Acquired Portosystemic Shunting in Two Cats
Acquired portosystemic shunts (PSS) are a clinical entity distinct from congenital PSS. Their apparent incidence in cats is low, which may reflect the rarity of predisposing hepatic parenchymal disease, such as cirrhosis, in this species. Two cats with acquired PSS associated with primary hepatobiliary disease are described. Relevant findings in acquired PSS are discussed, as are potential reasons for the apparently low incidence in the cat.
Introduction
Unlike anomalous congenital portosystemic shunts (PSS), acquired PSS are formed as a compensatory response to portal hypertension.1–4 These shunts seem to develop more commonly in dogs with hepatobiliary disease than in cats.5–7 The authors are aware of only two descriptions of PSS resulting from acquired hepatobiliary disease in cats in the veterinary literature.89 This report describes two additional cats in which acquired PSS were identified in association with primary hepatobiliary disease. Relevant aspects of this condition are discussed, as are potential reasons for its rarity.
Case Reports
Case No. 1
A 4-year-old, 2.98-kg, spayed female, domestic shorthair cat was presented to the University of Missouri-Columbia Veterinary Medical Teaching Hospital (UMC-VMTH) for further evaluation of suspected hepatic disease. Hypersalivation, weight loss, and lethargy were noted over the 2 weeks prior to presentation. Blood work [see Table] performed by the referring veterinarian demonstrated elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The cat was negative for both feline leukemia virus (FeLV) and feline immuno-deficiency virus (FIV) by enzyme-linked immunosorbent assay (ELISA).a Marked ammonium biurate crystalluria was identified and tapeworms were found on fecal flotation. Therapy consisted of esiprantel (4.2 mg/kg body weight, per os [PO] once) and subcutaneous (SC) fluids prior to referral.
Upon presentation, the cat was alert, thin, mildly dehydrated, and markedly icteric. Temperature was 102.3°F, pulse was 240 beats per minute, and respiration was 60 breaths per minute. No other abnormalities were detected on physical examination. Hematological abnormalities consisted of monocytosis and a few Heinz bodies and Howell-Jolly bodies [see Table]. Serum biochemical abnormalities consisted of low blood urea nitrogen (BUN), hyperproteinemia, hyperglobulinemia, hyperbilirubinemia, and elevated ALT [see Table]. Urinalysis revealed 3+ bilirubinuria, trace ketonuria, 3+ occult blood, pyuria, bacteruria, and uric acid and tyrosine crystalluria. Activated partial thromboplastin time (APTT) was slightly prolonged (24.2 seconds; control, 16.5 seconds), but one-stage pro-thrombin time (OSPT) was within reference ranges. Bile acids test was not performed due to the presence of icterus.
Additional diagnostic tests consisted of abdominal ultra-sonography, serum toxoplasmosis titers (i.e., immunoglobulin G and immunoglobulin M), serum feline coronavirus ELISA,b and a fasting blood ammonia level. Abdominal ultrasonography demonstrated mild peritoneal effusion and a markedly distended gall bladder and common bile duct. Toxoplasmosis titers were negative, and feline coronavirus ELISA was positive. The fasting blood ammonia level was high normal (63 μmol/L; reference range, 17 to 69 μmol/L). Evaluation of the peritoneal effusion obtained by abdominocentesis at the time of ultrasound demonstrated dark straw-colored, cloudy fluid that cleared with centrifugation and had a specific gravity of 1.022, total protein of 3.3 g/dL, total nucleated cell count of 2,060/μL, and packed cell volume <2%. Polymerase chain reaction (PCR) test of the effusion for feline coronavirus was negative. Cytopathological evaluation revealed highly cellular fluid with 65% neutrophils, 25% macrophages, and 10% lymphocytes. Multiple clusters of large, uniform cells with high nuclear to cytoplasmic ratios and prominent nucleoli were noted. Interpretation of the fluid cytopathology was consistent with a mixed-inflammatory exudate with the presence of reactive mesothelial cells. Carcinoma and mesothelioma were also considered differentials.
Therapy consisted of intravenous (IV) 0.9% saline (4 mL/kg per hour) and amoxicillin/clavulanic acidc (21 mg/kg body weight, PO q 12 hours). Pyrexia developed 1 day after admission, but therapy remained unchanged. An exploratory celiotomy was performed 3 days after admission. Surgical exploration revealed multiple, small masses in the omentum and right body wall. The gallbladder wall was thickened, and both the gallbladder and bile ducts were severely distended. It was not possible to express the gall-bladder. Further manipulation of the gallbladder demonstrated a small perforation that was leaking bile. A mass was noted in the pancreas. Multiple extrahepatic PSS were identified originating from the renal vein. The patient was euthanized intraoperatively as per the owner’s wishes.
Necropsy was performed with no additional abnormalities noted grossly. Sections of gallbladder prepared for histopathological evaluation revealed the presence of biliary adenocarcinoma, and omental masses were found to be adenocarcinoma metastases. The pancreatic mass was an adenoma. Histopathology of the liver demonstrated bridging portal fibrosis, biliary hyperplasia, and multifocal to coalescing foci of hepatocellular vacuolation and necrosis. Mild periportal lymphocyte accumulation was noted [Figure 1]. Moderate cerebrocortical white-matter spongiosis was present.
Case No. 2
A 6-year-old, 3.57-kg, female spayed domestic shorthair cat was presented to the UMC-VMTH for evaluation of chronic liver disease. Recent history included depression, anorexia, weight loss, stranguria, and pollakiuria. The cat had a history of hepatic disease since 1 year of age, with intermittent clinical signs during the 5 years prior to presentation. Severe ascites was noted 3 years prior to presentation but had subsequently resolved. Intermittent icterus was well documented. Two months prior to presentation, markedly elevated fasting bile acids (184.8 μM/L; reference range, 1.5 to 5.0 μM/L) were documented. Two weeks prior to presentation, the referring veterinarian identified a normocytic, normochromic, nonregenerative anemia; low BUN; hypokalemia; hypoalbuminemia; hyperbilirubinemia; and elevated alkaline phosphatase (ALP) [see Table]. Therapy at the time of presentation consisted of ursodeoxycholic acid (13.4 mg/kg body weight, PO q 12 hours), metronidazole (8.4 mg/kg body weight, PO q 12 hours), lactulose (0.22 g/kg body weight, PO q 12 hours), and intermittent oral potassium supplementation.
Upon presentation to the UMC-VMTH, the cat was slightly depressed. Mucous membranes were pale with normal capillary refill time, and a grade II/VI systolic, left heart base murmur was ausculted. A firm area associated with the liver was palpated in the cranial abdomen. Hematological abnormalities consisted of a normocytic, normochromic, nonregenerative anemia (reticulocytes, 0.2%); lymphopenia; mild monocytosis; and a moderately decreased platelet estimate [see Table]. Red blood cell morphology demonstrated elliptocytosis, blister cells, keratocytosis, schizocytosis, anisocytosis, and Howell-Jolly bodies. Serum biochemical abnormalities consisted of hypoalbuminemia, hypoproteinemia, hypokalemia, a mild decrease in creatinine, hyperbilirubinemia, and an elevated ALP [see Table]. Coagulation was abnormal with a prolonged APTT (40.8 seconds; control, 12.5 seconds), but OSPT was within reference range. Bile acids were not tested again because of previously documented elevation. Urinalysis was not performed. Both FeLV and FIV testsa were negative. Thoracic radiographs were unremarkable, and abdominal radiographs demonstrated a large, mineralized mass associated with the liver in the area of the gallbladder [Figure 2]. Multiple, smaller, adjacent mineralized densities were also present and were believed to represent choleliths. A cystic calculus was also noted. Abdominal ultrasound demonstrated hyperechogenic areas in the gallbladder and hepatic parenchyma that were consistent with choleliths, and the described cystic calculus was visualized.
Therapy consisted of lactulosed (0.22 g/kg body weight, PO q 12 hours), vitamin K1e (0.5 mg/kg body weight, SC q 8 hours), heparinf (75 IU/kg body weight, SC q 8 hours), amoxicilling (14 mg/kg body weight, PO q 12 hours), and SC 0.9% saline (90 mL, sid). Two days after admission, a whole blood transfusion was administered and exploratory celiotomy was performed. Surgical exploration demonstrated a small, firm, irregular liver. The gallbladder could not be manually expressed, and multiple choleliths were palpated externally, as was one cystic calculus. Multiple extrahepatic PSS were noted [Figure 3]. Several pancreatic nodules were also identified. The owners elected euthanasia intraoperatively because of the likely inability to reverse the chronic disease process and the poor long-term prognosis.
Gross necropsy findings were consistent with surgical findings. Hepatic histopathology was similar to that of case no. 1. The liver demonstrated bridging portal fibrosis, and markedly dilated bile ducts were lined by hyperplastic epithelium and were surrounded by dense, fibrous connective tissue. Portal areas frequently contained moderate accumulations of lymphocytes. Pancreatic histopathology demonstrated dilated and fibrotic pancreatic ducts. The choleliths and cystic calculus were not analyzed.
Discussion
Acquired PSS develop as a response to portal hypertension.1–4 In contrast, congenital PSS are developmental anomalies typically unassociated with portal hypertension.310 Although their incidence is apparently low, feline congenital PSS have been well described in the veterinary literature.124611–14 Acquired PSS in cats are believed to be rare and have not been as well described.1516
Acquired PSS develop as portal hypertension increases resistance to blood flow through the portal vein. Multiple, small collateral vessels that, under normal conditions, would have little to no blood flow become the path of least resistance, and these vessels increase in size and functionality.2361417 The anatomical source for portal hypertension may be hepatic, prehepatic, or posthepatic in location. Not all causes of portal hypertension are equally likely to result in portosystemic shunting. Acquired shunting is only associated with hemodynamic situations in which an alternate, lower-pressure route of blood flow is achieved through the opening of collateral vasculature.23 This situation is most often found in association with diffuse intrahepatic disease such as hepatic fibrosis or cirrhosis, although inflammatory and infiltrative intrahepatic diseases or congenital portal vein atresia may also cause portal hypertension.3 In the dog, experimental ligation of the common bile duct leads to portal fibrosis (potentially attributable to bile acid retention), portal hypertension, and subsequent portosystemic shunting.1819 Posthepatic conditions such as obstruction of the caudal vena cava or Budd-Chiari-like syndrome (i.e., hepatic vein occlusion), or prehepatic conditions such as portal vein obstruction or arteriovenous fistulas, may occasionally lead to the development of acquired PSS.35
Acquired PSS in cats are poorly described in the veterinary literature. Experimental partial occlusion of the portal trunk leads to the development of acquired PSS in cats, with the most extensive shunting occurring via portopostcaval communications, especially the gastrophrenic and left colic anastomoses.17 Acquired PSS have been reported in cats with congenital hepatic arteriovenous fistula,20 congenital intrahepatic portal vein atresia,113 and surgically attenuated congenital PSS.1121 While the incidence and common sites of development for naturally occurring acquired PSS are described in both dogs and humans, these characteristics have not been examined in cats.1922–24 In fact, the authors could find reference to only two documented cases of acquired hepatobiliary disease resulting in formation of PSS in cats; both cases were in association with hepatic cirrhosis.89
It is difficult to determine if the paucity of clinical reports is due to a very low incidence of acquired PSS in cats, or to some confounding factor. The presence of shunts may be overshadowed by the severity of the primary process initiating portal hypertension. There may be a tendency to accept acquired PSS as a consequence of underlying hepatic disease with no separate documentation of the shunts. In fact, the Standard Nomenclature of Veterinary Disease and Operations system of medical records coding used at the UMC-VMTH does not contain a code for acquired PSS. A review of medical records from the UMC-VMTH for the years 1969–2000 using the terms portosystemic shunt, cirrhosis, extrahepatic portosystemic shunt, or multiple portosystemic shunts failed to document any additional cases of acquired PSS in cats. Likewise, record review from the UMC Veterinary Medical Diagnostic Laboratory (UMC-VMDL) between the years 1993–2000 failed to document additional cases of feline acquired PSS.
Although reports of acquired PSS in cats are rare, feline hepatobiliary disease is common.151625–27 The most frequently documented histopathological diagnoses in cats with hepatobiliary disease are reported to be hepatic lipidosis, inflammatory hepatic disease (e.g., cholangiohepatitis, lymphocytic portal hepatitis), and neoplasia. Of 497 feline hepatopathies identified at the UMC-VMDL by either biopsy or necropsy between 1993 and the present, the three most frequent histopathological diagnoses were hepatic lipidosis (222 cats [44.7%]), biliary stasis (68 cats [13.7%]), and cholangiohepatitis (59 cats [11.9%]). Twenty-one (4.2%) cats were described as having fibrotic changes.h Although portal fibrosis can lead to portal hypertension and acquired PSS even in the absence of cirrhosis,3 none of these 21 cats were noted to have PSS. No cats were identified as having cirrhosis, which is the most common cause of acquired PSS in dogs3 and humans.23
Hepatic cirrhosis, a common cause of acquired PSS in species other than the cat, is most often defined as a loss of normal microscopic lobular architecture, with the presence of both fibrosis and structurally abnormal nodular regeneration. Many inciting causes culminate in the irreversible deposition of connective tissue and compression by regenerative nodules, which characterize the cirrhosis that often leads to portal hypertension and subsequent acquired PSS.24 The hepatic diseases identified most commonly in the cat are quite different than the conditions that frequently lead to hepatic cirrhosis in either dogs or humans. In dogs, infectious hepatitis, drug and toxin exposure, hepatic necrosis, and several breed-associated hepatopathies are important causes of cirrhosis.72228 While feline inflammatory hepatic diseases typically center around the biliary tree, the mentioned canine hepatopathies usually result in parenchymal damage.729 Parenchymal damage is also characteristic of the diseases that lead to cirrhosis in humans, most commonly alcohol-induced hepatic damage, viral hepatitis, and immune-mediated hepatitis.2324
It has been reported that cats with chronic hepatic disease do not often develop cirrhosis; the common acquired hepatic diseases in the cat may simply not often progress to cirrhosis.3515162527 Nodular regeneration associated with cirrhosis contributes to compression of hepatic sinusoidal blood flow and subsequent development of portal hypertension, ascites, and acquired PSS.24 It is possible that cats may not have the same exuberant hepatic regenerative capacity as do dogs or humans. Although hepatic fibrosis was recognized in 21 cats from the authors’ institution, none were noted to have the accompanying regenerative nodules characteristic of cirrhosis. If cats possess less regenerative capability than other species, it might explain why they exhibit less cirrhosis and fewer acquired PSS. In this report, neither of the two cases of feline acquired PSS exhibited cirrhosis. Fibrosis alone, which was observed in both cats of this report, may lead to portal hypertension and acquired PSS.3
Perhaps cats afflicted with the more common feline hepatopathies are less likely to develop acquired PSS because they either recover or die before portal hypertension can exert its consequences. Untreated lipidosis, untreated cholangiohepatitis, neoplasia, or hepatopathy due to feline infectious peritonitis can lead to rapid death. Some authors postulate that diseases like cholangiohepatitis do not often progress to cirrhosis, because affected cats simply do not live long enough.1527 Conversely, feline hepatic lipidosis is often a curable disease, and full recovery from cholangiohepatitis may occur as well.30 These disease syndromes may resolve prior to the development of portal hypertension or cirrhosis.
Case no. 1 of this paper exhibited biliary obstruction, portal fibrosis, and biliary hyperplasia associated with biliary adenocarcinoma. It is impossible to know whether the observed abnormalities occurred after the neoplasia developed or if they may have preceded the cancer. In humans, a number of hepatic neoplasms, including hepatocellular carcinoma, result from chronic hepatic inflammation.24 The observed abnormalities may also have resulted from hepatic inflammation due to the neoplasia and resultant biliary obstruction. Acquired PSS can develop acutely in cats, as early as 6 days after experimental portal vein attenuation.17
The cause for portal fibrosis and acquired PSS observed in case no. 2 was suspected to be chronic biliary obstruction and chronic inflammatory hepatic disease with associated cholelithiasis. Cholelithiasis may have been either a primary factor or a reflection of abnormal bile kinetics and chronic inflammation or infection.162731 In this case, there was evidence of a recurrent hepatopathy during 5 of the 6 years of the cat’s life. Despite the early onset of signs, congenital PSS was considered unlikely due to the presence of previously documented icterus, ascites, and the presence of multiple shunts, none of which are typical of congenital feline PSS.332
The clinical consequences of PSS are similar, regardless of whether the shunt is acquired or congenital; therefore, animals may present with signs related to shunting but no evidence of other hepatic disease. Evidence of hepatic encephalopathy, red cell microcytosis, ammonium biurate crystalluria or calculi, elevated liver enzymes, elevated ammonia levels, microhepatica, and abnormal rectal scintigraphy each contribute to a tentative diagnosis of PSS but cannot differentiate between acquired and congenital shunts. Determination of serum bile acids can be a sensitive means of detecting PSS. Elevations of both pre- and postprandial values, or marked elevation of the postprandial values in relationship to the preprandial values, may suggest the presence of PSS but cannot help to distinguish acquired from congenital shunts.2 Ultrasonography may or may not be effective at identifying extrahepatic PSS, but unless multiple shunts are identified, it cannot differentiate congenital from acquired PSS.33 Many of the classic historical and laboratory findings associated with PSS were noted in the cats of this report, but shunts were not identified by ultrasound in either cat.
The differentiation of acquired PSS from the more commonly reported congenital PSS is crucial, because both treatment and prognosis differ greatly. Noninvasive differentiation between acquired and congenital shunts may be difficult. Although most animals with congenital shunts are recognized at a young age, signs may not be evident for years.1 Similarly, young animals may develop diseases leading to portal hypertension and acquired shunting. Historical evidence of chronic hepatic disease, especially documentation of prior or current ascites or icterus, is suggestive of acquired shunting. Icterus was noted in case no. 1, and milder hyperbilirubinemia was noted in case no. 2. Icterus does not typically coexist with congenital PSS and would therefore suggest that accompanying shunts were acquired.13 Ascites is a consequence of portal hypertension, and thus its presence (or historical presence, as in case no. 2) strongly suggests that accompanying PSS were acquired. Congenital PSS are typically not associated with portal hypertension and ascites.3 Congenital hepatic diseases that do result in portal hypertension, such as arteriovenous fistulas and intrahepatic portal vein atresia, are uncommon.23 Splenic portography can be performed percutaneously and may document portal venous system architecture and aid in the diagnosis of acquired PSS.34
Ultimately, the most certain method for identification of acquired PSS is direct visualization at surgery or laparoscopy. Both allow the opportunity to further investigate the portal venous system, document portal hypertension, and acquire hepatic biopsies. Acquired PSS are readily diagnosed visually, and intraoperative portograms are rarely necessary. Intraoperative manometry may be valuable to document portal hypertension causing acquired PSS, and the degree of elevation may provide prognostic information. Portal pressure measurement via direct mesenteric vein catheterization or indirectly via splenic pulp pressure has been described.101935 Acquired PSS that develop as a result of persistent portal hypertension typically do not relieve hypertension completely; therefore, elevated portal pressures are often, but not always, present even when shunting has occurred.1022
In the two cases presented here, surgical intervention was planned largely as a diagnostic and potentially therapeutic tool, and the acquired PSS were incidental findings. Intraoperative portograms were not considered necessary in these cases. While direct manometry was not performed during surgery in these cats, it should have been performed and may have provided valuable information and documentation of this rare condition in cats.
Diagnosis of the underlying disease pathology should take precedence over the diagnosis of acquired PSS. The additional documentation of acquired PSS provides prognostic information and may prompt specific therapy for hepatic encephalopathy. Acquired PSS are poor prognostic indicators and lead to progressive hepatic dysfunction, impaired hepatic regenerative ability, and hepatic encephalopathy.2
Therapy for cats with acquired PSS is aimed at control of hepatic encephalopathy and treatment of the underlying disease process. Surgical occlusion of acquired PSS may lead to fatal splanchnic congestion and is therefore contraindicated.1414 Banding of the vena cava, in an attempt to change portal pressures so that shunting is no longer favored, has not been reported in cats. This procedure has not proven beneficial in dogs.22 Medical management of hepatic encephalopathy has been well described and includes such measures as restricted protein diets, lactulose, and oral antibiotic therapy.36 Based on a poor long-term prognosis, the owners of both cats of this report chose euthanasia rather than supportive medical care.
Acknowledgments
The authors thank Drs. Karen Felder and Jerry Williams for their valuable assistance.
FeLV/FIV antibody test kit; Idexx Laboratories, Inc., Westbrook, ME
CELISA FIP; Idexx Laboratories, Inc., Westbrook, ME
Clavamox Drops; SmithKline Beecham Pharmaceuticals, Philadelphia, PA
Lactulose solution, USP; Morton Grove Pharmaceuticals, Inc., Morton Grove, IL
Vitamin K1 injection; Phoenix Scientific, Inc., Morton Grove, IL
Heparin sodium injection, USP; Elkins-Sinn, Inc., Cherry Hill, NJ
Amoxi-Tabs; SmithKline Beecham Pharmaceuticals, Philadelphia, PA
Previously unpublished data collected by the authors from the UMC-VMDL databases
Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380021
Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380021
Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380021
Liver histopathology from case no. 1. Marked portal fibrosis (PF) is evident outlining hepatic parenchyma demonstrating moderate vacuolization (L). Biliary hyperplasia is present (arrows). Mild portal lymphocytic accumulation is noted (Hematoxylin and eosin stain; bar=52 μ).
Lateral abdominal radiograph of a 6-year-old cat (case no. 2) with chronic hepatic disease and a recent history of stranguria. Mineralized density in the area of the gall-bladder are apparent.
Intraoperative photograph of case no. 2. Multiple, tortuous, acquired portosystemic shunts are demonstrated in the perirenal area.
Contributor Notes
