Pathogenesis

In humans, functional or structural obstruc­tion of the cystic or common bile duct is the most common cause for GB MCs, this, how­ever, has not been shown to be the case in dogs.

Conditions shown to be associated with poor GB motility and abnormal cholesterol and lipid metabolism include some endo- crinopathies (diabetes mellitus (DM), hypo­thyroidism, and Cushing's disease), exogenous administration of corticosteroids as well as some dyslipidemias (hypertriglyc­eridemia, hypercholesterolemia). Dogs with Cushing's disease are 29 times more likely to have an MC than those without the disease and there is significant association between GB MC and hypothyroidism (Mesich et al. 2009). Complete resolution of spontaneous GB MCs has been shown in two dogs when treatment of concurrent hypothyroidism was initiated (Walter et al. 2008).

Another study looking at the effect admin­istration of hydrocortisone has on bile acid composition demonstrated a reversible change in the bile acid composition in treated dogs compared to controls, with increased concentrations of the more hydrophobic unconjugated bile acids seen. The shift to less water soluble, more hydrophobic caustic bile acids may be responsible for mucosal irrita­tion and hence trigger mucinous hyperplasia (Kook et al. 2011).

There is a potential genetic component to the disease as it has been shown that there is significant association of a mutation in the ABCB4 gene in Shetland sheepdogs and other dogs with biliary MCs (Mealey et al. 2010). This gene is responsible for encoding for the secretion of phosphatidyl choline (PC) across the bile canaliculi. PC is respon­sible for reducing bile salt cytotoxicity and protecting the biliary mucous from damage. The toxic bile acids are thought to be respon­sible for the cystic epithelial pathology that manifests.