Ammonia

Ammonia is produced in the gastrointestinal tract by the action of bacterial and mucosal cell 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. High ammonia levels interfere with neuron transmission, leading to hepatic encephalopathy. Ammonia also enters astrocytes, where glutamine synthetase converts ammonia and glutamate into glutamine, which acts as an osmolyte. Astrocyte volume is increased, leading to brain edema. The risk of cerebral edema increases with arterial ammonia levels that exceed 200 μmol per liter (340 μg per deciliter).

Measuring plasma ammonia may be useful in suggesting a hepatic origin for an encephalopathy of unknown origin. Measurement of ammonia in patients with known hepatic encephalopathy is controversial. If a patient is known to have chronic liver disease, a normal level does not rule out hepatic encephalopathy. Elevated ammonia levels correlate to some extent with the severity of hepatic encephalopathy, but ammonia levels substantially overlap among patients with differing clinical grades of hepatic encephalopathy.

Management of hepatic encephalopathy includes administration of lactulose or lactilol which are nonabsorbable disaccharides with laxative effects. They change the gut microbiome to non–urease-producing bacteria, reducing intestinal ammonia production. Measuring serum ammonia levels may be helpful in monitoring the efficacy of ammonia lowering therapy.

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 to 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 varies with age.

Age Ammonia Level (uMol/L)
Birth to 14 days 4 - 107
15 days to 1 month 56 - 92
1 month to 18 years 21 - 50
>18 years 9 - 35

Ideally, arterial, rather than venous, specimens should be collected. Postprandial ammonia levels may be more closely related to minimal hepatic encephalopathy than fasting levels.  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 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.

Ong JP, Aggarwal A, Krieger D, et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 2003;114:188-193.

Ge PS, Runyon BA. Serum ammonia level for the evaluation of hepatic encephalopathy. JAMA 2014;312:643-644

AddThis Social Bookmark Button