Hyperammonemia : Signs, Symptoms And Treatment
Hyperammonemia (or hyperammonaemia) is metabolic disturbance characterized by ammonia in the blood. This is a dangerous situation which can cause brain injury and death. It can be primary or secondary.
Ammonia is a substance in which nitrogen is present. This is a product of protein synthesis. Before immersion of urine in urine, it is converted into less poisonous substances urea. Metabolic pathways that synthesize urea include reactions that start in mitochondria and then go into cytosol. The procedure is known as urea cycle, in which many enzymes are employed in sequence.
Signs and Symptoms
Hyperammonemia is one of the metabolic inadequacies that contributes to hepatic encephalopathy, which can cause inflammation of the astrocytes in the brain and stimulation of NMDA-receptors. The susceptibility of NMDA-receptors leads to stimulation.
Primary vs. Secondary
• Primary hyperammonemia is due to many innate errors in metabolism, which is characterized by the low activity of any activity of enzymes in the urea cycle. The most common example is ornithine transcarbamylase deficiency, which is inherited in X-linked fashion.
• Secondary hyperammonemia is caused by the inborn errors of mediated metabolism, which is characterized by low activity of enzymes, which are not part of the urea cycle or failure of cells that make major contributions to metabolism. Examples of the former are propionic acidemia and methylmalonic acidemia,, and later examples are hepatic cirrhosis with severe liver failure and hepatic failure.
Acquired vs. congenital
• Acquired hyperammonemia is usually caused by diseases, which results in acute hepatic failure, such as exposure to overwhelming hepatitis B or hepatocytes, or cirrhosis of the liver, with older hepatic failure. Chronic hepatitis B, chronic hepatitis C, and excessive alcohol consumption are common causes of cirrhosis. Physical results of cirrhosis include the reduction of blood from the liver at least in vena cava, resulting in reduced blood filtration and removal of nitrogen-rich toxic substances by the liver and then hyperammonemia. In order to kill bacteria that initially produce ammonia, this kind of hyperammonemia can be treated with antibiotics, although this does not work, as well as to remove proteins from its digestion to ammonia, often lactulose administration Is achieved by (3-4 per day) bowel movement.
• Drug induced hyperammonemia can occur with Valproic acid overdose, and due to lack of carnitine. Its treatment is the carnitine replacement.
• Acute dehydration and bacterial overflow in small intestines can also cause hyperammonemia.
• Glycine poisoning causes hyperammonemia, which appears in the form of symptoms and nausea of CNS. Transient blindness can also occur.
• Congenital hyperammonemia is usually caused by genetic defects in the urea cycle enzymes, such as ornithine transcarbamylase deficiency, which leads to low production of urea from ammonia.
The objective is to correct biochemical abnormalities and ensure adequate nutrition intake. Treatments include compounds that increase the removal of nitrogen waste. These compounds convert nitrogen to products other than urea, which are then emitted; Therefore, the load on the urea cycle has decreased. The first compounds used were sodium benzoate and arginine. Later, phenylacetate was used, which has now been replaced by phenylbutyrate.
Treatment of Newborn hyperammonemic Coma
• Protein intake should be stopped.
• Calories should be supplied with hypertonic 10% glucose.
• Hemodialysis should be started in all comet neonates immediately with a level of plasma ammonium exceeding 10 minutes reference limit. Plasma ammonium levels are reduced quickly and total dialysis times are smaller with Hemodialysis than peritoneal dialysis. Continuous arterial or toxic hemofiltration can be used as alternate method.
• Once the upper limit of the plasma ammonium-level reference range falls 3-4 times, the intravenous sodium benzoate and phenylacetate should be started.
• Intravenous arginine should be provided.
• Corticosteroids are not indicated for the management of increasing intracranial pressure in hyperammonemia because they inspire negative nitrogen balance. Mannitol is not effective in treating cerebral edema induced by hyperammonemia.
• Valproic acid should not be used for the treatment of the tour because it reduces the urea cycle function and increases the level of serum ammonia.