Most experts attribute this syndrome to ammonia intoxication of the brain, but the precise etiology is unknown. Normally, the ammonia produced by protein breakdown in the bowel is metabolized to urea in the liver. When portal blood shunts past the liver, ammonia directly enters the systemic circulation and is carried to the brain. Such shunting may result from the collateral venous circulation that develops in portal hypertension or
from surgically created portal-systemic shunts. Cirrhosis further compounds this problem because impaired hepatocellular function prevents conversion of ammonia that reaches the liver.

Other factors that may lead to rising ammonia levels include excessive protein intake, sepsis, excessive accumulation of nitrogenous body wastes (from constipation or GI hemorrhage), and bacterial action on protein and urea to form ammonia.

Certain other factors heighten the brain’s sensitivity to ammonia intoxication: fluid and electrolyte imbalance (especially metabolic alkalosis), hypoxia, azotemia, impaired glucose metabolism, infection, and administration of sedatives, narcotics, and general anesthetics.

Hepatic encephalopathy can lead to irreversible coma and death.

Clinical features vary, depending on the severity of neurologic involvement. The disorder usually progresses through four stages, but the patient’s symptoms can fluctuate from one stage to another.

In the prodromal stage, early symptoms are typically overlooked because they’re so subtle. The patient’s history, obtained from the patient or from a family member or caregiver, may reveal slight personality changes, such as agitation, belligerence, disorientation, or forgetfulness. The patient may also have trouble concentrating or thinking clearly. He may report feeling fatigued or drowsy. He may have slurred or slowed speech. On inspection, you may observe a slight tremor.

In the impending stage, the patient undergoes continuing mental changes. He may be confused and disoriented as to time, place, and person. Inspection continues to reveal tremor that has progressed to asterixis (liver flap, flapping tremor). The hallmark of hepatic encephalopathy, asterixis refers to quick, irregular extensions and flexions of the wrists and fingers, when the wrists are held out straight and the hands flexed upward. On inspection, you may observe lethargy and aberrant behavior. Some patients demonstrate apraxia. When asked, the patient can’t reproduce a simple design such as a star.

In the stuporous stage, the patient shows marked mental confusion. On inspection, he appears drowsy and stuporous. Yet he can still be aroused and is often noisy and abusive when aroused. Hyperventilation, muscle twitching, and asterixis are also evident.