CONGENITAL PORTOSYSTEMIC SHUNT
Portosystemic shunts (PSSs) are vascular communications between the portal and systemic venous systems that allow portal blood to reach the systemic circulation without first passing through the liver. Signs of HE dominate the clinical picture because of inadequate hepatic clearance of enterically derived toxins such as ammonia, mercaptans, short-chain fatty acids, gamma-aminobutyric acid, and endogenous benzodiazepines. Decreased hepatic blood flow and lack of hepatotropic factors such as insulin, glucagon, and nutrients result in hepatic atrophy. Urate urolithiasis, an important complication of PSSs, occurs because of increased urinary excretion of ammonia and uric acid. Renal, cystic, or urethral calculi may occur. Urolithiasis may be a complication in as many as 50 per cent of animals with congenital PSS.
PSSs in dogs and cats can be either congenital or acquired. The congenital form is most commonly recognized. Congenital PSSs are anomalous embryonal vessels that usually occur as single shunts (either intrahepatic or extrahepatic) and are not associated with portal hypertension. The genetic basis for congenital PSS is unknown, although affected lines have been recognized in Miniature
Schnauzers, Irish Wolfhounds, Old English Sheepdogs, and Cairn
Terriers. An autosomal polygenic mechanism is suspected in Irish wolfhounds. Acquired PSSs, which form in response to portal hypertension, are typically multiple extrahepatic shunts that connect the portal system and the caudal vena cava.
Single intrahepatic PSSs provide a communication between the portal vein and the caudal vena cava. Intrahepatic shunts can be classified as left, central, or right divisional . The morphology of the left divisional shunt (via the left hepatic vein) is consistent with failure of the fetal ductus venosus to close. The ductus venosus, a fetal vessel that allows oxygenated blood to be shunted from the umbilical vein directly into the caudal vena cava, normally closes within the first few days after birth. The underlying mechanisms associated with failure of the ductus to close are unknown. The pathogenesis of intrahepatic PSSs that occur in the right medial (central divisional) or right lateral (right divisional) liver lobes is unknown. Single intrahepatic PSSs are most common in large breed dogs.
Single extrahepatic PSSs usually connect the portal vein or one of its tributaries (often the left gastric or splenic vein) with the caudal vena cava cranial to the phrenicoabdominal veins. Less frequently, the anomalous vessel enters the azygos vein or other systemic vessel. Single extrahepatic PSSs represent a developmental abnormality of the vitelline system. Single extrahepatic PSSs are most common in cats and small breed dogs.
In dogs and cats with congenital PSS, the liver is grossly small and often mottled in appearance. Liver biopsy most consistently reveals hepatocyte atrophy with small or absent portal veins and arteriolar hyperplasia, although biopsy abnormalities may be subtle. Additional features may include sinusoidal congestion, periportal vacuolization, biliary hyperplasia, lipogranulomas, and increased periportal connective tissue. Biopsy findings are indistinguishable from those in hepatic microvascular dysplasia. Microscopic abnormalities of the central nervous system consist of polyinicrocavitation of the brain stem and cerebellum and astrocytosis of the cerebral cortex.
Congenital PSSs occur more commonly in purebred than in mixed breed dogs. Breeds at increased risk include Miniature
Schnauzers, Yorkshire Terriers, Irish Wolfhounds, Cairn Terriers, Maltese, Australian
Cattle Dogs, Golden Retrievers, Old English Sheepdogs, and Labrador
Retrievers. In contrast, mixed breed cats are affected more commonly than purebred Cats. Of the affected purebreds, Persian and Himalayan cats appear to be at increased risk.
A slight predilection for male cats and female dogs has been suggested and affected male dogs and cats are commonly cryptorchid. Age is an important diagnostic clue because most animals develop signs by 6 months of age. A congenital PSS should still be a diagnostic consideration in middle-aged or older dogs, because signs may be subtle and some dogs with congenital PISS go undiagnosed until as late as 10 years of age. This is especially true for dogs with urate urolithiasis who may not have an obvious history of HE.
Clinical signs of congenital PSS are referable to the central nervous system, gastrointestinal system, or urinary tract. Signs of HE usually predominate. The most consistent signs of HE are often subtle, such as anorexia, depression, and lethargy. Other common findings indicative of diffuse cerebral disease include episodic weakness, ataxia, head pressing, disorientation, circling, pacing, behavioral changes, amaurotic blindness, seizures, and coma. Bizarre aggressive behavior, seizures, and blindness appear more likely in cats. Hypersalivation is also a prominent sign in cats but also occurs in dogs. Clinical signs of HE tend to wax and wane and are often interspersed with normal periods, reflecting the variable production and absorption of enteric products that are neurotoxic. Signs of HE may be exacerbated by a protein-rich meal; gastrointestinal bleeding associated with parasites, ulcers, or drug therapy; or administration of methionine-containing urinary acidifiers or lipotropic agents. Clinical improvement of HE after fluid therapy is common and most likely attributed to correction of dehydration and promotion of urinary excretion of ammonia and other toxins. Improvement with broad-spectrum antibiotic therapy reflects the effect of antibiotics on the toxin-producing
Gastrointestinal signs of intermittent anorexia, vomiting, and diarrhea are common
non-specific features of hepatic dysfunction and are not necessarily accompanied by overt signs of HE. Many affected animals have a history of stunted growth, failure to gain weight compared with unaffected littermates, or weight loss.
Polydipsia and polyuria are common in dogs but not in cats. Some dogs are able to concentrate their urine after water deprivation, suggesting a primary psychogenic polydipsia. Other dogs have partial or incomplete urine-concentrating ability, consistent with medullary washout secondary to polyuria and polydipsia or a primary renal concentrating defect. Increased free cortisol levels have been documented in dogs with PSS and HE, suggesting an altered hypothalamic-pituitary-adrenal axis. If urolithiasis is a complicating feature, pollakiuria, dysuria, and hematuria may occur. Some animals are presented primarily for evaluation of urolithiasis without obvious HE or gastrointestinal signs.
A history of prolonged recovery after general anesthesia or excessive sedation after treatment with tranquilizers, anticonvulsants, or organophosphates can be attributed to impaired hepatic metabolism of these substances. Other less consistent clinical findings include polyphagia, pica and foreign body ingestion, intermittent fever, recurrent upper respiratory signs in cats, and intense pruritus in dogs.
Physical examination may be unremarkable except for -small body stature or weight loss. The neurologic examination is normal, or if overt signs of HE are present, neurologic findings are consistent with diffuse cerebral disease. Many affected cats have golden or copper-colored irises. Heart murmurs have also been auscultated in some affected cats. Ascites and edema are rare findings unless a congenital PSS is complicated by hypoalbuminemia (albumin less than 1.0 g/dL). Ascites is more likely with acquired hepatic disorders that cause portal hypertension and multiple acquired PSS.
In young animals with consistent clinical features of a congenital PSS but without a demonstrable shunt on portography or transcolonic portal scintigraphy, hepatic microvascular dysplasia should be considered (see later). Rarely, a congenital urea cycle enzyme deficiency has been associated with hyperammonemia and HE in young animals (see later section on urea cycle enzyme deficiency). Other disorders that are associated with central nervous system signs in young dogs and cats that must be considered in the differential diagnosis include infectious diseases (canine distemper, FIP, toxoplasmosis, and feline leukemia virus [FeLV]- or feline immunodeficiency virus [FIV]-related diseases), toxicities, hydrocephalus, idiopathic epilepsy, and metabolic disorders such as hypoglycemia and thiamine deficiency.
Routine hematologic and biochemical findings are often unremarkable in dogs and cats with congenital PSS. Hematologic findings include erythrocytic microcytosis, target cells, poikilocytosis (especially in cats), and mild nonregenerative anemia. These red blood cell changes can be subtle but important diagnostic clues in an otherwise normal CBC. The cause of microcytosis is not known; however, decreased serum iron concentration, normal to increased ferritin concentration, and accumulation of stainable iron in the liver suggest that microcytosis is associated with abnormal iron metabolism (impaired iron transport or sequestration of iron) rather than absolute iron deficiency. Decreased availability of iron for hemoglobin synthesis appears to occur despite adequate tissue iron stores.
Isosthenuria or hyposthenuria is frequently detected, by urinalysis of dogs that are polyuric and polydipsic. Ammonium biurate crystals are a common finding on urine sediment examination and are an important clue to underlying liver disease in dogs and cats. If urolithiasis is a complication of congenital PSS, additional findings may include hematuria, proteinuria, and pyuria. Coagulation tests in dogs may show increased partial thromboplastin times and hypofibrinogenemia, but clinical evidence of a bleeding problem is rare.
Hepatocellular dysfunction is suggested by hypoproteinemia, hypoalbuminemia, hypoglobulinemia, hypoglycemia, decreased BUN, and hypocholesterolemia. Hypoalbuminemia and hypoglobulinemia are common findings in dogs with congenital PSS but less so in affected cats. Hypoglycemia, especially after a prolonged fast, is most likely in affected toy breeds of dogs such as Yorkshire
Terriers. Potential mechanisms for hypoglycemia include decreased hepatic glycogen stores, decreased insulin catabolism, and endotoxemia. The total serum bilirubin concentration is typically normal. The serum liver enzyme activity (ALP, ALT, and AST) is normal to mildly (two or three times) increased consistent with a lesion of hepatic atrophy and minimal hepatocellular injury or intrahepatic cholestasis.
Serum bile acid concentrations should be determined to document hepatic dysfunction in dogs and cats suspected to have congenital PSSs. The fasting SBA is often increased but can be normal, because during prolonged fasting, the liver may eventually clear the bile acids from the systemic circulation. Postprandial SBA is consistently abnormal and is a good screening test for animals suspected to have PSSs. Postprandial SBA concentrations typically exceed 100 umol/L. If postprandial SBA concentrations are consistently in the normal range, a diagnosis of congenital PSS is unlikely. Hyperammonemia is a common finding in dogs and cats with PSSs, although A fasting blood ammonia concentration may be normal. The ammonia tolerance test is consistently abnormal and is equal in sensitivity to postprandial SBA in detecting hepatic dysfunction associated with congenital PSS. Blood ammonia is not a suitable screening test for congenital PSS in young Irish
Wolfhounds because a transient metabolic hyperammonemia unassociated with liver disease occurs in this breed. Prolonged BSP dye retention is a common but inconsistent finding in animals with congenital PSSs and its use has largely been replaced by measurement of SBA concentrations.
Survey abdominal radiographs are often obtained for animals with suspected PSS to evaluate for microhepatica or presence of urinary calculi and to investigate other causes of gastrointestinal or urinary tract signs. Microhepatica, a common finding on survey abdominal radiographs of dogs with congenital PSS, is a less consistent finding in cats. In many animals, the size of the liver is difficult to evaluate because of the lack of intra-abdominal fat. Cranial displacement of the stomach is often an indirect indication of a small liver. Mild renomegaly is occasionally noted in dogs and cats with congenital PSS. Ammonium urate calculi are not usually visible on survey radiographs unless they also contain substantial amounts of magnesium and phosphate.
Additional radiographic imaging techniques, such as ultrasonography, contrast portography, or transcolonic portal scintigraphy, can provide important information about the presence, location, and type-of PSS. Use of these techniques may be limited by equipment availability or operator experience. Although ultrasonography and transcolonic portal scintigraphy have the advantage of being noninvasive, contrast portography is still considered the "gold standard" for the anatomic evaluation of the portal vasculature. The advantages and disadvantages of each of the imaging techniques used for evaluation of PSS are discussed in more detail in the following. The experienced surgeon may elect to bypass further diagnostic imaging and go directly to an abdominal exploratory examination for diagnosis and treatment of a suspected PSS, especially in small dogs or cats (who are most likely to have an easily recognized extrahepatic shunt) with typical historical, clinical, and laboratory features.
Ultrasonography is a useful noninvasive method for evaluating animals with a suspected congenital PSS. Intrahepatic PSSs are more reliably detected with this procedure than are extrahepatic PSSs. It is a rapid technique that can be performed without sedation or anesthesia but is highly dependent on the experience of the operator. Ultrasonographically, the liver usually appears small, there is a consistent decrease in the number and size of intrahepatic veins, and the shunting vessel may be identified. The kidneys and bladder should also be routinely scanned to detect urate urolithiasis.
Positive-contrast portography is the procedure of choice for accurate characterization of the anatomic location of a PSS. Techniques described include mesenteric (or jejunal) portography, splenoportography, and cranial mesenteric or celiac arterial portography. Operative mesenteric portography is the preferred technique because it allows a highquality study of the portal system, does not require special equipment, and results in few complications. Mesenteric portography is performed with general anesthesia. A loop of jejunum is isolated through a ventral midline incision. Two ligatures are placed around a jejunal vein and an over-the-needle catheter is positioned within the vessel. After the ligatures are tied and the catheter is secured to the vessel, the abdominal incision is temporarily closed. A water-soluble contrast agent (0.5 to 1 mI/lb body weight) is injected as a bolus into the catheter. If a rapid film changer is not available, a radiograph is taken as the final milliliter is injected. Lateral and ventrodorsal radiographs should be obtained, which requires a separate dye injection for each view.
In normal animals, the portal blood (and injected dye) flows to the liver, outlining the portal vein and its multiple intrahepatic branches. With a single congenital PSS, the shunting vessel is outlined as blood is diverted directly into the lower pressure systemic venous system (usually the caudal vena cava). Intrahepatic portal vein branches may or may not be opacified. Opacification of the intrahepatic portal system during portography is a favorable prognostic factor. Failure to visualize the intrahepatic portal system is not a reliable indicator of portal atresia but may suggest higher intrahepatic vascular resistance and a greater likelihood of postoperative complications. Repeated portography performed after temporary occlusion of the shunt may provide additional information about the severity of intrahepatic portal atresia.
Transcolonic portal scintigraphy using technetium 99m pertechnetate is a noninvasive alternative to mesenteric portography that does not require sedation or anesthesia. Tech ietiurn 99m pertechnetate, given by rectum, is rapidly absorbed from the colon into the portal blood, and in normal animals radioactivity is detected first in the liver and later in the heart. With portosystemic shunting, radioactivity reaches the heart before or at the same time as it reaches the liver. The shunt fraction, determined by computer analysis, represents the percentage of portal blood that bypasses the liver. This procedure does not provide reliable anatomic infotmation, and the type and location of the shunt must be further determined at surgery. Potential causes of a falsenegative, study include shunts from the gastric vein to the caudal vena cava (a common type of shunt in cats), because portal blood from the colon does not typically pass through this vessel. In addition, if a shunt occurs adjacent to the liver, the degree of shunting may be underestimated if the shunting vessel is included in the liver region of interest. Transcolonic portal scintigraphy is more likely to detect shunts from the distal portal system (e.g., colonic vein to caudal vena cava) than a mesenteric portogram. Transcolonic scintigraphy is especially useful for monitoring progressive postoperative closure of a shunt after partial suture ligation or ameroid constrictor placement. A period of isolation (usually 12 to 18 hours) is required after the procedure until radiation levels are reduced. Because of equipment expense, availability of transcolonic portal scintigraphy is limited to referral institutions.
Medical management of HE in dogs and cats with congenital PSS is indicated before anesthesia and definitive surgical correction. The cornerstone of therapy is a diet that is moderately protein restricted with the bulk of calories derived from carbohydrates and fat (see Table Vegetable (soy protein) and dairy (cottage cheese, yogurt) proteins are preferred. Meat and egg proteins are poorly tolerated. The recommended dietary protein intake on a dry matter basis for patients with HE is 18 to 22 per cent (dogs) and 30 to 35 percent (cats). The protein content of the diet should be increased to the maximum amount tolerated without signs of HE. Dietary supplementation with soluble fiber (psyllium 1 to 3 teaspoons per day) appears to be beneficial in managing HE by mechanisms similar to those with lactulose and may allow higher levels of dietary protein to be tolerated.
Lactulose, a nonmetabolizable disaccharide, acidifies colonic contents (causing ammonia trapping), shortens the intestinal transit time, alters colonic flora, promotes incorporation of ammonia into bacterial proteins, and reduces production of potentially toxic short-chain fatty acids (SCFA) by producing the nontoxic SCFA acetate. The dose is 0.1 to 0.22 mL/lb by mouth every 8 to 12 hours to achieve two or three soft stools per day. It can be safely given on a long-term basis. It is currently available as a sweet syrup, but a crystalline form (powder) is to be marketed in 10- and 20-g packets. Antibiotics such as neomycin (10 mg/lb by mouth every 8 to 12 hours) or metronidazole (4 mg/lb by mouth every 12 hours) are commonly used on a
short-term basis to alter the urease-producing intestinal bacterial population. Systemic antibiotics such as amoxicillin or ampicillin are also effective.
When severe CNS depression or coma prevents oral administration of lactulose and neomycin, these drugs are administered by enema. Acute decompensation of HE requires fluid therapy for correction of dehydration, correction of electrolyte and acid-base imbalances, and maintenance of blood glucose. Lactated Ringer's solution should be avoided. Precipitating causes of HE such as hypoglycemia, gastrointestinal bleeding, hypokalemia, and alkalosis should be identified and corrected whenever possible. Benzodiazepines, sedatives, and tranquilizers should be avoided. In addition to routine management of HE, control of seizures with anticonvulsant therapy (potassium bromide or phenobarbital) is indicated before general anesthesia and surgery.
The short-term response to therapy for HE in dogs with congenital PSS is often dramatic. Most dogs are clinically normal with therapy, even before surgical shunt ligation. The response of cats to medical management of HE may not be as rewarding. If surgical shunt correction is not feasible or is declined by the owner, long-term medical management can adequately control clinical signs for as long as 2 to 4 years in some dogs. However, most dogs managed medically on a long-term basis are not clinically normal. and eventually have refractory neurologic signs. Medical therapy does not reverse the progressive hepatic atrophy and associated alterations in carbohydrate, lipid, and protein metabolism.
The treatment of choice for dogs and cats with a congenital PSS is surgical attenuation or ligation of the anomalous vessel.", 97,91 Single intrahepatic shunts are technically more difficult to correct than single extrahepatic shunts. Total surgical ligation of a single congenital PSS is preferred; however, in many cases only partial (60 to 80 per cent) ligation of the shunt can be safely performed because of the risk of portal hypertension (PH). PH occurs because the intrahepatic vasculature cannot accommodate the additional volume of portal blood that is diverted back to the liver after total occlusion of the shunt vessel. Many animals with partial suture ligation of a single extrahepatic PSS eventually have complete closure of their shunt, as assessed by transcolonic scintigraphy. However, recurrence of clinical signs (41 to 50 per cent of dogs) is more likely if a partial rather than complete ligation has been performed. A liver biopsy specimen is also taken at the time of surgery.
Use of an ameroid constrictor for gradual occlusion of single extrahepatic PSS has been described. The ameroid constrictor is a specialized device consisting of hydroscopic casein material in a stainless steel ring. The device is surgically placed around the shunt, and as fluid is absorbed the lumen of the ring becomes progressively smaller, causing shunt occlusion. Advantages of this procedure include gradual progressive occlusion of the shunt over a 30- to 60-day period (thus preventing acute postoperative PH), decreased surgical and anesthesia time, and lack of need to monitor portal pressures during surgery. This technique appears preferable to suture ligation for single extrahepatic PSS and makes the surgical issue of partial versus complete shunt ligation obsolete. Suture ligation is still indicated for most intrahepatic PSSs because ameroid constrictors may not be available in large enough sizes and surgical access to the shunt is more difficult. Successful use of transvenous coil embolization for gradual occlusion of a patent ductus venosus under radiographic guidance has also been described.
When suture attenuation or ligation is performed, PH may occur 2 to 24 hours after surgery. Signs of acute severe PH include abdominal distention and pain, bloody diarrhea, ileus, endotoxic shock, and peracute cardiovascular collapse. If severe portal hypertension occurs, an emergency laparotomy is required to remove the ligature. However, most animals do not survive. Concurrent medical therapy consists of shock doses of intravenous fluids (0.45 per cent saline or Ringer's solution with 5 per cent dextrose), systemic antibiotics such as gentamicin combined with penicillin, and glucocorticoids. Because the associated gastrointestinal bleeding can exacerbate HE, lactulose enemas may also be beneficial. After emergency surgery, the animal should be stabilized medically for 2 to 3 weeks and then a second attempt at surgical shunt ligation can be performed. Transient abdominal distention and ascites are signs of mild PH but are not usually an indication for ligature removal unless accompanied by other signs. In the postoperative period, ascites may be exacerbated by severe hypoalbuminemia or overzealous fluid therapy. Ascites usually resolves within 14 to 21 days after surgery. Sustained PH that is not immediately
life-threatening can result in the development of multiple acquired PSSs after I to 2 months.
On occasion, seizures and status epilepticus are a complication of surgical shunt ligation. The use of an ameroid constrictor does not appear to prevent the likelihood of this complication. Dogs older than 18 months of age may be at increased risk. The pathogenesis is obscure, but seizures do not appear to be caused by simple hypoglycemia or HE. It is possible that the brain may have adapted to an altered metabolism. Sudden withdrawal of the anticonvulsant effects of endogenous benzodiazepines (produced in the gut) after ligation of the PSS has been hypothesized. Patients should be evaluated for hyperammonemia, hypoglycemia, hypoxia, electrolyte imbalances, acid-base imbalances, and systemic hypertension. In addition to routine management of HE and correction of underlying metabolic imbalances (including thiamine administration in cats), seizures should be managed with intravenous phenobarbital or oral loading doses of potassium bromide. If seizures cannot be controlled, intravenous propofol is recommended to induce general anesthesia for 12 to 24 hours. An endotracheal tube is placed and a respirator is used to maintain the partial pressures of oxygen and carbon dioxide. Anesthesia can be maintained by propofol drip or isoflurane gas anesthesia. Mannitol (0.44 g/lb intravenously) may be indicated for control of cerebral edema. The prognosis for recovery from this complication is poor. Other perioperative complications of shunt ligation include intraoperative hypothermia and hypoglycemia, anesthetic complications, fever and positive blood cultures, portal vein thrombosis, acute pancreatitis, cardiac arrythmias, and hemorrhage.
Routine postoperative management consists of systemic antibiotics and fluid therapy. Oral lactulose and neomycin (or metronidazole) and a protein-restricted diet are usually continued for at least 4 to 8 weeks or longer, depending on the individual patient's clinical response. On a long-term basis, many dogs are clinically normal and do not require a protein-restricted diet or medications for HE, especially if total shunt ligation has been performed. After shunt ligation, hepatic regeneration and an increase in liver blood flow result in liver enlargement and reversal of histopathologic abnormalities. Indicators of hepatic function such as SBA concentrations often improve but do not usually return to normal, even in dogs that become clinically normal. Persistent hepatic dysfunction may be related to coexisting hepatic microvascular
dysplasia and persistent microscopic shunting of portal blood (see following section). In one study, there was no correlation between follow-up SBA concentrations and the clinical response.
Transcolonic scintigraphy is useful for assessing shunt closure after ameroid constrictor placement or partial suture ligation and should be performed 2 to 3 months after surgery to be sure complete occlusion has occurred. A portogram should be obtained if there is persistent shunting on transcolonic scintigraphy or no improvement or only transient improvement in clinical signs. Potential findings include failure of the shunt to close, recanalization of the shunt, identification of a second previously undetected shunt, or development of multiple acquired PSSs secondary to surgically induced PH.
The prognosis in dogs for resolution of signs after total surgical ligation of the shunt is excellent if the dog survives the immediate postoperative period. In dogs with partial shunt ligation, the prognosis is not as good. 100 Although clinical signs may resolve after surgery and the response appears favorable in the first few years, long-term follow-up (more than 3 years) suggests that signs recur in 40 to 50 percent of dogs with partial shunt legations. 100 On the basis of this information, dogs who have previously undergone a partial ligation should be
re-evaluated by transcolonic scintigraphy. If shunting persists, surgical exploration to perform complete suture ligation or ameroid constrictor placement is indicated.
The response to surgical correction of a congenital PSS in cats appears to be less encouraging than in dogs. With partial shunt ligation, clinical improvement is usually noted after surgery, but relapse of clinical signs is common. Persistent seizures and blindness are also more likely to occur when partial rather than total ligation is performed. Total shunt ligation may not be possible because of the high likelihood of severe intrahepatic portal atresia and associated PH. The development of multiple acquired PSSs after surgery appears to be more likely in cats than in dogs.