Ammonia has direct access to the circulatory system and it is able to reach the brain. Only a small amount can leak through the blood-brain barrier , but if the levels of NH3 in blood are very high, then more of it will enter. An excess of ammonia is toxic and causes neurological disorders and damages, leading to a condition called Encephalopathy. As listed in the case, possible symptoms are disorientation, lethargy, slurred speech, behavior change and also motor skills impairments such as Asterixis and hyperreflexia.
Brain hyperammonemia initiates a series of reactions with major consequences: swelling of astrocytes (glial cells) with related communication problems between neurons, and disruption of cerebral metabolism and energy production.
Initially, ammonia is incorporated into glutamate to form glutamine via glutamine …show more content…
Sodium entry is accompanied by water leading to more cell swelling. Additionally, an intracellular Ca2+ overload, together with oxidative stress, activates a set of enzyme capable of producing Nitric Oxide, substance behind astrocytes swelling and destruction of cells structures. NO actions are strictly connected to CNS disorders.
Another effect of toxic ammonia is the inhibition of the key enzyme alpha-ketoglutarate-dehydrogenase -which takes part in the tricarbolxylic acid cycle and is responsible for the oxidative deamination of glutamate to ammonium and ketoglutarate-, with consequential decrement of substrate 2-oxoglutarate availability. The latter is necessary for the Citric acid cycle and ATP production. ATP depletion will make it impossible to control the ion transport across membrane (Na+/K+ membrane pumps).
An excess of ammonia induces metabolic changes: increment of brain levels of lactate, pyruvate, and free glucose, and decrement in brain levels of glycogen and ketone
Brain hyperammonemia initiates a series of reactions with major consequences: swelling of astrocytes (glial cells) with related communication problems between neurons, and disruption of cerebral metabolism and energy production.
Initially, ammonia is incorporated into glutamate to form glutamine via glutamine …show more content…
Sodium entry is accompanied by water leading to more cell swelling. Additionally, an intracellular Ca2+ overload, together with oxidative stress, activates a set of enzyme capable of producing Nitric Oxide, substance behind astrocytes swelling and destruction of cells structures. NO actions are strictly connected to CNS disorders.
Another effect of toxic ammonia is the inhibition of the key enzyme alpha-ketoglutarate-dehydrogenase -which takes part in the tricarbolxylic acid cycle and is responsible for the oxidative deamination of glutamate to ammonium and ketoglutarate-, with consequential decrement of substrate 2-oxoglutarate availability. The latter is necessary for the Citric acid cycle and ATP production. ATP depletion will make it impossible to control the ion transport across membrane (Na+/K+ membrane pumps).
An excess of ammonia induces metabolic changes: increment of brain levels of lactate, pyruvate, and free glucose, and decrement in brain levels of glycogen and ketone