Ammonia is a nitrogen-containing compound produced during protein metabolism. Monitoring its concentration in the bloodstream is a diagnostic step, especially when a patient shows signs of neurological dysfunction. Measuring the level assesses the body’s ability to process and eliminate this molecule. Measuring the level directly from an artery, rather than a vein, provides a distinct and more informative assessment of the body’s toxic load.
Ammonia Production and Metabolic Clearance
Ammonia is primarily generated in two main areas: the gastrointestinal tract and the body’s peripheral tissues. Bacteria within the colon break down proteins and urea, releasing a significant amount of ammonia into the portal circulation. Simultaneously, the deamination of amino acids, which occurs during the normal breakdown of proteins for energy, produces ammonia in tissues like muscle and the kidneys.
The liver is the central organ responsible for neutralizing ammonia. It uses a series of biochemical reactions known as the urea cycle to convert toxic ammonia into urea, a much less toxic compound. Urea is then released into the bloodstream and filtered out by the kidneys for excretion in the urine, effectively maintaining a very low concentration of ammonia in the blood.
Arterial blood analysis is often preferred because it reflects the ammonia concentration traveling to the tissues, particularly the brain. This measurement represents the immediate toxic load delivered to the central nervous system before the blood has passed through and been “cleaned” by peripheral tissues. Venous blood, conversely, reflects the level after some ammonia has been extracted and metabolized by muscle and other peripheral cells.
The concentration of ammonia delivered to the brain drives neurological toxicity. While venous sampling is less invasive, the arterial measurement offers a more accurate assessment of the body’s hyperammonemic state. The arterial reading correlates better with the partial pressure of ammonia gas, the form that readily crosses the blood-brain barrier.
Clinical Significance of Elevated Arterial Ammonia
When the liver’s ability to perform the urea cycle is compromised, ammonia levels in the blood begin to rise, a condition called hyperammonemia. The most common cause of this is advanced liver disease, which can lead to a serious neurological syndrome known as Hepatic Encephalopathy (HE). In this condition, the failing liver cannot detoxify the ammonia produced by the gut and body, allowing it to accumulate.
Once it crosses the blood-brain barrier, ammonia is neurotoxic and can cause swelling in brain cells called astrocytes. This leads to cerebral edema and, in severe cases, dangerous intracranial hypertension. In patients with acute liver failure, an arterial ammonia level exceeding \(200 \mu \text{mol/L}\) is strongly associated with the development of intracranial hypertension.
Arterial ammonia measurement is also a diagnostic tool for other hyperammonemic conditions. These include inherited Urea Cycle Disorders (UCDs), which are genetic defects in the enzymes required for the urea cycle, often presenting in newborns or during metabolic stress. Reye’s Syndrome, a rare condition causing swelling in the liver and brain, is another setting where ammonia levels may become elevated.
Sample Collection and Result Interpretation
Obtaining an accurate arterial ammonia measurement requires careful execution. The blood sample is typically drawn from an artery, most commonly the radial artery in the wrist, using a specialized syringe containing heparin to prevent clotting. This collection site ensures the sample reflects the concentration of ammonia in the systemic circulation before it reaches peripheral tissues.
The most critical step in this testing process is handling the collected sample, as ammonia is highly labile. The sample must be immediately placed on ice to slow down metabolic processes within the red blood cells, which can otherwise continue to generate ammonia after collection. Failure to cool the sample promptly can lead to a falsely elevated result.
To ensure reliability, the blood plasma must be separated from the red blood cells, ideally within 15 minutes of collection. After separation, the plasma is typically analyzed immediately or frozen for later testing, as the ammonia is more stable once isolated. Any delay in processing can render the result inaccurate, potentially leading to incorrect clinical decisions.
Interpretation relies on the laboratory’s specific reference range, but normal adult arterial ammonia levels are typically less than \(30\) or \(35 \mu \text{mol/L}\). A level greater than \(150 \mu \text{mol/L}\) is considered a significant threshold in adults and often prompts aggressive treatment. Critically high levels, especially those above \(200 \mu \text{mol/L}\), signify a severe hyperammonemic state requiring immediate medical intervention to prevent neurological damage.