Abdominal ultrasonographic findings of cats with feline infectious peritonitis: an update.

OBJECTIVES: The aim of this study was to describe the abdominal ultrasonographic findings in cats with confirmed or presumed feline infectious peritonitis (FIP). METHODS: This was a retrospective study performed in an academic veterinary hospital. The diagnosis of FIP was reached on review of history, signalment, clinical presentation, complete blood count, biochemistry panel, peritoneal fluid analysis, cytology and/or histopathology results from abnormal organs, and/or molecular testing (immunohistochemical or FIP coronavirus [FCoV] RT-PCR). Cats with confirmed FIP by molecular testing or with a highly suspicious diagnosis of FIP were included. Abdominal ultrasound examination findings were reviewed. RESULTS: In total, 25 cats were included. Common clinical signs/pathology findings included hyperglobulinemia (96%), anorexia/hyporexia (80%) and lethargy (56%). Abdominal ultrasound findings included effusion in 88% and lymphadenopathy in 80%. Hepatic changes were noted in 80%, the most common being hepatomegaly (58%) and a hypoechoic liver (48%). Intestinal changes were noted in 68% of cats, characterized by asymmetric wall thickening and/or loss of wall layering, with 52% being ileocecocolic junction and/or colonic in location. Splenic changes were present in 36% of cats, including splenomegaly, mottled parenchyma and hypoechoic nodules. Renal changes were present in 32%, encompassing a hypoechoic subcapsular rim and/or cortical nodules. Mesenteric and peritoneal abnormalities were seen in 28% and 16% of cats, respectively. Most cats (92%) had two or more locations of abdominal abnormalities on ultrasound. CONCLUSIONS AND RELEVANCE: The present study documents a wider range and distribution of ultrasonographic lesions in cats with FIP than previously reported. The presence of effusion and lymph node, hepatic and/or gastrointestinal tract changes were the most common findings, and most of the cats had a combination of two or more abdominal abnormalities.

Ultrasonographic evaluation of cholecystoduodenostomy sites in six cats.

CASE SERIES SUMMARY: This case series describes the postoperative ultrasonographic findings in six cats that underwent a cholecystoduodenostomy as treatment for extrahepatic biliary obstruction. The surgery site was identified in all six cats, most often within the right cranial abdomen as a thick-walled gall bladder, with a broad-based connection to the descending duodenum. Postoperatively, the biliary tree often remained distended, similar to its preoperative appearance. Recurrent extrahepatic biliary obstruction was suspected in three cats with worsening hyperbilirubinemia. Common bile duct distension was progressive in one of these cats and unchanged in another, but improved in the third. Intrahepatic bile duct distension resolved in one cat following surgery but reappeared with suspected recurrent biliary obstruction. In two cats, progressive echogenic biliary contents were associated with locally aggressive cholangiocarcinoma. Our findings suggest that in cats with cholecystoduodenostomy and progressive increases in hyperbilirubinemia following surgery, progressive or recurrent biliary distension and/or progressive echogenic biliary contents should prompt further investigation. RELEVANCE AND NOVEL INFORMATION: Biliary diversion surgery in cats is associated with high morbidity and mortality. The ultrasonographic appearance of a postoperative cholecystoduodenostomy site has not been described, making differentiation of the expected appearance from postoperative abnormalities difficult. The goal of this study was to determine the expected ultrasonographic appearance, in order to assist in managing cats with recurrent, persistent or worsening clinical signs and biochemical abnormalities following surgery.

Hyperammonemia in azotemic cats.

OBJECTIVES: Hyperammonemia occurs in cats with hepatobiliary and nutritional (cobalamin and arginine deficiency) disorders, and has also been documented in four cats with renal azotemia. We hypothesized that in cats with renal azotemia, fasting hyperammonemia would correlate with indices of worsening kidney function, and would be independent of cobalamin, potassium, systemic inflammation or urinary tract infection (UTI) with urease-producing bacteria. METHODS: A fasted blood sample was prospectively collected for ammonia and cobalamin analysis from 18 client-owned cats with renal azotemia (creatinine [Cr] ⩾1.6 mg/dl, urine specific gravity <1.030 or documentation of historical chronic kidney disease [CKD]). Correlations between blood ammonia and selected biochemical parameters were analyzed using Pearson's correlation coefficient. RESULTS: Seven castrated males and 11 spayed females with a median age of 12 years (range 4-19 years) were enrolled. Ten of 18 (56%) cats presented for acute kidney injury (AKI) or acute on chronic kidney disease (AoCKD), and 8/18 (44%) presented for progressive CKD. The median Cr was 5.9 mg/dl (range 1.9-24.7 mg/dl). Hyperammonemia was documented in 4/18 (22%) cats, with a median of 95 µmol/dl (range 85-98 µmol/dl), and all four of these cats were classified as AKI/AoCKD. Blood ammonia concentrations had a significant moderate positive correlation between blood urea nitrogen (BUN) (r = 0.645, P = 0.003), Cr (r = 0.578, P = 0.012) and serum phosphorus (r = 0.714, P = 0.0009) but not with cobalamin, potassium or white blood cell count. No cats had UTIs with urease-producing bacteria. CONCLUSIONS AND RELEVANCE: A correlation exists between blood ammonia and BUN, Cr and phosphorus in cats with renal azotemia. Future studies are warranted in a larger population of cats to determine the true prevalence, etiology and potential therapeutic effect of medical management of hyperammonemia on long-term prognosis in cats with kidney disease.

Thromboelastography in cats with cholestatic liver disease.

OBJECTIVES: While thromboelastography (TEG) has helped define a complex state of hemostasis in dogs and humans with hepatobiliary disease, it has not been explored in cats with cholestatic liver disease (CLD). The objective of this study was to describe TEG parameters in cats with CLD and to compare these parameters with conventional plasma-based coagulation tests, white blood cell (WBC) count and biochemical indicators of liver disease grade and severity. METHODS: Eighteen cats with CLD, defined by a serum bilirubin ⩾3 mg/dl and a greater than two-fold increase in serum alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) activity, were prospectively enrolled. All cats received vitamin K1 subcutaneously for 24-36 h prior to acquisition of blood for kaolin-activated TEG analysis, prothrombin time (PT) and activated partial thromboplastin time (aPTT). Patient total solids, packed cell volume, platelet count, WBC count, and serum liver enzymes and bilirubin were extracted from the medical record and correlated with coagulation test results. RESULTS: TEG global clot strength (TEG G) values defined 9/18 (50%), 5/18 (28%) and 4/18 (22%) cats as hypercoagulable, normocoagulable or hypocoagulable, respectively. TEG G was significantly negatively correlated with PT, aPTT and serum ALP activity and positively correlated with total solids. Five cats (5/18, 28%) were hyperfibrinolytic with clot lysis at 60 mins (LY 60) >15.3%. LY 60 was significantly positively correlated with PT. CONCLUSIONS AND RELEVANCE: By TEG analysis, cholestatic cats replete with vitamin K1 display a variety of coagulation profiles. Indications of synthetic failure (prolonged PT and aPTT) were associated with hypocoagulable and hyperfibrinolytic TEG parameters. High disease activity (serum ALP) was associated with a hypocoagulable state.

Serum vitamin D status in sick cats with and without cholestatic liver disease.

OBJECTIVES: Vitamin D deficiency accompanies chronic cholestatic liver disease (CLD) in humans. The vitamin D status of cats with CLD is unknown. The objectives of this study were to describe serum vitamin D concentrations in cats with CLD and to determine if they correlated with indices of liver disease severity. METHODS: Thirty-six cats with CLD, defined by increases in serum bilirubin and serum alanine aminotransferase, and 23 sick cats with non-hepatobiliary diseases were prospectively enrolled. Serum 25-hydroxyvitamin D (25[OH]D), parathyroid hormone (PTH) and ionized calcium were measured. Signalment, clinical signs, comorbidities, diet history, serum bilirubin, liver enzyme activity, albumin, phosphorus, white blood cell count, prothrombin time and final hepatic cytologic/histopathologic diagnosis, when available, were recorded. RESULTS: Median serum 25(OH)D levels were similar in cats with CLD (89.5 nmol/l; range 21-112 nmol/l) and sick cats (89.0 nmol/l; range 49-115 nmol/l). Overall 12/36 (33%) cats with CLD and 4/23 (17%) sick cats had 25(OH)D levels below the lower limit of the reference interval (<65 nmol/l). Median PTH concentrations in cats with CLD were significantly higher (0.95 pmol/l; range 0-11.3 pmol/l) than in sick cats (0.70 pmol/l; range 0.5-6 pmol/l). In cats with CLD, 6/36 (17%) had high PTH levels in contrast to only 1/23 (4%) sick cats. In cats with CLD, 25(OH)D concentrations did not correlate with serum bilirubin, albumin or serum liver enzymes but were moderately negatively correlated with white blood cell count (r = - 0.402, P = 0.013). Cats with hepatic lipidosis had the highest prevalence of 25(OH)D concentrations that fell below the reference interval. CONCLUSIONS AND RELEVANCE: Many cats with CLD have serum 25(OH)D concentrations below the lower limit of the reference interval. Further study is warranted to determine the clinical relevance and whether supplementation would provide benefits.

Bleeding risk and complications associated with percutaneous ultrasound-guided liver biopsy in cats.

OBJECTIVES: Liver biopsy is necessary for a diagnosis of liver disease; however, post-biopsy bleeding is a concern. The aim of this study was to describe the extent of bleeding and the occurrence of complications after percutaneous ultrasound-guided liver biopsy (PUGLB) in cats. METHODS: The medical records of 30 cats that had a PUGLB were retrospectively reviewed. Using human guidelines, bleeding was classified as minor or major when the absolute change in packed cell volume (ΔPCV) was <0 and >-6% or ≤-6%, respectively. Complications were defined as physiologic compromise necessitating an intervention, or death. The relationship between ΔPCV and the occurrence of complications and the signalment, initial PCV, coagulation parameters, serum liver enzymes and bilirubin, number of biopsies, histological diagnosis, ultrasound findings, radiologist experience, concurrent procedures and vitamin K administration were assessed using Fisher's exact test, ANOVA and Pearson's correlation coefficient, with a P value <0.05 considered significant. RESULTS: All cats had a decrease in PCV after biopsy. The mean ΔPCV was -6.9% ± 4.1%. Minor and major bleeding occurred in 13/30 (43.3%) and 17/30 (56.7%) cats, respectively, and non-lethal bleeding complications occurred in 5/30 (16.7%). Cats with complications had a lower pre-biopsy PCV ( P <0.003). Major bleeding was more likely with a diagnosis of hepatic lipidosis ( P = 0.03). There was no correlation between ΔPCV or complications and signalment, coagulation parameters, serum parameters, number of biopsies, ultrasound findings, radiologist experience, concurrent procedures and vitamin K administration. CONCLUSIONS AND RELEVANCE: PUGLB is a relatively safe procedure in cats, although many cats have a subclinical decrease in PCV. As conventional coagulation tests did not predict complications or the magnitude of ΔPCV, there is a need for more sensitive indicators of bleeding risk in cats undergoing PUGLB.

Ultrasonographic and clinicopathologic features of segmental dilatations of the common bile duct in four cats.

CASE SERIES SUMMARY: This case series documents ultrasonographic and clinicopathologic features of four cats with marked segmental dilatations of the common bile duct (CBD). All cats had additional ultrasonographic changes to the hepatobiliary system, including hepatomegaly, tubular to saccular intra/extrahepatic biliary duct dilatation and biliary debris accumulation. Based on all available data the presence of extrahepatic biliary duct obstruction (EHBDO) was ruled out in 3/4 cases and was equivocal in one case. One cat underwent re-routing surgery to address the CBD dilatation after multiple recurrent infections, one cat was euthanized and had a post-mortem examination and two cats were medically managed with antibiotics, liver protectants, gastroprotectants and cholerectics. RELEVANCE AND NOVEL INFORMATION: The ultrasonographic features of the CBD in this population of cats were supportive of choledochal cysts (CCs). The maximal diameter of the CBD dilatations exceeded 5 mm in all cases, a sign that has been previously reported to be consistent with EHBDO. In our study, dilatations were segmental rather than diffuse. Given the high morbidity and mortality associated with hepatobiliary surgery in cats, segmental dilatation of the CBD should not prompt emergency surgery. Some cats may respond to medical management. Careful planning for cyst resection was beneficial in one cat. Evaluation of CC morphology (eg, size, location, concurrent intrahepatic anomalies) may assist in selecting cats that could benefit from surgical intervention.

Cyclic AMP-guanine exchange factor activation inhibits JNK-dependent lipopolysaccharide-induced apoptosis in rat hepatocytes.

Lipopolysaccharide (LPS) is known to damage hepatocytes by cytokines released from activated Kupffer cells, but the ancillary role of LPS as a direct hepatotoxin is less well characterized. The aim of this study was to determine the direct effect of LPS on hepatocyte viability and the underlying signaling mechanism. Rat hepatocyte cultures treated overnight with LPS (500 ng/mL) induced apoptosis as monitored morphologically (Hoechst 33258) and biochemically (cleavage of caspase 3 and 9 and the appearance of cytochrome C in the cytoplasm). LPS-induced apoptosis was additive to that induced by glycochenodeoxycholate or Fas ligand, was associated with activation of c-Jun N-terminal kinase B (JNK) and p38 mitogen-activated protein kinases (MAPK), and inhibition of protein kinase (AKT). Inhibition of JNK by SP600125, but not of p38 MAPK by SB203580 attenuated LPS-induced apoptosis, indicating JNK dependency. CPT-2-Me-cAMP, an activator of cAMP-GEF, decreased apoptosis due to LPS alone or in combination with glycochenodeoxycholate or Fas ligand. CPT-2-Me-cAMP also prevented LPS-induced activation of JNK and inhibition of AKT. Taken together, these results suggest that LPS can induce hepatocyte apoptosis directly in vitro in a JNK-dependent manner and activation of cAMP-GEF protects against the LPS-induced apoptosis most likely by reversing the effect of LPS on JNK and AKT.

Activation of focal adhesion kinase and JNK contributes to the extracellular matrix and cAMP-GEF mediated survival from bile acid induced apoptosis in rat hepatocytes.

BACKGROUND/AIMS: Adherence to an extracellular matrix (ECM) rescues hepatocytes from apoptosis, but how hepatocytes adhered to different ECM and respond to apoptotic and cytoprotective stimuli is unknown. METHODS: Rat hepatocytes were plated on type 1 collagen (CI), laminin (LM) or polylysine (PL) and the amount of apoptosis induced by glycochenodeoxycholate (GCDC), deoxycholate (DCA), Fas ligand or serum withdrawal was determined by Hoechst staining. The response to cytoprotection by cAMP-guanine exchange factor (cAMP-GEF) activation was determined. Kinase activation was determined by immunoblotting with phosphospecific antibodies. RESULTS: Hepatocytes on LM and PL had more apoptosis in response to all apoptotic stimuli. GCDC increased c-jun-N-terminal kinase (JNK) phosphorylation 2-fold in hepatocytes on CI, but 15- and 30-fold in hepatocytes on PL or LM. SP-600125, a JNK inhibitor, prevented LM and PL potentiation of bile acid apoptosis. GCDC induced dephosphorylation of focal adhesion kinase (FAK) was prevented by cAMP-GEF activation. Cytochalasin B which decreased FAK phosphorylation prevented cAMP-GEF cytoprotection. CONCLUSIONS: JNK activation augments apoptosis in hepatocytes plated on PL and LM. Decreased FAK phosphorylation as seen in cells treated with bile acids or attached to PL and LM promotes hepatocyte apoptosis.