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Luciana Sonne , Djeison Lutier Raymundo , Bianca Santana de Cecco , Adriana da Silva Santos , Caroline Argenta Pescador , Eduardo Conceição de Oliveira1 & David Driemeier
ABSTRACT
Background: Kernicterus or bilirubin encephalopathy is a condition rarely observed in animal characterized by a yellowish
discoloration of the central nervous system. It is a potentially fatal condition due to bilirubin neurotoxic effects caused by
the increase of non-conjugated bilirubin pigment, which passes blood brain barrier and has been attributed to an imbalance
between albumin and bilirubin levels. Intracellular bilirubin is toxic for cells and can cause decrease in protein synthesis,
specially albumin, depression of cell respiration and cellular death. This paper describes kernicterus in a 2-year-old Great
Dane female dog.
Case: Clinically, the animal showed apathy, lethargy, weight loss and jaundice, which progressed to vomiting and neurological
signs characterized by loss of consciousness and eventually coma. Blood parameters were within normal range, except
for high levels of alanine aminotransferase (523 U/L), suggesting a liver lesion. The animal was submitted to euthanasia
due to the poor prognosis, and at post-mortem examination it showed dehydration and severe jaundice, especially oral,
vaginal and ocular mucosas, subcutaneous tissue and blood vessels intima surface. The liver had an accentuated lobular
pattern, and the stomach mucosa was reddened. Multiple petechiae were observed in the epicardium, as well as icterus in
the blood vessels of the heart. Furthermore, the brain and cerebellum cortex, thalamic region and nuclei region of brainstem
showed extensive icteric areas. Microscopically, the liver presented a mononuclear portal hepatitis, centrilobular necrosis
and presence of yellowish pigments. The brain had neuronal necrosis, mild vacuolization of the white matter, perineuronal
edema and Alzheimer type II astrocytes, while cerebellum showed Purkinje cells necrosis. Hepatic cooper measurement
was within range values, and direct imunofluorescence for the detection of Leptospira sp. was negative.
Discussion: Kernicterus pathogenesis has been extensively studied, as the condition is commonly seen in neonatal humans.
Diagnosis is based on gross and microscopic lesions in brain, which are consistent with bilirubin encephalopathy caused by
the necrosis and degeneration of neurons. This condition is related to cases of intense hyperbilirubinemia, which exceeds
the albumin binding capacity and, therefore, the excess of unconjugated bilirubin that can pass through the blood brain
barrier. Liver disease causes deficient production of protein, especially albumin, decreasing the potential binding capacity
to bilirubin, and consequently causing hyperbilirubinemia. In this case, the previously detected hepatic lesion suggested
by liver enzymes increased, probably led to protein production dysfunction, causing hypoalbuminemia and hyperbilirubinemia.
Unfortunately, albumin and bilirubin seric levels could not be measured. Decrease in albumin production along with the excess of unconjugated bilirubin caused the jaundice, and in cases like this one described, the blood brain barrier
is compromised and the kernicterus occurs. Unconjugated bilirubin has negative effect in the glutamate uptake causing
extracellular accumulation of it, which is consequently neurotoxic, causing necrosis and degeneration leading to a characteristic
encephalopathy in animals with kernicterus. In this report, it was not possible to determine the primary hepatic
disease, however this caused clinical neurotoxic disease, known as bilirubin encephalopathy.
