Septic Bile Peritonitis in a Dog: Case Study

Nicole J. Guisto, DVM; Heather L. Tarpley, DVM; Bruce E. LeRoy, DVM, PhD; Kenneth S. Latimer, DVM, PhD

Class of 2005 (Guisto) and Department of Pathology (Tarpley,LeRoy, Latimer) College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388

Signalment - Canine, Italian Greyhound, female spayed, 10-year-old

Medical history - The patient had a 2-day history of lethargy with decreased appetite. Altered mental status had been observed for the last 24 hours. A single, extrahepatic, portosystemic shunt had been surgically corrected five weeks earlier. Surgery and post-operative recovery were uneventful. During hospitalization, thrombocytopenia was discovered and ultrasonographic examination revealed a spherical, hyperechogenic structure in the biliary tract interpreted to be a biliary calculus. The dog was discharged and medical management included oral administration of S-adenosyl-L-methionine (SAMe), vitamin E, metronidazole, neomycin, lactulose, and ursodiol.

Physical Examination – Vital signs included a body temperature of 102ºF, pulse of 160 beats per minute, and respiratory rate of 28 breaths per minute. The patient was responsive but was disoriented and appeared unaware of her surroundings. Significant abdominal distention was present, but masses were not detected and the abdomen was nonpainful upon palpation. A positive skin tent was found and her mucous membranes were tacky, suggesting dehydration and/or shock. Other abnormalities were not noted. Emergency laboratory data indicated the following: PCV 56%, refractometric total protein 6.4 g/dl, Azostix reading of 15-26 mg/dl, and a blood glucose value of 52 mg/dl.

Laboratory Data on Day 1 —

Complete Blood Cell Count

Selected Biochemical Testing

Abdominocentesis

Figure 1. Abdominal effusion fluid containing degenerative neutrophils, macrophages, and free bile pigment (black material) (Dog, bile peritonitis, Wright-Leishman stain).	Figure 2. Higher magnification of two macrophages containing phagocytosed bile pigment that appears black. Extracellular bile deposits stain greenish-brown. Scattered degenerative neutrophils also are present. (Dog, bile peritonitis, Wright-Leishman stain).

Cytologic Diagnosis - Septic purulent inflammation with bile.

Abdominal Ultrasonography - Obvious abnormalities were not discerned in hepatic blood flow. A gall stone was not detected. A significant quantity of abdominal fluid was present.

Problems –

1. Septic purulent inflammation of the abdomen with bile. This finding is indicative of septic bile peritonitis. The presence of phagocytosed bacteria and bile pigment within neutrophils and macrophages confirm this diagnosis. The abdominal effusion was characterized by a high protein concentration (3.5 g/dl) and markedly elevated cell count (38,500), classifying it as an exudate. The degree of abdominal effusion contributed to the patient’s hypoproteinemia and hypovolemia. Peritonitis is associated with increased vascular permeability, allowing albumin loss into the abdominal cavity causing high protein effusion. This patient is at a greater disadvantage to compensate for hypoproteinemia due a history of portosystemic shunting and hepatic atrophy. In bile peritonitis, the color of the abdominal fluid may range from yellowish-green to black. The color of the effusion in this patient was orange (a color that is not anticipated in this condition).

2. Increased ALP and ALT activities. Significant increases in ALP isoenzymes in the serum of dogs may be derived from hepatic (cholestasis), corticosteroid-induced, or bone isoenzymes of ALP. Increased ALP activity in the serum of this dog is most likely due to cholestasis; however, some contribution from the corticosteroid-induced isoenzyme may result from the stress of illness. A levamisole inhibition test of ALP activity may have clarified this situation. The patient’s history of cholelithiasis makes gall bladder obstruction with subsequent cholecystitis and gall bladder rupture the most likely cause of cholestasis. The elevated activity of ALT is most likely due to increased hepatocellular membrane permeability secondary to cholestasis, extravasation of bile, purulent inflammation, and sepsis. In addition, hypoxia due to shock may induce centrilobular hepatocellular necrosis.

Treatment -

Surgery - An exploratory laparotomy was performed and the abdomen was found to contain a large amount of yellow fluid. A gall bladder was not present. The parietal peritoneum and serosal surfaces of most organs were grossly inflamed. The cystic duct and a hepatic duct were ligated. The abdomen was left open and managed as an abscess, with suction at 120mm Hg post-surgery. Two days later, the patient was returned to surgery for further debridement and definitive closure of the abdominal cavity.

Medical Treatment - Broad spectrum antibiotic treatment (ampicillin and enrofloxacin IV) and buprenorphine were administered initially. The patient was placed on nasal O₂ and vital signs and selected laboratory parameters were monitored periodically. Additional supportive care included a plasma transfusion to restore total protein concentration and placement of a nasoesophageal tube to assist feeding.

Laboratory Findings on Post-operative Days 2 Through 7 -

Complete Blood Cell Count

Selected Biochemical Testing

Problems –

1. Increased activity of hepatic enzymes and increased total bilirubin concentration. ALT and ALP activities, as well as total bilirubin concentration, continued to rise post-operatively. Considering the nature of bile peritonitis and the surgical treatment, these are not unexpected findings. The increase in ALT activity is most likely due to liver manipulation and surgical trauma of muscle which contains significant enzymatic activity. Infection, inflammation, and sepsis also can cause hepatocellular damage. The increase in ALP activity is likely due to cholestasis caused by the ligation of a hepatic duct and by inflammation and sepsis. The hyperbilirubinemia is likely hepatic and post hepatic in nature. The liver disease caused by the portosystemic shunt, as well as the presence of on going liver damage associated with the peritonitis, plays a major role. Cholestasis with the subsequent regurgitation of bilirubin into the blood also contributes to the hyperbilirubinemia

2. Neutrophilia with a left shift and toxic changes. The neutrophilia is due to bacterial and bile peritonitis as well as to systemic inflammation. Toxic changes of neutrophil are due to toxemia-induced disturbances of cellular maturation.

3. Microcytic, hypochromic, non-regenerative anemia. Microcytosis can be due to iron deficiency, hepatic disease (including development of portosystemic shunts), or the presence of spherocytes in the blood. Microcytosis also may be observed in healthy dogs of Asian breeds. The microcytosis in this case is most likely associated with the history of a portosystemic shunt and liver disease. The nonregenerative anemia may be the result of chronic inflammation because the lack of hypochromia tends to exclude the possibility of iron deficiency.

Laboratory Findings on Post-operative Day 9 -

Complete Blood Cell Count

Selected Biochemical Testing

Abdominocentesis

Cytologic diagnosis - Purulent inflammation without evidence of sepsis.

Problems –

1. Purulent inflammation of the abdominal cavity with no evidence of sepsis. The lack of degenerative changes in neutrophils and lack of visible bacteria in cytologic preparations indicate progressive resolution of the peritonitis. The decreased evidence of bile in the peritoneal fluid (yellow green material present in macrophages), is a sign that the surgery was successful in containing the extravasation of bile. The decreased nucleated cell count and total protein concentration suggest diminished inflammation and vascular permeability. The decreased exudation of protein and increased food intake both contributed to the increased total protein and albumin concentrations.

Treatment and evaluation - The patient began to show significant clinical improvement on the post-operative day 4. She was bright, alert, responsive, urinating normally, and eating unassisted. Intravenous fluid administration and nasoesophageal feeding were discontinued on post-operative day 6. Decreased neutrophilia, decreased total bilirubin concentration, increased total protein concentration, and increased regenerative response were observed by post-operative day 9.

Hospital discharge on post-operative day 10 - Due to clinical and laboratory improvement of the patient, she was discharged from the hospital. Post-discharge treatment included administration of oral antibiotics (enrofloxacin and ampicillin). The owners were instructed to report any lethargy, depression, anorexia, vomiting, or diarrhea. Follow up physical examination and laboratory blood work were scheduled one week from release.

Discussion

Rupture of the gall bladder in small animals can be caused by necrotizing cholecystitis, cholelithiasis, trauma, neoplasia, or parasites.³ Bile located outside of the biliary tree is irritating to the peritoneum. This chemical peritonitis leads to vasculitis with extravasation of fluid and plasma proteins and emigration of phagocytic cells (neutrophils and macrophages) from the blood into the peritoneal cavity. The effusion is usually a modified transudate early in the course of the disease, but progresses to an exudate.¹

Exudates arise from chemotaxis of inflammatory cells, altered vascular permeability, and leakage of plasma proteins. Although the definition of an exudate and modified transudate differs depending on the source cited, modified transudates contain 1,000 to 7,000 nucleated cells /µL and / or a protein concentration of 2.5 to 7.5 g/dL. Exudates contain > 5,000 nucleated cells /µL and > 3.0 g/ dL of protein.¹

Bile peritonitis usually begins as an aseptic process though bacteria can be present in normal bile due to enterohepatic circulation and gut flora.⁴ Cholangiohepatits may increase the number of bacteria present. Even with an initially sterile process, a secondary bacterial infection often occurs due to necrosis of tissue and changes in mucosal permeability, causing translocation of enteric flora into the abdominal cavity.³ Translocation of bacteria from the intestinal tract may be enhanced by ileus secondary to chemical peritonitis. Experimentally, the volume of the effusion has been shown to correlate positively with increased bacterial proliferation, slowed bacterial clearance, and an increased mortality rate.⁴

Bile salts have been reported to reduce the immune system’s effectiveness by lowering surface tension, altering cell adhesion, and lysing red blood cells to release hemoglobin into the peritoneal cavity. Hemoglobin reduces leukocyte chemotaxis, phagocytosis, and intracellular killing. Hemoglobin also may play a role by providing iron to bacteria and reducing bacterial clearance by interfering with lymphatic drainage.⁴

Abdominocentesis is valuable in the diagnosis of peritonitis. Fluid can be obtained for analysis by four quadrant paracentesis, if necessary. If fluid cannot be obtained by paracentesis, a diagnostic peritoneal lavage can be performed.

Any abdominal effusion that is collected should be placed into a sterile EDTA tube for cytologic examination, total nucleated cell count, and determination of total protein concentration. Some fluid should be saved in a clot tube for biochemical analysis and a portion should be placed in appropriate media for aerobic and anaerobic culture. Fluid analysis includes a subjective description of the color and clarity of the fluid, measurement of the total nucleated cell count using an automated analyzer or hemocytometer, measurement of packed cell volume (if the fluid is visibly red), and determination of total protein concentration. If bile peritonitis is suspected, a total bilirubin concentration can be performed on the fluid and compared to the serum bilirubin concentration. If concentration of bilirubin is greater in the fluid bilirubin than in the serum, the diagnosis of bile peritonitis is confirmed. Bilirubin should not be present in peritoneal fluid of healthy individuals.¹ Smears of abdominal fluid can be evaluated for leukocyte populations and the presence of bacteria. Leukocyte morphology and the presence of bacteria are more important than the total number of leukocytes in septic peritonitis. The presence of degenerative neutrophils, as well as the presence of bacteria or bile, indicate that abdominal exploratory surgery is warranted. Abdominal radiography and ultrasonography are useful to determine whether abdominocentesis is necessary. Survey radiographs can reveal a decrease in abdominal detail, while ultrasound is useful in detecting small quantities of peritoneal effusion, gall stones, and cholecystitis.^2,4

Hematological and biochemical findings are often non-specific with septic peritonitis. Serial evaluation of hematological and biochemical parameters is useful to evaluate a patient’s response to therapy and to make further treatment decisions. Common abnormalities that may be encountered are neutrophilic leukocytosis with a left shift, hypoproteinemia, hypoglycemia, increased BUN concentration, increased liver enzyme activities, and hyperbilirubinemia.⁵

Common clinical signs of bile peritonitis include vomiting, diarrhea, abdominal pain, abdominal distention, and shock (increased heart rate, pale mucous membranes, poor capillary refill time, and weak pulses).⁵ Fever and abdominal pain are common findings but are not always observed. Dehydration is often present due to lack of fluid intake and loss of fluid via vomiting, diarrhea, and peritoneal effusion.⁴

The presence of septic bile peritonitis is associated with significant patient mortality. The clinical prognosis often is guarded to poor, with some studies showing approximately 50% mortality.³

References

1. Connelly HE: Cytology and fluid analysis of the acute abdomen. Clinical Techniques in Small Animal Practice 2003; 18:39-44.

2. Cruz-Arambulo R, et al: Ultrasonography of the Acute Abdomen. Clinical Techniques in Small Animal Practice 2003; 18:20-31.

3. Ettinger S, Feldman E (eds): Textbook of Veterinary Internal Medicine, 6th ed. W. B. Saunders Co., St. Louis, Missouri, 2003, pp. 1478-1482.

4. Slatter D: Textbook of Small Animal Surgery, 3rd ed. W. B. Saunders Co., Philadelphia, 2003, pp. 414-436.

5. Tams T: Handbook of Small Animal Gastroenterology, 2nd ed. W. B. Saunders Co., St. Louis, Missouri, 2003, pp. 340-347.

Acknowledgement

The image "Italian Greyhounds" by Margaret Sweeney (© Limited Edition Prints by Margaret Sweeney, 2003) is from the website Fine Art Dog Prints and is used with permission.

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