Hyperglutaminemia

Abstract: OBJECTIVE We report a case of a woman with hyperammonemic encephalopathy following glutamine supplementation. DESIGN Case report. INTERVENTIONS Plasma amino acid analysis suggestive of a urea cycle defect and initiation of a treatment with lactulose and the two ammonia scavenger drugs sodium benzoate and phenylacetate. Together with a restricted protein intake ammonia and glutamine plasma levels decreased with subsequent improvement of the neurological status. MEASUREMENTS AND MAIN RESULTS Massive catabolism and exogenous glutamine administration may have contributed to hyperammonemia and hyperglutaminemia in this patient. CONCLUSION This case adds further concerns regarding glutamine administration to critically ill patients and implies the importance of monitoring ammonia and glutamine serum levels in such patients.

Abstract: In order to specify the role of peripheral muscular tissue in ammonia metabolism, we studied, in rats, the variations of ammonia and glutamine levels in arterial and femoral venous blood after hepatectomy and abdominal evisceration with nephrectomy. In non-fasting rats this operation was immediately followed by an important hyperammonemia which was due to ammonia muscular release; glutamine blood levels increased only slightly without any modification in their arterio-femoral venous differences. The hyperammonemia induced by hepatectomy-evisceration was greatly reduced in animals which had been fasting for 48 hours but was not modified by a 72hrs preoperative sucrose feeding. These nutritional conditions did not change the blood glutamine variations which were first related to the abdominal evisceration. Indeed, in abdominal eviscerated rats without hepatectomy there was an important hyperglutaminemia with only a slight increase in blood ammonia. These results indicate that in rat 1) the liver plays an important part in skeletal muscle ammonia metabolism, 2) this metabolism is related to food ingestion, 3) the gastrointestinal tissue intervenes in glutamine metabolism.

Abstract: Summary Background Glutamine plasma concentrations outside the normal range at intensive care unit (ICU) admission are associated with unfavorable outcomes. Based on the hypothesis that hypoglutaminemia in the ICU is the result of an increased utilization of glutamine which cannot be fully met by endogenous production, extra glutamine supplementation has been advocated to ICU patients with hypoglutaminemia. However, it is still unclear whether there is a causal relation between hypo- and hyperglutaminemia and outcomes. Present guidelines advise against supplementation, although there is no evidence available for patients with hypoglutaminemia. The pathophysiology of abnormal glutamine levels and whether glutamine production or glutamine utilization is compromised is largely unknown. Therefore, the aim of this study was to elucidate the relationship between plasma glutamine levels and the endogenous glutamine production in ICU patients. Method In this observational study, a technique using a small bolus of intravenous glutamine with an isotopic label was used to measure glutamine production. Results There was a statistically significant correlation between de novo endogenous production of glutamine (not emanating directly from protein breakdown) and plasma glutamine concentrations in the low and normal range in circulatory stabilized ICU patients (n = 19), R2 = 0.35 (P ≤ 0.01). Conclusion The predictive value of a low plasma glutamine concentration at ICU admission on outcomes may thus be related to a low endogenous production, which may need to be supplemented in the best interest of this cohort of patients.

Abstract: The kinetics of ammonia, glutamine, and urea in the kidney has been studied in experiments on 203 white rats (females) at the end of chronic tetrachloromethane (CCl4) exposure (65 days) and within 14 days after cessation of CCl4. It was found that on the 65th day of CCl4 administration the arterial hyperammoniemia is formed, which lasts for 14 days after the abolition of the toxin. This is accompanied by an increased excretion of ammonia in the urine and an increase in its concentration in the blood of renal veins, which does not prevent its accumulation in renal tissue. In chronic CCl4-hepatitis model are the changes of glutamine concentration in arterial blood are developing by type of hypo- and hyperglutaminemia. CCl4 stimulates accumulation of glutamine by the kidneys at the end of exposure and at early stage of the recovery period. Toxin cessation activates processes which are stabilizing the normal concentration of glutamine in the kidney by changing glutamine incretion from kidney to renal blood flow. Long-lasting CCl4 exposure increases the concentration of urea in the arterial blood and its urinary excretion. Simultaneously urea reabsorption is activated in the kidneys, which contributes to an increase in its concentration in the blood of the renal veins.