High ammonia levels can cause seizures when they reach dangerously elevated concentrations in the bloodstream, a serious medical condition known as hyperammonemia. This state represents a profound metabolic failure that results in ammonia, a potent neurotoxin, crossing the blood-brain barrier and severely disrupting normal brain function. Seizures are a severe neurological outcome, often occurring alongside confusion, disorientation, and potentially coma.
Ammonia: A Normal Metabolic Byproduct
Ammonia is continually produced in the body as a natural consequence of metabolic processes. The primary source of this compound is the breakdown of dietary proteins and amino acids, a process known as catabolism. Additionally, bacteria in the gastrointestinal tract generate significant amounts of ammonia when they act on proteins present in the gut.
Because ammonia is highly toxic to the central nervous system, the body has a dedicated process for its detoxification. The liver is the main organ responsible for this clearance, converting the toxic ammonia into a harmless compound called urea. This conversion occurs through the Urea Cycle. The resulting urea is then released into the bloodstream and eventually eliminated from the body through the kidneys in urine.
The Dangerous Rise: Causes of Hyperammonemia
Hyperammonemia occurs when the body’s capacity to detoxify ammonia is exceeded, causing the compound to accumulate in the blood. The most frequent cause in adults is severe liver dysfunction, such as cirrhosis or acute liver failure, where damaged liver cells cannot perform the Urea Cycle effectively. This failure leads to a neurological syndrome called Hepatic Encephalopathy (HE), which includes confusion and, in advanced stages, seizures.
A second major cause is an inherited Urea Cycle Disorder (UCD). These genetic disorders involve a deficiency in one of the specific enzymes necessary for the Urea Cycle to function. In newborns with UCDs, hyperammonemia can present acutely, but late-onset forms can also manifest in older children and adults, often triggered by stress, infection, or high protein intake.
Less common scenarios include infections with urease-producing organisms, which increase ammonia production in the urinary tract. The use of certain medications that interfere with the liver’s ability to process nitrogen waste can also contribute. In all cases, the common factor is the overwhelmed detoxification system, which allows neurotoxic concentrations of ammonia to circulate.
Neurotoxicity: How Ammonia Disrupts Brain Function
Ammonia’s ability to cause seizures stems from its direct toxic effects on brain cells after it crosses the blood-brain barrier. The primary cells affected are astrocytes, which are support cells responsible for maintaining the chemical balance around neurons. Astrocytes attempt to detoxify the excess ammonia by converting it into glutamine using the enzyme glutamine synthetase.
This detoxification process is quickly overwhelmed, leading to a massive accumulation of glutamine within the astrocytes. Since glutamine is osmotically active, its buildup draws water into the astrocytes, causing them to swell, a condition known as cerebral edema. This swelling increases pressure within the skull and is a major contributor to severe neurological symptoms, including coma and brain herniation.
High ammonia levels also disrupt the brain’s neurotransmitter balance, which is the direct cause of seizures. Ammonia interferes with the normal cycling of glutamate, the brain’s main excitatory neurotransmitter, and gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter. This imbalance shifts the brain toward a state of hyperexcitability, making neurons much more likely to fire in uncontrolled bursts.
Clinical Interventions for High Ammonia
The management of acute hyperammonemia focuses on rapidly reducing the blood ammonia concentration to prevent irreversible brain damage. For cases related to liver disease, medical interventions often target the gut to reduce ammonia production. This is commonly achieved using non-absorbable disaccharides like lactulose, which promote the elimination of ammonia from the intestines.
Another strategy involves using oral antibiotics, such as rifaximin, which reduce the number of ammonia-producing bacteria in the gut. In severe cases, particularly with very high ammonia levels, emergency treatment includes dialysis. Hemodialysis is the most effective method for quickly removing ammonia from the blood.
For patients with inherited Urea Cycle Disorders, treatment includes medications that act as nitrogen-scavengers, such as sodium benzoate and phenylacetate. These drugs provide alternative pathways for the body to excrete nitrogen waste, bypassing the defective Urea Cycle. Long-term management addresses the underlying cause, whether treating chronic liver disease or maintaining a strict low-protein diet and specialized supplement regimen for a UCD.