Hepatic encephalopathyppt - 投影片 1.pptVIP

Hepatic Encephalopathy, Hyperammonemia, and Current Treatment ICU meeting April 29, 2002 Ri 劉佳穎 Hepatic Encephalopathy Hepatic (portal-systemic) encephalopathy is a complex neuropsychiatric syndrome disturbances in consciousness and behavior, personality changes fluctuating neurologic signs, asterixis or flapping tremor, distinctive electroencephalographic changes. Hepatic Encephalopathy may be acute and reversible or chronic and progressive. In severe cases, irreversible coma and death may occur. Acute episodes may recur with variable frequency The diagnosis of hepatic encephalopathy is usually one of exclusion Hepatic Encephalopathy Classifications Pathogenesis of HE Endogenous Endotoxins Increased permeability of brain-blood barrier Change in Neurotransmitter and receptors Others Endotoxins of HE Ammonia Mercaptans Phenols Short-chain and Mid-chain fatty acids Ammonia Healthy individuals: equilibrium between the production and detoxications Main sites of synthesis: Intestine Muscle Kidneys Ammonia Production Small intestine: The degradation of glutamine produced ammonia Large intestine: Breakdown of Urea and proteins by normal flora Muscles: proportion to muscle work Kidney: increased production when hypokalemia and diuretic therapy Ammonia Liver: detoxified ammonia into urea and glutamine Brain can also detoxified ammonia into glutamine and glutamate Hyperammonemia in Adults Toxic Effects in CNS Brain: detoxification is ATP-dependent Hyperammonemia ? more energy consumption Swelling of Astroyctes No linear correlation between ammonia level and CNS dysfunction Toxic Effects in CNS Ammonia infusion: induced IICP and cerebral edema in rats Ammonia ? glutamine ? osmotic gradient Can be blocked by Methoximine sulphate, a glutamine synthase inhibitor Increase NO synthase Glutamine/Glutamate: Excitatory toxins; overstimulation of NMDA receptors increased osmotic pressure exchange with Tryptophan Other Neurotoxins Mercaptans: Degraded from sulfur-containing