History

An 11-year-old 3.6-kg (7.9-lb) spayed female domestic longhair cat was brought to the North Carolina State University Veterinary Health Complex (Small Animal) for further evaluation of anorexia, vomiting, high serum alanine aminotransferase activity, and hyperbilirubinemia of 2 days’ duration. No treatments were performed prior to the evaluation. The cat had received radioactive iodine treatment for hyperthyroidism 9 months prior after which it had recovered uneventfully. The cat was kept indoors but had outdoor access; there were 4 other cats and 3 dogs in the household. The cat's vaccination status was current and it was regularly treated with heartworm preventative.

Clinical and Clinicopathologic Findings

On examination, the cat was bright, alert, and responsive. Its body condition score was 4/9, and rectal temperature was 39.1°C (102.4°F). The cat was approximately 5% dehydrated, and the oral mucous membranes were slightly icteric. Heart rate was 210 beats/min and regular; a grade 2/6 left parasternal systolic heart murmur was auscultated. On palpation, the abdomen was soft and nonpainful, and there was no evidence of masses or organomegaly. The remainder of the physical examination revealed no abnormalities. A CBC, serum biochemical analysis, and urinalysis were performed (designated as day 1 [Table 1]). The cat had mild neutrophilia with a mild regenerative left shift, mild monocytosis, and a low number of reactive lymphocytes, all of which were consistent with an inflammatory leukogram. The cat was negative for anti-FIV antibody and FeLV antigen. Serum thyroxine concentration was 1.5 μg/dL (reference interval, 0.78 to 4.27 μg/dL). Abdominal ultrasonography revealed diffusely hypoechoic hepatic parenchyma, a prominent common bile duct measuring 3 mm in diameter, mildly thickened gallbladder and bile duct walls, and hyperechoic mesentery adjacent to the bile duct. There were 2 small hyperechoic structures within the gallbladder lumen consistent with cholecystoliths. In addition, mild, segmental disproportionate thickening of the muscularis layer of the jejunum was noted. Three-view thoracic radiographic findings were unremarkable.

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Additional Findings

During the abdominal ultrsonographic examination, fine-needle aspirate specimens of the liver and the gallbladder contents were obtained without complications. The gallbladder fluid was macroscopically clear, colorless, and viscous; it lacked the characteristic dark brown to green-brown color of normal feline gallbladder bile (Figure 1). Given the ultrasonographic findings for the hepatobiliary tract and markedly high alanine aminotransferase activity in the absence of evident hemolysis, feline cholangitischolangiohepatitis syndrome (CCHS) causing bile stasis and hepatocellular injury was likely the reason for hyperbilirubinemia and bilirubinuria. To assess hepatic function, plasma ammonia concentration was measured and was within the reference interval.

Photographs of fluid aspirated from the gallbladder of an 11-year-old domestic longhair cat that was evaluated because of anorexia, vomiting, high serum alanine aminotransferase activity, and hyperbilirubinemia of 2 days’ duration (A) and comparison of that fluid sample with bile from a healthy cat (B). The biliary fluid from the patient is clear and appears viscous. In panel B, the left syringe contains the fluid sample from the patient and the right syringe contains bile from a healthy cat. Notice that the healthy cat has macroscopically unremarkable dark, green-brown bile.

Citation: Journal of the American Veterinary Medical Association 251, 7; 10.2460/javma.251.7.793

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Photographs of fluid aspirated from the gallbladder of an 11-year-old domestic longhair cat that was evaluated because of anorexia, vomiting, high serum alanine aminotransferase activity, and hyperbilirubinemia of 2 days’ duration (A) and comparison of that fluid sample with bile from a healthy cat (B). The biliary fluid from the patient is clear and appears viscous. In panel B, the left syringe contains the fluid sample from the patient and the right syringe contains bile from a healthy cat. Notice that the healthy cat has macroscopically unremarkable dark, green-brown bile.

Citation: Journal of the American Veterinary Medical Association 251, 7; 10.2460/javma.251.7.793

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Photographs of fluid aspirated from the gallbladder of an 11-year-old domestic longhair cat that was evaluated because of anorexia, vomiting, high serum alanine aminotransferase activity, and hyperbilirubinemia of 2 days’ duration (A) and comparison of that fluid sample with bile from a healthy cat (B). The biliary fluid from the patient is clear and appears viscous. In panel B, the left syringe contains the fluid sample from the patient and the right syringe contains bile from a healthy cat. Notice that the healthy cat has macroscopically unremarkable dark, green-brown bile.

Citation: Journal of the American Veterinary Medical Association 251, 7; 10.2460/javma.251.7.793

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Microscopic examination of a Wright-Giemsastained direct smear of the gallbladder fluid revealed acellularity with small, variably sized, round, occasionally refractile, pink-stained globular dots and a background that contained abundant fine granular pale pink mucinous material (Figure 2). No etiologic agents, no inflammatory cells, and no evidence of normal bile (blue-gray to green-gray, finely granular material) were identified. The fluid was devoid of bilirubin (Table 1). Special stains were applied to air-dried and methanol-fixed direct smears; Hall bile staining for bilirubin yielded negative results, whereas periodic acid-Schiff and Mayer mucicarmine staining both yielded positive results, indicative of acid mucosubstances. The clear, colorless biliary fluid was considered consistent with so-called while bile. Cytologic examination of the liver aspirate specimen revealed mild hepatocellular lipid vacuolar change and mild mixed inflammation with plasma cells, macrophages with phagocytized debris, and neutrophils.

Photomicrographs of direct smears of the clear, colorless biliary fluid (so-called white bile) obtained from the patient (A) and bile obtained from the healthy cat (B) in Figure 1. In panel A, the white bile has occasional small, variably sized, round, pink-stained globular dots and a background that contains abundant fine granular pale pink mucinous material. In panel B, the normal cytologically unremarkable bile is characterized by a background of abundant blue-gray stippled material and occasional smoother, thicker amorphous aggregates. In both panels, Wright-Giemsa stain; bar = 10 μm.

Citation: Journal of the American Veterinary Medical Association 251, 7; 10.2460/javma.251.7.793

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Photomicrographs of direct smears of the clear, colorless biliary fluid (so-called white bile) obtained from the patient (A) and bile obtained from the healthy cat (B) in Figure 1. In panel A, the white bile has occasional small, variably sized, round, pink-stained globular dots and a background that contains abundant fine granular pale pink mucinous material. In panel B, the normal cytologically unremarkable bile is characterized by a background of abundant blue-gray stippled material and occasional smoother, thicker amorphous aggregates. In both panels, Wright-Giemsa stain; bar = 10 μm.

Citation: Journal of the American Veterinary Medical Association 251, 7; 10.2460/javma.251.7.793

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Photomicrographs of direct smears of the clear, colorless biliary fluid (so-called white bile) obtained from the patient (A) and bile obtained from the healthy cat (B) in Figure 1. In panel A, the white bile has occasional small, variably sized, round, pink-stained globular dots and a background that contains abundant fine granular pale pink mucinous material. In panel B, the normal cytologically unremarkable bile is characterized by a background of abundant blue-gray stippled material and occasional smoother, thicker amorphous aggregates. In both panels, Wright-Giemsa stain; bar = 10 μm.

Citation: Journal of the American Veterinary Medical Association 251, 7; 10.2460/javma.251.7.793

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Intravenous fluid therapy,^a-c administration of an anti-emetic agent,^d and treatment for presumptive cholangiohepatitis^e-g (including IV administration of ciprofloxacin¹¹ and clindamycinⁱ) were initiated. An esophagostomy tube was placed to provide nutrition. Serum feline pancreatic lipase activity was within the reference interval and was not suggestive of acute, clinically relevant pancreatitis. The cat was seronegative for Toxoplasma gondii-specific IgG and IgM; thus, toxoplasmosis as the cause of CHHS was not supported, and clindamycin administration was discontinued. Aerobic and anaerobic bacterial culture of the gallbladder fluid yielded growth of Sphingomonas paucimobilis, which was susceptible to ciprofloxacin.

Following initiation of treatment, the cat's condition improved considerably. Repeated clinicopathologic analyses (on days 3, 5, and 14) revealed marked decreases in serum alanine aminotransferase activity and hyperbilirubinemia (Table 2). Ciprofloxacin was discontinued on day 5 and the cat was discharged from the hospital with the feeding tube in place on day 7; marbofloxacin,^j denamarin,^k and ursodiol^h were administered orally for 6 weeks. The cat's condition continued to improve at home; it started to eat consistently and the feeding tube was eventually removed. Findings of a 3-month recheck examination and clinicopathologic analyses performed by the referring veterinarian were unremarkable. Repeated abdominal ultrasonography and cholecystocentesis were not performed.

Diagnosis and Case Summary

Diagnosis and case summary: presumptive cholangitis or cholangiohepatitis (with the presence of clear biliary fluid [so-called white bile]) in a cat.

Comments

White bile is a colorless fluid that is predominantly composed of mucinous material and thought to be largely devoid of bile pigments, bile salts, and cholesterol.^1–3 It is an uncommon finding in human and veterinary medicine, and reports are rare. White bile is associated with biliary obstructive disorders^1,2,4,5; the incidence of white bile in humans is 3%, with biliary obstruction caused by choleliths, bile duct stricture, pancreatitis, cholangitis, and neoplasia.^2,6 White bile was found in abdominal fluid in 3 dogs with bile peritonitis⁷ and in a cat with sclerosing hepatitis⁸; it can be a component of canine gallbladder mucoceles.⁴ Although the term white bile has been used for nearly 100 years, it is proposed to be a misnomer.^6,9 The fluid is translucent, clear, and colorless, which is in contrast to normal bile that, by definition, is a brown to green fluid secreted by the liver.⁹ The mucin-rich fluid devoid of bile constituents is the consequence of biliary obstruction. When the pressure in the biliary tract exceeds the secretory pressure of hepatocytes, liver bile secretion ceases; however, biliary surface epithelia continue to secrete mucinous fluid.^6,10 Subsequently, bile leaks from canaliculi and hepatocytes into hepatic lymphatics and venous blood.^5,11 Bile pigments can also be removed by reabsorption of bilirubin into the biliary mucosa,^1,3 by bilirubin degradation into colorless substances (with or without the presence of biliary infection^2,5,12), and by segregation of bile-containing pigment from fluid secreted distal to the obstruction.⁴ A normally functioning gallbladder is thought to prevent white bile formation because of its water absorption capacity, allowing pressure compensation and flow of bile from liver even with concurrent biliary obstruction.^3,5,12

For the cat of the present report, the short duration of illness, left-shifted leukogram, hyperbilirubinemia, markedly high alanine aminotransferase activity, evidence of inflammation in the liver aspirate specimen, and ultrasonographic characteristics of the hepatobiliary tract supported feline suppurative CCHS⁴ as the likely cause of the hepatopathy and white bile formation, although histologic examination of liver tissue would be required for confirmation. Interestingly, similar to the case described in the present report, cholestatic enzyme (alkaline phosphatase and γ-glutamyltransferase) activities that are within reference intervals are not an uncommon finding in cats with suppurative CCHS.^4,13 The clinical importance of this cat's cholecystoliths was uncertain because most choleliths in dogs and cats are clinically silent.⁴ The gallbladder stones were likely a consequence of the underlying disease, because bile stasis, local inflammation, and infection often accompany feline CHHS and can promote cholelith precipitation.⁴ Ultrasonography did not reveal overt evidence of biliary obstruction at the time of the examination, but recent onset of obstruction that was not yet ultrasonographically identifiable and viscous sludged bile causing transient bile duct occlusion in combination with gallbladder pathological changes (cholecystitis) could have been responsible for white bile formation in this cat. Bacterial culture of bile yielded growth of S paucimobilis, an opportunistic bacterium that is found in water, soil, and hospital environments.¹⁴ Normal hepatobiliary-enteric bacterial circulation usually permits rapid drainage and clearance of opportunistic bacteria from bile, and when bacterial cholangiohepatitis in cats develops, it is most commonly associated with enteric organisms.^4,13 In the cat of the present report, bacteria were not evident in a direct smear of the clear, colorless, viscous fluid; therefore, sample contamination cannot be excluded. However, S paucimobilis can be pathogenic in humans with immunosuppression and underlying disease that result in increased susceptibility to infection.¹⁴ In the case described in the present report, bile stasis, mechanical trauma as a result of cholecystolithiasis, and perhaps reduced antimicrobial activity of white bile could have been predisposing factors for colonization and infection of the biliary tree.^3,4,13 Likewise, neutrophilia with a left shift and the cat's rapid improvement in clinical condition and laboratory variables following initiation of treatment (including antimicrobials) support biliary infection rather than contamination.

Short-term follow-up indicated a favorable outcome for the cat of the present report, which contrasts with other reports of dogs and a cat that were euthanized soon following diagnosis owing to poor prognosis for the underlying disease.^7,8 In humans, presence of white bile has been associated with higher operative risk⁶ and with shorter survival time in patients with malignant biliary obstructive disorders.³

Regardless of species, a finding of clear, biliary fluid warrants further investigation for underlying biliary obstructive disorders. In the cat of the present report, functional and space-occupying biliary obstruction caused by inflammation, sludged bile, and perhaps infection and cholelithiasis were the proposed mechanisms of white bile formation. Given the low number of cases reported in veterinary medicine to date, the prognostic importance of white bile remains to be determined.