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ORIGINAL STUDIES

Gallbladder Sludge in Dogs: Ultrasonographic and


Clinical Findings in 200 Patients
Audrey K. Cook, BVM&S, DACVIM, DECVIM, DABVP (Feline), Anisha V. Jambhekar, DVM*, Allison M. Dylewski, DVM†

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)

Introduction GB accompanied by hyperplasia of the mucus-secreting epithelium.


The biliary tract is routinely examined during ultrasonographic Although choleliths appear to be relatively uncommon in dogs,
(US) scans in dogs, and the contents of the gallbladder (GB) are these are characterized as markedly hyperechoic structures with
easily evaluated. These may be uniformly nonechogenic, with no acoustic shadowing. Depending on the density of the surrounding
evidence of solid debris. Alternatively, variable amounts of biliary bile, these are generally mobile and gravity dependent.
sludge, defined as gravity-dependent hyperechoic variably partic- In human patients, biliary sludge is a complex mixture of
1
ulate material without acoustic shadowing, may be noted. Less cholesterol crystals, bile pigments, and bile salts, embedded in
commonly, GB contents may appear solid and non–gravity mucin.3 This material often includes particles 1 mm, referred to
dependent. The presence of radial hyperechoic striations within as microliths, which are thought to precede gallstone formation.3
this solid material and a hypoechoic rim suggests a GB mucocele People with sludge and microlithiasis may report colicky pain and
1,2
(MC). This is defined as an accumulation of mucin within the postprandial discomfort. Intervention is recommended to prevent

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.

Q 2016 by American Animal Hospital Association JAAHA.ORG 125


support this hypothesis, and similar influences have not been
TABLE 1 reported for biliary sludge.13,14
Grading Scale for Ultrasonographic Assessment of Gallbladder The goals of this study were to determine the prevalence of
Sludge in Dogs echogenic material (‘‘sludge’’) within the GB of dogs undergoing
Grade Description routine diagnostic abdominal US examination at a veterinary
1 Bile uniformly hypoechoic; no sediment teaching hospital, to describe population characteristics for dogs
2 1–25% of bile hyperechoic; gravity dependent with minimal versus substantial (.25%) GB sludge, to evaluate
3 26–50% of bile hyperechoic; gravity dependent and compare selected clinicopathological data for dogs from these
4 51–75% of bile hyperechoic; gravity dependent subsets, and to identify the impact of concurrent endocrine
5 .75% of bile hyperechoic disorders on GB contents.
MC Solid, hyperechoic, non–gravity dependent; hyperechoic striations
Materials and Methods
A grading scheme was created to allow crude quantification of the
cholelithiasis and often includes ursodeoxycholic acid (ursodiol)
percentage of hyperechoic material within the GB, as determined
and cholecystectomy.4 The composition of spontaneous biliary
during real-time US examination (Table 1). This grading tool was
sludge in dogs has not been reported, but low incidence of
then used to score GB contents in 200 sequential examinations
gallstones in this species compared to people suggests that canine
performed on canine patients undergoing routine abdominal
sludge may have a different composition or etiology.5 This is
studies at Texas A&M University Veterinary Medical Teaching
supported by experimental studies indicating that canine biliary
Hospital from November 2009–April 2010. All US scans were
sludge does not contain substantial amounts of cholesterol.6–8
performed by Diplomates of the American College of Veterinary
The clinical implication of biliary sludge in dogs is unclear. An
Radiology or a radiology resident under direct supervision of a
early study suggested a weak association between sludge and
board-certified radiologist. Two different US systemsa,b were used,
patient age but did not identify a connection to naturally occurring
depending on availability and radiologist preference. Transducer
hepatobiliary disease.9 It was concluded that GB sludge should be
type and frequency were selected by the attending radiologist based
considered an incidental finding in this species. This is somewhat on patient size, configuration, and imaging characteristics.
contradicted by a later study, in which mobile sludge or precipitate Patients were positioned in dorsal or lateral recumbency
was reported in 24/45 dogs with GB disease; nine of these 24 during the examination, depending on radiologist preference.
(37.5%) ruptured.1 More recently, abnormal GB contents (both Sedation was administered as necessary at the direction of the
sludge and MC) were associated with impaired emptying following attending clinician. Although fasting is recommended at this
a meal challenge in dogs.10 However, it was not determined if institution prior to US examination, patients were variably fed
decreased GB contractility was the cause or consequence of the within the preceding 8 hr. Contemporary standard of care was
abnormal contents. provided to each animal.
In recent years, both genetic and metabolic factors have been For each dog, the contents of the GB were assessed during the
implicated in MC formation in dogs. An insertion mutation in the US scan, and the findings were recorded immediately following the
ABCB4 gene was identified in 14/15 affected Shetland sheepdogs, examination. The amount of sludge (if present) was estimated as a
but not in 20/21 unaffected individuals, and may explain the percentage of total GB contents during several seconds of scanning
predisposition of this breed to MC formation.11 This mutation time, using views from various angles, including longitudinal and
impairs secretion of a protective phospholipid across the sagittal views. The GB contents were classified as consistent with a
canalicular membrane, thereby making the GB epithelium more MC if the overall appearance matched that described in the current
vulnerable to the irritant properties of bile. In a retrospective study veterinary literature, i.e., essentially solid, non–gravity dependent,
of 78 dogs diagnosed with MC, age- and breed- matched controls hyperechoic bile with hyperechoic striations, creating a starfish/
12
were used to identify the impact of a concurrent endocrinopathy. kiwifruit appearance.1,2 Results were excluded from the final
In this population, the odds of MC in dogs with hyperadrenocor- analysis if the patient had previously been scored. Still images were
ticism (HAC) were 29 times that of dogs without HAC. A weaker collected by the radiologist during the study and stored in a digital
association was found for hypothyroidism (HT), with a threefold image archive. A detailed written description of the US findings
increased risk. Although various sources suggest that sludge may was generated for each case within 3 d of the examination and
precede MC formation, there is presently little direct evidence to included in the computerized medical record.

126 JAAHA | 52:3 May/Jun 2016


Gallbladder Sludge in Dogs

Patients diagnosed by the attending clinician with inadequate


TABLE 2 thyroid function and those receiving thyroid supplementation at
Results of Ultrasonographic Gallbladder Scoring in 200 Canine the time of examination were classified as HT. The appropriateness
Patients of a prior diagnosis of HT was not investigated, and the efficacy of
Grade Number (%) of Dogs therapy for dogs on thyroid supplementation was not evaluated. A
1 67 (33.5%) diagnosis of DM was listed for any patient with blood glucose
2 94 (47%) .200 mg/dl (reference range: 65–130 mg/dl) or currently receiving
3 26 (13%) insulin therapy.
4 5 (2.5%) Statistical analysis of the data was performed using a
5 4 (2%) commercial software programd; findings were considered signifi-
MC 4 (2%) cant if P , 0.05. Where appropriate, data sets were tested for
normality using the D’Agostino and Pearson omnibus normality
test. The median values of selected data sets were compared using
GB volume was estimated from stored digital images using a
the Mann-Whitney test for unpaired data. Fischer’s exact test was
modification of the method proposed by Dodds et al., in which
used to compare population characteristics. Odds ratios are
width was substituted for height.15 Measurement of length and
reported with a 95% confidence interval (CI).
width were determined from long axis images in which the neck of
the GB was evident. If more than one long axis image was available,
Results
the one with the greater longitudinal dimension was used. GB
Abnormal GB contents were noted in 133 dogs (66.5%) (Table 2).
volume was calculated using the following equation:
Almost half (47%) of the dogs examined had a small amount of
Volume ¼ Length ðmmÞ 3 width ðmmÞ 3 width ðmmÞ 3 p=6 echogenic material within the GB lumen (,25% of total GB
p=6 approximated to 0:52 contents). Four dogs (2%) had .75% hyperechoic bile (grade 5
sludge), and four (2%) were categorized as having a MC. For
GB volumes were then indexed for body weight in kilograms. statistical purposes, dogs with normal to minimally abnormal bile
Information regarding patient age, breed, gender, and weight (i.e., grades 1 and 2; n ¼ 161: 80.5%) were compared to those with
was obtained from computerized medical records. A body .25% sludge (grades 3–5; n ¼ 35: 17.5%). Dogs with a MC (n ¼ 4)
condition score (BCS) was derived from documents within the were considered separately.
medical record and converted (if necessary) to a 9-point scale. Suitable images for estimating GB volume were available for
Clinicopathological data reported within 24 hr of US scanning were all but six dogs (all graded 1 or 2). The median volume for dogs
reviewed; serum cholesterol and bilirubin concentrations and graded 1 and 2 was 0.73 ml3/kg (range 0.08–3.65 ml3/kg); this was
alkaline phosphatase (ALP) and gamma-glutamyl transferase significantly less than for those graded 3–5 (1.04 ml3/kg; range
(GGT) activities were recorded. Serum biochemical analyses were 0.31–7.86 ml3/kg; P , 0.001; Figure 1).
all performed at the in-house clinical pathology laboratory using an Patients ranged in age from 0.25–17 yr, with a median of 9 yr.
automated analyzerc. Medications administered within the previ- The median age for dogs graded 1 and 2 was 8 yr; this was
ous 8 wk were noted, including sedatives administered to facilitate significantly lower than for the dogs with grade 3–5 sludge (11 yr; P
ultrasonography. , 0.0002; Figure 2). A total of 41 breeds were listed in the study
One of the authors (A.K.C. a board-certified internist) population, with Labrador retriever (n ¼ 20), Yorkshire terrier (n ¼
reviewed each medical record and classified the patient into one 16), and miniature schnauzer (n ¼ 15) most frequently reported.
of eight disease groups based on the reason(s) for performing Thirty-one dogs were of mixed breeding. Breed lists for dogs with
ultrasonography, clinical complaints, and final diagnoses. These grade 1 and 2 sludge were similar to those with grade 3–5, and no
disease groups were hepatobiliary (icterus, increased enzyme breed predispositions were noted. Overall gender distribution was
activity, hyperammonemia), endocrine (diabetes mellitus [DM], evenly divided, with 54% female and 46% male, and was similar for
HAC), urinary (renal, bladder, prostatic), gastrointestinal (includ- dogs with grade 1 and 2 sludge and those with grade 3–5. Median
ing pancreatic), neurologic, neoplastic, thoracic, and other body weight for both subsets was 12.1 kg, with a range of 1–63.8 kg.
(immune mediated/ nonspecific/systemic/undefined). BCS was available for 50 dogs graded 1 and 2 (median: 5; range 2–
Patients were classified as having spontaneous HAC if the 9) and 11 dogs graded 3–5 (median 6; range 5–9); these results were
attending clinician listed this diagnosis in the visit summary. not significantly different.

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.

128 JAAHA | 52:3 May/Jun 2016


Gallbladder Sludge in Dogs

Discussion increasing age is consistently identified as a strong risk factor. In


fact, the incidence of gallstones increases 4–10-fold after age 40.5
Echogenic luminal contents were noted in two-thirds of canine
Obesity and insulin resistance are commonly implicated in
patients undergoing routine diagnostic US examination of the
human microlithiasis. In our patient population, the median BCS
abdomen at this institution. This is substantially higher than the
for dogs with grade 1 and 2 sludge was not significantly different
prevalence reported in a recent study from Brazil, in which sludge
from those graded 3–5. Unfortunately, BCS was not available for
was reported in 35% of 1021 dogs undergoing abdominal US
.2/3 of dogs, which limited statistical power. It is interesting to
evaluation.16 This may reflect different patient demographics or
note that none of the dogs graded 3–5 were judged to be
other characteristics. Certainly, animals examined at our institution
underweight (i.e., BCS 4).
may not reliably reflect the canine population in general, and
All of the serum biochemical parameters evaluated (i.e.,
conclusions regarding the true prevalence of sludge in this species
cholesterol, bilirubin, ALP, and GGT) were not apparently
should be made with caution. It is interesting to note that four dogs influenced by the extent of biliary sludging. As both ALP and
(2% of those examined) had US evidence of a MC. This number is GGT activity indicate cholestatic processes within the liver and
higher than expected and does suggest that findings from a tertiary biliary tree, it seems unlikely that sludge formation is necessarily
referral center are subject to substantial bias. related to compromised bile flow.18 Hypercholesterolemia is
In this report, dogs with .75% hyperechoic bile and those strongly associated with biliary sludging and cholelithiasis in
with US findings indicating a MC were classified separately. In fact, people, and cholesterol is a primary constituent of human biliary
the diagnosis of a MC requires documentation of mucinous sludge.5 The fact that serum cholesterol concentrations were not
hyperplasia of the GB epithelium and cannot be definitively related to sludge severity in our patient population concurs with
determined on the basis of US or gross findings alone.17 However, the findings of a similar study and supports the hypothesis that
the majority of canine GB MCs have such a distinctive US cholesterol is unlikely to be a major component of canine biliary
appearance that this imaging modality is considered to be highly sludge.16
specific for this condition.1,2 Although it is possible that some of Biliary sludge has been induced in dogs by cystic duct ligation
these eight patients were incorrectly categorized, it was important or through dietary manipulation.6,7 In both models, the sludge
to attempt to separate dogs with severe sludge (.75%) from those consisted primarily of bilirubinate and mucin, variably complexed
with a MC. Failure to separate these patients would have implied with calcium carbonate. As this material coalesced into pigmentary
some commonality between these two conditions and may have gallstones, it may have limited similarities to spontaneous 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

population, but recent feeding may certainly influence these


parameters. In addition, several radiologists participated in the REFERENCES

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