Portosystemic Vascular Malformations in Small Animals
The most common circulatory anomalies of the liver in dogs are microvascular dysplasia (MVD) and portosystemic vascular anomalies (PSVAs, also referred to as portosystemic shunts or portocaval shunts). Cats also are affected with PSVAs but less commonly than dogs. MVD and PSVAs are related polygenic disorders affecting small-breed dogs. PSVAs may be extrahepatic (more common in small-breed dogs) or intrahepatic (more common in large-breed dogs). MVD has not been characterized in large-breed dogs or in cats.
MVD is far more common than PSVAs in affected kindreds of small “terrier” type dogs. A diagnosis of MVD denotes abnormal development of the fine (tertiary) branches of the intrahepatic portal veins and is associated with lobular atrophy and a compensatory increase in arterial perfusion (hepatic arterial buffer response), which manifests as coiling of hepatic arteriole branches and development of arterial twigs. The arteriolar response results in increased numbers of thick-walled arterial cross-sections in portal tracts and orphaned random arterioles within the hepatic parenchyma. Other additional MVD microanatomic abnormalities variably include large numbers of binucleate hepatocytes (especially adjacent to the portal tract), merging of hepatic venules with portal tracts, abnormal sinusoidal organization and expansion, thickening of the throttling muscle of the hepatic venule in dogs, and formation of random foci of lipogranulomas. A diagnosis of "portal hypoplasia" cannot be made on the basis of a liver biopsy, because any reduction in hepatic portal venous perfusion causes identical microanatomic changes. Rather, this histologic pattern is better termed "portal hypoperfusion." Dogs with MVD have high TSBA concentrations but do not demonstrate clinical illness or other laboratory abnormalities found in dogs with PSVAs. They do not demonstrate HE, do not develop ammonium biurate crystalluria, and typically have a normal protein C activity. A normal lifespan should be expected in dogs with MVD. This diagnosis does not warrant feeding a special diet or liver-specific medications (eg, lactulose, SAMe, milk thistle). However, because dogs with MVD may have trouble metabolizing drugs that require rapid hepatic delivery and extraction, care is necessary when prescribing certain medications. Because MVD is genetically linked with PSVAs, TSBAs should be measured in all young puppies of predisposed breeds for future health care considerations; discovery of high TSBA concentrations during an illness may lead to inappropriate, invasive, and expensive diagnostic testing. Selection of breeding stock in affected kindreds should target dogs with normal TSBA concentrations. However, because the trait is polygenic, breeding dogs with normal TSBAs may result in puppies affected with MVD and PSVAs. Once high TSBA concentrations are detected in young (<6 mo) small terrier-type breeds lacking clinical signs of PSVA, repeated bile acid measurements are not warranted; TSBA concentrations will remain variably increased for the animal's life. Knowing that a dog has high bile acids likely caused by MVD will define utility of the TSBA test for future health care assessments.
Definitive diagnosis of MVD is possible only by consideration of the liver biopsy and vascular imaging studies. Liver biopsy demonstrates lesions identical to those of PSVAs. The severity of MVD lesions varies among liver lobes, necessitating collection of samples from three different lobes for definitive characterization. Liver biopsy by the tru-cut method is strongly discouraged for diagnosis of portal hypoperfusion (PSVAs, MVD) because this diagnosis is based on examination of multiple acinar units to detect lobular atrophy, portal triad arteriolarization, and other characteristic features. Needle biopsies restrict the number of acinar units sampled. However, steps to pursue a definitive diagnosis are not recommended in most dogs with suspected MVD (no clinical signs, no hematologic or biochemical markers typical of PSVA). Instead, it is prudent to consider that a dog at risk of hepatic vascular malformations has MVD as the underlying cause of high TSBAs unless it exhibits clinical (HE) or clinicopathologic features (RBC microcytosis, low BUN, creatinine, and cholesterol concentrations, low protein C activity) associated with PSVAs.
A portosystemic vascular anomaly (PSVA) is a grossly apparent aberrant connection between the extrahepatic portal vasculature and the systemic circulation (connecting a branch of the portal vein to the vena cava or azygous vein) that diverts blood to the systemic circulation, bypassing the liver. Reduced portal flow to the liver causes hepatic lobular atrophy. Because the portal circulation transports microorganisms, toxins, nutrients, and other materials from the intestines to the liver, detoured blood is not cleansed or processed before circulation to the brain and systemic circulation. Consequently, neurotoxic substances that can provoke encephalopathic effects can be circulated directly to the brain, causing HE. Other noxious products and infectious agents inefficiently removed by the liver in animals with PSVAs result in a more severe clinical challenge to what should be mild health concerns (eg, infectious diarrhea, infected wounds, dermatitis, tick bites, other).
Congenital PSVAs are seen primarily in purebred dogs with extrahepatic PSVAs, predominantly in small purebred terrier-type dogs (eg, Yorkshire Terriers, Maltese, Shih Tzu, Havanese, Papillon, Miniature Schnauzers, Pugs, Cairn Terriers, Norfolk Terriers, Tibetan Spaniels, and others). Intrahepatic PSVAs predominate in large-breed dogs, including (but not exclusively) Irish Wolfhounds, Old English Sheepdogs, Labrador Retrievers, and Golden Retrievers. Extrahepatic PSVAs usually arise from the portal vein, left gastric vein, or splenic vein and connect to the caudal vena cava (most common), the azygous vein, or rarely another systemic vessel. An intrahepatic PSVA represents the retention of an embryonic vessel that carries fetal blood from the placenta to the heart, through the middle of the liver but bypassing the hepatic circulation (ductus venosus). This malformation is only occassionally seen in small-breed dogs and cats.
Congenital PSVAs in cats are seen more frequently in mixed breeds, but the prevalence may be increased in purebred Himalayans and Persians. However, the higher prevalence of polycystic liver disease and associated portal hypertension and acquired portosystemic shunts in these breeds complicates diagnosis of PSVAs. In cats, extrahepatic PSVAs involving the left gastric vein are most common.
Animals with PSVAs are often smaller than littermates, fail to thrive, and can have other congenital abnormalities (eg, cryptorchidism in dogs and cats, heart murmurs in cats). Clinical signs are highly variable, and 10%–20% of affected animals may be asymptomatic. The presence of clinical signs depends on the severity of portosystemic shunting. In symptomatic animals, clinical signs are usually evident by 6 mo of age in cats and before 1 yr in dogs. Clinical signs include nausea, ptyalism (especially cats), vomiting, diarrhea, pica, intermittent anorexia, PU/PD, amaurosis (unexplained blindness), excessive vocalization, hallucinations, apparent neck or spinal pain, hematuria, pollakiuria, stranguria, urethral obstruction associated with formation of ammonia biurate uroliths, and additional neurobehavioral signs reflecting HE. Signs referable to urinary tract calculi may be the only presenting complaint. Cats with PSVAs have a unique, homogenous, copper-colored iris that appears to be genetically linked with the disorder; the exception is blue-eyed cats. However, because a copper-colored iris is typical for Persians and Russian blue cats that do not have a PSVA, it is important to consider this observation in perspective of clinical signs and finding high TSBA concentrations.
Laboratory abnormalities may include microcytic RBCs (low MCV), mild nonregenerative anemia, poikilocytosis (cats), target cells (dogs), mild hypoproteinemia and hypoalbuminemia, hypoglycemia (rare, primarily young toy-breed dogs), low BUN and creatinine, hypocholesterolemia, normal to mildly increased liver enzyme activity (ALT, AST, and ALP), normal bilirubin, dilute urine (hyposthenuria or isothenuria), and ammonia biurate crystalluria. Fasting and postprandial TSBA concentrations are usually markedly increased; however, measurement of TSBAs or ammonia after a prolonged fast may yield normal values. Postprandial TSBAs and ammonia (after NH4Cl administration) are markedly abnormal. Routine coagulation assessments are usually within normal limits, but protein C activity is usually <70%. The protein C test is valid for use in dogs. This test reflects the severity of shunting; the lower the value, seemingly the more severe the shunt. In asymptomatic PSVA dogs with a protein C >70%, surgical ligation has been very successful. Those with a protein C <70% may not tolerate complete shunt attenuation.
Abdominal radiographs reveal microhepatica and “plump” kidneys. Ammonium biurate uroliths are radiolucent and thus not detected with radiographic imaging. Ultrasonography can noninvasively identify a PSVA if done by an experienced operator using color-flow Doppler in a fasted, cooperative patient. However, extrahepatic PSVAs can be missed on ultrasonographic imaging and even falsely identified in animals with MVD. Although discovery of intrahepatic PSVAs is relatively easy using ultrasonography, identification of extrahepatic PSVAs can be challenging because bowel gas and animal cooperation may limit imaging in critical regions. Ultrasonographic examination can identify radiolucent uroliths in the renal pelvis or urinary bladder. Colorectal portal scintigraphy or splenoportal scintigraphy, available in specialty clinics or teaching hospitals, can clearly determine the presence of portosystemic shunting. However, scintigraphy is unable to identify the anatomic location of involved shunting vasculature with certainty. Splenoportal scintigraphy requires percutaneous injection of isotope into the spleen, is considered an invasive test, and does not provide better resolution, specificity, or sensitivity over routine colorectal scintigraphy to determine the presence of portosystemic shunting or definitively identify the involved vasculature. Contrast radiographic portography, the traditional gold standard test to confirm PSVAs, requires catheterization of a branch of the portal vein and injection of radiodense iodinated contrast to illustrate portal vascular anatomy. Noninvasive multisector CT has replaced simple contrast radiographic portography, providing better anatomic mapping of portal vasculature. This imaging modality requires short-term anesthesia with contrast injected into a peripheral vessel and permits 3-dimensional anatomic reconstruction of the splanchnic circulation, vascular anomaly, and adjacent viscera. A liver biopsy is always indicated in PSVA patients during surgical shunt ligation, or if multiple shunts are noted, to determine primary underlying disorders or acquired liver diseases that may coexist and require specific intervention.
Although the treatment of choice for symptomatic PSVAs is surgical attenuation or ligation, not all dogs can tolerate shunt attenuation, and a subset of dogs (asymptomatic, minimally symptomatic) survive with good quality of life with medical management only. Surgical management of PSVAs may include direct shunt ligation at surgery to the animal's tolerance (judged by measurements of portal pressure, vital signs, local visceral response) or application of an ameroid ring (inner lining gradually expands over a few days to slowly occlude the shunting vasculature). The most common postsurgical complication of PSVA attenuation is short-term benign abdominal effusion that typically resolves within a few days. The most serious postsurgical complication is acute portal hypertension, characterized by development of abdominal effusion, bloody diarrhea, abdominal pain, ileus, endotoxic shock, and cardiovascular collapse. This complication requires immediate removal of the shunt ligature. Other complications include seizures (rare) and formation of blood clots within the portal vein. Unfortunately, in some dogs, acquired portosystemic shunts silently develop at varying intervals after surgery for a PSVA. The ligation site also may be circumvented by formation of a medusa of vessels around the ligated site or recanalization of the PSVA that reestablishes portosystemic shunting several years after initial surgery. The greatest risk of insidious postoperative complications is associated with ameroid constrictors, because the extent of vessel occlusion remains ill defined unless repeat imaging studies are undertaken. In rare cases, ameroids have eroded through the shunting vasculature, causing acute collapse, hemoabdomen, and death that may occur months after their application. Excellent outcomes have been observed with careful intraoperative graded ligation of extrahepatic PSVAs (observing portal pressure and visceral response, systemic blood pressure, and heart rate) as well as with application of ameroid rings. Surgical intervention for intrahepatic shunts is more complicated and less successful. Coil embolization of intrahepatic shunting vessels by interventional radiographic technique is an alternative procedure but can be associated with adverse effects (portal hypertension, portal or vena caval clot formation) and can be prohibitively expensive; in addition, more than a single intervention may be needed to substantially reduce portosystemic shunting. Survival analyses of >450 dogs with PSVAs managed with surgical versus longterm medical management estimated a median survival time of 11 yr for dogs with extrahepatic PSVAs treated surgically, with no significant difference for dogs treated solely by medical management. However, this result is biased, because owners of the population of dogs optimally responding to medical management were more inclined to decline surgical intervention. Median survival time in dogs with intrahepatic PSVAs (n=34) treated surgically was estimated as 5 yr and was not significantly different from a larger population of dogs treated by medical management alone. In a report of 96 dogs with intrahepatic shunts treated by one or more coil embolization procedures, the estimated median survival time was 6 yr.
Male dogs with repeated bouts of ammonium biurate urolithiasis requiring medical or surgical resolution (those undergoing surgical correction of PSVAs in which the shunt could not be fully attenuated as in those on medical management) should have a permanent prescrotal urethrostomy created to allow passage of small calculi. This will avert subsequent development of an obstructive uropathy.
Overall, prognosis after surgical ligation of a single extrahepatic PSVA is usually good. Prognosis is less favorable in dogs with multiple acquired shunts secondary to severe intrahepatic portal vein atresia and in those with intrahepatic shunts. Surgery is less successful in cats than in dogs, with cats more likely to develop multiple acquired portosystemic shunts after PSVA ligation. Staging surgeries to gradually attenuate PSVAs in dogs or cats has not improved outcomes.
Dogs with relatively asymptomatic PSVAs can often be managed with special diets indicated for hepatic insufficiency. Lifelong dietary support is required, but good health and normal lifespan can be achieved. However, dogs managed medically are always at risk of more severe effects from health issues involving other organ systems, infections, or GI signs. The best protein sources for dogs are soy and dairy quality protein with a protein intake starting at 2.5 g/kg/day. Red meat, fish, and organ meats must be avoided. Additional dairy quality protein is usually easily tolerated and can be used to increase protein, phosphate, and fermentable carbohydrate intake. Treats of raw vegetables (eg, broccoli, carrots), cheese, probiotic yogurt, popcorn, modest numbers of dog biscuits, animal crackers, and limited supervised activity with rawhide bones can be offered without adverse consequences. If rawhide chews result in oral hemorrhage, they should be avoided because swallowed blood can provoke encephalopathic signs. Variation in the need for daily lactulose and metronidazole administration (see Hepatic Encephalopathy in Small Animals) is broad, such that individualization of treatments is advised. Medically managed dogs remain at risk of developing HE. Owners should be educated to recognize early signs of HE and complicating health issues, how to administer cleansing and retention enemas, and how to administer subcutaneous fluids. This training allows early intervention of HE episodes and reduces the number of emergency veterinary visits.