Ammonia is a simple, nitrogen-containing compound produced constantly as a byproduct of metabolism, primarily during the breakdown of proteins and amino acids. While a small amount is necessary for certain bodily functions, ammonia is highly toxic at elevated concentrations. The body must efficiently remove this waste product to prevent damage, especially to the nervous system. The concentration of ammonia in the blood is tightly regulated, and deviations from the normal range often signal a significant underlying medical issue.
Ammonia Production and Purpose in the Body
The primary source of ammonia production is the colon, where intestinal bacteria break down undigested protein and urea using the enzyme urease. This process generates a substantial amount of ammonia, which is then absorbed into the bloodstream. Ammonia is also produced internally during normal metabolic processes, such as the breakdown of amino acids in muscle tissue and the kidneys.
Ammonia plays necessary roles in the body. In the kidneys, its production is stimulated during acidosis to help maintain the body’s acid-base balance. The kidneys excrete ammonia as the ammonium ion (\(\text{NH}_4^+\)), which eliminates excess acid. The compound is also involved in creating molecules like the amino acid glutamine, which serves as a temporary, non-toxic storage and transport form of nitrogen.
Defining Normal Reference Levels
A normal blood ammonia level is generally considered to be less than 30 to 50 micromoles per liter (\(\mu\)mol/L) for adults. Specific ranges can vary slightly between different clinical laboratories, but a commonly cited upper limit is around 30 \(\mu\)mol/L.
Normal ranges are higher in children and significantly elevated in newborns. For children older than one month, the normal level is often cited as less than 50 \(\mu\)mol/L. Healthy term neonates may have upper limits of up to 80 to 110 \(\mu\)mol/L in the first few days of life before their systems fully mature.
The accuracy of an ammonia measurement depends highly on how the blood sample is collected and handled. Since ammonia levels can rise rapidly after collection, the sample must be drawn without prolonged tourniquet use, immediately placed on ice, and processed quickly, usually within 15 minutes. Clinicians must also note whether the sample is drawn from a vein or an artery, as arterial levels tend to be slightly higher.
Why Ammonia Levels Become Elevated
Elevated blood ammonia, or hyperammonemia, results from a failure in the Urea Cycle. This series of metabolic reactions takes place primarily in the liver, converting toxic ammonia into urea, a less harmful compound.
The most common cause of hyperammonemia in adults is advanced liver disease, such as cirrhosis. When the liver is scarred or damaged, its capacity to run the urea cycle is severely diminished, preventing the conversion of ammonia into urea. Acute liver failure also causes a rapid, life-threatening spike in ammonia levels.
Another significant cause is portosystemic shunting, common in cirrhosis, which diverts blood away from the liver. This shunting allows ammonia-rich blood from the gut to bypass the liver’s detoxification process and enter the general circulation. Less common but severe causes include inherited urea cycle disorders (UCDs), involving a genetic deficiency in one of the six required enzymes.
Other non-hepatic conditions can also contribute to elevated ammonia. These include kidney failure, which impairs urea excretion, and gastrointestinal bleeding, which provides a massive influx of protein for gut bacteria to break down. Certain medications, such as the anti-seizure drug valproic acid, can also interfere with urea cycle enzymes, leading to ammonia buildup.
Health Effects of Hyperammonemia and Treatment Overview
Hyperammonemia is dangerous due to ammonia’s direct toxicity to the central nervous system. Ammonia molecules readily cross the blood-brain barrier and interfere with brain cell function. The resulting neurological symptoms are known as Hepatic Encephalopathy (HE).
Symptoms are progressive, beginning with subtle changes like difficulty concentrating, irritability, and sleep disturbances. As ammonia levels rise further, the condition advances to confusion, disorientation, slurred speech, and a characteristic flapping hand tremor called asterixis. Patients can become unresponsive, fall into a coma, and develop dangerous brain swelling, which can be fatal.
Treatment focuses on rapidly lowering the blood ammonia concentration and addressing the underlying cause. Medications like lactulose are frequently used to treat HE; this synthetic sugar works in the colon to trap ammonia and promote its excretion through the stool. Another common therapy is the antibiotic rifaximin, which reduces the number of ammonia-producing bacteria in the gut. In acute, life-threatening cases, particularly in newborns or those with acute liver failure, aggressive measures like hemodialysis may be necessary to directly filter ammonia from the blood.