Portosystemic shunt (PSS) is an abnormal vessel that shunts portal blood from the splanchnic circulation to flow directly to the systemic circulation by passing the liver. Toxins, hormones, nutrients, escaping bacteria, and exogenous drugs also bypass the liver resulting in hepatic encephalopathy (HE).
Portosystemic shunt (PSS) is an abnormal vessel that shunts portal blood from the splanchnic circulation to flow directly to the systemic circulation by passing the liver. Toxins, hormones, nutrients, escaping bacteria, and exogenous drugs also bypass the liver resulting in hepatic encephalopathy (HE). Hepatic growth and size are maintained by normal portal blood flow (80% of the total liver blood flow) and hepatotrophic hormones (insulin, glucagon). Diversion of portal blood flow results in atrophy of the liver inducing further deterioration of liver function. Dogs or cats with congenital portosystemic shunt present with multiple clinical signs related to HE. Differentiation between single congenital and multiple acquired shunts is important, as their treatment and prognosis differ greatly. Treatment of choice for congenital shunt is partial or complete surgical ligation of the anomalous vessel; this may result in fatal portal hypertension in patients with acquired shunt. Portal hypertension secondary to primary liver disease (i.e. hepatic cirrhosis) result generally in the development of acquired shunts.
Congenital portosystemic shunts may be classified as single or multiple and intrahepatic or extrahepatic. Five types of PSS have been described. Eighty percent of the PSS are single, 72% are extrahepatic, and 95% are between the portal vein and the caudal vena cava.
Hepatic Encephalopathy (HE) is related to accumulation of neurotoxins in the systemic circulation normally extracted by the liver. The two most common causes for the HE are liver failure (with significant reduction in the liver function) or PSS. Ammonia, mercaptans, tryptophane, aromatic amino acids, short chain fatty acids, "false" neurotransmitters, and gamma amino butyric acid are the major toxins known to participate in the pathophysiology of HE.
Ammonia is derived from the degradation of dietary or endogenous proteins and amino acids by bacteria in the gut. Urease positive bacteria in the normal flora of the intestine produce ammonia from urea. In the liver, ammonia transported by the portal circulation is transformed to urea. In patients with PSS however, ammonia is distributed unchanged to the systemic circulation where it acts as a potent neurotoxin. It also increases the permeability of the blood brain barrier. Ammonia may also increase cerebral concentrations of inhibitory neurotransmitters. Although ammonia is a potent neurotoxin there is no correlation between patient ammonia blood level and severity of neurologic signs. This may suggest the importance of other toxins.
Mercaptan is the result of bacterial metabolism of methionine in the gut. Methanethiol is the most toxic metabolite of mercaptan. At low dose, it acts synergistically with ammonia and short chain fatty acids to induce HE and coma.
Metabolism of dietary medium-chain triglycerides produce Short Chain Fatty Acids (SCFA); (butyric, octanoic, valeric acids). SCFA alter brain energy metabolism but are less neurotoxic than ammonia or mercaptans.
Other toxins that may be involved in the pathogenesis of HE include phenols, bile salts, and "middle molecule." These neurotoxins do not induce HE alone but have a synergistic effect with ammonia .
Concentration of circulating Aromatic Amino Acids (AAA) (phenylalanine, tyrosine, and tryptophane), increases during HE. AAA induce synthesis of weak neurotransmitters and/or inhibitor neurotransmitters. Phenylalanine and tyrosine are precursors for synthesis of the weak neurotransmitters (octopamine and beta-phenylalanine) whereas tryptophane is a precursor of serotonine, a potent inhibitor. Tryptophane by itself is highly neurotoxic and can induce neurologic signs. Gamma Aminobutyric Acid (GABA), an inhibitory neurotransmitter is found in increased concentration in cerebrospinal fluid of patients with HE. GABA-like activity substances are produced by bacteria in the GI tract. The importance of GABA as an inhibitory neurotransmitter binding to benzodiazepin receptors in the brain is controversial in the pathogenesis of HE.
No breed, or sex predilection have been shown in patients with PSS; however purebred dogs seems to have a higher incidence. Schnauzer, Yorkshire Terrier, Bernese Mountain dog, Husky, German sheperd dog, and Irish Wolfhound are most frequently represented. Most patients with PSS are diagnosed at approximately 1 year of age, however clinical signs can occur as early as 6 weeks or as late as 8 years of age.
The most consistent presenting signs in patients with PSS include small body stature, failure to grow, and weight loss. Frequently, patients show signs of hepatic encephalopathy, gastrointestinal disorders, urinary track abnormalities, and intolerance to various drugs. The most common signs of hepatic encephalopathy include listlessness, depression, ataxia, head pressing , cortical blindness and seizures. Behavior changes have been reported in dogs and cats. Cats frequently present with ptyalism. Because of the pathogenesis of HE, 25% of patients with PSS have an exacerbation of clinical signs with ingestion of a protein meal. Anorexia, vomiting and diarrhea unresponsive to medical therapy are common gastrointestinal signs. Infrequently, dogs may be polyphagic. Polakiuria, hematuria, dysuria are some common signs associated with urate crystals in patients with PSS. Enzyme uricase in the liver normally converts uric acid, a purine metabolism by-product, into water-soluble allantoin. Presumably, hyperuricemia and hyperammonemia in patients with PSS lead to increased urinary urate and ammonia excretion, which in turn leads to ammonium biurate crystal formation. Patients with a PSS have longer recovery times after surgery if benzodiazepin, barbiturate and phenothiazine have been used. These drugs have a longer half-life because their detoxification requires normal liver function. Clinical signs can be extremely variable at time of presentation making diagnosis confusing.
Clinical laboratory findings in patients with PSS are also variable. Fifty percent of dogs and 15% of cats have a microcytic normochromic anemia. Alkaline phosphatase (ALP) and alanine amino transferase (ALT) are usually mildly elevated. Increase in ALP is partially due to bone turnover in young animals. Bilirubin is generally normal as obstruction to bile flow is not present and only a small portion of functional liver is necessary to conjugate free bilirubin. Decrease BUN, secondary to decrease conversion of ammonia to urea, is found in 64% of patients with PSS. Hypoglycemia is a consistent finding due to decreased insulin metabolism by the liver and insufficient hepatic glycogen storage. Portosystemic Shunt may lead to hyperglucagonemia. Hypocholesterolemia is present in 65% of the cases. Protein and specifically albumin levels are reduced in patients with PSS. In one study 90% of dogs had a decreased albumin concentration. Hepatocytes are responsible for albumin synthesis. Because of decreased functional liver capacity in patient with PSS, albumin production is decreased. If hypoalbuminemia is severe enough it could lead to ascites.
Liver function tests are important for the diagnosis of PSS. Bromosulfophtaleine, ammonia tolerance, and bile acids are tests most commonly used. However, bile acids is the only test dependent upon portal systemic vascular flow. The plasma concentration of bile acid is dependent on enterohepatic circulation. Bile acid evaluation is as sensitive as ATT for the detection of circulatory abnormalities. Evaluation of postprandial bile acids improves the diagnostic capabilities of the fasting values for PSS. After 12 hours fasting a venous blood sample is collected for preprandial bile acid concentration. The animal is fed a high protein meal. Serum bile acid concentration is determined 2 hours after the meal. Normal value for fasting bile acids are < 5 microM/l in dogs and < 2 microM/l in cats. Normal postprandial values are < 15.5 microM/l in dogs and < 10.0 microM/l in cats.
Urinanalysis may reveal ammonium biurate crystals. Ammonium biurate uroliths are an important diagnostic finding; they have been reported in 50 to 64% of patients with PSS.
Ultasound can be used to diagnose a PSS. Ultrasound is very sensitive for intrahepatic shunt. Abdominal radiographs reveal a generalized decrease in contrast because of the decrease of abdominal fat. Size of the liver is commonly reduced (atrophy) and kidneys enlarged.
Per rectal portal scintigraphy using 99m Technetium Pertechnetate is the method of choice for the diagnosis of PSS. It is a non-invasive technique that tests the integrity of the portal circulation. After an enema, a dose of 1 mCi/kg of 99m Technetium Pertechnetate is placed in the descending colon with a soft plastic pediatric feeding tube. Images are recorded by a gamma-camera immediately after injection and for 3 minutes. In a normal dog, liver uptake of the radioisotope is higher than uptake by the heart. However, when a PSS is present, uptake by the heart is higher and earlier than uptake by the liver. A shunt fraction [the ratio of the heart activity/(liver + heart)activity] gives an idea of the significance of the shunt. Normal dogs have a shunt fraction < 10% while dogs with PSS have a shunt fraction > 50%.
Surgery is recognized as the treatment of choice for PSS. Because liver needs hepatotrophic substances from portal blood flow, deterioration of liver function can be expected if the shunted blood flow is not surgically corrected in a physiologic direction. Medical treatment will not correct this alteration, therefore long term survival is not expected. In one study, only 2 of 8 dogs with medical treatment were still alive at 6 months. Life expectancy of 2 months to 2 years is generally reported; the actual time presumably being dependent on the amount of portal blood flow. Restoring the flow of hepatotrophic substances to sinusoidal milieu results in substantial hepatic regeneration and reversal of functional impairment.
Pre-operative medical treatment is used to decrease acute signs of hepatic encephalopathy (coma, seizure, abnormal behavior) resulting in a patient in better condition for anesthesia and surgery. The goal of medical treatment is to decrease production of ammonium and its absorption from the intestine. Patients presenting with seizures or coma require emergency treatment including: fluid therapy, betadine enema, oral neomycin (20 mg/kg) or metronidazole (7.5 mg/kg three-times a day) and oral lactulose when oral administration is feasible. Dehydration should be treated aggressively as azotemia can aggravate the encephalopathic state by increasing intestinal production of ammonia. Replacement fluids using 0.45% NaCl with 2.5% dextrose is recommended. Animals with liver disease tend to become hypoglycemic and retain sodium. Benzodiazepin or barbiturate to control seizure should be used with caution because of increase drug sensitivity. Mannitol (0.5 mg/kg IV) can be used to reduce intracranial pressure. Electrolyte disorders and acid base imbalance should be corrected as needed according to biochemical profile. All oral intake of food is stopped for 24 to 48 hours. Betadine enema and antimicrobial therapy decrease colonic bacterial flora. Once the animal is stabilized and improving chronic treatment for HE should be instituted and surgery planned. Antimicrobial therapy and lactulose decrease ammonia production by decreasing colonic flora. Lactulose acts by acidifying intestinal content thus reduces absorption of ammonia, decreases transit time, and reduces colonic bacterial population. The dose of lactulose used is extremely variable: 2.5 ml to 25 ml three time a day in a dog. Protein restricted diet is required to reduce the amount of ammonia in the intestine.| The ideal diet should be: highly digestible (little residue reaches the colonic bacteria), contain high biological value protein (high levels of branched chain amino acids and arginine and low levels of aromatic amino acids and methionine), and have a highly digestible carbohydrate as the primary source of calories. Protein content should be 14 to 17% for the dog and 30 to 35% for the cat.
Patients with PSS experience a reduction in absorption, metabolism, and clearance of drugs due to liver impairment. Fentanyl can be used for sedation. Mask induction with isoflurane followed by endotracheal intubation is the method of choice. Dextrose (2.5%) is important during surgery and the immediate postoperative period to maintain blood glucose. Cephalosporin perioperatively is recommended. Ischemic episode can occur in the bowel during manipulation of the PSS that will may result in bacterial embolization.
Identification of the shunt
A standard ventral midline celiotomy is performed from the xiphoid to pubis to explore the portal system. The portal vein and caudal vena cava are located by retracting the duodenum medially. The portal vein is identified ventral to the caudal vena cava at the most dorsal aspect of the mesoduodenum. The caudal vena cava is examine for identification of any abnormal blood vessels. Normally, from the renal and phrenicoabdominal veins to the hile of the liver there should be no blood vessels entering the caudal vena cava ventrally. Any blood vessel in this area should be suspect as an extrahepatic shunting blood vessel. Turbulence in this portion of the vena cava is another important clue for locating a possible shunt. If nothing abnormal is noticed the left omental bursa is entered and all tributaries from the portal vein are identified. Most often, shunting vessels come from the gastrosplenic vein in dogs and left gastric vein in cats. If no shunting vessel can be located, investigation for an intrahepatic shunt is started. Inspection of the hepatic veins cranial to the liver and inspection of liver lobes for dilation are the first steps in identification of an intrahepatic shunt.
Ligation of the shunt
Complete occlusion of the shunt at the time of surgery is associated with a better prognosis. However, complete occlusion may not be possible at the time of surgery because the liver parenchyma cannot accommodate the augmentation in blood flow. It then results in portal hypertension. Occlusion of a PSS has been performed traditionally with a suture placed around the shunt and tight while the portal pressure was measured. This technique resulted in acute or chronic portal hypertension in 15 to 20% of the cases. Acute portal hypertension resulted in death in most of the cases. Chronic portal hypertension induced ascites and the opening of acquired shunts.
To palliate to these problems and achieve complete occlusion of the PSS gradual occlusion has been performed with ameroid constrictor or cellophane band. Both of these devices induce a slow and complete occlusion of the PSS over 4 to 8 weeks. The liver parenchyma can then accommodate the augmentation in blood flow without inducing portal hypertension.
Postoperatively, patients are examined for signs of portal hypertension: sepsis, abdominal pain, bloody diarrhea, and ascites. If signs of portal hypertension occur, the patient is taken back to surgery and the suture released. Failure to remove the ligature will result in septic shock and death. Hypothermia during surgery and postoperatively should be corrected aggressively. Dextrose (2.5%) intravenously is maintained. Thrombosis of the portal vein has been reported as complication of a partial ligation of intrahepatic PSS. Postoperative seizures have been reported as a complication of ligation of PSS and they carry a poor prognosis. Seizures may occur immediately or up to 3 days postoperatively.
Surgical mortality associated with treatment of PSS can be as high as 20%. The intraoperative and immediate postoperative periods are most critical. Hypothermia and hypoglycemia should be anticipated and treated promptly. With the devices for gradual occlusion the incidence of complications seems significantly reduced.
Post-operatively the animals should be maintained on a low protein diet, amoxicillin or neomycin, and lactulose. Bile acids should be monitored at one, three and six months after surgery. Lactulose should be interrupted one month after surgery. The antibiotics should then be removed from the treatment. Three months after surgery the diet can be progressively return to normal. If the animal is showing signs of hepatic encephalopathy then the low protein diet is re-instituted.