How does liver shunt happen?

This much-discussed disorder is most commonly the result of improper fetal development of the circulatory system. To thoroughly understand liver shunts, it is important to have an understanding of the development of blood vessels in the fetus. The fetus, through the placenta, umbilical vein and artery, is connected to the mother's circulatory system (bloodstream). Therefore, the liquid portion of the blood of the fetus can move into the mother's bloodstream, but the cells cannot. The mother's liver then performs the important liver functions, such as eliminating wastes, for the fetus. The mother's liver is necessary for this, since the fetal liver is just developing and is not yet capable of many functions including removing metabolic wastes from the fetal bloodstream, storing minerals, and enzyme production. Because the fetal liver is underdeveloped, the fetus possesses blood vessels which transport blood around the developing liver rather than to and through it. This is necessary, since the small developing fetal liver cannot filter or handle the full quantity of blood that needs to be filtered. When the fetus is born, the placenta, umbilical vein and artery (jointly referred to as the umbilical cord) are severed and are no longer functional. Once the umbilical cord is cut at birth, there is no longer this connection between the mother and the just-born puppy. At this point, the puppy must rely on his own liver functions and not that of his mother.

At or about the time of birthing (whelping), the blood vessels within the fetus, which allowed blood to bypass the developing fetal liver, must close. Once these vessels close, the puppy's blood is forced to pass through the puppy's now developed liver. If these fetal vessels fail to close, then blood is allowed to abnormally be shunted around the liver, hence the name liver shunt. When blood is shunted around the liver rather than to and through it, the liver is not able to filter all of the blood, and therefore, toxic metabolic wastes such as ammonia are not adequately removed from the bloodstream. The degree to which blood is shunted around the liver is dependent on the extent to which shunting vessels persist. Liver shunts may be large allowing much blood to bypass the liver, or they may be partially closed allowing only small amounts of blood to shunt around the liver. The extent of blood shunting varies with every dog.

What are the symptoms? The symptoms of liver shunts vary and are directly related to the extent of blood shunting. If the liver is receiving and processing 95 percent of the puppy's blood, the symptoms may be few, if any. More severe shunts are life threatening with many symptoms. Symptoms may be evident in these puppies at only a few weeks of age and may include low growth rates, vomiting, diarrhea, constipation, salivation, increased urination, seizures, and death. Dogs with less severe liver shunts may not exhibit any clinical signs until the puppy is much older, even up to a year of age.

What are the risks? All liver shunts, whether mild or severe, are considered serious and life threatening. Even mild liver shunts generally exhibit greater symptoms as the puppy increases in body size. The larger the puppy the more metabolic wastes produced, and therefore, the more the liver is needed. Most affected dogs will not live a normal life expectancy unless the abnormality is corrected.

What is the management? Management techniques for liver shunts have improved. The best and preferred treatment is to identify the abnormal blood vessels and surgically close them, eliminating the shunt. This will require sophisticated testing and may include radiographs (x-rays), laboratory blood analysis, ultrasound and intraveneous dye studies. The expense and results are variable depending on the degree of shunting, age, and symptoms. In addition to surgery, alterations in diet, and administration of medications are often beneficial. Restricted protein diets help reduce the production of the toxic waste, ammonia, and will therefore help lessen the need for liver detoxification. Owners and veterinarians should thoroughly discuss the seriousness, expense, and expected outcome associated with the management of all individuals suspected of having a liver shunt.

Information gathered from Foster & Smith

Pathophysiology

Clinical signs associated with portosystemic shunts commonly involve the nervous system, gastrointestinal tract, and urinary tract. General clinical signs include poor growth rate, weight loss, fever, and anesthetic or tranquilizer intolerance. Neurologic dysfunction is seen in most animals with PSS and includes lethargy and depression, ataxia, seizures, behavioral changes, and blindness. Head pressing, circling, and development of a head tilt have also been reported. Gastrointestinal clinical abnormalities include anorexia, vomiting, and diarrhea. Some dogs have no apparent signs or present with signs of cystitis or urinary tract obstruction. Many cats have hypersalivation and some have unusual copper colored irises.

Abnormalities found on hemograms of animals with PSS include leukocytosis, anemia, and microcytosis. Most animals with congenital PSS have normal coagulation profiles. Biochemical abnormalities associated with PSS include decreases in blood urea nitrogen, protein, albumin, glucose, and cholesterol; and increases in serum alanine aminotransferase and alkaline phosphatase. Increase in alkaline phosphatase is most likely from bone growth, since cholestasis is not usually a problem in animals with shunts. Cats with PSS usually have normal albumin concentrations. Urinalysis abnormalities include low urine specific gravity and ammonium biurate crystalluria. At magnifications of 400x or more, ammonium biurate crystals often have a spikey, thornapple or starfish shape and golden color. Because of increased urinary excretion of ammonia and uric acid, dogs and cats may also develop uroliths. Urate uroliths are often radiolucent and therefore may not be detectable on survey radiographs unless they are combined with struvite. Abnormal urine sediment suggestive of cystitis (hematuria, pyuria, and proteinuria) has been described in animals with PSS and may be associated with crystalluria or urolithiasis.

Hepatic histologic changes in animals with PSS include generalized congestion of central veins and sinusoids, lobular collapse, bile duct proliferation, hypoplasia of intrahepatic portal tributaries, proliferation of small vessels and lymphatics, diffuse fatty infiltration, hepatocellular atrophy, and cytoplasmic vacuolization. These pathology changes can also be seen in dogs with hepatic microvascular dysplasia that do not have single congneital shunts. Pathologic changes may be present in the central nervous system, especially in encephalopathic animals.

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Hepatic Encephalopathy

Hepatic encephalopathy has been recognized in animals with PSS, end-stage liver disease, and congenital urea cycle enzyme deficiencies. Clinical signs include depression, dementia, stupor, and coma. Muscle tremors, motor abnormalities, and focal and generalized seizures have also been reported. The etiology of hepatic encephalopathy is probably dependent on several factors, including circulating toxins, alterations in amino acid concentrations, and increased cerebral sensitivity to drugs and toxins. Toxins that have been implicated in hepatic encephalopathy include ammonia, mercaptans, short chain fatty acids, indoles, aromatic amino acids, and biogenic amines.

Precipitating factors of hepatic encephalopathy include diuretics, protein overload, hypokalemia, alkalosis, and transfusion of stored red cells, hypoxia, hypovolemia, gastrointestinal hemorrhage, infection, and constipation. Increased cerebral sensitivity to sedative, analgesic, and anesthetic agents may induce coma in animals with PSS, even when normal dosages are used. Protein overload and gastrointestinal hemorrhage provide substrates for bacterial production of ammonia, and constipation can increase retention and absorption of ammonia and other encephalopathic substances. Blood which has been stored for 24 hours contains 170 ug of ammonia/dL, and ammonia concentrations will continue to increase with prolonged storage.

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How To Diagnose Liver Shunt

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.

Diagnostic Imaging

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.

Differential Diagnoses

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.

All information on this page is courtesy of the University of Tennessee Veterinary Medicine Website