What is being tested?

Ammonia is a waste product produced primarily by gut bacteria during protein digestion. A waste product, ammonia is normally transported to the liver, where it is converted into urea. The urea is then carried by the blood to the kidneys, where it is excreted in the urine. If ammonia is not efficiently converted to urea (‘urea cycle’) by the liver it builds up in the blood and passes into the brain.

In the brain, ammonia and other compounds normally processed by the liver can cause hepatic (liver) encephalopathy – mental and neurological changes that can lead to confusion, disorientation, sleepiness, and eventually to coma and even death. Infants and children with increased ammonia levels may vomit frequently, be irritable, and be increasingly lethargic. If left untreated, they may experience seizures, have difficulty breathing, and may fall into a coma.

Problems with ammonia processing can arise from several sources, including:

• Rare inherited defects in the urea cycle – a deficiency or defect in one or more of the enzymes necessary to complete the conversion of ammonia to urea
• Severe liver disease – damage limits the ability of the liver to metabolise ammonia. Sudden increases in ammonia may be seen in patients with stable liver disease, especially following a triggering event such as a bleed in the stomach.
• Decreased blood flow to the liver – ammonia is less able to be processed by the liver  Drugs – some drugs e.g. the antiepileptic valproate may sometimes lead to increased ammonia. Aspirin is thought to be involved in Reye’s syndrome, a cause of increased ammonia in children.

How is it used?

The ammonia test is primarily used to help investigate the cause of changes in behaviour and consciousness. It may be ordered, along with other tests (such as glucose, electrolytes, and kidney and liver function tests), to help diagnose the cause of a coma or to help support the diagnosis of Reye’s syndrome or hepatic (liver) encephalopathy. An ammonia test may also be ordered to help detect and evaluate the severity of a urea cycle defect.

Some doctors use the ammonia test to monitor the effectiveness of treatment of hepatic encephalopathy, but there is not widespread agreement on its clinical utility. Since hepatic encephalopathy can be caused by the build-up of a variety of toxins in the blood and brain, blood ammonia levels correlate poorly with the degree of impairment.

When is it requested?

An ammonia test may be ordered on a newborn when symptoms such as irritability, vomiting, lethargy and seizures arise in the first few days after birth. It may be performed when a child develops these symptoms about a week following a viral illness such as flu or a cold and the doctor suspects that the child may have Reye’s syndrome.

When adults experience mental changes, disorientation, sleepiness, or go into a coma, an ammonia test may be ordered to help evaluate the cause of the change in consciousness especially with pre-existing liver disease. In patients with stable liver disease, an ammonia level may be ordered, along with other liver function tests, when a patient suddenly ‘takes a turn for the worse’ and becomes more acutely ill.

What does the result mean?

Significantly increased concentrations of ammonia in the blood indicate that the body is not effectively processing ammonia but do not indicate the cause. In infants, extremely high levels are associated with an inherited urea cycle enzyme deficiency or defect. Moderate short-lived increases in ammonia are relatively common in newborns, where the levels may rise and fall without causing detectable symptoms. Acute illness and seizures may cause raised blood ammonia levels, especially in children.

Increased ammonia levels and decreased glucose levels may indicate the presence of Reye’s syndrome in symptomatic children and adolescents. Increased concentrations may also indicate a previously undiagnosed enzymatic defect of the urea cycle. In children and adults, elevated ammonia levels may also indicate liver or kidney damage. Frequently, an acute or chronic illness will act as a trigger, increasing ammonia levels to the point that an affected patient has difficulty clearing them.

Normal concentrations of ammonia do not rule out hepatic encephalopathy. Not only do other wastes contribute to the changes in mental function and consciousness, but brain levels of ammonia may be much higher than blood levels, making correlation of symptoms to blood levels of ammonia difficult.

Is there anything else I should know?

Increased levels of ammonia may also be seen with:

• Gastrointestinal bleeding – blood cells are haemolysed (broken apart) in the intestines, releasing protein which is digested, absorbed and converted into ammonia.
• Muscular exertion – muscles produce ammonia when active and absorb it when resting.
• Tourniquet use – ammonia levels can be increased in the blood sample collected when the tourniquet has been applied for a long time.
• Use of certain drugs such as valproate.
• Smoking

Some of the urea cycle disorders may be routinely tested in certain newborn screening programmes.

Common questions

• Is ammonia testing used to detect or monitor ammonia poisoning?

No, it is not considered clinically useful. In most cases, ammonia acts locally, burning or irritating whatever it comes in contact with but, according to the Agency for Toxic Substances and Disease Registry (ATSDR), it does not usually act as a systemic poison. Concentrated commercial ammonia, in a liquid or vapour form, causes more severe burns than the more dilute liquid household ammonia, but both can cause damage to the eyes, skin, respiratory tract, and to the mouth, throat and stomach if swallowed.

More information

RCPA Manual: Ammonia