Fig. 2. Summary of the involvement of microglia and astrocytes in HE pathology.
The liver can lose its ability to function during acute liver failure or chronic liver disease. When this occurs, toxins, such as ammonia, enter the circulation and can enter the brain. After accumulating in neural tissue, they cause a disruption of astrocyte and microglia cellular function. Astrocytes metabolize ammonia, leading to an increase of glutamine, cell swelling, cerebral edema, oxidative stress and hyperlactatemia. Microglia become activated leading to increased neuroinflammation due to pro-inflammatory cytokine release and oxidative stress. Together, these changes in neural cellular function lead to increased HE pathology, resulting in increased morbidity and mortality.
Abbreviations: HE, hepatic encephalopathy; NH3, ammonia.