Canine gallbladder mucocele (GBM) is characterized by progressive accumulation of tenacious pale yellow to dark green mucin-laden bile, which may extend into the cystic, hepatic, and common bile ducts, resulting in variable degrees of bile duct obstruction. Progressive expansion of a GBM leads to gallbladder ischemia and necrosis, bile peritonitis, and sometimes opportunistic infection. Gallbladder stasis, perhaps reflecting dysmotility, and distention predispose to cholecystitis.
Canine gallbladder mucocele (GBM) is characterized by progressive accumulation of tenacious pale yellow to dark green mucin-laden bile, which may extend into the cystic, hepatic, and common bile ducts, resulting in variable degrees of bile duct obstruction. Progressive expansion of a GBM leads to gallbladder ischemia and necrosis, bile peritonitis, and sometimes opportunistic infection. Gallbladder stasis, perhaps reflecting dysmotility, and distention predispose to cholecystitis.
A GBM should be considered when sequential ultrasonographic examinations fail to indicate a decrease in gallbladder volume after feeding, confirming lack of movement of luminal “sludge.” Feeding a dog (100 g of food) and recording gallbladder dimensions at 0, 15, 30, 45, 60, 90, and 120 minutes, recorded in cm ([width × height × length] × 0.52), yields the gallbladder volume in mL.
Failure to decrease baseline gallbladder volume by at least 25% suggests dysmotility.
Erythromycin (0.5–1 mg/kg, PO, one dose) combined with a small meal also may stimulate initiation of gallbladder motility; however, in healthy dogs studied, neither feeding with nor without erythromycin was consistently superior to initiate contraction.
Dogs with GBM range in age from 3 to 14 years old with no sex predisposition. Incidence is increased in Shetland Sheepdogs, Miniature Schnauzers, and Cocker Spaniels. A genetic mutation in the ABCB4 (MDR3) phospholipase flippase transporter was demonstrated in Shetland Sheepdogs and other dogs with GBM. All affected dogs were heterozygous for this mutation.
Factors predisposing to GBM formation include:
middle to older age
endocrinopathies (typical and atypical hyperadrenocorticism, hypothyroidism, diabetes mellitus)
hyperlipidemia or hypercholesterolemia (idiopathic, nephrotic syndrome, feeding of a high-fat diet, pancreatitis)
gallbladder dysmotility
cystic hyperplasia of the gallbladder mucosa (shown to be inducible by progestins in dogs)
The inciting cause of mucus hypersecretion or accumulation is unproved and may be multifactorial. Nevertheless, mucin imparts important viscoelastic properties to bile and likely importantly contributes to GBM formation. Decreased gallbladder motility leads to luminal bile stasis and enhanced absorption of electrolytes and fluid, promoting biliary sludge formation.
Dogs with risk factors may rapidly mature a developing mucocele after beginning glucocorticoid treatment or a high-fat diet (eg, some diets for renal disease or hepatic insufficiency). Because concurrent vacuolar hepatopathy (VH) is common, associated underlying disorders should be investigated.
In the gallbladder, mucin intimately integrates with the mucosal epithelial folds and contributes to a biofilm niche that can function as an infection sump in animals with persistent or recurrent bileborne bacterial infections.
Gallbladder mucin in healthy dogs and dogs with gallbladder mucocele (GBM) was shown to be dominated by gel-forming mucins (Muc5b and Muc5ac), with Muc5b being the major component.
Upon dehydration, gel-forming mucin transforms into a gelatinous-rubbery mass, consistent with the gallbladder contents in dogs with GBM. A 17-fold greater Muc5ac was shown in gallbladder contents from dogs with GBM compared to healthy dogs, without change in Muc5b. A greater Muc5ac:Muc5b ratio coordinates with the extreme viscosity associated with GBM where mucin tightly adheres to the gallbladder mucosal interface. Yet the physical association between gel-forming mucin and GBM may not represent a causal association but rather a response to gallbladder distention and dysmotility or other pathologies.
The ultrasonographic imaging pattern typifying a mature GBM is highly recognizable. There is substantial survival advantage to early diagnosis and surgical intervention (interventional cholecystectomy) in this syndrome.
In some dogs with a mature gallbladder mucocele, mucus with the GBM dislodges, obstructing hepatic or common bile duct drainage, causing jaundice and critical acute illness. Others with a mature GBM may progress to gallbladder rupture and bile peritonitis.
Cats have fewer mucus glands in their gallbladder, which may explain why GBM is comparatively uncommon in cats versus dogs. It is the author’s impression that canine gallbladder dysmotility develops antecedent to appearance of gallbladder mucocele; one study of dogs with mobile and immobile gallbladder sludge demonstrated significantly decreased gallbladder ejection fraction (estimated motility) in healthy control dogs.
Clinical Findings and Diagnosis of Canine Gallbladder Mucocele
Ultrasonography
Clinical illness with canine gallbladder mucocele averages ~5 days, although some dogs have vague episodic clinical signs (ie, inappetence, vomiting, vague abdominal pain) for months. In decreasing order of frequency, clinical signs include vomiting, abdominal discomfort, anorexia or hyporexia, jaundice, tachypnea, tachycardia, polyuria/polydipsia (PU/PD), fever, diarrhea, and abdominal distention.
Dogs progressing to gallbladder rupture usually demonstrate abdominal pain, jaundice, tachycardia, tachypnea, and fever. However, occasionally, ruptured GBMs clinically normal with a free-moving congealed mucocele have been imaged in the peritoneal cavity.
Typical clinicopathologic indicators include leukocytosis with a mature neutrophilia and monocytosis and sometimes a left shift, high liver enzyme activities (alkaline phosphatase [ALP], gamma-glutamyl transferase, ALT, and AST), hyperbilirubinemia, and inconsistent hypercholesterolemia.
Aerobic bacteria may be cultured from bile or the gallbladder wall, with a number of enteric organisms identified, including Escherichia coli, Enterobacter spp, Enterococcus spp, Staphylococcus spp, Micrococcus spp, and Streptococcus spp.
Development of gallbladder dysmotility is often insidious and enigmatic but nevertheless may increase risk for canine GBM.
Real-time ultrasonographic gallbladder motility assessment can assist in identifying dogs with gallbladder dysmotility. A described protocol quantifies the maximum ejection fraction achieved over a 3-hour postprandial interval.
Healthy dogs should exhibit a gallbladder ejection volume of at least 25% relative to baseline volume, at some point within this postprandial imaging interval.
The utility of a gallbladder motility study is to help identify dogs with risk for GBM, which has helped strategize the propriety of preemptive elective cholecystectomy before GBM maturation, especially in geriatric dogs of predisposed breeds.
Use of CT imaging has not improved assessment of gallbladder motility or gallbladder size assessments in dogs compared to real-time ultrasonography using dynamic motility assessments.
Transhepatic ultrasound–guided cholecystocentesis should not be performed if a GBM is suspected. Ultrasonography may detect hepatomegaly and either a heterogeneous or hyperechoic hepatic parenchyma. Hypoechoic nodules correspond to a severe VH with formation of reticulin-defined nodules and regenerative repair.
After gallbladder removal, sequential hepatic ultrasonographic evaluations are necessary to determine whether parenchymal lesions resolve. A liver biopsy should be collected from a liver lobe distant to the gallbladder to evaluate for underlying or coexisting disorders; sections collected adjacent to the gallbladder contain peribiliary glands and numerous ductal elements that may result in erroneous assessments.
Histologically, cystic mucosal hyperplasia of the gallbladder wall is common. All dogs have thick biliary debris; some components may be profoundly viscous and mucin laden, others more liquid, some dark green to black, some with white bile. Some contain gritty black material, and some contain a firm, organized gelatinous matrix. Transmural ischemic necrosis may develop and lead to necrotizing cholecystitis and gallbladder rupture.
Liver biopsies may disclose a VH or mild to moderate portal hepatitis or periductal fibrosis; the latter changes reflect associated cholangitis or transient biliary tree occlusion. Some dogs lack concurrent hepatic lesions, especially when cholecystectomy is done preemptively (before GBM maturation).
Treatment of Canine Gallbladder Mucocele
Hydrocholeresis
SAMe
Antimicrobial treatment
Cholecystectomy
Dogs with canine gallbladder mucocele without clinical signs of mucocele leakage or biliary tree obstruction at the time of initial diagnosis may benefit from hydrocholeresis induced by administration of ursodeoxycholic acid (15–25 mg/kg, PO, divided every 12 hours and given with food), SAMe (20–40 mg/kg, PO after an overnight fast, every 24 hours; food should also be withheld for 2 hours after dosing), and antimicrobial coverage. Biochemical and ultrasonographic evaluations every 6 weeks are useful to monitor treatment response or syndrome progression.
Rarely, an evolving GBM may resolve with medical treatment. However, progression in any clinical, clinicopathologic, or imaging parameter indicates poor control and need for surgical intervention.
Cholecystectomy is the best course of treatment and is essential for most dogs with clinical signs and clinicopathologic findings consistent with biliary tree inflammation, obstruction, or rupture. Because bile stasis predisposes to infection, broad-spectrum antimicrobials should be initiated before surgical intervention.
Examination and staining of cytologic preparations of bile and imprints of liver and biliary tree biopsies may be invaluable if antimicrobial coverage interferes with submitted cultures. Evidence of bacteria in cytologic samples or histologic confirmation of suppurative cholecystitis or cholangitis indicates a need for chronic postoperative antimicrobial administration. The resected gallbladder should be submitted for histologic examination (sectioned before fixation to allow formalin penetration), and a liver biopsy collected distant to the site of surgery.
Perioperative mortality rate is high for clinically affected dogs with a ruptured gallbladder complicated by sepsis. If bile peritonitis is present, the peritoneal cavity must be extensively cleansed with sterile, warm, polyionic fluids to remove debris, bacteria, and injurious bile salts. Abdominal drains may be necessary. Antimicrobials should be administered for 4–6 weeks after surgery.
Cholecystotomy for removal of gallbladder contents without cholecystectomy is not advised, because GBMs usually recur. Furthermore, necrosis of the gallbladder wall may not be grossly evident at surgery, leading to postoperative gallbladder rupture.
After gallbladder resection, chronic choleretic treatment is recommended, especially for Shetland Sheepdogs in which a genetic risk is surmised for sludged bile. Underlying causes of hyperlipidemia or endocrine disorders should be identified and managed appropriately.
Clinicopathologic abnormalities (high ALP usually) normalize after gallbladder removal in most dogs, except those with associated suppurative cholangiohepatitis, unresolved endocrinopathies, persistent hyperlipidemia, or surgical complications of cholecystectomy.
Feeding a protein-restricted, high-fat diet to hyperlipidemic animals may be detrimental and is not recommended.
Key Points
Canine gallbladder mucocele (GBM) is characterized by progressive accumulation of tenacious pale yellow to dark green mucin-laden bile
Early diagnosis and surgical intervention (interventional cholecystectomy) are key for GBM.
Cholecystectomy is the treatment of choice
