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Systemic inflammation and ammonia in hepatic encephalopathy
Thomas H Tranah1, Godhev K Manakkat Vijay, Jennifer M Ryan
1Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, King's College Hospital, Denmark Hill, London, UK.
Metabolic Brain Disease
|December 11, 2012
Summary
Systemic inflammation and hyperammonemia synergistically drive hepatic encephalopathy (HE) pathogenesis. Targeting inflammation and ammonia may improve HE outcomes and guide new therapies.
Area of Science:
- Neuroscience
- Immunology
- Hepatology
Background:
- Inflammation is linked to delirium and worsens neurological issues in liver failure.
- Hepatic encephalopathy (HE) involves brain inflammation (astrocytic, microglial, neuronal dysfunction) and systemic inflammation impacting brain function.
- Systemic inflammation post-liver injury causes hyperammonemia and releases pro-inflammatory mediators, affecting brain ammonia levels.
Purpose of the Study:
- To review evidence on the combined role of systemic inflammation and hyperammonemia in hepatic encephalopathy (HE) development.
- To explore how inflammation and ammonia interact to cause neurological dysfunction in liver failure.
Main Methods:
- Literature review synthesizing current research on inflammation, hyperammonemia, and HE.
- Analysis of mechanisms involving immune cell activation, oxidative stress, and blood-brain barrier permeability.
Main Results:
- Systemic inflammation and ammonia trigger neutrophil degranulation and reactive oxygen species release, potentially crossing the blood-brain barrier.
- Gut-derived endotoxin, sepsis, and hyperammonemia increase Toll-like receptor expression, indicating immune system activation.
- Inflammation and hyperammonemia create a 'cytotoxic soup' that exacerbates brain dysfunction in HE.
Conclusions:
- Systemic inflammation and hyperammonemia are key synergistic drivers in the pathogenesis of hepatic encephalopathy.
- Early detection and management of inflammation are crucial for improving HE outcomes.
- Understanding these mechanisms can lead to novel therapeutic strategies targeting endotoxemia and immune dysfunction in HE.
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