Pathophysiology

A gall bladder mucocoele describes cystic mucinous hyperplasia of the gall bladder wall with accumulation of thick mucus. A mucocele can be subclinical and an incidental finding on diagnostic imaging but can cause obstruction of the biliary tract secondary to the thick mucus and when it becomes very large, it can also stretch the gall bladder wall and cause pressure necrosis and rupture.

Gall bladder mucoceles were first reported in dogs in 1995. They are uncommon but appear to be increasing in frequency.

The underlying cause of gall bladder mucoceles remains poorly understood, but there does appear to be a strong association with hypertriglyceridemia and hypercholesterolemia in dogs. Other proposed associations include biliary tract infection, disruption to gall bladder motility and drainage and genetic mutations. A very interesting recent study has suggested an association with neonicotinoid (imidacloprid) use particularly in Shelties – which is an attractive explanation for the apparent sudden appearance of this new disease. Studies repeatedly report an increased incidence in small breed dogs with a strong overlap with breeds reported to suffer from familial hyperlipidemia: for example, Aquirre et al. (2007) report gall bladder mucocele in 38 Shetland sheepdogs and Malek et al. (2013) report gall bladder mucocele in 43 dogs including 10 cocker spaniels, 5 Shetland sheepdogs and 4 miniature schnauzers. A Japanese case-control study of gall bladder mucocele showed a significant association with increased cholesterol or triglycerides and miniature schnauzers were one of the breeds predisposed to mucocele.

Aguirre et al. (2007) proposed an association between gall bladder mucocele and ‘dyslipidemia’ with an increase in serum triglycerides and/or cholesterol reported in all cases in which they were measured. Six out of 38 of their cases had hyperadrenocorticism, 5 had hypothyroidism and one had diabetes mellitus. Malek at al. (2013) also reported dogs with hyperadrenocorticism, diabetes mellitus and hypothyroidism and a study of 30 dogs with gall bladder mucocele included seven dogs with hyperadrenocorticism and two dogs on long-term steroid therapy. Another retrospective case-control study of gall bladder mucocele found a very significant association with hyperadrenocorticism but questioned the association with hypothyroidism since many dogs were tested after the mucocele was diagnosed, introducing a significant source of bias. However, in a study of iatrogenic hyperadrenocorticism in 12 beagles, no increase in biliary sludge and no mucoceles were reported about 3 months of treatment with 8 mg/kg hydrocortisone every 12 hours.

There are plausible reasons why high serum lipids should predispose to gall bladder disease. Studies in prairie dogs fed high-cholesterol diets have shown an increase in bile viscosity, a reduction in bile flow and gall bladder mucosal hyperplasia, presumably due to the irritant effects of the bile acids in the thick, stationary bile. However, similar studies have not been reported in dogs and cholesterol and fat metabolism differ between species.

The pathophysiological relationship between hyperlipidemia and gall bladder mucocele therefore remains poorly understood, but evidence to date suggests that any dog with persistent hypertriglyceridaemia and/or hypercholesterolaemia should be investigated for clinically significant biliary tract disease.

Gall bladder mucoceles are rarely reported in cats. There are two single case reports in cats and one case report was a cat with concurrent hepatic lipidosis, which does suggest a potential association with hyperlipidemia in this species also, albeit rare.

Treatment

Clinically significant gall bladder mucocoeles should be treated and most authors recommend surgery for cholecystectomy. The prognosis is reasonable if the gall bladder has not ruptured and if biliary diversion surgery is not necessary. However, there is a real risk of perioperative mortality and bile leakage and cholecystectomy is generally considered to be a referral procedure. Successful medical management has been reported – particularly when the underlying cause is also identified and treated. Complete resolution has been reported in two hypothyroid dogs after supplementing thyroid hormones together with medical management. Medical management should only be attempted where there is no evidence of bile leakage or gall bladder wall thinning or necrosis on ultrasound. The owners should be warned of the potential risk of gall bladder rupture and the mucocoele should be regularly monitored for this with ultrasound. Medical treatment involves feeding a low-fat diet and giving ursodeoxycholic acid and antioxidants.

It is unknown whether there is any benefit to medically managing asymptomatic mucocoeles. Surgical management would not be advisable in the absence of any clinical or clinicopathological abnormalities because of the risk of perioperative mortality. It is not known if asymptomatic mucocoeles progress nor if they do, how fast. It is also unknown if medical management will delay progression but the author uses ursodeoxycholic acid routinely in asymptomatic cases and monitors them with repeat ultrasound examinations every 2–4 months.

References

1.  Aguirre AL, Center SA, Randolph JF, Yeager AE, Keegan AM, Harvey HJ, Erb HN. Gallbladder disease in Shetland sheepdogs: 38 cases (1995–2005). Journal of the American Veterinary Medical Association. 2007;231(1):79–88.

2.  Bennett SL, Milne M, Slocombe RF, Landon BP. Gallbladder mucocoele and concurrent hepatic lipidosis in a cat. Australian Veterinary Journal. 2007;85(10):397–400.

3.  Gookin JL, Correa MT, Peters A, Malueg A, Mathews KG, Cullen J, Seiler G. Association of gallbladder mucocele histologic diagnosis with selected drug use in dogs: a matched case-control study. Journal of Veterinary Internal Medicine. 2015;29(6):1464–72.

4.  Kook PH, Schellenberg S, Rentsch KM, Reusch CE, Glaus TM. Effects of iatrogenic hypercortisolism on gallbladder sludge formation and biochemical bile constituents in dogs. The Veterinary Journal. 2012;191(2), 225–230.

5.  Kutsunai M, Kanemoto H, Fukushima K, Fujino Y, Ohno K, Tsujimoto H. The association between gall bladder mucoceles and hyperlipidaemia in dogs: a retrospective case control study. The Veterinary Journal. 2014;199(1):76–9.

6.  Li YF, Moody FG, Weisbrodt NW, Zalewsky CA, Coelho JC, Senninger N, Gouma D. Gallbladder contractility and mucus secretion after cholesterol feeding in the prairie dog. Surgery. 1986;100(5):900–904.

7.  Malek S, Sinclair E, Hosgood G, Moens NM, Baily T, Boston SE. Clinical findings and prognostic factors for dogs undergoing cholecystectomy for gall bladder mucocele. Veterinary Surgery. 2013;42(4):418–26.

8.  Mesich MLL, Mayhew PD, Paek M, Holt DE, Brown DC. Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study. Journal of Small Animal Practice. 2009;50(12):630–635.

9.  Newell SM, Selcer BA, Mahaffey MB, Gray ML, Jameson PH, Cornelius LM, Downs MO. Gallbladder mucocele causing biliary obstruction in two dogs: ultrasonographic, scintigraphic, and pathological findings. Journal of the American Animal Hospital Association. 1995;31(6):467–472.

10.  Pike FS, Berg J, King NW, Penninck DG, Webster CR. Gallbladder mucocele in dogs: 30 cases (2000–2002). Journal of the American Veterinary Medical Association. 2004;224(10):1615–1622.

11.  Walter R, et al. Nonsurgical resolution of gallbladder mucocele in two dogs. Journal of the American Veterinary Medical Association. 2008;232(11):1688–1693.

12.  Woods KS, Brisson BA, Defarges AM, Oblak ML. Congenital duplex gallbladder and biliary mucocele associated with partial hepatic cholestasis and cholelithiasis in a cat. The Canadian Veterinary Journal. 2012;53(3):269.