Cholangiohepatitis and pancreatitis secondary to severe gastroduodenal ulceration in a foal

Abstract

A 2-month-old foal was presented with clinical signs of colic. Gastroduodenal ulceration was suspected. A poor response to medical treatment and signs of gastroduodenal obstruction led to celiotomy and an attempted bypass procedure. The foal was euthanized and postmortem examination revealed gastric ulceration, segmental duodenal stenosis, and severe chronic cholangiohepatitis and pancreatitis.

A 2-month-old, 140 kg, male standardbred foal was referred to the Atlantic Veterinary College (AVC) with a 2-day history of depression that had progressed to anorexia, lack of defecation, increased time spent in lateral recumbency, intermittent fever, ptyalism, and bruxism. One week prior to the onset of these signs, the foal had an episode of diarrhea. Treatment administered prior to admission included electrolyte solution, IV; ketoprofen; and trimethoprim-sulfamethoxazole.

Upon presentation to the AVC, the foal was depressed and grinding his teeth. Rectal temperature (38.8°C), heart rate (76 beats/min), and respiratory rate (18 breaths/min) were all within normal limits. Mucous membranes were pink with a capillary refill time of ~ 3 s. The foal was subjectively assessed to be ~ 8% dehydrated. No abnormalities were detected on auscultation of the lung fields. Gut sounds were absent dorsally; occasional weak borborygmi were heard ventrally. The foal strained to defecate once during the examination, producing a small (1 cm × 2 cm), firm fecal ball, and coughed twice, producing a greenish, watery discharge present in both the oral and nasal cavities.

The stomach was intubated and approximately 1 L of the watery, greenish, malodorous fluid was recovered. Abdominocentesis was attempted 4 times, but fluid was not recovered. Transcutaneous abdominal ultrasonography indicated 1 section of thickened bowel wall, but produced no evidence of obstruction or perforation. Preliminary clinicopathologic results included normal serum electrolyte levels and a normal leukogram.

Initial medical therapy consisted of 0.9% NaCl with 20 mEq KCl/L, IV, at a rate of 120 mL/kg body weight (BW)/d, and ranitidine HCl (Zantac; Glaxo Wellcome, Mississauga, Ontario), 1.5 mg/kg, IV, q8h. An indwelling nasogastric tube was maintained to permit continuous gastric decompression. This treatment was continued for 2 d, but there was no significant clinical improvement. On the 3rd day of treatment, blood samples taken on days 1 and 3 were submitted for full biochemical and hematologic analysis (Table 1). Results from the day 1 complete blood cell count were within normal limits. The day 3 clinicopathologic abnormalities included elevated red blood cell and platelet counts, consistent with dehydration. There was mild leukocytosis characterized by a mature neutrophilia and increased fibrinogen concentration, indicating mild systemic inflammation.

Table 1.

Serum biochemical abnormalities at the time of admission included increases in hepatic enzyme concentrations consistent with cholestasis. By day 3, these abnormalities had become more marked and were interpreted as being indicative of hepatic disease due to cholestasis with progressive hepatocellular damage. Icterus present in the day 1 blood sample had progressed from mild to moderate by day 3. Findings suggestive of mild systemic inflammation and possible cholangiohepatitis prompted the addition of trimethoprim-sulfadiazine (Tribrissen; Schering-Plough, Pointe Claire, Quebec), 30 mg/kg BW, IV, q12h, to the treatment regime. Transcutaneous abdominal ultrasonography was repeated to assess progression of the disease. There was poor gastric motility accompanied by a large amount of fluid in the stomach. These findings were consistent with gastric outflow obstruction. Due to the poor response to medical treatment, an exploratory laparotomy was recommended. Consent for celiotomy was given 36 h later.

Preoperative treatments consisted of ketoprofen (Anafen; Merial Canada, Baie d'Urfé, Quebec), 2.2 mg/kg BW, IV, and penicillin G sodium (Penicillin G Sodium for Injection; Novopharm, Toronto, Ontario), 22 000 IU/kg BW, IV. The foal was premedicated with xylazine HCl (Rompun; Bayer, Etobicoke, Ontario), 0.8 mg/kg BW, IV, and diazepam (Diazepam injection USP; Sabex, Boucherville, Quebec), 0.08 mg/kg BW, IV. A 2nd dose of xylazine HCl was administered, 2 mg/kg BW, IV. Anaesthesia was induced and maintained with isoflurane (Isoflurane; Bimeda-MTC Animal Health, Cambridge, Ontario).

A midline ventral laparotomy was performed. On examination of the abdominal organs, a segment of duodenal stenosis, originating immediately distal to the pylorus and extending beyond the major duodenal papilla, and distention and enlargement of the common bile duct were found. Bypass of the segment of duodenal stenosis was achieved by performing a 2-layer, hand-sewn, side-to-side anastomosis between the antimesenteric surface of a proximal loop of jejunum and the visceral surface of the prepyloric antrum (gastrojejunostomy). Hepaticojejunostomy was attempted in order to bypass the occluded major duodenal papilla. A stab incision was made on the antimesenteric side of a 2nd loop of proximal jejunum. The tip of a 10 French Foley catheter was inserted into the jejunal lumen, threaded craniad for 5 cm, and then passed back out of the jejunum via a 2nd antimesenteric stab incision. An incision was then made in the wall of the common bile duct and the tip of the catheter was inserted into the common bile duct lumen. Luminal contents from the duct, consisting of gastric reflux and purulent material leaked out around the inflated tip of the Foley catheter. As the reflux consisted of fibrous food particles and copious amounts of purulent fluid, the owner was consulted and advised of the associated grave prognosis. The owner requested euthanasia.

A necropsy was performed. The foal had lost 18 kg since admission 5 d earlier. There was a moderate generalized loss of muscle mass and body fat stores. The carcass also showed generalized icterus. The distal esophagus had multiple foci of mild mucosal erosions, which were considered to be caused by the indwelling nasogastric tube. There was a 5-cm × 10-cm focal area of gastric ulceration present in the nonglandular portion of the stomach. The proximal duodenum had a 10-cm segment of mural thickening that involved its entire circumference and congestion that markedly reduced the diameter of the lumen. The stenosis began immediately distal to the pyloric sphincter and extended beyond the major duodenal papilla. On histologic examination, there was marked mucosal and submucosal fibrosis with luminal stenosis, sloughing of the epithelium, and marked infiltration of neutrophils and macrophages.

The pancreas was enlarged and friable in consistency. Upon histologic examination, subacute to chronic diffuse suppurative pancreatitis with fibrosis was observed. On gross examination, the liver was enlarged and displayed a moderate nutmeg type pattern on cut surface. All major bile and pancreatic ducts, as well as the intrahepatic biliary tree, were filled with a gray-white viscous fluid. Histologically, there was subacute to chronic multifocal cholangiohepatitis with moderate periportal fibrosis and marked biliary hyperplasia. Bacterial cultures of the viscous contents of the bile ducts resulted in the culture of an α-hemolytic Streptococcus sp., Streptococcus zooepidemicus, Eshcerichia coli, and Klebsiella pneumoniae.

Gastric ulcer disease in foals is complex. Lesions most commonly occur in the nonglandular portion of the stomach, but they may also occur in the glandular mucosa, the pylorus, and proximal duodenum (1,2,3). Ulcers may be primary or develop secondary to an underlying problem. Four clinical syndromes have been described in foals: subclinical, clinical, and perforating ulcers, and ulcer- associated gastric or duodenal obstruction (3). Clinical signs may include diarrhea, colic, rolling, lying in dorsal recumbency, ptyalism, and bruxism. In the neonate, the only clinical signs may be depression or anorexia, unless a more catastrophic event, such as perforation or , occurs (1,2,3). Perforating duodenal ulcers develop by 2 mo of age, whereas strictures are typically seen in 2- to 3-month-old foals (4,5).

Ulcers associated with duodenal obstruction are associated with lesions in the gastric mucosa extending from the pylorus into the proximal duodenum (1,3). Involvement of the duodenum is rare in adult horses, but it is relatively common in foals (3,4,5,6). A segmental, ulcerative duodenitis, often occurring near the common bile duct entrance, is found more commonly than a discrete duodenal ulcer (4,5,6). Healing of these ulcers may lead to stricture of the pylorus or proximal duodenum (3,6). The current case was a classic illustration of this phenomenon.

The severe duodenal stenosis in this case extended beyond the major duodenal papilla. The resulting outflow impairment resulted in duodenal contents refluxing back into both the stomach and the common bile duct. In this foal, the severity of the cholangiohepatitis and hepatic injury was surprising, given the apparently short clinical course. Reflux of duodenal contents into the stomach leads to increases in gastric acid, bile salts, and digestive enzymes in the stomach (7). The predominant mechanism of equine gastric squamous mucosal injury is thought to be excessive exposure to gastric acid (8). An acidic pH, combined with an increased concentration of bile salts within gastric contents, is reported to be even more injurious to the equine squamous gastric mucosa than is acid alone (7). Thus, the large gastric ulcer may have been secondary to obstruction of the duodenal outflow. However, it is also possible that the gastric ulcer was a result of the same unknown disease process that resulted in the primary duodenal ulceration. Many duodenal lesions seem to be associated with enteritis, but duodenitis in foals is still a poorly understood disease (8). The foal in this case had a history of diarrhea 1 wk prior to presentation, lending support to this association.

Regurgitation of duodenal contents into the common bile duct and the duct systems of both the pancreas and the liver occurred, but involvement of the pancreas was not diagnosed antemortem. Elevated serum gamma-glutamyl transferase (GGT) was noted antemortem, but it was thought to be associated with the cholestasis. This enzyme also exists in high concentrations in the pancreas. The pancreatitis may have contributed to the enzyme elevation, but pancreatitis is a rarely reported condition in foals, so it was not possible to differentiate the contribution of the pancreas to the GGT level from elevations presumably due to the severe hepatic involvement (4). Another unexpected finding, given the apparent short duration of clinical signs of obstruction, was the amount of fibrosis present histologically in both the pancreas and the liver. The apparent chronicity of the lesions suggests that the influx into the common bile duct began before the obstruction to the duodenal outflow was complete and, possibly, was due to prior intermittent outflow obstruction. The retrograde passage of duodenal contents may have been facilitated by spasm of the major duodenal papilla, secondary to duodenal inflammation (9) or due to inflammation of the duct opening itself (6). Thus, the chronicity of the pancreatitis and cholangiohepatitis, as seen histologically, may reflect the duration of duodenal inflammation rather than of obstruction of intestinal outflow.

Initial management of gastroduodenal ulcer disease typically consists of medical therapy, and the evaluation of the response to treatment. One report states that improvement should be evident within 5 d (10). However, the foal in this report deteriorated clinically over that time span, indicating that by the time clinical signs of duodenal obstruction or increased serum hepatic enzymes are noted, the disease and its sequellae may have been quite advanced; it is likely that the severe segmental duodenal stenosis resulted in secondary gastric ulceration, pancreatitis, and cholangiohepatitis. Cholangiohepatitis in foals, secondary to common hepatic duct obstructions, may resolve after hepaticojejunostomy (4). The outcome of this case supports the contention that early surgical intervention is recommended to optimize the chances of success.