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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:

  • 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.

  • Arterial levels are 20 – 30 umol/L higher than venous in patients with hepatic insufficiency
  • Arteriovenous difference is zero in normal individuals at rest
  • Tourniquet use during venipuncture increases ammonia levels
  • High protein intake increases ammonia levels
  • Exercise increases ammonia up to threefold (produced by muscle)
  • Smoking 1 cigarette increases ammonia by 10 umol/L
  • Delay in separation of plasma from RBCs increases ammonia by 20% in 1 hour and 100% in 2 hours.
  • Valproic acid increases ammonia production.
  • Irrigation fluids containing glycine increase ammonia production.

Reference range is 10 - 40 umol/L.

Ideally, arterial, rather than venous, specimens should be collected. Specimen requirement is one sodium or lithium heparin green top tube. 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.

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