Ammonia, a byproduct of protein metabolism, naturally exists in the body. While typically processed by the liver and excreted, elevated levels can be harmful. The body’s urea cycle transforms ammonia into urea, which is then eliminated through the kidneys. When this system falters, ammonia can accumulate, posing significant health risks.
Understanding High Ammonia Levels
High ammonia levels, known as hyperammonemia, indicate an imbalance in the body’s detoxification processes. Ammonia is primarily produced by bacterial metabolism of protein and urea in the gut, and amino acid transamination in skeletal muscle.
When liver function is impaired, such as in cirrhosis or acute liver failure, ammonia cannot be efficiently converted to urea and accumulates. Genetic metabolic disorders, particularly urea cycle disorders, also contribute to ammonia buildup by affecting necessary enzymes. Kidney failure can similarly lead to elevated ammonia as the kidneys are unable to effectively eliminate urea. Excess ammonia is neurotoxic and can cross the blood-brain barrier, leading to cerebral dysfunction, brain swelling, and increased intracranial pressure.
Diagnosing High Ammonia Levels
Diagnosing elevated ammonia levels begins with a blood test to measure ammonia concentration. This test is often performed when symptoms suggest an issue. Normal ammonia levels in adults are generally less than 30 micromoles per liter (µmol/L), though this can vary slightly by laboratory.
The blood sample for an ammonia test requires careful handling, including collection in an EDTA-containing tube, immediate placement on ice, and rapid transport to the laboratory to ensure accurate results. If elevated ammonia levels are confirmed, additional tests are usually conducted to pinpoint the underlying cause. These may include liver function tests, kidney function tests, and genetic screening for metabolic disorders like urea cycle defects. Neuroimaging, such as CT or MRI scans, can also be used to evaluate the effects of ammonia on the brain.
Medical Interventions for Treatment
Medical interventions for high ammonia levels focus on reducing ammonia production and enhancing its excretion. Lactulose, a synthetic sugar, is a common first-line treatment. It works by being fermented by gut bacteria, which acidifies the colon and converts ammonia (NH3) into non-absorbable ammonium (NH4+), trapping it in the gut for excretion. Lactulose also acts as an osmotic laxative, increasing bowel movements and accelerating ammonia excretion.
Rifaximin, a poorly absorbed antibiotic, is often used with lactulose. This medication reduces ammonia-producing bacteria in the gut, decreasing ammonia production. For acute, severe hyperammonemia, particularly in newborns with inborn errors of metabolism, intravenous ammonia-scavenging agents like sodium benzoate and phenylacetate may be administered. These agents convert nitrogenous waste into compounds that can be excreted by the kidneys, bypassing the urea cycle.
Dialysis, particularly hemodialysis, is considered for rapid ammonia removal when levels are very high (typically above 200 µmol/L) or when other treatments are insufficient, especially in cases of cerebral edema. Treating the underlying cause, such as managing liver disease or addressing genetic disorders, remains a central aspect of long-term medical management.
Dietary and Lifestyle Management
Dietary adjustments play a role in managing high ammonia levels, often complementing medical treatments. Historically, protein restriction was a common strategy to lower ammonia production, as protein digestion is a source of ammonia. However, current recommendations for individuals with chronic liver disease emphasize providing adequate calories and protein to avoid malnutrition, often starting protein intake at 0.5 g/kg/day and gradually increasing it to 1.0–1.5 g/kg/day as tolerated. Vegetable proteins are generally better tolerated than animal proteins.
Maintaining adequate hydration is important for overall health and can support kidney function, which is involved in urea excretion. Avoiding alcohol is a significant lifestyle consideration, especially for individuals with liver disease, as alcohol can exacerbate liver damage and contribute to ammonia accumulation. Managing constipation is important, as it can reduce the time for bacterial ammonia production and absorption in the gut. These dietary and lifestyle modifications should always be implemented under the guidance of a healthcare professional to ensure they are appropriate for an individual’s specific condition and nutritional needs.