Portosystemic encephalopathy (PSE)

PSE refers to a chronic neuropsychiatric syndrome secondary to chronic liver disease. This condition occurs with cirrhosis, but a similar acute encephalopathy can occur in FHF. Encephalopathy is potentially reversible.

Pathogenesis:

Unknown mechanism, but several factors have been implicated

In cirrhosis, the blood bypasses the liver via the collaterals and the ‘toxic’ metabolites pass directly to the brain to produce the encephalopathy

Many ‘toxic’ substances have been suggested as the causative factor, including:

Ammonia

Free fatty acids

Mercaptans

Accumulation of false NTs (octopamine)

Activation of the GABA inhibitory NT system

Accumulation of ammonia seems to be the most important of the factors

Clinical features:

An acute onset often has a precipitating factor (see below)

The pt becomes increasingly drowsy and comatose

Chronically, there is a disorder of personality, mood and intellect, with the reversal of normal sleep rhythm

These changes may be fluctuating and a hx from a relative must be obtained

The pt is irritable, confused, disorientated and has slow slurred speech

General features include nausea, vomiting and weakness

Convulsions and coma occur as the encephalopathy becomes more marked

Hyperventilation and pyrexia are seen

Signs:

Fetor hepaticus

Asterixis (hand flap)

Constructional apraxia

Decreased mental function

Precipitating factors:

High dietary protein

GI haemorrhage

Constipation

Infection

Fluid/electrolyte disturbances due to diuretic therapy and/or paracentesis

Drugs (e.g. any CNS depressant)

Any surgical procedure

Progressive liver damage

Development of HCC

Portosystemic encephalopathy (PSE)

Investigations:

Dx is clinical. Routine LFTs merely confirm the presence of liver disease, not the presence of encephalopathy.

Electroencephalogram (EEG):

Shows a decrease in the frequency of the normal α-waves (8-13Hz) to δ-waves of 1.5-3Hz. These changes occur before coma supervenes

Visual evoked responses also detect subclinical encephalopathy

Arterial blood ammonia is occasionally useful in the differential dx of the cause of the coma and to follow the course of the PSE, but is not readily available

Immediate management:

Identify and remove the possible precipitating cause

Give purgation and enemas to empty the bowels of nitrogenous substances

Institute a protein-free diet, with adequate calories, given (if necessary) via a fine-bore NG tube

Give antibiotics

Stop or reduce diuretic therapy

Correct any electrolyte balance

Give IV fluids as necessary (beware of too much sodium)

Flumazenil (a BDZ receptor antagonist) can induce a transient improvement

Long-term management:

Increase protein in the diet to the limit of tolerance (20-50g) as the encephalopathy improves

Give Lactulose 10-30ml, three times a day to avoid constipation

Avoid precipitating factors (if possible)

Course and prognosis:

Acute encephalopathy, often seen after FHF, has a very poor prognosis as the disease itself has a high mortality.

In cirrhosis, chronic PSE is very variable and the prognosis is that of the underlying liver disease