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 brainstemshowed 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 exceedsthe 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 barrieris 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.Keywords: kernicterus, icterus, dog.

Highlights

  • Kernicterus, known as nuclear jaundice or bilirubin encephalopathy, is a neurological condition characterized by bright yellow pigment deposition in the basal ganglia, hippocampus, subthalamic nucleus, cerebellum and spinal cord [3,5,9]

  • Kernicterus diagnosis was based on gross and histological brain alterations. This condition is related to cases of intense hyperbilirubinemia, which exceeds the albumin binding capacity

  • Hepatic lesions may cause reduced albumin production, leading to hypoalbuminemia, which increases unbound bilirubin concentration; levels of bilirubin and albumin were not analyzed in this case

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Summary

Introduction

Kernicterus, known as nuclear jaundice or bilirubin encephalopathy, is a neurological condition characterized by bright yellow pigment deposition in the basal ganglia, hippocampus, subthalamic nucleus, cerebellum and spinal cord [3,5,9]. Kernicterus is caused by unconjugated bilirubin passage through the blood brain barrier [9]. Intracellular bilirubin is toxic for cells, and may cause a decrease in protein synthesis, respiration depression, glycolysis increase, changes in mitochondrial oxidative phosphorylation and cellular death [2,8].

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