1. “Little Man” 2/18/16

2. Signalment and history 8 year old MC Maltese dog ~2-3 week history of increased liver enzymes noted at rDVM before dental & anesthesia. ALT ~500 U/L at this time; pre-bile acids ~160 Went ahead and performed anesthesia, dental; referred when liver enzymes continued to be increased Clinical signs of lethargy, vomiting Only Rx trilostane for Cushing’s (questionable ACTH stim…), meloxicam (dose unknown) Previous “recent” (time unknown) rDVM testing for thyroid – not hypothyroid

3. Labwork at Auburn ALT – ↑ 480 U/L AST – ↑ 336 U/L ALP – ↑ 240 U/L Total bilirubin – normal @ 0.10 mg/dL Glucose – normal at 106 mg/dL Cholesterol normal at 309 mg/dL BUN normal at 17.6 mg/dL Albumin low normal at 3.0 g/dL

4. Labwork at Auburn Pre-prandial bile acids – ↑ 268 umol/L (RI 0.1-6.5) Post-prandial bile acids – ↑ 53 umol/L (RI 0.6 – 11) Ammonia – ↑ 144 ug/dL (RI 0-100)

5. Abdominal ultrasound Enlarged and hyperechoic liver Aspiration felt “gooey” per radiologist Bilateral small adrenal glands FNA cytology to follow…

6. Liver, 10x, modified WG

7. Liver, 20x, modified WG

8. CBC WBC – 16,150/uL no bands HCT – 42% PLT – 771k/uL Mild polychromasia, mild anisocytosis, mild to moderate macrocytosis Morphologic changes to 5-10% of neutrophils…

9. Neutrophil inclusions – original mag 100x, modified WG stain

10. Neutrophil vacuoles – original mag 100x, modified WG stain

11. Other tests Thoracic radiographs – no significant findings Baseline cortisol – pending Coagulation panel followed by liver biopsy recommended…

12. Summary Evidence of hepatocellular injury and hepatic insufficiency based on bile acids and ammonia Enlarged, hyperechoic liver packed with lipid DM definitively ruled out Hypothyroidism not likely per clinician and rDVM tests Baseline cortisol to rule out Addison’s pending Odd inclusions and vacuoles in minority of neutrophils, no other leukocytes

13. Open Questions What differential(s) do you have for canine hepatic lipidosis (or lipid-type vacuolar change, if you prefer) in a patient in which diabetes mellitus and hypothyroidism have been (apparently) ruled out? Can hepatocellular injury from toxic/infectious/inflammatory/ other disease present with marked lipid change in your experience? Are the inclusions and vacuoles in the neutrophils of any significance or a red herring??? If this is compatible with a lipid/lysosomal storage disorder (LSD), why such a late onset, without neuro signs??? Can you have subclinical LSD that is aggravated by anesthesia, drugs, toxins, etc???