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Gall Bladder Mucoceles: An Emerging Disease Syndrome in the Dog

kirsten johnsonby Kirstin Johnson, DVM, DACVIM (internal medicine)
angell.org/internalmedicine
617-541-5186
internalmedicine@angell.org

In the last 10 years, gall bladder mucoceles have become one of the most common causes of gallbladder disease in the dog. Before this time, gall bladder mucoceles were rarely reported as a post mortem finding.  Many associations have been made with this disease and risk factors have been identified. However, the pathophysiology of mucocele formation is not yet completely understood.

The gallbladder is lined by a microvilli mucosa where electrolytes, lipids, proteins and water are resorbed and exchanged. The gallbladder concentrates and acidifies the bile. Within the mucosa, mucus glands produce mucin which protects the luminal epithelium from the cytotoxic effects of bile acids. The presence of free fatty acids, amino acids and gastric distension cause cholecystokinin and motilin release from the duodenum; thereby signaling gallbladder contraction. Bile then moves down the common bile duct and across the sphincter of odie to enter the lumen of the duodenum.1

gall bladder mucocelesA gall bladder mucocele is a condition of the gall bladder characterized by an inappropriate accumulation of intraluminal, inspissated bile and mucus. This inspissated bile may enter into the cystic duct and down the biliary tree leading to obstruction.2 Excessive mucin production and poor gall bladder contraction are believed to be the major contributing factors to gallbladder mucocele formation.  Cats have fewer mucus glands in their gallbladders which may explain why occurrence of gallbladder mucocele in the cat is extremely rare.1

There are likely several factors that lead to increased mucus production and decrease in contractility of the gallbladder. It has been demonstrated that mucus production is stimulated by inflammatory cytokines, endotoxins and prostaglandins. In one study of 30 dogs with gall bladder mucoceles, histopathology found cystic hyperplasia of the mucus secreting cells within the gallbadder mucosa.3 Mucus cell hyperplasia and increased mucus production may be secondary to exposure to excessive bile acids or may be an inherited disorder of the mucus cells.1

Several predisposing factors including breed association have been identified in our canine patients with gallbladder mucoceles. Shetland sheepdogs are predisposed to gallbladder mucoele formation.4 Other breeds that have been more commonly reported to develop gallbladder mucoceles include Cocker spaniels, Pomeranians, Miniature Schnauzers and Chihuahuas. A recent study found that many of these dogs have a mutation in the gene that codes for ABCB4. ABCB4 is a protein within hepatocyte cell membranes that is necessary for the transfer of phospholipids from the hepatocyte into the bile ducts. Without the protective effect of phospholipids, bile salts cause chronic irritation of the gallbladder wall and lead to increased mucus production. Thus potentially leading to a mucocele.5

Other predisposing conditions which have been identified or suspected in gall bladder mucocele formation include hypothyroidism, hyperadrenocorticism and hyperlipidemia. Diabetes mellitus does not seem to be associated with gallbladder mucocele formation as previously suspected.2,6  One study identified Cushing’s disease in 23% of 30 dogs diagnosed with a gallbladder mucocele.3 Another study reported that dogs with Cushing’s disease were 29 times more likely to develop gallbladder mucoceles vs dogs without this endocrine disorder.2

A recent study looking at selective drug use and association with gallbladder mucocele formation found that imidacloprid administration in Shetland sheepdogs could be a contributing or exacerbating factor in gallbladder mucocele formation. In their study, Shelties diagnosed with a mucoceles were 9.3 times more likely to have been exposed to imidacloprid vs control Shelties. It was hypothesized that metabolites of this drug excreted into the biliary tract could stimulate nicotinic actetylcholine receptors leading to an increase in mucus production, an increase in viscosity of mucus and relaxation of the gallbladder.6

The average age of dogs diagnosed with gall bladder mucocele is around 10 years old. Most of these dogs are small to medium sized. No sex predilection has been reported. In 20-44% of dogs, the mucocele is an incidental finding on abdominal ultrasound.3,7 Dogs with clinical signs associated with their mucocele usually have a history of lethargy, vomiting and inappetance. Many of these dogs are PU/PD and some have diarrhea. The most common physical exam findings are abdominal pain and icterus.3

Many dogs with gallbladder mucoceles have inflammatory leukograms. About 75% of dogs have elevated ALP, ALT and GGT however only about 50% of dogs have elevated bilirubin. It is important to note that a recent paper described 5 cases of gallbladder rupture in dogs with bilirubin levels that were within reference range. All 5 of these dogs had abdominal pain and some amount of abdominal effusion.8

Ultrasound confirms the diagnosis of gallbladder mucocele by finding immobile bile sludge that does not change location in accordance to gravity. The ultrasound also typically shows echogenic bile in a stellate pattern or a finely striated pattern described as a kiwi fruit.7,9 Six ultrasonic patterns of gall bladder mucoceles have been described. However, one retrospective study found that bile pattern seen on ultrasound does not predict a patient’s symptoms or risk of rupture. This same study also found 44% of dogs with a gallbladder mucocelle were asymptomatic. Of the remaining dogs that had symptoms, 46% had a rupture of the gallbladder. The sensitivity and specificity of ultrasound to predict gallbladder rupture were 78.6% and 100%.8

Medical management of gallbladder mucoceles can be considered in patients who are asymptomatic or have very mild clinical signs and bilirubin within the reference range.  In dogs with more severe clinical signs and certainly in those with abdominal pain, surgery is recommended. Reports vary on the percentage of gallbladder mucoceles that contain bacteria. When infection is present, it is often a mix of bacteria. Because infection is possible, broad spectrum antibiotic therapy is recommended in medical management of gallbladder mucoceles. In addition to antibiotics, ursodiol and SAMe are prescribed to provide choleretic and antioxidant benefits. Medical therapy should be continued long term and the patient should have recheck blood work and ultrasound of the gallbladder performed every 4-6 weeks to look for resolution of the mucocele.1,10 If hypothyroidism or Cushing’s disease is suspected in these patients, a definitive diagnosis of endocrine disease should be obtained and treatment started as soon as possible. Lastly, a low fat diet is recommended for patients who have hyperlipidemia.4

Patients who have significant clinical signs including any patient with abdominal pain or an elevated bilirubin should be sent for an exploratory celiotomy and cholecystectomy. Patients going to surgery should be started on SQ vitamin K and antibiotics if sepsis is suspected. During surgery, bile or the gall bladder wall should be collected for culture as well as liver biopsies for histopathology. Many of these dogs have some type of concurrent liver disease. If there is suspicion that a patient’s gallbladder has ruptured, emergency surgery is warranted. One study found in 23 dogs that underwent cholecystectomy, 20% died or were euthanized during post-op hospitalization. Four of these dogs had a gallbladder rupture. The remaining patients who were discharged from the hospital had an excellent prognosis.3

For more information, or to refer a suspected case of gall bladder mucoceles, contact Angell’s internal medicine department at 617-541-5186 or internalmedicine@angell.org.

 

REFERENCES:

  1. Center, SA. Diseases of the gallbladder and biliary tree. Vet Clin Small Anim . 2009; 39 (3) :543-598.
  2. Mesich ML, Mayhew PD, Paek M, Holt DE, Brown DC: Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study. J Small Anim Pract. 2009 Dec;50(12):630-5.
  3. Pike FS, Berg J, King NW, et al. Gallbladder mucocele in dogs: 30 cases (2000–2002) J Am Vet Med Assoc. 2004;224:1615–1622.
  4. Aguirre AL, Center SA, Randolph JF, et al. Gallbladder disease in Shetland sheepdogs: 38 cases (1995–2005) J Am Vet Med Assoc. 2007;231:79–88.
  5. Mealey KL, Minch JD, White SN, Snekvik KR, Mattoon JS: An insertion mutation in ABCB4 is associated with gallbladder mucocele formation in dogs. Comp Hepatol. 2010 Jul 3;9:6.
  6. Gookin JL, Correa MT, Peters A, et al. Association of gallbladder mucocele histologic diagnosis with selected drug use in dogs: A matched case-control study. J Vet Intern Med. 2015;29:1465-1472.
  7. Besso JG, Wrigley RH, Gliatto JM, et al. Ultrasonographic appearance and clinical findings in 14 dogs with gallbladder mucocele. Vet Radiol Ultrasound. 2000;41:261–271.
  8. Guess SC, Harkin KR, Biller DS. Anicteric gallbladder rupture in dogs: 5 cases (2007-2013). J Am Vet Med Assoc.2015; 247 (12): 1412-1414.
  9. Choi J, Kim A, Seoyeon K et all. Comparison between ultrasonographic and clinical findings in 43 dogs with gallbladder mucoceles. Vet Radiol Ultrasound. 2014. 55 (2) 202-207.
  10. Walter R, Dunn ME, d’Anjou MA, Lecuyer M. Nonsurgical resolution of gallbladder mucocele in two dogs. J Am Vet Med Assoc.2008; 232 (11): 1688-1693.
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