Portosystemic vascular anomalies in dogs and cats (Proceedings)

The normal liver receives arterial blood from the hepatic artery and venous blood from the portal vein. Regarding arterial blood flow, the celiac artery branches off of the aorta and the hepatic artery branches off of the celiac artery. The cranial and caudal mesenteric veins as well as the splenic vein drain into the portal vein. Blood from the hepatic artery and portal vein enters the portal triad, flows through the hepatic sinusoids to the central vein and eventually leaves the liver in the hepatic vein. The hepatic vein drains into the caudal vena cava. Portosystemic shunting is the result of portal blood entering systemic circulation without first passing through the liver and hepatic sinusoids.1,2

Etiology

Portosystemic shunts may be congenital or acquired. Congenital shunts are the result of abnormal communications between the portal and systemic venous circulation including single congenital portosystemic shunts (CPSS), arterioportal fistulas and primary hypoplasia of the portal vein (PHPV). Most animals have a single type of portosystemic shunt but rarely multiple anomalies are present.1,3

Congenital portosystemic shunts can be intra or extrahepatic. In dogs intrahepatic CPSS are usually single but on rare occasions two vessels may be involved. Intrahepatic CPSS originate from the left or right portal branch and terminate in the caudal vena cava directly or via the hepatic vein of dogs.2,4 In cats intrahepatic shunts may arise from smaller branches of the portal vein.2,4 Intrahepatic portosystemic shunts account for approximately 25% - 33% of portosystemic shunts in dogs and cats.1,3

Extrahepatic CPSS may originate from the splenic vein, right gastric vein or both and enter the abdominal or thoracic caudal vena cava via the azygous vein.2,4 Splenocaval shunts are the most common form of extrahepatic CPSS in dogs.2,4 Cats do not have shunts that arise from the right gastric vein but have two additional unique types of shunts.2 One originates prior to the bifurcation of the portal branches and enters the hepatic vein or caudal vena cava.2 The second originates from the cranial mesenteric vein or portal vein and enters the left renal vein or caudal vena cava.2 Single extrahepatic portosystemic shunts account for 66% to 75% of portosystemic shunts in dogs and cats.1,3

Arterioportal fistulas (a.k.a. hepatic arteriovenous malformations) are rare in dogs and cats. These are usually congenital and result from one or, more commonly, multiple communications between hepatic arterial and portal venous circulation.1,3

Primary hypoplasia of the portal vein (a.k.a. portal vein hypoplasia) is uncommon in dogs and extremely rare in cats. Portal hypoplasia can be intrahepatic, extrahepatic or both.2 Primary hypoplasia of the portal vein can occur alone or with CPSS and arterioportal fistulas.2 Dogs and cats with only PHPV present with less severe signs later in life than those with additional shunt types.3 Milder forms of PHPV were previously referred to as microvascular dysplasia.3 Severe forms of PHPV that result in ascites, have previously been referred to as portal vein hypoplasia with portal hypertension, idiopathic noncirrhotic portal hypertension, hepatoportal fibrosis, veno-occlusive disease.3 It is now believed that these are not unrelated disease processes but different manifestations of the same malformation.1,3

Acquired vascular anomalies occur when collateral vessels open secondary to increased intrahepatic pressure (cirrhosis, arterioportal fistulas, severe forms of portal vein hypoplasia) or portal system pressures (thrombosis, compression). They occur most commonly by the left kidney and the root of the mesentery. Acquired portosystemic shunts occur in a small percentage of extrahepatic CPSS that have been banded with the ameroid constrictor.3 Ascites secondary to increased hydrostatic pressures is common.1,3

Signalment

Intrahepatic CPSS are more common in large breed dogs with an increased prevalence in Irish Wolfhounds, Labrador Retrievers, Golden Retrievers, Australian Shepherds, Australian Cattle Dogs, German Shepherd Dogs, Doberman pinschers, Irish Setters, and Samoyeds.3,4 Extrahepatic CPSS are more common in small and toy breed dogs including Havanese, Yorkshire Terrier, miniature schnauzer, pug, Shih tzu, Bichon fries, Jack Russell Terrier and maltese.3,4 Extrahepatic CPSS are more common in cats with increased prevalence in DSH, Siamese, Himalayan, Persian, and Burmese.3,5 There is evidence of a genetic predisposition in Yorkshire terriers, Cairn terriers, maltese, Irish Wolfhounds, and Australian Cattle Dogs but the mode of inheritance is unknown.3,6,7,8 Cairn terriers and Yorkshire Terriers also have an increased incidence of PHPV.4 In dogs and cats with CPSS, congenital arterioportal fistulas and PHPV, signs are most commonly seen in young animals but occasionally older animals are diagnosed.3,4 In general, animals with less severe forms of PHPV present with milder signs at an older age than those with CPSS.3 Dogs with acquired portosystemic shunts may be young if they form secondary to congenital arterioportal fistulas or PHPV. Animals with acquired portosystemic shunts may be older if the collaterals have formed secondary to extensive fibrosis or cirrhosis.

Clinical Findings

Clinical findings of CPSS and PHPV are related to hepatic insufficiency (due to loss of hepatic trophic factors and nutrients) and hepatic encephalopathy. The most prominent clinical signs seen with portosystemic vascular anomalies are those associated with hepatic encephalopathy. These include lethargy, poor appetite, vomiting, polyuria, polydipsia, behavioral changes, pacing, ataxia, circling, altered mentation (stupor, coma), and seizures.3,4 Ptyalism is common in cats.3,4 Signs often worsen after meals. These dogs and cats may be small in size with a lower body condition score. Urinary tract signs secondary to the presence of ammonium urate calculi include dysuria, pollakiuria and hematuria.3,4 Cats may also have copper colored irises and blindness (intermittent or persistent).3,4 There is a high incidence of cryptorchidism in male dogs and cats with CPSS.3 Abdominal distention and ascites may be seen with portal hypertension secondary to arterioportal fistulas and in severe forms of PHPV.3,4 With CPSS, a low pressure shunt has been established so portal hypertension and ascites do not occur. A bruit can be ausculted over the liver of dogs and cats with arterioportal fistulas.3,4

The severity of signs depends on the size of the shunt (bigger is bad) and type of shunt.3 For example, a splenocaval shunt does not contain blood from the gi tract and less portal blood is diverted so signs may be slower in onset and milder than with an intrahepatic shunt in which a large volume of portal blood is diverted. As discussed above, less severe forms of PHPV may present with more mild signs than CPSS.3

Laboratory Findings

There may be no laboratory abnormalities. A microcytic normocytic normochromic anemia may be seen with CPSS and is believed to be due to iron deficiency.9 Microcytosis is not seen with PHPV. Abnormalities in erythrocyte shape and target cells may be observed and due to cholesterol abnormalities.3 Decreases in albumin, cholesterol, blood urea nitrogen, and glucose are relatively common in animals with CPSS.3 Liver enzymes may be normal or mildly increased.3 Urine is often isosthenuric or hyposthenuric and increased protein as well as ammonium urate crystals may be seen.4 Clotting function (PT, aPPT, clotting factors, platelets) is abnormal in dogs with CPSS.10,11 Spontaneous hemorrhage is not usually a problem with these animals but intra-operative hemorrhage can be severe.

Serum bile acids have historically been the most common test utilized to screen for portosystemic shunting. It is important to obtain both fasting and post-prandial samples. Spot urine bile acids can also be performed with a similar sensitivity and specificity to serum bile acids for diagnosing liver disease in dogs.12 The advantage of urine testing is that no venipuncture is required. Resting blood ammonia is a fairly sensitive test for hepatic disease in animals displaying hepatic encephalopathy but an ammonia challenge (oral, rectal) may be required for asymptomatic animals or with a prolonged fast. Ammonia tolerance testing should never be performed on animals with hepatic encephalopathy as it may worsen their signs. Neither bile acids or ammonia levels can differentiate between types of liver disease. There is evidence that fasting blood ammonia is a more sensitive and specific indicator of portosystemic shunting than fasting bile acids but obtaining a post-prandial bile acid increases the sensitivity of bile acids dramatically for diagnosing portosystemic vascular anomalies.13,14

Diagnostic Imaging

Radiography is utilized to evaluate liver size and may reveal evidence of fluid. The majority of animals with CPSS have small livers and some have enlarged kidneys.3,4 Dogs with primary hypoplasia of the portal vein typically have livers and kidneys of normal size.3,4 Hepatomegaly may be noted with arterioportal fistulas.4

Ultrasonography has a high sensitivity and specificity for detecting CPSS and acquired PSS in dogs and cats.15,16,17 With acquired portosystemic collaterals in the dog, the liver may be small with increased echogenicity depending on the amount of fibrosis present in the liver. Collateral vessels can sometimes be visualized by the left kidney (left gonadal vein) and abdominal fluid may be seen.2,3 Arterioportal fistulas can easily be visualized with ultrasound.2,3 The urinary tract can be evaluated for urolithiasis.

Although most CPSS are diagnosed with ultrasound, some may be missed. In cases in which a CPSS is not found on ultrasound but strongly suspected, additional imaging modalities such as iodinated contrast studies, computed tomography, nuclear scintigraphy, or magnetic resonance may be utilized.

Portovenography was commonly used to diagnose portosystemic shunts until replaced by other faster, less-invasive means. Iodinated contrast can be administered pre-operatively using radiography, ultrasonography or fluoroscopy. Intra-operative portograms can also be performed as well to identify CPSS. Contrast can be injected into the spleen, splenic vein, celiac artery, cranial mesenteric artery, or jejunal vein.3,4 Retrograde portograms utilizing venous occlusion with balloon catheters can also be performed with contrast administered into the azygous vein and caudal vena cava.4

Computed tomography utilizing angiography has been successful in identifying CPSS and acquired shunts in dogs.18,19 When performed, both venous and arterial phases are recommended to better evaluate vessels of interest.4

Nuclear scintigraphy utilizing 99 mTechnetium can be used to document portosystemic shunting. The radioisotope is given per rectum or transplenic (via ultrasound). Transplenic administration has been shown to have the same sensitivity (100%) to rectal scintigraphy, requires smaller doses of radioisotope (safer) and better defines shunts in dogs.20,21 If a CPSS is present, there will be a decrease in uptake in the liver. With PHPV, there may or may not be normal uptake by the liver.3

Magnetic resonance imaging has been used for the diagnosis of portosystemic shunts. Magnetic resonance imaging utilizing contrast-enhanced magnetic resonance angiography was investigated in 10 dogs suspected of having CPSS.22 A single shunt was correctly identified in all dogs utilizing this technique and confirmed at surgery. Magnetic resonance may prove useful for diagnosis of shunt types. This study shows a higher sensitivity than a previous study evaluating magnetic resonance angiography in 23 dogs with different shunt types in which a sensitivity of 79% was reported.23 In this study gadolinium contrast was not used which may have affected the results.

Liver Histopathology

While CPSS and arterioportal fistulas can be easily identified with ultrasonography, primary hypoplasia of the portal vein requires a liver biopsy for diagnosis. Histologic findings are not specific for PHPV and include portal vein hypoplasia and hepatic arteriolar hypertrophy and proliferation.2,3 Bile duct proliferation, minimal fibrosis, sinusoidal dilatation, hepatocellular atrophy and lipogranulomas are seen less frequently.2,3 Arterioportal fistulas and CPSS can produce similar histologic changes which is why it is important to utilize other diagnostic tests (ultrasonography, nuclear scintigraphy) to eliminate these disorders. Arterioportal fistulas typically affect a single lobe but histologic abnormalities are found throughout the liver.2,3

Treatment

Surgery is the treatment of choice for CPSS and arterioportal fistulas.24 In a study of 136 dogs with a single CPSS, there was a significant difference between survival times in dogs that were managed medically vs. surgically.24 A good long term outcome can be expected independent of age.24,25 Dogs and cats with CPSS will continue to lose function of the liver so surgical attenuation of the shunt is recommended to return blood flow and function to the liver. The goal is complete closure of the shunt but this sometimes requires multiple surgeries or is not possible.

For extrahepatic shunts, ameroid constrictors and cellophane bands are most commonly used to obtain a more gradual closure (vs. ligation techniques) and avoid portal hypertension more common with ligature techniques.3,4 Ameroid constrictors accomplish this through swelling of the constrictor, fibrosis and thrombus formation. Cellophane bands elicit an acute and chronic inflammatory response responsible for its effects. Cellophane is believed to cause a slower, more complete closure of the shunt than ameroid constrictors.

With both devices incomplete closure and portal hypertension are possible but uncommon. Intrahepatic CPSS are more difficult to locate and often larger so closure may be more difficult. For intrahepatic CPSS, silk ligature is most common but occasionally ameroid constrictors are used.3,4 Vascular coil techniques have also been described with decreased long term mortality over ligation and gradual occlusion devices.3,4,26

For arterioportal fistulas the affected liver lobe is often removed to prevent additional damage leading to fibrosis and portal hypertension. Glue embolization has also been described for arteriovenous fistulas.3

Post-operatively, animals are evaluated for evidence of portal hypertension and neurologic signs. Portal hypertension develops within hours of surgery and may result in abdominal distention, abdominal pain, vomiting, hemorrhagic diarrhea, endotoxic shock, and death.3,4 If this occurs, return to surgery for removal or loosening of the ligature is recommended. Seizures occur in a small percent of animals post-operatively requiring short term and, in some cases, long term management.3,27,28 Incomplete occlusion does occur and can be documented with persistence or return of signs, bile acids test and diagnostic imaging.3,4 Medical management as described below is continued post-operatively but may not be required life long.

Medical management is recommended in animals to stabilize surgical candidates, for dogs with primary hypoplasia of the portal vein and when surgery is declined for whatever reason. There is evidence that dogs presenting with clinical signs when older live longer with medical management than dogs diagnosed at a younger age.29 Medical management primarily consists of controlling signs of hepatic encephalopathy. This includes correcting dehydration, correcting electrolyte and acid-base abnormalities, controlling intestinal ammonia production and absorption, and controlling intestinal hemorrhage. Some avoid the use of lactated ringers due to the need to convert the lactate to bicarbonate in a poorly functional liver. Hypokalemia, metabolic alkalosis and metabolic acidosis can occur in these animals. Potassium can be supplemented parenterally in intravenous fluids or orally as potassium gluconate. Metabolic acidosis is corrected with intravenous fluids. Restricting dietary protein to 18% to 22% in the dog and 30% to 35% in the cat is recommended to reduce protein substrate.3 Lactulose is a disaccharide given orally with hepatic encephalopathy to acidify the colon and trap ammonium ions so they can not be absorbed through the intestinal tract. Lactulose also increases intestinal transit time which may be beneficial. Oral antibiotics (amoxicillin, neomycin) are recommended to decrease the ammonia production in the intestinal tract. Intestinal bleeding is common with liver disease and may precipitate hepatic encephalopathy which is why antacids ± protectants are used with hepatic encephalopathy. Antacids such as H2 antagonists and proton inhibitors as well as sucralfate are commonly given when gastric ulceration is suspected. Antacids are used by some chronically and there is evidence that it may improve long term survival in dogs with intrahepatic shunts treated with coil embolization.3

Seizures may occur pre-operatively or post-operatively in these animals. Some recommend avoiding benzodiazepines because increased benzodiazepines are thought to be a contributor to hepatic encephalopathy but this is controversial. Phenobarbital, propofol and potassium bromide have all been used successfully.3 Mannitol is also advocated when cerebral edema is suspected.

Ascites occurs with arterioportal fistulas and PHPV but is rare with CPSS. If due to portal hypertension then abdominocentesis, sodium restriction and diuretics can be used. The aldosterone antagonist, spirinolactone, is recommended due to its potassium sparing effects but a more potent loop diuretic, like furosemide, may have to be added to increase effect.

Antioxidants (vitamin E, silymarin, s-adenyl methionine, ursodeoxycholic acid) are now recommended in the absence of surgical correction and resolution because of evidence of oxidative damage to hepatocytes that is believed to occur with portosystemic shunts.3

Prognosis

Extrahepatic congenital portosystemic shunts that are treated surgically carry a good prognosis with mortality rates of 2 to 20% reported.3,27,28,30 Mortality rates of 0% to 28% for intrahepatic CPSS have also been reported.3 Complication and mortality rates tend to be higher with silk ligature as opposed to gradual occlusion devices. Long term mortality rates are higher with intrahepatic CPSS (up to 63%) when using ligature and gradual occlusion devices but dramatically improved with coil techniques (< 30%).3 It appears that post-operative complications are more common in cats.31,32 For most animals hepatic function, bile acids and blood ammonia return to normal and medical management is discontinued after several months.27,28 Some animals do well long term with just medical management and some with incomplete closure have indefinite resolution of their signs.

For arterioportal fistulas, long term survival rates of 38% to 70% have been reported. Survival rates were higher for glue embolization but some required multiple procedures.33 75% of dogs required long term medical management.3,33

References

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