Updated: 11/27/2019

Hepatic Encephalopathy

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Snapshot
  • A 45-year-old man with a history of alcoholic cirrhosis is found on the sidewalk with altered mental status. He is brought in to the emergency room by the police. He has had multiple similar visits for intoxication. This time, however, he is noted to be markedly lethargic and jaundiced. On physical exam, he has pronounced asterixis, ascites, and other signs of liver disease such as telangiectasias and palmar erythema. Laboratory evaluation reveals negative serum alcohol levels but elevated ammonia and liver enzymes. A hepatic ultrasound shows a hyperechoic mass in his liver, which is concerning for malignancy in the setting of chronic cirrhosis and was thought to be the possible trigger for his episode of hepatic encephalopathy.
Introduction
  • Overview
    • a reversible complication of liver failure characterized by altered mental status and asterixis
    • often precipitated by acute stressors such as dehydration or infection
  • Epidemiology
    • incidence
      • 30-40% of patients with cirrhosis
    • risk factors
      • alcohol use
      • hepatitis
  • Etiology
    • acute triggers
      • dehydration
      • infection
      • gastrointestinal bleed
      • fluid and electrolyte abnormalities
      • sedatives
      • hepatocellular carcinoma
      • transjugular intrahepatic portosystemic shunt (TIPS)
  • Pathogenesis
    • mechanism 
      • ↓ ammonia clearance due to liver dysfunction
        • ammonia is normally metabolized in the liver to urea, which is easily excreted
      • portosystemic shunts causing blood to bypass the liver
      • ammonia is neurotoxic 
        • crosses blood-brain barrier and is converted to glutamine, which is an osmolyte and promotes swelling of brain cells
        • this leads to cerebral edema
        • alteres neurotransmitter function
  • Associated conditions
    • acute liver failure
    • cirrhosis
      • other complications of cirrhosis include portal hypertension, esophageal varices, and hepatocellular carcinoma
  • Prognosis
    • hepatic encephalopathy is reversible
Classification
  • Classification by underlying disease
    • type A
      • acute liver failure
    • type B
      • portosystemic bypass or shunting with preserved liver function
    • type C
      • cirrhosis
Presentation
  • Symptoms
    • common symptoms
      • mood changes
      • slow to respond
      • unsteadiness
  • Physical exam
    • inspection
      • signs of liver disease
        • jaundice
        • ascites
        • spider angiomata
        • palmar erythema
      • asterixis
        • flapping tremor of wrists
      • altered mental status
      • coma/stupor in severe cases
Imaging
  • CT or MRI of the head
    • indication
      • rule out intracranial hemorrhage or mass as a cause of encephalopathy
    • findings
      • cerebral edema
Studies
  • Serum labs
    • ↑ ammonia
    • also check
      • liver function panel
      • blood urea nitrogen
      • electrolytes
Differential
  • Other metabolic encephalopathies
    • diabetic ketoacidosis
      • distinguishing factor
        • hyperglycemia with ketones in the blood and anion gap metabolic acidosis
    • uremic encephalopathy
      • distinguishing factor
        • elevated urea and normal ammonia
    • acute alcoholic intoxication
      • distinguishing factor
        • elevated blood alcohol level
Treatment
  • Nonoperative
    • correct precipitating factor and electrolyte derangements 
    • lactulose 
      • mechanism
        • gastrointestinal flora degrades lactulose into lactic acid and acetic acid, which results in the clearance of ammonia 
      • indication
        • treatment and prevention
    • rifaximin
      • mechanism
        • ↓ bacteria that produce ammonia
      • indication
        • treatment and prevention alongside lactulose
Complications
  • Persistent learning impairment
 

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Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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