Diagnosis

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Subacute liver disease resulting in hepatic failure, hepatoencephalopathy and photosensitization.

Discussion The leukogram is characterized by a mild leuko-

cytosis, mature neutrophilia and lymphopenia compati- ble with stress and inflammation. The elevated hematocrit reflects dehydration and hemoconcentra- tion. Thrombocytopenia, elevated fibrin degradation products (FDP), mild hypofibrinogenemia and mild pro- longation of prothrombin time are all compatible with disseminated intravascular coagulation (DIC).’ How- ever, severe hepatic dysfunction might also result in failure of hepatic production of protein clotting factors I I , VII, IX and X with prolongation of clotting parameters.2 Decreased hepatic synthesis would also explain the low fibrinogen levels. Elevation of FDP occurs with liver disease due to failure of the reticuloendothelial cells to metabolize FDP and plasminogen activator^.^ Low blood urea nitrogen (BUN) accompanies liver failure, since urea nitrogen is produced by the liver. The normal protein electrophoresis profile is not surprising, since hypoalbuminemia is uncommon in horses with liver failure due to the long half-life of albumin in that spe- c i e ~ . ~ Conjugated bilirubin comprised 30% of the marked hyperbilirubinemia indicating significant hepatocellular disease with possible cholestasis or par- tial cholestatic obstr~ct ion.~ The hemolysis observed in early blood samples probably contributed to the increase in total and indirect bilirubin concentrations. Hemolysis, due to hepatic failure, is often a terminal event and indicates a grave prognosis.6 Bilirubinuria represents water soluble, conjugated bilirubin and can occur with hepatocellular disease or obstructive cho- lestasis. Elevated serum levels of the liver isoenzyme lac t i c dehydrogenase (LLDH) and s o r b i t o l dehydrogenase (SDH) were compat ib le wi th hepatocellular disease. Limited studies suggest LLDH is a reliable indicator of equine hepatocellular disease.’ The increase in gamma glutamyl transferase (GGT) suggests chronic liver disease with biliary stasis and/or obstruction and is compatible with the histopathologic lesions of diffuse bile duct hyperplasia seen in this case.

Truncal ataxia and agitated, disoriented mentation are characteristic of the peripheral deficits and central nervous system (CNS) behavioral aberrations associ- ated with hepatoencephalopathy.8 An increase in false neurotransmitter substances is considered responsible for the CNS signs accompanying hepatic failure. The ulcerative dermatitis involving only unpigmented skin is typical of secondary photosensitive dermatitis resulting from the liver’s inability to excrete phylloerythrin.

The mare was confined to a padded stall and intra- venous polyionic fluids were administered to correct dehydration. A constant intravenous infusion of a 5% dextrose solution (2 L/hr) was started to provide a read- ily metabolizable energy source. Supplemental glucose was administered by stomach tube. Additional therapy included intramuscular injections of B-complex vitamins and intravenous trimethoprim sulfadiazine (15 mg/kg b.i.d.). On hospital Day 2 the mare was quiet, responsive and interested in eating. A mixed grain concentrate and timothy grass hay were provided. A liver biopsy was attempted but was unsuccessful. By Day 6 the mare was eating and drinking normally and the intravenous dex- trose solution was discontinued. Within 24 hours, signs of hepatoencephalopathy returned. The mare became recumbent, depressed and began to seizure. Permis- sion for euthanasia was granted.

Necropsy revealed generalized icterus and severe photosensitization of unpigmented skin. Multifocal cere- bral encephalopathy was observed. The liver was mod- erately enlarged, f i rm, and green-t inged with accentuated lobulation. Multiple impression smears of the liver were examined to compare rapidly available cytological interpretation with the histopathologic diag- nosis. The impression smears (Fig. 1) revealed many hepatocytes of varying sizes and shapes containing pleomorphic nuclei. Many lymphocytes and occasional plasma cells were observed. Long spindle cells sug- gestive of fibroblasts were seen. There were large amounts of pigment within some hepatocytes, which was compatible with bile stasis and/or retention. Paraf- fin-embedded, H&E-stained sections (Fig. 2) show marked distortion of hepatic architecture. There is wide- spread dropout of hepatocytes, with concomitant col- lapse and stacking of the reticulin framework. This change is most pronounced in the centrilobular areas (Zone 3), but present to some degree in all zones and bridging from lobule to lobule. There is multifocal acute hemorrhage in the areas of collapse, and a widespread scattering of a mixture of inflammatory cells including lymphocytes, macrophages and neutrophils. Trichrome staining shows a minimal amount of early collagen dep- osition. Surviving hepatocytes sometimes have mild vacuolation of their cytoplasm (mild fatty change) and large or multiple nuclei consistent with regenerative attempts. These changes are consistent with the histo- pathologic descriptions of Theiler’s disease in horsesg

Although elevated levels of GGT and minimal fibrosis suggests chronicity, the absence of significant weight loss suggests a more subacute disease process. Nor- mal albumin values imply that liver dysfunction was not severe enough or of sufficient duration to affect albumin turn over. The close correlation between impression smear cytology and the results of histopathology dem- onstrate the potential usefulness of clinical cytology as a prognostic and diagnostic aid in determining the cause and extent of liver disease.