gallbladder was moderately distended and filled with a gelatinous, semi-solid material. The dog recovered uneventfully.
Ultrasound image of the gallbladder (arrows) of an asymptomatic 8-year-old Sheltie with a gallbladder mucocele. The mucocele appears as a stellate-shaped gray object within the gallbladder. The inside of a normal gallbladder would be uniformly black.
Figure 2 (A-C):
The photos of a gallbladder and mucocele removed from the same Sheltie as in Figure 1. (A) Intact gallbladder shortly after surgical removal. The gallbladder is distended.
An incision has been made along the long axis of the gallbladder revealing the gelatinous mass of the mucocele. In a normal dog, the gallbladder would have collapsed and the fluid contents spilled onto the towel when incised.
The gallbladder and mucocele have been cut in half.
Mucocele being peeled away from the gallbladder wall.
The mucocele was tightly adhered to the gallbladder wall.
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‡  Parkanzky M, Grimes J, Schmiedt C, et al: Long‐term survival of dogs treated for gallbladder mucocele by cholecystectomy, medical management, or both. J Vet Intern Med. 2019. Sep-Oct; 33(5): 2057–2066. https://doi.org/10.1111/jvim.15611
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Ronald Lyman: Gallbladder mucoceles: Surgery still recommended due to risk of rupture: Vet Med, 2009, DVM 360. http://veterinarynews.dvm360.com/dvm/Gastroenterology/Gallbladder-mucoceles-Surgery-still-recommended-du/ArticleStandard/Article/detail/616664
* Both spellings of “gallbladder” and gall bladder are found in the literature with the former being preferred in American scientific literature and medical dictionaries with the latter found more often in the British.
† Studies supported by the American Shetland Sheepdog Association either through promoting owner participation or through the Shetland Sheepdog Donor Advisory Fund within the American Kennel Club Canine Health Foundation.
‡ A variety of medical therapies were used in this retrospective study and are presented in Supplemental Table S1 in the supporting information section at the end of the article. https://doi.org/10.1111/jvim.15611 .
Gallbladder mucocele research supported by the ASSA: