Ammonia

Adult: 10-80 mcg/dL or 6-47 μmol/L (SI units)

Child: 40-80 mcg/dL

Newborn: 90-150 mcg/dL

Ammonia: < 50 mcg/dL paracentesis fluid

Ammonia cerebrospinal fluid (CSF) level: 10-35 mg/dL (5.87-20.5 mmol/L) ^[1]

Conditions associated with “high” ammonia levels include the following ^[2] :

• Inherited urea cycle defect

• Hemolytic disease in infants (erythroblastosis fetalis)

• Reye syndrome

• Liver disease, cirrhosis

• Hepatic coma (not reflective of degree of coma)

• Gastrointestinal (GI) hemorrhage

• Renal disease

• HHH syndrome: hyperornithinemia, hyperammonemia, homocitrullinuria

• Transient hyperammonemia of newborn

• Certain inborn errors of metabolism of urea (which the exception of argininosuccinic aciduria)

• Total parenteral nutrition (TPN)

• Ureterosigmoidostomy

• GI tract infection with distention and stasis

• Asparagine intoxication

• Portal hypertension

• Severe heart failure with congestive hepatomegaly

• GI bleeding with mild liver disease

• GI obstruction with mild liver disease ^[1]

• Disseminated Ureaplasma bacteria ^[3]

​Conditions associated with “low” ammonia levels include the following:

• Essential or malignant hypertension

• Use of certain antibiotics  (eg, neomycin)

• Hyperornithinemia

• Hypothyroidism (rare) ^[4]

Other states that can affect ammonia levels include the following:

• Severe GI bleeding

• Muscle activity

• Excessive tourniquet use to collect blood samples

• Hemolysis

• Cigarette smoking ^[1]

• Cannabis intake ^[5]

• Delays in transportation to the laboratory after collection or before completion of analysis ^[6]

Drugs that can increase ammonia levels include the following:

• Alcohol

• Barbiturates

• Diuretics

• Valproate

• Narcotics

• Smoking

Drugs that may cause decreased levels include the following ^[1] :

• Broad-spectrum antibiotics

• Lactobacillus

• Lactulose

• Levodopa

• Potassium salts

Specifics regarding collection and panels are as follows:

• Specimen type: Blood plasma; serum not acceptable, urine ammonia

• Container: Vacutainer (chilled heparin tube)

• Collection method: Venipuncture

Blood should be brought on ice within 10 minutes to the laboratory for testing.

• Panels: Urine analysis

• Related test: Liver panel

Description

Ammonia is a compound produced by intestinal bacteria and cells during the digestion of protein. It is transported through the portal vein to the liver, where the ammonia is converted to glutamine that is then metabolized by the kidneys into the final product, urea, which is excreted. If the liver is diseased, the ammonia, instead of being broken down, will build up in the blood. It can pass through the blood-brain barrier, ultimately causing hepatic encephalopathy, a condition that produces mental and neurologic changes that manifest as confusion, disorientation, and sleeplessness. Untreated patients may experience seizures and breathing difficulty and may lapse into a coma. ^{[7, 8, 9, 10]}

Hyperammonemia causes hyperbilirubinemia, as it inhibits cell growth, induces apoptosis, and damages the mitochondria of the hepatocytes. This results in reduced energy synthesis, which in turn impacts the expression of enzymes associated with bilirubin metabolism. ^[11]

Moreover, hyperammonemia mediates increased skeletal muscle autophagy and may contribute to sarcopenia of cirrhosis. ^[12]

Metabolic recycling of ammonia via glutamate dehydrogenase 2 increases glutamate production, which supports breast cancer biomass and cancer cell proliferation under glutamine depletion. ^{[13, 14]}

Indications/Applications

The test is used to help determine the cause of changes in behavior and consciousness, to confirm a diagnosis of Reye syndrome or hepatic encephalopathy caused by liver disease, to evaluate a urea cycle defect, or to investigate the cause of coma of unknown origin.

Indications for the test in newborns include the following:

• Irritability

• Vomiting

• Lethargy

• Seizures in the first few days following birth

Indications for the test in children in whom Reye syndrome is suspected include the following:

• Irritability

• Vomiting

• Lethargy

• Seizures following a viral illness

• Infection

• Cold

Indications for the test in adults include the following:

• Mental changes

• Sleepiness

• Coma

• An acute change for the worse in patients with liver disease

• TPN use (hyperalimentation)

Causes of problems in metabolizing/breaking down ammonia include the following:

• Liver disease

• Decreased blood flow to the liver

• Reye syndrome (increased ammonia and decreased glucose)

• Renal failure

• Inherited defects in the urea cycle enzyme deficiency

• Hemolytic disease of the newborn

Causes of increased ammonia levels in patients with advanced liver disease include the following:

• High protein intake

• Gastrointestinal bleeding

• Hypokalemia

• Metabolic alkalosis

• High-dose chemotherapy

• TPN

• Renal insufficiency

• Shock

• Ureterosigmoidostomy

Note: In hepatic encephalopathy, brain levels of ammonia may be much higher than blood ammonia levels.

Considerations

The test measures the amount of ammonia in the blood. Patients should not smoke before collection of the sample.

Because other waste products can result in changes in mental and neurological performance, the ammonia level may not correlate accurately with the patient's symptoms.

Hemolysis should be avoided and the specimen should be sent promptly to the laboratory. ^[1]

Glucose levels over 500 mg/dL may interfere with the test.