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.