Hepatic encephalopathy

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Hepatic encephalopathy
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(?) ?????(ammonia intoxication)

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liver
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2.?????(FNT)
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CNS??
AAAaromatic amino acid BCAAbranch chain amino
acid
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AAA?

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5-HTP
5-HT
5HIAA
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(?) ?-???? (GABA)??
??GABA??? ?????
Cl- Cl- Cl- Cl-
GABA-R
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Cl-
Cl- channel
BZ-R
BARB-R
GABA-D
Cl- -C
Steroid-D
BZ-D
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Barbital-D
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??GABA????

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GABA?????
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(CNS)
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GABA

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HE???aa???? HE??GABA????
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HE??

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Hepatic encephalopathy stages
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Grading of symptoms

• Stage 1- Mild confusion, decreased attention,
  irritability, reversed sleep pattern. flapping
  trema
• Stage 2- Drowsiness, personality changes,
  intermittent disorientation, flapping trema
• Stage 3- Gross disorientation, marked confusion,
  slurred speech , flapping trema
• Stage 4- Frank coma

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Lab abnormalities

• Hepatic synthetic and biochemical dysfunction
• Electrolyte disturbances
• Ammonia
• EEG - high-amplitude low-frequency waves and
  triphasic waves.
• Evoked potentials
• Psychometric tests
• Magnetic resonance spectroscopy

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Psychometric testing

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Diagnosis

• Hepatic encephalopathy is a diagnosis of
  exclusion
• Existence of acute or chronic liver disease,
  and/or a prior history of HE are clinical
  elements
• needed for diagnosis.
• Positive test of liver dysfunction
• Conscious disturbance ,abnormal behavior, coma
• Neuromuscular function Flapping tremor
• EEG

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Differential Diagnosis

• Metabolic encephalopathy
• Diabetes ( hypoglycemia, ketoacidosis)
• Hypoxia
• CO2 narcosis
• Electrolyte imbalances

• Toxic encephalopathy
• Alcohol
• Recreational drugs
• Infections
• encephalitis
• abscess
• Intra cranial lesions
• Intracerebral bleed
• tumors

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Principles of Treatment

• Eliminating or correcting precipitating factors
• Reducing plasma ammonia and other toxins
• Correcting plasma amino acid imbalance and
  supplying normal neurotrasmitters
• Improving hepatocyte functions
• Liver transplantation

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Treatment

• Identification and correction of the
  precipitating factors.
• Correction of hypokalemia
• Reduction in ammoniagenic substrates
• NG lavage in GI bleeding
• Treatment of constipation
• Limiting protein intake 40 to 70 g/day

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Lactulose and lactitol
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• Currently mainstay of treatment
• Can be given orally, thro NG tube or as a
  retention enema
• Dose is 45-90 gms per day
• Titrated to achieve 2-3 soft stools per day
• Side effects include abdominal cramping,
  diarrhea, and flatulence

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Oral antibiotics

• Rifamixin Therapeutic alternatives if patient
  cannot tolerate disaccharides
• Neomycin
• 3- 6 gms/ day PO
• assd with ototoxicity and nephrotoxicity
• Metronidazole
• 250 mg BID
• Neurotoxicity in cirrhotics
• Vancomycin

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Other treatments

• Ornithine-aspartate
• lower serum ammonia levels through stimulation of
  the urea cycle and urea formation
• Probiotics and prebiotics
• BCAA infusions
• L-Dopa
• Liver transplantation
• Artificial support

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