Severe hyperammonaemia in adults not explained by liver disease

Abstract

Ammonia is produced continuously in the body. It crosses the blood-brain barrier readily and at increased concentration it is toxic to the brain. A highly integrated system protects against this: ammonia produced during metabolism is detoxified temporarily by incorporation into the non-toxic amino acid glutamine. This is transported safely in the circulation to the small intestine, where ammonia is released, carried directly to the liver in the portal blood, converted to non-toxic urea and finally excreted in urine. As a result, plasma concentrations of ammonia in the systemic circulation are normally very low (,40 mmol/L). Hyperammonaemia develops if the urea cycle cannot control the ammonia load. This occurs when the load is excessive, portal blood from the intestines bypasses the liver and/or the urea cycle functions poorly. By far, the commonest cause is liver damage. This review focuses on other causes in adults. Because they are much less common, the diagnosis may be missed or delayed, with disastrous consequences. There is effective treatment for most of them, but it must be instituted promptly to avoid fatality or long-term neurological damage. Of particular concern are unsuspected inherited defects of the urea cycle and fatty acid oxidation presenting with catastrophic illness in previously normal individuals. Early identification of the problem is the challenge.

Hyperammonemia in ICU patients: A frequent finding associated with high mortality

“…Hyperammonemia may induce encephalopathy, which can range from mild cognitive disturbances to coma, cerebral edema, brain stem herniation, and death [1]. Critically ill patients constitute a population where several risk factors for NHH are present [2,3].…”

Morphological changes of cortical pyramidal neurons in hepatic encephalopathy

“…It can diffuse into the capillaries of gut, and thence transferred to the hepatocytes for urea cycle [3]. The liver maintains the concentration of ammonia in the systemic circulation [4]. Hyperammonaemia develops if the urea cycle cannot control the ammonia overload.…”

Sudden severe hyperammonemia and status epilepticus -a case report-

“…Causes worth considering in patients with non-hepatic hyperammonemia include inborn errors of metabolism (defects of the urea cycle, fatty acid oxidation, organic acid disorders), circulatory shock with or without portosystemic shunt, hematological malignancies, urinary infection with urease-producing bacteria, anticonvulsants or chemotherapeutic drugs, and excessive amino acid load/increased catabolism [7]. Laboratory tests pertaining to enzyme deficiencies were not conducted in the present case because it was considered less worthwhile given the rapid clinical deterioration of the patient.…”