Pathophysiology
Clinical signs associated with portosystemic shunts commonly involve
the nervous system, gastrointestinal tract, and urinary tract. General
clinical signs include poor growth rate, weight loss, fever, and
anesthetic or tranquilizer intolerance. Neurologic dysfunction is seen
in most animals with PSS and includes lethargy and depression, ataxia,
seizures, behavioral changes, and blindness. Head pressing, circling,
and development of a head tilt have also been reported. Gastrointestinal
clinical abnormalities include anorexia, vomiting, and diarrhea. Some
dogs have no apparent signs or present with signs of cystitis or urinary
tract obstruction. Many cats have hypersalivation and some have unusual
copper colored irises.
Abnormalities found on hemograms of animals with PSS include
leukocytosis, anemia, and microcytosis. Most animals with congenital PSS
have normal coagulation profiles. Biochemical abnormalities associated
with PSS include decreases in blood urea nitrogen, protein, albumin,
glucose, and cholesterol; and increases in serum alanine
aminotransferase and alkaline phosphatase. Increase in alkaline
phosphatase is most likely from bone growth, since cholestasis is not
usually a problem in animals with shunts. Cats with PSS usually have
normal albumin concentrations. Urinalysis abnormalities include low
urine specific gravity and ammonium biurate crystalluria. At
magnifications of 400x or more, ammonium biurate crystals often have a
spikey, thornapple or starfish shape and golden color. Because of
increased urinary excretion of ammonia and uric acid, dogs and cats may
also develop uroliths. Urate uroliths are often radiolucent and
therefore may not be detectable on survey radiographs unless they are
combined with struvite. Abnormal urine sediment suggestive of cystitis
(hematuria, pyuria, and proteinuria) has been described in animals with
PSS and may be associated with crystalluria or urolithiasis.
Hepatic histologic changes in animals with PSS include generalized
congestion of central veins and sinusoids, lobular collapse, bile duct
proliferation, hypoplasia of intrahepatic portal tributaries,
proliferation of small vessels and lymphatics, diffuse fatty
infiltration, hepatocellular atrophy, and cytoplasmic vacuolization.
These pathology changes can also be seen in dogs with hepatic
microvascular dysplasia that do not have single congneital shunts.
Pathologic changes may be present in the central nervous system,
especially in encephalopathic animals.
Hepatic Encephalopathy
Hepatic encephalopathy has been recognized in animals with PSS,
end-stage liver disease, and congenital urea cycle enzyme deficiencies.
Clinical signs include depression, dementia, stupor, and coma. Muscle
tremors, motor abnormalities, and focal and generalized seizures have
also been reported. The etiology of hepatic encephalopathy is probably
dependent on several factors, including circulating toxins, alterations
in amino acid concentrations, and increased cerebral sensitivity to
drugs and toxins. Toxins that have been implicated in hepatic
encephalopathy include ammonia, mercaptans, short chain fatty acids,
indoles, aromatic amino acids, and biogenic amines.
Precipitating factors of hepatic encephalopathy include diuretics,
protein overload, hypokalemia, alkalosis, and transfusion of stored red
cells, hypoxia, hypovolemia, gastrointestinal hemorrhage, infection, and
constipation. Increased cerebral sensitivity to sedative, analgesic,
and anesthetic agents may induce coma in animals with PSS, even when
normal dosages are used. Protein overload and gastrointestinal
hemorrhage provide substrates for bacterial production of ammonia, and
constipation can increase retention and absorption of ammonia and other
encephalopathic substances. Blood which has been stored for 24 hours
contains 170 ug of ammonia/dL, and ammonia concentrations will continue
to increase with prolonged storage.