Cholangiohepatitis and cholecystitis associated with biliary peritonitis in a dog - case reportABSTRACT
Cholangitis is a disorder of the bile ducts characterized by inflammation and cholestasis, while cholecystitis is inflammation of the gallbladder. Both conditions cause non-specific signs such as vomiting, abdominal pain, weight loss, anorexia, as well as fever and jaundice in some cases. The aim of this article is to report the case of a five-year-old male canine patient who presented with cholangiohepatitis and cholecystitis associated with biliary peritonitis. On ultrasound, it was possible to identify grade 4/6 biliary sludge, heterogeneity of the liver parenchyma associated with mesenteric inflammation and abdominal effusion. In view of the urgent clinical situation, the patient was referred for cholecystectomy and liver biopsy. In addition, during the procedure, maneuvers were performed to correct abdominal hemorrhagic foci. The histopathological evaluation revealed necrotic hepatopathy associated with mixed chronic-active cholangiohepatitis and cholecystitis. The patient remained stable and showed no clinical signs after the surgical procedure.
Keywords:
bilirubin; canine; cholecystectomy; gallbladder
RESUMO
A colangite é um distúrbio das vias biliares que se caracteriza por inflamação e colestase, enquanto a colecistite é a inflamação da vesícula biliar. Ambas as condições ocasionam sinais inespecíficos, como vômito, abdominalgia, perda de peso, anorexia, além de febre e icterícia em alguns casos. O presente artigo tem como objetivo relatar o caso de um paciente canino, macho, de cinco anos que apresentou quadro de colangio-hepatite e colecistite associadas à peritonite biliar. Na avaliação ultrassonográfica foi possível identificar lama biliar grau 4/6, heterogenicidade do parênquima hepático associada à inflamação mesentérica e à efusão abdominal. Diante do quadro clínico urgente, o paciente foi encaminhado para procedimento cirúrgico de colecistectomia e biópsia hepática. Além disso, durante o procedimento foram realizadas manobras para correção de focos hemorrágicos abdominais. A avaliação histopatológica revelou hepatopatia necrótica associada à colangio-hepatite e colecistite crônico-ativas mistas. O paciente permaneceu estável e sem sinais clínicos após o procedimento cirúrgico.
Palavras-chave:
bilirrubina; canino; colecistectomia; vesícula biliar.
INTRODUCTION
Cholangitis, defined as inflammation of the bile ducts, is a relevant clinical condition in dogs and can develop into serious complications such as biliary peritonitis (BP). This type of peritonitis occurs due to the extravasation of bile into the abdominal cavity, which results in an exacerbated inflammatory response. Extravasation can be secondary to inflammatory or infectious processes that compromise the integrity of the biliary system, even in the absence of macroscopic ruptures (Silva et al., 2004).
Bile salts and other constituents of bile are toxic when extravasated from the enterohepatic tract, promoting increased vascular permeability, tissue necrosis and inflammation, factors which worsen the prognosis (Church and Matthiesen, 1988; Crews, 2009; Mehler, 2011). The main causes of BP are biliary tract rupture, extrahepatic biliary obstruction, trauma, duodenal perforation and inflammatory diseases of the biliary tract (Thompson et al., 2021).
Among hepatobiliary diseases, cholangitis and cholecystitis stand out as the main causes of altered bile flow, which can predispose to BP (Center, 2009). Clinically, these conditions can be silent or manifest as non-specific signs such as vomiting, depression, weight loss, fever, dehydration, gastroenteritis and abdominal pain (Slatter, 1998; Willard and Fossum, 2005). Ultrasound is an essential method for diagnosing alterations in the biliary system and for helping to assess the severity of the inflammatory process and its complications (Willard and Fossum, 2005).
Cholangitis can progress to cholangiohepatitis when there is inflammatory involvement of the adjacent liver parenchyma (O'Neill et al., 2006). Although this disease is considered rare in dogs, the pathophysiology of acute cases suggests that intestinal bacteria can ascend through the bile duct, especially in animals with predisposing diseases such as chronic pancreatitis, chronic inflammatory enteropathy, cholestasis and cholelithiasis, as well as immunosuppression and changes in intestinal motility (Kearns, 2009).
The definitive diagnosis of chronic cholangiohepatitis and cholecystitis requires histopathological examination, which usually shows lymphoplasmocytic inflammation associated with necrosis, apoptosis, hepatocellular regeneration, fibrosis and ductular hyperplasia. Microbiological analysis is important for differential diagnosis. Although there is no universally established therapeutic protocol, immunosuppressive therapy is frequently used, in addition to supportive treatment (Amsellem et al., 2006).
The aim of this study is to report a case of cholangiohepatitis and cholecystitis associated with biliary peritonitis in a dog.
ETHICAL ASPECTS
This study was not submitted to the Ethics Committee on Animal Use, but the person responsible signed a free and informed consent form authorizing the publication of the data.
CASE REPORT
A domesticated dog, approximately 5 years old, of the Pug breed and with a body condition score of 3/5, was received for emergency care with a history of signs of gastroenteritis to be clarified. After stabilizing the clinical condition, the animal underwent an abdominal ultrasound evaluation which indicated findings in the liver compatible with an inflammatory process (hepatitis/colangiohepatitis), grade 4/6 biliary sludge and an inflammatory process associated with possible gallbladder rupture, as well as ultrasound findings in the abdominal cavity compatible with free fluid and focal peritonitis (Fig. 1).
In addition, hematological laboratory tests such as blood count, serum biochemistry (creatinine, alanine aminotransferase (ALT) and albumin) and cavitary fluid analysis were also requested. No major alterations were found in the tests, except for the exacerbated ALT values and the presence of bilirubin in the abdominal effusion fluid (Table 1).
The animal was referred for celiotomy, cholecystectomy and liver biopsy. Fentanyl citrate (Fentanyl®, Janssen-Cilag, São José dos Campos, SP) 2mg/kg, propofol (Provive®, Claris, Barueri, SP) 4mg/kg and ketamine hydrochloride (Cetamin®, Syntec, Santana da Parnaíba, SP) 1mg/kg intravenously were used to induce anesthesia. During transanesthesia, the patient was kept on a continuous infusion of remifentanil hydrochloride (Remifentanil®, Eurofarma, Itapevi, SP) 10mcg/kg/h and the reinhalation anesthetic circuit was made with isoflurane (Isoflurane®, Syntec, Santana da Parnaíba, SP) at a minimum alveolar concentration (MAC) of 1.3%.
The retroumbilical celiotomy was accessed via the linea alba, and the falciform ligament was removed using a monopolar scalpel. All the abdominal organs were assessed and a diffuse hemorrhagic focus was found in the gallbladder and in the right medial and square hepatic lobes, as well as the presence of a hematoma in the hiatus of the vena cava in the diaphragm, duodenum, pylorus and pancreas, making it necessary to drain the blood accumulated in the abdominal cavity with a surgical aspirator (Fig. 2A). Tranexamic acid (Transamin®, Zydus, Ilha do Governador, RJ) 15mg/kg and vitamin K (Monovin K®, Bravet, Rio de Janeiro, RJ) 2.5mg/kg intravenously were also used as a single dose of medication during surgery.
For cholecystectomy, the gallbladder was divided from the hepatic lobes, as there was adjacent adherence and fibrosis, wall edema and pale portions of the gallbladder that suggested foci of ischemia and necrosis. After complete dissection, the cystic duct was ligated using Miller's knot with 2-0 poliglecaprone thread, the vesicle was removed and omentalized (Figs. 2B and 2C). There was diffuse bleeding from the liver, which was controlled with manual compression and a hemostatic sponge (Hemospon Cote®, Maquira, Maringá, PR).
After cholecystectomy, a liver biopsy was carried out in the left medial lobe using a 3 mm surgical punch and a hemostatic sponge (Hemospon Cote®, Maquira, Maringá, PR, Brazil) to control local bleeding. Two liver fragments and one gallbladder fragment were placed in 10% buffered formalin for histopathological examination. Celiorrhaphy was performed using 2-0 polyglcaprone thread in a reverdin pattern (Fig. 2D), the subcutaneous tissue was reduced using 3-0 polyglcaprone thread in a continuous Wolff pattern and dermorrhaphy using a simple continuous stitch and 2-0 nailon thread.
Abdominal ultrasound images of a 5-year-old male Pug dog diagnosed with cholangiohepatitis and cholecystitis associated with biliary peritonitis. A) Gallbladder with regular contour, not intact, with hyperechogenic wall and hypoechogenic foci, markedly thickened and filled with amorphous echodense content (biliary sludge). B) Power Doppler evaluation showing absence of vascularization in the gallbladder wall. C) Heterogeneous pancreas with mixed echogenicity and increased dimensions. D) Moderate amount of free fluid in the abdominal cavity with thickened and hyperechogenic mesentery.
Intraoperative images of cholecystectomy performed on a 5-year-old male Pug dog. A) Exposure of hepatic lobe with hemorrhagic aspect and icteric omentum (white arrows). B) Gallbladder excised with long curved Kelly hemostatic forceps and 2-0 polyglactin suture used for anchoring. C) Gallbladder incision showing accumulation of bilious content. D) Abdominal wall closure with 2-0 polyglactin suture using a Reverdin pattern.
The results of the histopathology of the liver fragments indicated moderate necrotic hepatopathy, associated with chronic-active cholangiohepatitis, mixed (lymphoplasmocytic and neutrophilic), discrete multifocal, as well as discrete steatosis. Analysis of the gallbladder revealed alterations compatible with chronic-active erosive, proliferative, diffuse and moderate cholecystitis (Fig. 3).
Histological section of the gallbladder from a 5-year-old male Pug dog with chronic-active cholecystitis. A) Denudation of the lining epithelium and adjacent accumulation of amorphous eosinophilic content (yellow arrow). HE, 40×. B) Moderate to marked mixed inflammatory infiltrate (asterisk) in the lamina propria, composed mainly of lymphocytes and neutrophils. HE, 40×.
During the post-operative hospitalization period, the following were administered intravenously: ondansetron hydrochloride (Emedron®, Agener União, Embu-Guaçu, SP) 0.5mg/kg every 8 hours; dipyrone sodium (D-500®, Zoetis, Campinas, SP) 25mg/kg every 12 hours; methadone hydrochloride (Mytedom®, Cristália, Itapira, SP) 0.3mg/kg every 6 hours; dexamethasone (Azium®, MSD, Cruzeiro, SP) 0.15mg/kg every 24 hours; ampicillin sodium and sulbactam sodium (Ampicillin sodium + Sulbactam sodium®, Fresenius Kabi, Barueri, SP) 30mg/kg every 8 hours; tranexamic acid (Transamin®, Zydus, Ilha do Governador, RJ) 10mg/kg every 8 hours and vitamin K (Monovin K®, Bravet, Rio de Janeiro, RJ) 2.5mg/kg every 24 hours. In addition, a commercial probiotic (Probiótico®, Vetnil, Louveira, SP) 2g/animal every 24 hours was prescribed for oral administration; glutamine (Glutamina®, Nutrisana, Pindamonhangaba, SP) 0.1mg/kg every 12 hours; omeprazole (Gaviz® V, Agener União, Embu-Guaçu, SP) 1mg/kg every 12 hours and sulcrafate (Sucrafilm®, SEM, Hortolândia, SP) 50mg/kg every 12 hours. The patient was discharged from hospital after three days. The skin stitches were removed 15 days after surgery and no complications or clinical manifestations were reported.
DISCUSSION
This paper describes the case of a 5-year-old adult male canine who presented with cholangiohepatitis and cholecystitis associated with gallbladder rupture and peritonitis. However, this differs from the description of the authors who found that alterations related to the bile ducts are more common in elderly animals or those with endocrinopathies (Kilpatrick and Andrew, 2017). Purice et al. (2023) found a higher prevalence among females and dogs aged between 6 and 10 years, also different from the patient described here.
The main conditions affecting the gallbladder include cholelithiasis, mucocele, cholecystitis and neoplasms (Kilpatrick and Andrew, 2017). Biliary sludge is an incidental finding in most cases and is found on imaging tests (Butler et al., 2022). At the time of diagnosis, the patient had biliary sludge grade 4/6, which suggests progression of the clinical picture and may be related to the origin of the cholecystitis. However, due to the lack of previous examinations and history, it was not possible to determine the exact etiology and risk factors.
The patient in this report was admitted with a history of gastroenteritis. Diseases affecting the biliary and hepatic tract are, in most cases, diagnosed based on a combination of clinical signs, laboratory tests and imaging (Center, 2009). The most common clinical manifestations include vomiting, anorexia and lethargy (Malek et al., 2013), while fever, abdominal pain, weight loss and dehydration may also occur (Willard and Fossum, 2005). However, some animals can be asymptomatic (Lawrence, 2019). In the present case, the clinical findings were partially consistent with the aforementioned authors, since the patient only presented with vomiting. The diagnosis, however, was suggested on the basis of ultrasound and laboratory findings, corroborating information in the literature (Center, 2009).
In hepatobiliary diseases in dogs, an increase in serum alkaline phosphatase (ALP), ALT, gamma glutamyl transferase (GGT), total bilirubin and fractions, triglycerides, cholesterol and creatinine is common, associated with hypoalbuminemia and hypocalcemia (Youn et al., 2018). Among the hematological alterations in the patient's tests were an increase in ALT, azotemia due to an increase in creatinine and hypoalbuminemia. A GGT test would be recommended to manage the case, since this enzyme is usually elevated in cholangitis (Youn et al., 2018). However, GGT was not measured in this study, nor were bilirubin, triglycerides and cholesterol. We recognize that the absence of these markers can compromise the diagnosis and therapeutic approaches, so we emphasize the importance of a complete laboratory evaluation in the management of canine hepatobiliary diseases.
Imaging tests have diagnostic limitations, but the most common ultrasound changes in cholecystitis include distension of the gallbladder and bile duct, thickening of the gallbladder wall and indications of peritonitis, as well as possible cholelithiasis (João, 2015). Thus, the ultrasound sensitivity for diagnosing gallbladder rupture is not high, however, in the present report the alterations found were sufficient to suspect rupture, mainly due to the characteristics of the non-intact wall associated with free abdominal fluid. The same author (João, 2015) includes the possibility of radiographic imaging, used in cases of suspected emphysematous cholecystitis, but radiography was not carried out in this case.
Histopathology of the gallbladder revealed a chronic active proliferative inflammatory process with no evidence of the presence of microorganisms. According to Tamborini et al. (2016), the acute form of cholecystitis is often associated with bacterial infection and trauma, while for Rogers et al. (2020) the chronic manifestation is not very well elucidated and may be associated with autoimmunity. Although in this report microscopy suggested a chronic inflammatory infiltrate with no infectious agents, cytological analysis of the bile, culture of the bile contents, gallbladder wall and liver would be essential for differential diagnosis and understanding the underlying cause.
Surgical intervention in cholecystitis with a risk of rupture reduces the risk of death (Mitsui et al., 2021). In the present report, the patient had abdominal effusion, in which total bilirubin levels were measured, in addition to cytological analysis. According to the literature, bilirubin concentration in the effusion twice that of the serum is indicative of BP (Mehler, 2011). However, as serum bilirubin was not measured in this case, the diagnosis was based on the ultrasound findings, the biochemical parameters of the effusion and trans-surgical observation.
CONCLUSION
In view of the above, the importance of diagnostic imaging methods in detecting disorders of the gastrointestinal tract and adnexal glands is clear. In this case, ultrasound was decisive in indicating the surgical procedure of cholecystectomy, which resolved the problem.
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