The pathophysiology of hepatic encephalopathy is complex and not really well understood. We use the case of a neuro consult for an obtunded hepatic failure patient to discuss the various (mostly hypothetical) components
- Ammonia toxicity, leading to
- intracerebral glutamine production in astrocytes, disrupting their function
- Disruption of blood brain barrier
- Increased cerebral blood flow (NO plays a role)
- Inflammation (prostaglandins play a role)
- Other neurotoxic agents (neurosteroids play a role)
As for triggers, we develop a differential for the usual reasons for worsening hepatic encephalopathy in cirrhosis, with infection/fever, dehydration, constipation, GI bleeding and electrolyte disturbances highest on the list.
The symptoms of HE are hard to understand, since most of the pathology takes place in the astrocyte rather than the neuron, but still you can easily list and grade them. It is important to stress that most of the symptoms and signs are not specific (not even asterixis!) and even a bright yellow patient is entitled to a proper differential diagnosis (think of, among others, subdurals, ICH, stroke, status, elyte disturbances, Wernicke’s, encephalitis) as well as some straightforward tests (CT/MRI, EEG, labs, maybe CSF).
With respect to therapy in the chronic case, we talk about the standard (lactulose or lactitole – some evidence, antibiotics – even less, probiotics – worse, diet – some hints) and the experimental approaches (indomethacin, sildenafil, …).
The final twist then is to understand the difference between two possible clinical scenarios:
- Worsening (or first ever signs) of HE in a cirrhotic patient
- Acute liver failure.
In the case of the latter, the astrocytes have no time to adapt to the bombardment by pathophysiological missiles, so hyperperfusion and rapidly increasing ICP lead to a fulminant clinical picture that requires immediate action:
- Transfer to a transplant center (if you don’t happen to be in one)
- ICP monitoring and control if grade > III
- experimental bridging regimens (MARS, …) until liver transplant
- A greek review of the pathophysiology and standard treatment in the slow case 2011
- Raghavan and Marik’s great review of the critical care management of acute liver failure from 2006 Neurocritical care
- An update from 2013 on the latter topic