Lab Test: Ammonia, NH3 (Blood) Level
Since the liver is primarily responsible for metabolizing ammonia to blood urea nitrogen for elimination, it is used most commonly for the evaluation and diagnosis of severe liver diseases (fulminant hepatitis or cirrhosis), in the work up and follow-up of hepatic encephalopathy, patients taking valproic acid while presenting with some change in mental status concerning for drug-induced hyperammonemia, and work up in a patient with acute changes in mental without a clear etiology.
- Adults: 10-80 mcg/dL (6-47 µmol/L)
- Neonates, 0 to 10 days (enzymatic): 170-341 mcg/dL (100-200 µmol/L)* (PDR). 90-150 mcg/dL
- Infants and toddlers, 10 days to 2 year (enzymatic): 68-136 mcg/dL (40-8- micromole/L)
- Children, older than 2 years (enzymatic): 19-60 mcg/dL(11-35 µmol/L)
- Suspected hepatic encephalopathy in liver cirrhosis - elevated levels correlate with the severity of hepatic encephalopathy. No significant difference between the correlation of venous ammonia with hepatic encephalopathy and the correlation of arterial ammonia with hepatic encephalopathy.
- Suspected inborn error of metabolism associated with hyperammonemia in children (ammonia levels and associated signs):
- 50 to 100 µmol/L: usually asymptomatic
- 100 to 200 µmol/L: anorexia, vomiting, ataxia, irritability, hyperactivity
- Above 200 µmol/L: Stage II coma, combative state followed by stupor
- Above 300 µmol/L: Stage III coma, responsive only to painful stimuli
- Above 500 µmol/L: Elevated intracranial pressure, stage IV coma, decerebrate posturing
- Above 1000 µmol/L: About 50% survive
- Ammonia levels seen in inborn errors of metabolism:
- Urea cycle defects: 500 to 2000 µmol/L
- Organic acidemia: 100 to 1000 µmol/L
- Transport defects of urea cycle intermediat4es: 100 to 300 µmol/L
- Fatty acid oxidation defects: Normal to 300 µmol/L
- Pyruvate metabolism disorders: Normal to 600 µmol/L
- Almost all patients with ammonia levels over 500 µmol/L likely have an inborn error of metabolism.
- Valproic acid use while also presenting with change in mental status.
- Suspected Reye's syndrome - due to fatty infiltration of the liver ammonia metabolism can be impaired and levels are elevated at least 150% in 90% of patients, typically in the range of 100 to 350 µmol/L.
- According to some sources, ammonia levels usually peak during the 2 to 3 days following the onset of vomiting and then decline rapidly. Levels may be normal if taken too early or too late in the course of illness.
- Peak ammonia levels usually occur within 4 hours of admission. Patients with levels greater than 3 times normal usually require fluid restriction, controlled hyperventilation, and mannitol, while those with levels greater than 5 times normal should be placed in a barbiturate coma.
- Peak ammonia level is a good predictor of the severity of illness. A level greater than 300 mcg/dL indicates a poor prognosis.
- Ammonia levels should be obtained daily during acute Reye's syndrome.
- Primary hepatocellular disease, Reye syndrome, asparagine intoxication: there are not enough functioning hepatocytes (liver cells) to metabolize the ammonia.
- Portal hypertension, severe heart failure with congestive hepatomegaly: portal blood flow from the gut to the liver is altered and.
- Hemolytic disease of newborn (erythroblastosis fetalis) RBCs contain high amounts of ammonia because the newborn liver is not mature enough to metabolize all the ammonia presented to it by the hemolysis that occurs in this disease.
- GI bleed: blood in the stomach is broken down and results in an increase in protein load that generate more BUN. This is usually seen as an elevated BUN:Cr of 20-30:1 because an impaired liver may not be able to keep up with the increased load of ammonia presented to it.
- Hepatic encephalopathy and hepatic coma: these neurologic states are a result of ammonia acting as false neurotransmitters. The brain cannot function properly.
- Genetic metabolic disorder of urea cycle - disruption of the urea cycle will inhibit excretion of ammonia and levels can be expected to rise.
- Alanine aminotransferase (ALT)
- Aspartate aminotransferase (AST)
- Alkaline phosphatase (ALP)
- Hemolysis increases ammonia levels because the red blood cells have about three times the ammonia level content of plasma.
- Muscular exertion can increase levels.
- Cigarette smoking can product significant increases in levels within 1 hour of inhalation.
- Ammonia levels may be factitiously increased if the tourniquet is too tight for a long period.
- Drugs that may cause increased ammonia levels include: acetazolamide, alcohol, ammonium chloride, barbiturates, diuretics (loop, thiazide), narcotics, parenteral nutrition, and valproic acid.
- Drugs that may cause decreased levels include: broad-spectrum antibiotics (e.g., neomycin), lactobacillus, lactulose levodopa, and potassium salts.
- Collect a venous blood sample. Note that some institutions require the specimens to be sent to the laboratory in an iced container.
- Avoid having patient clench fist or using tight tourniquet during blood draw because muscle contraction and ischemia may cause ammonia to be released into venous blood.
- Avoid hemolysis.
- Apply pressure or a pressure dressing to the venipuncture site and assess the site for bleeding.
- Many patients with liver disease have prolonged clotting times.
- Place specimen on ice and transport to lab immediately because levels increase on standing.
- Explain the procedure to the patient. Note that no fasting is required.
Ammonia is a by-product of both endogenous and exogenous protein catabolism. However, much of it is made by bacteria acting on proteins present in the gastrointestinal tract. Once ammonia is produced, it goes to the liver, where it is normally converted into urea and then secreted by the kidneys (as blood urea nitrogen; BUN). Once a significant amount of hepatocellular dysfunction occurs, ammonia cannot be catabolized and thus begins to accumulate. Furthermore, when portal blood flow to the liver is altered, as in portal hypertension ammonia cannot reach the liver to be catabolized.
Congenital disorders can include inherited deficiencies of urea cycle enzymes, inherited metabolic disorders of organic acids, and the dibasic amino acids lysine and ornithine, which are all known to be associated with high ammonia levels in infants and adults. If there is impaired renal function present it only further diminishes excretion of ammonia, and the blood levels rise that can give rise to the development of encephalopathy and coma.
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