Ammonia
Ammonia is produced in the gastrointestinal tract by the action of bacterial enzymes on proteins
and amino acids. It enters the portal circulation and is normally metabolized in the liver to urea
and glutamine. When the liver is unable to perform this function, increased amounts of
ammonia enter the arterial circulation and diffuse across the blood-brain barrier. Helicobacter
pylori in the stomach appear to be an important source of ammonia in patients with cirrhosis.
The use of ammonia for monitoring patients with hepatic encephalopathy is controversial. It is
unlikely that ammonia is solely responsible for the encephalopathy of hepatic insufficiency.
Plasma ammonia levels have usually been found to correlate poorly with the clinical stage of
hepatic encephalopathy. A normal level does not rule out early stage hepatic encephalopathy.
Measuring plasma ammonia may be useful in suggesting a hepatic origin for an encephalopathy
of unknown origin. It is not useful in patients with known liver disease.
Elevated levels are also seen in:
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Reye's syndrome and other urea cycle enzyme deficiencies
Acute leukemia
Bone marrow transplantation
Blood transfusion
Portal-systemic shunts
Gastrointestinal bleeding
Chronic renal failure
Many factors can affect ammonia levels:
Age Four- to eightfold higher in neonates; two- to threefold higher in children ,3 years; reaches
adult concentrations by adolescence
Specimen source: Arterial ammonia is higher than venous; differences are greater in renal,
hepatic disease; capillary blood shows falsely increased because of NH3 is present in sweat if
skin inadequately cleaned. Arterial NH3 correlates better with change in liver function than
venous NH3; tourniquet use, clenching fist increase venous NH3
Exercise Increases up to threefold after exercise. Increase is greater in males than in females.
Smoking Increases 10 mmol/L after 1 cigarette
Delay in analysis NH3 increases because of metabolism by red blood cells: 20% in 1 h and 100%
by 2 h. Use of ice water, rapid centrifugation, and separation of plasma minimize increases; rate
of increase higher in liver disease because of high GGT activity in specimen releasing NH3 from
peptides
Other factors Increased in acute leukemia, blood transfusion, bone marrow transplantation,
portal-systemic shunts, gastrointestinal bleeding, or high protein intake
Medications Valproic acid and glycine (in irrigation fluids used in prostate, endometrial
resection) increase NH3 production
Reference range is 10 - 40 umol/L.
Cautions
 Ideally, arterial, rather than venous, specimens should be used
 Plasma should be separated from cells within 15 min of collection to prevent artifactual
increases in NH3
 Blood should be drawn without a tourniquet and then placed in ice for immediate
transport to the lab. The tube should be full and must be kept tightly stoppered. It
should be centrifuged immediately and the plasma separated into a screw top plastic
vial. If the vial cannot be delivered to the lab immediately, it should be frozen at -70 C.
Reference
D. Robert Dufour,John A. Lott, Frederick S. Nolte, David R. Gretch,Raymond S. Koff, and Leonard
B. Seeff Diagnosis and Monitoring of Hepatic Injury. I. Performance Characteristics of
Laboratory Tests Clinical Chemistry 46:12 2027–2049 (2000)
Howanitz JH, Howanitz PJ, Skrodzki CA, Iwanski JA. Influences of specimen processing and
storage conditions on results for plasma ammonia. Clin Chem 1984;30:906–8.