Professional Documents
Culture Documents
Gallbladder Sludge in Dogs Ultrasonographic and
Gallbladder Sludge in Dogs Ultrasonographic and
ABSTRACT
Echogenic luminal contents are often noted during ultrasonographic examination of the gallbladder (GB) in canine
patients, but the significance of biliary sludge is not well understood. GB contents were evaluated during 200 sequential
ultrasonographic scans performed at a veterinary school, and sludge was quantified using a 1–5 scale. GB volume was
retrospectively estimated from stored images. Medical records were used to determine patient demographics,
clinicopathologic findings, and diagnoses/disorders. The majority of dogs (66.5%) had some hyperechoic material
within the GB. Four dogs were diagnosed with a mucocele. For statistical purposes, dogs with uniformly nonechogenic
bile or minimal sludge (80.5%) were compared to those with .25% sludge (17.5%). Dogs with .25% sludge were
significantly older than those with minimal sludge (8 versus 11 yr). Serum cholesterol and bilirubin concentrations and
activities of both alkaline phosphatase and gamma-glutamyl transferase were not correlated with the presence of GB
sludge. Dogs with spontaneous hyperadrenocorticism or hypothyroidism were more likely to have .25% sludge (odds
ratio: 5.04). In addition, .25% sludge was associated with increased GB volume, suggesting that changes in GB
function or contractility may impact the formation of biliary sludge in dogs. (J Am Anim Hosp Assoc 2016; 52:125–131. DOI
10.5326/JAAHA-MS-6282)
From the Department of Small Animal Clinical Sciences, College of ALP (alkaline phosphatase); BCS (body condition score); CI
Veterinary Medicine and Biomedical Sciences, Texas A&M (confidence interval); DM (diabetes mellitus); GB (gallbladder); GGT
University, College Station, TX. (gamma-glutamyl transferase); HAC (hyperadrenocorticism); HT
(hypothyroidism); MC (mucocele); US (ultrasonographic)
Correspondence: akcook@cvm.tamu.edu (A.K.C)
*
A. Jambhekar’s present affiliation is the Department of Veterinary
Clinical Medicine, College of Veterinary Medicine, University of Illinois
at Urbana Champaign, Urbana, IL.
†
A. Dylewski’s present affiliation is Northwest PA Pet Emergency
Center, Erie, PA.
JAAHA.ORG 127
FIGURE 2 Vertical scatterplot showing age (in yr) of dogs with
FIGURE 1 Vertical scatter plot showing estimated gallbladder
gallbladder contents graded 1 and 2 (n ¼ 161) and 3–5 (n ¼ 35). The
volumes for dogs with contents graded 1 and 2 (n ¼ 159) and 3–5 (n ¼
median age for each group is indicated by the horizontal line. The
35). The median volume for each group is indicated by the horizontal
median age for dogs graded 1 and 2 was 8 yr; the median age for dogs
line. The median volume for dogs graded 1 and 2 was 0.73 ml3/kg;
graded 3–5 was 11 yr (P , 0.0002).
median volume for dogs graded 3–5 was 1.04 ml3/kg (P , 0.001).
One data point is outside the axis limits and is not shown.
MC, but the proportion of dogs with grade 3–5 sludge was higher
than for dogs without hepatobiliary disease (30.7% versus 15.9%;
Contemporaneous laboratory findings were available for 142
odds ratio: 2.65; CI 1.03–6.80; P ¼ 0.048). The most common
dogs graded 1 and 2 (88.2%) and 34 dogs graded 3–5 (97.1%).
reason for ultrasonography was gastrointestinal disease, with 49
Median serum cholesterol concentration (reference range: 120–147
(24.5%) of dogs, followed by 41 (20.5%) dogs with neoplastic
mg/dl) for dogs graded 1 and 2 was 219 mg/dl (range: 53-861 mg/
disease and 34 (17%) with urinary tract disorders.
dl); this was not significantly different from that for dogs graded 3–
Eleven dogs underwent ultrasonography for evaluation of a
5 (242 mg/dl; range 88–643 mg/dl). Serum bilirubin concentrations
suspected or known endocrinopathy, although concurrent HAC,
(reference range: 0–0.8 mg/dl) were similar for the two patient
HT, or DM was reported in 26 dogs (13%). Three patients were
subsets, with medians of 0.2 (range: ,0.1–14.6 mg/dl) and 0.3 mg/
diagnosed with more than one endocrinopathy. HT was the most
dl (range: ,0.1–12.9 mg/dl), respectively. ALP activities (reference
common endocrinopathy, affecting 16 (8%) dogs, all of which were
range: 24–147 U/L) were also similar: the median for dogs graded 1
diagnosed prior to this visit; DM was reported in eight dogs (4%)
and 2 was 161 U/L (range 20–5259 U/L); the median for dogs
and HAC in five dogs (2.5%).
graded 3–5 was 183 U/L (range: 20–5202 U/L). Median GGT
Overall, the prevalence of an endocrinopathy (DM, HT, or
activity (reference range: 0–25 U/L) was not significantly different HAC) in dogs with grade 3–5 sludge was similar to that in dogs
for dogs graded 1–2 (11 U/L; range 8–284 U/L) compared to the with grade 1 and 2 sludge (17.1 % and 10.6%, respectively).
grade 3–5 group (12 U/L; range 8–122 U/L). However, dogs with HAC and/or HT were substantially more likely
The majority of patients (124; 62%) were sedated prior to to have grade 3–5 sludge (n ¼ 9) than grade 1 and 2 (n ¼ 11) when
ultrasonography, primarily with opioids such as butrophanol (n ¼ compared to the rest of the study population (odds ratio 5.04; CI:
74), buprenorphine (n ¼ 27) and fentanyl (n ¼ 9). Sedation did not 1.90–13.33; P , 0.002%).
appear to impact GB score, with a median score of 2 for both Fifteen dogs had received exogenous glucocorticoids for .4
sedated and nonsedated dogs. GB volumes were also similar for the wk prior to examination. Agents administered included prednisone
sedated and nonsedated dogs, with median values of 0.89 ml/kg (n ¼ 13; median dose 1.1 mg/kg/d; range 0.2–2.2 mg/kg/d),
and 0.75 ml/kg, respectively. dexamethasone (n ¼ 1; 0.16 mg/kg), and budesonide (n ¼ 1; 0.15
Only 26 dogs (13%) underwent ultrasonography for suspected mg/kg). The administration of exogenous steroids for .4 wk was
or established hepatobiliary disease. None of these patients had an not associated with increased sludge.
biased our results. GB contents were analyzed in one Shetland sheepdog with a MC;
the material was shown to have a similar composition to the
Overall, dogs with grade 3–5 sludge had larger GB volumes
experimentally induced sludge.19 However, as this breed has a
(indexed for body weight) compared to those with grade 1 and 2
strong genetic predisposition for defective phoshatidylcholine
sludge. Since compromised GB emptying has been associated with
secretion and subsequent MC formation, this finding may not
microlithiasis in people, this is the most likely explanation for this
reliably reflect events in other breeds.11
finding in this patient population.5 GB emptying is triggered by the
Both HAC and HT have been identified as a risk factor for MC
arrival of ingesta in the proximal small intestine and is mediated by
formation in dogs.12 In our study, the presence of HAC or HT was
cholecystokinin. Impaired emptying may reflect a derangement in
significantly associated with substantial GB sludge (odds ratio
the normal signaling process or an inability to effectively move
5.04). This finding suggests a link between biliary sludge and the
abnormally dense contents. Prospective, dynamic studies using
development of a MC. Various sources have proposed that the two
timed meals or cholecystokinin analogues are needed to investigate are interconnected and that substantial sludge precedes the
potential associations between GB sludge and emptying in dogs. generation of a MC. This has not been proven, although sludge
In common with previous veterinary studies, our findings has been reported around or embedded within MCs.13 In
indicate that biliary sludge is more likely to be noted in older experimental studies, glucocorticoids have been shown to alter
dogs.9,16 However, the development of sludge cannot be predicted bile acid profiles in dogs, with a shift towards the more irritant
simply on the basis of advancing age, as there was no evidence of a hydrophobic forms.20 This change may impact GB epithelial
linear relationship between these parameters, and several dogs with function and mucus production. Subnormal thyroid levels have
uniformly hypoechoic bile were .10 yr of age. The development of been associated with delayed emptying of bile into the intestine in
biliary sludge in people is thought to be multifactorial, but people, and it has been suggested that chronic bile stasis may lead
JAAHA.ORG 129
to the formation of sludge and excessive mucus secretion.21 Conclusion
Although 16 dogs in this study population were classified as HT, This study suggests that echogenic liminal material is routinely
there was inadequate information regarding the initial diagnosis noted within the GB of dogs during transabdominal US
and the duration and efficacy of supplementation. One clinical examination at a veterinary teaching hospital, with echogenic
report suggests that effective thyroid supplementation may result in contents reported in two-thirds of patients. Sludge formation was
a resolution of GB MC, but its impact on sludge has not been associated with increasing patient age but was not apparently
described in dogs.13 Prospective studies looking at GB contents at influenced by patient weight or obesity. Dogs with clinical evidence
the time of diagnosis and following treatment are needed. of hepatobiliary disease were more likely to have hyperechoic GB
In this patient population, the administration of exogenous contents than the general population, but the presence of
glucocorticoids for at least 4 wk did not appear to impact the substantial sludge was not associated with routine biochemical
formation of sludge. However, this finding may reflect a relatively markers of biliary status (i.e., serum cholesterol and bilirubin
short duration of administration in some dogs and substantial concentrations; serum ALP or GGT activities). Similar to reports of
variation in glucocorticoid dosing. A recent study of dogs receiving dogs with MCs, biliary sludge was strongly associated with
high doses of exogenous glucocorticoids for 3 mo reported that all spontaneous HAC. Abnormal emptying was suggested by increased
treated dogs (n ¼ 6) developed GB sludge.8 However, this was not median GB volume in dogs with .25% sludge. Further studies are
significantly different to the control group (n ¼ 6), half of which needed to determine the indications for intervention in dogs with
also developed sludge over the same time period. Further work is biliary sludge and its possible connection to MC formation or other
needed to assess the impact of prolonged administration of biliary tract disorders.
exogenous glucocorticoids on GB status in dogs.
Although this study provides some useful insight into canine FOOTNOTES
a
biliary sludge, it has several limitations. As this was an Acuson Sequoia 512; Siemens Medical Solutions USA Inc., Mountain
observational study, and not a prospective one, variables such View, CA
b
Acuson Antares; Siemens Medical Solutions USA Inc., Mountain View,
as duration of fasting and administration of sedation prior to US CA
c
evaluation could not be controlled. Sedation did not appear to Vitros 250; Ortho-Clinical Diagnostics, Rochester, NY
d
impact US findings (% sludge, GB volume) in this patient GraphPad Prism Version 5.01; GraphPad Software Inc., La Jolla, CA
grading process and may not have been consistent with their 1. Crews LJ, Feeney DA, Jessen CR, et al. Clinical, ultrasonographic, and
laboratory findings associated with gallbladder disease and rupture in
assessments. Conclusions regarding GB volume must be made
dogs: 45 cases (1997-2007). J Am Vet Med Assoc 2009;234:359–366.
cautiously, as volumes were estimated used a modification of a 2. Besso JG, Wrigley RH, Gilatto JM, et al. Ultrasonographic appearance
reported formula, the reliability of which has not been and clinical findings in 14 dogs with gallbladder mucocele. Vet Radiol
established. Ultrasoun 2000;41:261–271.
3. Ko CE, Schulte SK, Lee SP. Biliary sludge is formed by modification of
For statistical purposes, dogs with .25% sludge (grades 3, 4, hepatic bile by the gallbladder mucosa. Clin Gastroenterol Hepatol
and 5) were considered together. This was necessary because of 2005;3:672–678.
small group sizes but may have limited our ability to detect 4. Jungst C, Kullak-Ublick GA, Jungst D. Microlithiasis and sludge. Best
Pract Res Clin Ga 2006;20:1053–1062.
differences between groups regarding the biochemical parameters 5. Stinton LM, Shafer EA. Epidemiology of Gallbladder Disease:
assessed. Larger studies may be needed to identify associations Cholelithiasis and Cancer Gut Liver 2012;6:172–187.
between routine clinicopathologic data and GB sludge in dogs. 6. Bernhoft RA, Pelligrini CA, Broderick WC, et al. Pigment sludge and
stone formation in the acutely ligated dog gallbladder. Gastroenterol
One of the major limitations to our understanding of canine 1983;85:1166–1171.
GB sludge is a lack of information regarding its composition. It is 7. Dawes LG, Nahrwold DL, Rege RV. Supersaturation of canine
possible that different biochemical constituents are present in gallbladder bile with calcium bilirubinate during formation of pigment
gallstones. Am J Surg 1989;157:82–88.
various dogs and may reflect varying etiologies. Additional 8. Kook PK, Schellenberg S, Rentsch KM, et al. Effects of iatrogenic
prospective longitudinal studies with larger patient numbers are hypercortisolism on gallbladder sludge formation and biochemical bile
needed to establish the clinical impact of biliary sludge in dogs. In constituents in dogs. Vet J 2012;191:225–230.
9. Bromel C, Barthez PY, Leveille R, et al. Prevalence of gallbladder sludge
particular, the relationship (if any) between sludge and the in dogs as assessed by ultrasonography. Vet Radiol Ultrasoun 1998;39:
development of the GB MC needs further investigation. 206–221.
10. Tsukagoshi T. Ohno K, Tsukamoto A, et al. Decreased gallbladder 15. Dodds WJ, Groh WJ, Darweesh RM, et al. Sonographic measurement of
emptying in dogs with biliary sludge or gallbladder mucocele. Vet gallbladder volume. Am J Roentgenol 1985;145:1009–1011.
Radiol Ultrasoun 2012;53:84–91. 16. Secchi P, Poppi AG, Ilha A, et al. Prevalence, risk factors, and
11. Mealey KL, Minch JD, White SN, et al. An insertion mutation in biochemical markers in dogs with ultrasound-diagnosed biliary sludge.
ABCB4 is associated with gallbladder mucocele formation in dogs. Res Vet Sci 2012;93:1185–1189.
Comp Hepatol 2010;9:6. 17. Pike FS, Berg J, King NW, et al. Gallbladder mucocele in dogs: 30 cases
(2000-2002). J Am Vet Med Assoc 2004;224:1615–1622.
12. Mesich MLL, Mayhew PD, Paek M, et al. Gall bladder mucoceles and
18. Center SA. Interpretation of liver enzymes. Vet Clin N Am-Small 2007;
their association with endocrinopathies in dogs: a retrospective case-
37:297–333.
control study. J Sm Anim Pract 2009;50:630–635.
19. Aguirre AL, Center SA, Randolph JF. Gallbladder disease in Shetland
13. Walter R, Dunn ME, d’Anjou MA, et al. Nonsurgical resolution of sheepdogs: 38 cases (1995-2005). J Am Vet Med Assoc 2007;231:79–88.
gallbladder mucocele in two dogs. J Am Vet Med Assoc 2008;232:1688– 20. Kook PK, Schellenberg S, Rentsch KM, et al. Effect of twice-daily oral
1693. administration of hydrocortisone on the bile acids composition of
14. Mehler SJ, Mayhew PD, Drobatz KJ, et al. Variable associated with gallbladder bile in dogs. Am J Vet Res 2001;72:1607–1612.
outcome in dogs undergoing extrahepatic biliary surgery: 60 cases. Vet 21. Laukkarinen J, Sand J, Saaristo R, et al. Is bile flow reduced in patients
Surg 2004;33:644–649. with hypothyroidism? Surgery 2003;133:288–293.
JAAHA.ORG 131