Diagnosis of Portosystemic Shunts: Liver Function Tests
Although history, physical examination, and routine laboratory tests may be suggestive of portosystemic shunting, liver function tests such as ammonia tolerance test (ATT) and measurement of fasting and postprandial serum bile acid concentrations are more reliable for diagnosing liver dysfunction.
Serum bile acids are synthesized in the liver from cholesterol. After conjugation with taurine, they are secreted into bile and stored in the gallbladder. During food intake, neurohumoral and hormonal factors such as cholecystokinin stimulate gallbladder contraction and excretion of bile acids into the small intestines where they form micelles that enhance lipid emulsification and absorption. At least 95% of intestinal bile acids are actively reabsorbed in the ileum and are transported by portal blood back to the liver (the "enterohepatic cycle"). Normally postprandial bile acid concentrations are minimally increased because of rapid first-pass hepatic extraction. Serum bile acid concentrations are elevated with cholestasis, jaundice, and portosystemic shunting. They are not significantly affected by dehydration, hypovolemia, or passive hepatic congestion, although they can be falsely increased by lipemia and hemolysis. No special techniques are required for handling and storage of serum for bile acid samples. Prolonged fasting may result in normal bile acid concentrations in animals with PSS; therefore, fasting and 2-hour postprandial samples should be analyzed. If the animal is sensitive to high protein meals, a low protein diet mixed with a few milliliters of corn oil can be used to stimulate gastrointestinal motility and cholecystokinin activity.
Normal hepatic function is essential for conversion of ammonia to urea. Increased resting ammonia concentration indicates decreased hepatic mass or shunting of portal blood. Concentrations of blood ammonia are not well correlated with severity of hepatic encephalopathy, and ammonia levels may be normal in 7% to 21% of dogs with PSS, especially after prolonged fasting. The ammonia tolerance test was developed to provide a more accurate diagnosis of liver dysfunction. A heparinized baseline sample is taken after a 12 hour fast, and ammonium chloride is administered orally by stomach tube or in gelatin capsules (0.1 g/kg, maximum 3 grams), or as an enema (2 ml/ kg of a 5% solution inserted 20 to 35 cm into the colon). A second blood sample is obtained 30 minutes after ammonium chloride administration. Blood samples are transported on ice for immediate plasma separation and analysis. Normal values vary with the method of analysis; results in animals with PSS should be compared to a control sample from a healthy animal to ensure accuracy. Improper sample cooling, incomplete plasma separation, or delays in sample analysis will result in falsely elevated values because of erythrocyte and plasma generation of ammonia. Results are invalid after oral ammonium chloride administration if vomiting occurs, and after rectal administration if diarrhea or shallow rectal instillation occurs.
Diagnosis of microhepatica from survey abdominal radiographs is usually based on an upright, more cranial stomach position. Renomegaly has been reported in dogs with PSS; its etiology has not been determined. Urate calculi normally are radiolucent but occasionally will be seen in the renal pelvis, ureter, or bladder on survey films.
To accurately diagnose a portosystemic shunt and determine its location, imaging techniques such as angiography, ultrasonography, and scintigraphy should be utilized. Intraoperative mesenteric portography provides excellent visualization of the portal system but usually requires a celiotomy. The dog is anesthetized and a small laparotomy is performed. Water-soluble contrast medium (maximum total dose, 2 ml/kg) is injected into a catheterized jejunal or splenic vein, and one or more radiographs are taken during completion of the injection. Alternatively the spleen can be injected directly and percutaneously in a sedated dog. However, there is a risk of splenic laceration with this technique, and the shunt will not be visible on radiographs if the contrast leaks out of the spleen or the spleen overlies the shunt. Because no dilution of contrast material occurs, intraoperative mesenteric portography provides an excellent image of the shunt if it is not too large. The technique is relatively simple and requires no special equipment. Differentiation of intrahepatic and extrahepatic PSS may be made on most portograms. If the most caudal loop of the shunt or the point where the shunt diverges from the portal vein is cranial to the T-13 vertebra, then the shunt location is probably intrahepatic. The shunt location will vary by one half to three fourths of a vertebral length depending on the phase of respiration.
Diagnosis of PSS may be made with hepatic ultrasonography. Ultrasonographic evidence of PSS includes microhepatica, decreased numbers of hepatic and portal veins, and detection of the anomalous vessel. Extrahepatic PSS are more difficult to diagnose with ultrasonography; their location is often obscured by gas-filled intestines. Overlying ribs and lungs may also interfere with a thorough ultrasonographic evaluation. Colorflow doppler is useful for detecting changes in the direction and rate of blood flow in the portal vein.
Nuclear scintigraphy is a noninvasive means of evaluating dogs for portal venous shunting. In dogs 99mtechnetium pertechnetate is extracted from the circulation primarily by the liver. In animals with shunts, the pertechnetate rapidly circulates to the heart and lungs. Normal dogs have a shunt fraction of less than 15% on scintigraphy; most dogs with shunts have fractions greater than 60%.
Magnetic resonance angiography (MRA) and CT scans have also been used to diagnose portosystemic shunts.
The ultimate diagnostic tool is laparotomy. Once experience is obtained, most extrahepatic shunts and approximately half of intrahepatic shunts can be identified on exploratory.
Single congenital portosystemic shunts must be differentiated from multiple acquired shunts secondary to portal hypertension, and from hepatic microvascular dysplasia. Hepatic microvascular dysplasia (HMD) signifies a disorganization of the liver's microscopic architecture which is similar to that of dogs with single congenital shunts. HMD has been reported in small breed dogs such as the Yorkshire terrier, Cairn terrier, Maltese, cocker spaniel, and poodle. Dogs with HMD display biochemical, hematologic, and clinical changes consistent with portosystemic shunting but lack a macroscopic portosystemic shunt. Definitive diagnosis is by ruling out a macroscopic shunt through exploratory laparotomy, nuclear scan, or portography. Signs of HMD are managed by low protein diet; lactulose is added if necessary.