Obstructive cholelithiasis and cholecystitis in a keeshond

Abstract

A 10-year-old, neutered male, keeshond was presented for vomiting, lethargy, icterus, and anorexia. Obstructive cholelithiasis was diagnosed based on analysis of a serum biochemical profile, abdominal radiographs, and ultrasonography. Choleliths were removed from the gall bladder and common bile duct via a cholecystotomy.

A 10-year-old, neutered male keeshond was presented to his veterinarian after 2 d of persistent vomiting, anorexia, lethargy, and icterus. A complete blood (cell) count (CBC) and serum biochemical profile were performed. There were no significant findings on the CBC. The serum biochemical profile revealed hypercholesterolemia, hypergammaglobulinemia, hyperbilirubinemia, and marked elevations in liver enzymes. Abdominal radiographs and ultrasonography showed calcification of the common bile duct. The veterinarian administered intravenous lactated Ringer’s solution, ampicillin, and enrofloxacin and referred the dog to the Western College of Veterinary Medicine Small Animal Teaching Hospital.

On physical examination, a grade III/VI systolic heart murmur was detected with maximum intensity over the mitral valve region. Mild discomfort was elicited on deep palpation of the abdomen. Otherwise the results of the physical examination were unremarkable.

Blood samples were submitted for a CBC (Abbott Cell-Dyn 3500R; Abbott Laboratories, Saint-Laurent, Quebec) and serum biochemical profile (Roche Hitachi 912; Montreal, Quebec). A lymphopenia (1.064 × 10⁹/L; reference range, 1.2 to 5.0 × 10⁹/L), and a monocytosis (1.73 × 10⁹/L; reference range, 0.08 to 1.0 × 10⁹/L), consistent with a stress response were noted. Alanine transferase (ALT) (627 U/L; reference range 19 to 59 U/L), sorbitol dehydrogenase (SDH)(21 U/L; reference range 0.0 to 4.0 U/L), alkaline phosphatase (ALP) (1372 U/L; reference range 9 to 90 U/L), cholesterol (9.37 mmol/L; reference range 2.70 to 5.94 mmol/L), gamma glutamyl transpeptidase (GGT)(26 U/L; reference range 0 to 8 U/L), and bilirubin (23 μmol/L; reference range 1.0 to 4.0 μmol/L) were elevated. The elevations in ALP, GGT, cholesterol, and bilirubin were suspected to be secondary to cholestasis, while the elevations in ALT and SDH were attributed to hepatocellular leakage. The hypergammaglobulinemia (40 g/L; reference range 23 to 37 g/L) and a decreased albumin/globulin (A/G) ratio (0.70; reference range 0.73 to 1.49) were indicative of chronic inflammation. The urea level was low (3.2 mmol/L; reference range 3.5 to 11.4 mmol/L), which was attributed to anorexia and dilution/ diuresis from prior fluid therapy. The dilute urine specific gravity of 1.016 was also attributed to prior fluid therapy.

Radiographs of the abdomen revealed multiple linear calcifications in the cranioventral part of the abdomen (Figure 1). The largest calcification measured 1.4 cm–cranial to caudal, 1 cm–dorsal to ventral, and 1 cm–medial to lateral on these radiographs. Ultrasonography of the abdomen localized the large calcification to the common bile duct at the entrance to the duodenum. Proximal to the obstruction, the common bile duct was markedly distended, measuring up to 2 cm in diameter. The average diameter of the normal canine bile duct is 0.3 cm (1). The gall bladder was distended and contained biliary sludge. Biliary sludge is a normal finding in 50% of dogs, but it is also associated with biliary stasis, especially in the presence of an enlarged gall bladder (2).

Figure 1.

Right lateral radiograph of the abdomen. Note the linearly arranged radiopaque calculi in the cranial abdomen (arrows).

Radiographs of the thorax revealed a mild generalized cardiomegaly. Echocardiography demonstrated a moderate dilatation of the left atrium, a mild dilatation of the left ventricle, and mitral insufficiency and regurgitation.

A coagulation panel, consisting of prothrombin time (PT) and partial prothrombin time (PTT), was done prior to surgery, since long-standing biliary tract obstruction can decrease absorption of fat-soluble vitamins, including vitamin K, which is required for activation of certain coagulation factors (3). Prothrombin time and PTT were both within normal reference ranges.

The dog was premedicated with hydromorphone (Sabex, Boucherville, Quebec), 0.1 mg/kg bodyweight (BW), IV, and anesthesia was induced with propofol (Diprivan; Novopharm, Toronto, Ontario), 4 mg/kg BW, IV, and maintained with 1.0 L/min oxygen and 2.0 L/min nitrous oxide with 1.5% isoflurane (Isoflo; Abbott Laboratories, St. Laurent, Quebec) for exploratory celiotomy via a ventral midline incision. An enlarged liver and a dilated common bile duct, measuring approximately 2.1 cm in diameter, were noted during abdominal exploration. Patency of the common bile duct was established by expressing bile into the intestine through gentle compression of the gall bladder. The gall bladder was incised and the larger stones were removed with a Lahey bile duct spoon (Figure 2), while those in the common bile duct were sectioned with Kelly forceps to facilitate removal. The smaller stones were flushed with sterile saline into the duodenum. A full thickness biopsy of the gall bladder and a guillotine biopsy of the left medial liver lobe (4) were submitted for histopathologic examination. Samples of the gall bladder stones, bile, and liver were collected aseptically and submitted for culture. The gall bladder was closed routinely. Several of the small biliary choleliths were also submitted for quantitative analysis. A jejunostomy tube (5) was placed for provision of postoperative nutrition and the abdomen was copiously lavaged with sterile saline and then closed routinely.

Figure 2.

Photomicrograph showing the incision into the gall bladder demonstrating multiple small choleliths (arrow)

Postoperatively, the dog was treated with ampicillin (Novopharm, Toronto, Ontario), 22 mg/kg BW, IV, q8h for 14d, and enrofloxacin (Baytril; Bayer, Toronto, Ontario), 5 mg/kg BW, IV, q24h for 14 d, for cholecystitis. Chronic ursodiol (Urso 250; Axcan Pharma, Mont Saint-Hilaire, Quebec) therapy, 10 mg/kg BW, PO, q12h, was initiated. The dog was fed a liquid diet (1/4 strength Clinicare Canine/Feline Liquid Diet, Abbott Laboratories, Abbott Park, Illinois, USA) at a rate of 5 mL/h through the jejunostomy tube until its removal 3 d post-surgery. Pain was managed postoperatively with hydromorphone (Sabex), 0.05 mg/kg BW, IV, q4–6h, and meloxicam (Metacam; Boehringer Ingelheim, Laval, Quebec), with a loading dose of 0.2 mg/kg BW followed by a maintenance dose of 0.1 mg/kg BW, SC, q24h.

Histopathological examination of the gall bladder was unremarkable. There was bile duct hyperplasia and mild to moderate cholestasis in the liver. No organisms were detected by using Gram’s staining of the liver, bile, and choleliths, or with aerobic, anaerobic, and enrichment cultures. Composite analysis of the collected gallstones was not completed, as they were lost.

Two days postsurgery, a serum biochemical profile revealed persistent elevations in ALT (190 U/L), SDH (7.0 U/L), ALP (515 U/L), GGT (14 U/L), and bilirubin (6 μmol/L), although all values had decreased. The dog’s hyperglobulinemia and hypercholesterolemia had resolved. Urea had further decreased (1.1 mmol/L) due to a combination of dilution from IV fluid therapy, decreased intake, and possibly decreased hepatic production or gastrointestinal loss. The dog’s albumin had decreased (22 g/L; reference range 28 to 38 G/L), which was suspected to be from decreased hepatic production or gastrointestinal loss. The owners have not reported any return of clinical signs in the 3 mo since surgery.

Discussion

The frequency of cholelithiasis in dogs is low (3,7,8,9,11). Choleliths are subclincal and not detected antemortem as they rarely result in clinical signs. Biliary calculi develop when bile becomes saturated with cholesterol relative to the other constituents of bile and precipitates. When cholesterol supersaturated bile enters the gall bladder, emptying is delayed, leading to stasis. The gall bladder mucosa responds to biliary stasis by secreting excessive amounts of mucin, which may induce cystic duct occlusion (8). Certain substances, such as bile pigments, mucoproteins, bacteria, and refluxed intestinal contents, can act as a nidus for microscopic calculi, which expand into larger calculi known as gallstones (9).

Possible etiologies for biliary calculi include trauma, biliary stasis, microbial and parasitic biliary infections, and diet alterations (7,9). Canine gallstones are composed of small amounts of cholesterol and are nonresponsive to chenodeoxycholic acid, traditionally used to dissolved cholesterol gallstones in humans (1,9). Three major types of biliary calculi have been reported in dogs: pure cholesterol choleliths, mixed choleliths (consisting primarily of cholesterol mixed with bile acids, pigment, calcium, and protein), and pigment choleliths (primarily composed of calcium bilirubinate) (9). Canine gallstones are primarily pigment gallstones (1), although cholesterol, bilirubin, and mixed gallstones are also reported (3). In this dog, the stones were pigmented and presumed to be composed of calcium bilirubinate. The bile associated with pigment gallstones is sterile and the cause for the inflammatory response and mucus hypersecretion is unknown (10).

Clinical signs associated with obstructive cholelithiasis are usually not specific and include anorexia, vomiting, diarrhea, lethargy, icterus, and abdominal pain and distension (7,9), as seen in this dog. Signs may wax and wane for several weeks before presentation. Severe disease manifests when choleliths cause extrahepatic biliary tract obstruction, or rupture of the gall bladder or common bile duct. Biochemical and hematological abnormalities are indicative of obstructive cholestasis and not specific to cholelithiasis. The most common clinical findings include high concentrations of serum ALT, ALP, cholesterol, and total bilirubin, and abnormal clotting times (3). The hematological abnormalities are inconsistent and may include mild to moderate leukocytosis with a left shift or a nonregenerative anemia (8). The first indication of obstruction is often bilirubinuria (3). The first change associated with complete extrahepatic biliary tract obstruction is bile duct dilatation, followed by intrahepatic bile duct dilatation 5 to 7 d after complete obstruction (11), as seen in this dog. Choleliths may be radiopaque or radiolucent. Radiopaque stones have been reported in 48% of cases; cholesterol stones are radiolucent, while mixed and bilirubin stones vary in opacity (7).

The recommended treatment for cholelithiasis is usually a surgical cholelithotomy (7). In this dog, a cholecystotomy was indicated due to the severity of the obstruction and subsequent dilation of the common bile duct, proximal to the largest cholelith. Cholecystotomy is the preferred surgical procedure; however, cholecystectomy is indicated if damage to the gall bladder is severe, and choledochotomy is indicated for choleliths in the common bile duct that are not amendable to removal by antegrade flushing (7).

Postsurgical management of cholelithiasis must include management of cholecystitis. Bacterbilia is common with cholelithiasis. Enterococci species constitute the majority of the bacterial isolates (7) associated with biliary stasis. Antimicrobial agents, such as cephalosporins, ampicillin or enrofloxacin (1,7), are used to target these gram-negative bacteria as they achieve high concentrations in the bile. This dog was empirically treated with ampicillin and enrofloxacin prior to surgery, which likely accounts for the negative bacterial cultures.

Chronic bile acid supplementation with a bile salt, such as ursodiol, will decrease the hepatic production and secretion of cholesterol, decrease intestinal reabsorption of cholesterol, and increase the flow of bile (6). This also decreases the cholesterol saturation of bile and allows for the solubilization of cholesterol containing calculi (6).

There are a limited number of reported cases of obstructive cholelithiasis in the literature. The surgical procedure associated with the lowest morbidity and mortality is a cholecystotomy (7), unless associated with complicating factors, such as septic peritonitis, increased serum creatinine concentration, or prolonged PTT (12). These factors were not present in this dog.