Ammonia is a metabolic waste product generated primarily from the breakdown of proteins and amino acids. If allowed to accumulate in the bloodstream, it becomes highly toxic, particularly to the brain. Measuring blood ammonia levels is an important diagnostic tool used to identify underlying metabolic disorders or severe organ dysfunction.
The Body’s Ammonia Processing System
The body constantly generates ammonia, mainly through bacterial action on protein in the intestines, but also from muscle activity and the kidneys. This ammonia is absorbed into the bloodstream and travels to the liver for detoxification. The liver uses the urea cycle, a sophisticated biochemical pathway, to convert the toxic ammonia into the less harmful compound called urea.
The urea cycle is a multi-step process that neutralizes ammonia, preventing harmful concentrations in the blood. The resulting urea is released from the liver back into the bloodstream. The kidneys then filter the urea out and excrete it from the body via urine. This continuous process maintains the low ammonia levels required for normal physiological function.
Reference Ranges and Testing Variables
Normal ammonia levels vary based on patient age and the laboratory’s specific testing methodology. For adults, the typical reference range for venous plasma ammonia is between \(16\) and \(53\ \mu\text{mol/L}\) (or \(22\) to \(74\ \mu\text{g/dL}\)). Newborn infants have higher normal levels, sometimes exceeding \(100\ \mu\text{mol/L}\) during the first week of life.
The accuracy of an ammonia test result is sensitive to the way the blood sample is collected and handled. Ammonia levels in a blood sample can increase rapidly after collection due to ongoing metabolic processes within the red blood cells. To prevent a falsely elevated result, the sample must be drawn without prolonged tourniquet application and immediately placed on ice for transport to the laboratory. The plasma must then be separated and analyzed, ideally within fifteen minutes of collection.
Primary Causes of Elevated Levels
Hyperammonemia occurs when ammonia levels rise above the normal range, usually due to failure in the liver’s detoxification system. Chronic liver diseases, such as cirrhosis from alcoholism or hepatitis, are common causes because they impair the urea cycle. Damaged and scarred liver tissue cannot efficiently convert ammonia into urea, leading to systemic buildup.
Acute liver failure, involving a sudden loss of function, also results in high ammonia levels. Less common, but often more severe, causes include inherited metabolic disorders known as Urea Cycle Disorders (UCDs). These genetic defects involve a missing or malfunctioning enzyme in the urea cycle, causing rapid ammonia accumulation, especially in infants.
Other factors contributing to hyperammonemia include gastrointestinal bleeding, which introduces a large protein load for bacterial breakdown. Certain medications, such as the anti-seizure drug valproic acid, and severe kidney failure, which impairs nitrogenous waste excretion, can also contribute.
Recognizing Symptoms of Hyperammonemia
The primary danger of hyperammonemia is neurotoxicity, as high concentrations of ammonia cross the blood-brain barrier and cause progressive neurological impairment known as hepatic encephalopathy. The earliest symptoms are often subtle, presenting as mild confusion, disorientation, or changes in sleep patterns. These changes represent the initial stages of brain function decline.
As ammonia levels rise, symptoms progress rapidly to include lethargy, stupor, and asterixis, a characteristic flapping tremor of the hands. The most advanced stage involves severe neurological decline, resulting in unresponsiveness and ultimately a coma. This progression constitutes a medical emergency requiring immediate intervention to prevent irreversible brain damage or death.