Case Studies
 

Hepatic Encephalopathy in a 4-year-old Shih Tsu mix Dog.

Hepatic Encephalopathy: Shih Tzu Mix

VETERINARIAN SPECIALTY CASE STUDY

Hepatic encephalopathy can be associated with extra-hepatic portosystemic shunts and/or hepatic microvascular dysplasia in small breed dogs. Pending surgical intervention, if an option, medical management of hepatic encephalopathy can help prevent secondary sequela.

By Peggy McMahon, DVM
Diplomate American College of Veterinary Emergency & Critical Care

1. Referral

Max is a 4-year-old Shih Tsu mix that was presented as a transfer for further evaluation of neurological signs and fever. Max was referred by Dr. Joni Nasser of Community Companion Animal Hospital. Two weeks prior to presentation Max was evaluated by his primary care veterinarian for ptyalism and reportedly strange posture. An elevated ALT was noted at that time. Max improved with fluid therapy over approximately 24 hours and was reportedly back to himself until the day of presentation to ASG. Twenty-four hours prior to presentation at ASG, Max became ataxic, was walking into walls, and collapsing. The owner reported a history of neurological signs that started one year prior which included circling, but the owner did not associate this with being particularly worse after meals. There was no other significant medical history or known toxin ingestion.

2. Examination

Weight 4.11 kg, Temperature 103.3 F, Pulse 140, Respiration 38, obtunded mentation that progressed to comatose, decreased facial sensation, PLRs intact, absent gag-reflex, sternally recumbent, severe dental disease, vomitus on muzzle, increased bronchovesicular sounds with increased effort, generalized muscle wasting

3. Diagnostics

Emergency Blood Screen Abnormalities

pH 7.298(7.32-7.48)
PvCO2 33.1(27-52.3 mmHg)
HCO3 16.2(19.3-28.4 mmol/L)
Na 172(144.5-153.8 mmol/L)
K 3.3(3.76-4.78 mmol/L)
Cl 149 (106.8-118.4 mmol/L)
Glucose 54(78-115 mg/dL)
Lactate 1.5(<2 mmol/L)
CBC: no significant findings

Chemistry

TP 5.5(5-7.4 g/dL)
Alb 2.7(2.7-4.4 g/dL)
Glob 2.8 (1.6-3.6 g/dL)
AST 641(15-66 IU/L)
ALT 552(12-118 IU/L)
ALP 55(5-131 IU/L)
GGT 12(1-12 IU/L)
TBili 0.3(0.1-0.3 mg/dL)
BUN 50(6-31 mg/dL)
Creat 1.3(0.5-1.6 mg/dL)
Phos 7.6(2.5-6 mg/dL)
Calcium 8.98.9-11.4 mg/dL)
Magnesium 2.6(1.5-2.5 mEq/L)
Sodium 159(139-154 mEq/L)
Potassium 4(3.6-5.5 mEq/L)
Chloride 126(102-120 mEq/L)
Cholesterol 133(92-324 mg/dL)
TG 147(29-291 mg/dL)
Amylase 1468(290-1125 IU/L)
CPK 5762 (59-895 IU/L)
T4: <0.5 (0.8-3.5 ug/dL)
PT 23(14-19)
PTT 165.5(94-125)

Urinalysis

USG 1.024(1.015-1.050)
T4: <0.5(0.8-3.5 ug/dL)
USG 1.024(1.015-1.050)
pH 7.0(5.5-7.0)
Protein 1+(Negative)
Glucose trace(Negative)
Ketones neg(Negative)
Bilirubin 2+(Neg to 1+)
Occult blood 3+(Negative)
WBC None(0-3)
RBC 21-50(0-3)
Casts Fine Gran2-3
CrystalsNone
BacteriaNone
Bile acids Pre-meal208.6 (<13 umol/L)
Bile acids Post-mealNot obtained due to inability to feed
Thoracic and abdominal radiographsAlveolar changes throughout the right cranial lung lobe and in portions of the left cranial and right middle lung lobes, consistent with aspiration pneumonia

4. Diagnosis

Hepatic encephalopathy, aspiration pneumonia

5. Treatment

Max was treated for severe signs of hepatic encephalopathy (HE) and aspiration pneumonia. He was treated with mannitol, hypertonic saline, dexamethasone SP once (for potential encephalitis prior to receiving bile acid result), IV fluids, lactulose enemas, ampicillin, vitamin K, and intubation due to loss of gag reflex. Max had persistent severe hypoglycemia despite dextrose administration, which was most likely due to a combination of hepatic insufficiency and severe septic aspiration pneumonia. Enrofloxacin, amikacin, and oxygen were used to address the aspiration pneumonia. Hypotension was managed with the addition of hetastarch and norepinephrine. Max developed a ventricular arrhythmia during his hospitalization that resolved with sotalol. Levetiracetam was added as a prophylactic anticonvulsant prior to discharge in the event that owners elected to move forward with portosystemic shunt surgical intervention following a definitive diagnosis.

6. Discussion

Hepatic encephalopathy is categorized according to etiology. Type A HE is secondary to acute liver failure without preexisting disease. Type B HE is due to portal systemic bypass without intrinsic liver disease. Type C HE is due to cirrhosis and portal hypertension or acquired portal systemic shunting. The cause of Max’s hepatic encephalopathy was unknown during his hospitalization. With his signalment, history, and signs the most likely cause of Max’s signs were due to congenital portal systemic shunting and/or hepatic microvascular dysplasia. Dogs with hepatic microvascular dysplasia have normal portal blood flow on nuclear scintigraphy portograms, and CT angiograms, but they have abnormal microscopic portal blood vessels on liver biopsy.

The pathogenesis of signs associated with hepatic encephalopathy are due to increased ammonia levels in the blood as well as other causes. Although increased blood ammonia concentrations strongly suggest HE, there are limitations of this diagnostic tool. Ammonia is produced by urease producing bacteria by breaking down nitrogenous waste products like urea and also from the metabolic activity of the intestinal mucosa itself. The liver uses the urea-cycle to break down ammonia into urea, a less toxic substance than ammonia, which is then excreted by the kidneys. In patients with hepatic encephalopathy, this metabolic pathway is compromised and ammonia accumulates. A second hepatic pathway to metabolize ammonia to less toxic glutamine is also compromised. Ammonia passes freely across the blood brain barrier. The exact mechanism for the cause of neurologic signs with increased ammonia levels in the bloodstream is unknown, but it has been postulated that astrocyte swelling may play a role. Neurosteroids are substances produced by the brain that may activate benzodiazepine receptors. Gamma-aminobutyric acid (GABA) is a centrally acting inhibitory neurotransmitter whose activity may be potentiated by endogenous benzodiazepines and neurosteroid modulation. Oxidative stress caused by intracellular accumulation of reactive oxygen and reactive nitrogen species, endogenous neurotoxic manganese, and amino acid imbalances have also been postulated to contribute to signs associated with HE.

Treatment of hepatic encephalopathy is aimed at reducing ammonia levels in the body. Lactulose is a non-absorbable disaccharide that acidifies the colonic lumen, leading to conversion of NH3 to NH4+, which is not absorbed. It also provides a cathartic effect and limits intestinal bacterial ammonia production. Alterations in the intestinal bacteria population via antibiotic use can be used to decrease numbers of urease producing bacteria. Commonly used antimicrobials include ampicillin or metronidazole. The use of neomycin has fallen out of favor.

Studies assessing the role of flumazenil in inhibiting endogenous benzodiazepines have shown that there may be short term effects in comatose patients, but it is more commonly used for patients who are comatose and have received exogenous benzodiazepines. The use of benzodiazepines in the treatment of seizures is controversial because GABA and its receptors are implicated in the pathogenesis of HE. Levetiracetam, propofol, phenobarbital, potassium bromide, zonisamide and others can also be considered for seizure control.

7. Summary:

Hepatic encephalopathy can be associated with extra-hepatic portosystemic shunts and/or hepatic microvascular dysplasia in small breed dogs. This patient’s signs were intermittent and chronic, but eventually progressed to signs of severe hepatic encephalopathy. Pending surgical intervention, if an option, medical management of hepatic encephalopathy can help prevent secondary sequela. Signs can be mild to include mild manifestations, such as apathy and mental obtundation, or severe to include seizures, coma, and even death.

8. Recovery

Over the course of his hospitalization Max’s mentation normalized and he regained the ability to walk. He became eupneic and his refractory hypoglycemia normalized. He was discharged with ongoing interventions to help decrease hepatic encephalopathy signs and continued treatment of pneumonia. Treatments included lactulose, amoxicillin, and a hepatic diet to help decrease recurrence of hepatic encephalopathy. Enrofloxacin was continued to address the pneumonia. Levetiracetam was also continued prophylactically. We recommended resolution of pneumonia prior to nuclear imaging.


Photo of Shih Tsu mix is not Max.

REFERENCES: [1] Buob, S., A. N. Johnston, and C. R. L. Webster. “Portal hypertension: pathophysiology, diagnosis, and treatment.” Journal of veterinary internal medicine 25.2 (2011): 169-186.; [2] Fryer, K. J., et al. “Incidence of postoperative seizures with and without levetiracetam pretreatment in dogs undergoing portosystemic shunt attenuation.” Journal of veterinary internal medicine 25.6 (2011): 1379-1384.; [3] Lidbury, Jonathan A., Audrey K. Cook, and Jörg M. Steiner. “Hepatic encephalopathy in dogs and cats.” Journal of Veterinary Emergency and Critical Care 26.4 (2016): 471-487.; [4] Silverstein, Deborah, and Kate Hopper. Small animal critical care medicine. Elsevier Health Sciences, 2014.

Animal Specialty Group

DVM, Diplomate American College of Veterinary Emergency + Critical Care

After receiving her Doctor of Veterinary Medicine degree with honors from the University of Illinois at Champaign-Urbana in 2011, Dr. McMahon migrated to Los Angeles where she completed both a Small Animal rotating internship as well as a Small Animal Emergency and Critical Care residency at Animal Specialty and Emergency Center. Shortly after joining Animal Specialty Group’s Emergency Team in 2016, she became board certified in veterinary emergency and critical care.