Clinical Pearls & Morning Reports
Published September 27, 2023
Delays in diagnosis and management of noncirrhotic hyperammonemia after Roux-en-Y gastric bypass may result in a poor prognosis with a high risk of death. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: How is ammonia primarily excreted by the body?
A: All tissues produce ammonia as a byproduct of amino acid metabolism. The primary route of ammonia excretion is through the urea cycle, with urinary excretion of ammonia as urea. Hyperammonemic encephalopathy can occur when perturbations in ammonia metabolism lead to an elevated ammonia level. When measuring the serum ammonia level, the specimen must be obtained from a free-flowing venipuncture without the use of a tourniquet, stored on ice, and sent immediately to the laboratory; deviations from this process may lead to falsely elevated results.
Q: Name some of the nutritional deficiencies that are associated with a Roux-en-Y gastric bypass.
A: Patients who have undergone Roux-en-Y gastric bypass may develop macronutrient and micronutrient deficiencies that are related to poor oral intake and alterations in critical absorptive surfaces. Deficiencies associated with previous Roux-en-Y gastric bypass include deficiencies in vitamin C, vitamin B6, vitamin A, and trace minerals (zinc, copper, and selenium). The most common nutritional deficiencies that cause altered mental status after Roux-en-Y gastric bypass are deficiencies in vitamins B1 and B3.
A: Hyperammonemia can be caused by an increased protein load from an oral or parenteral source or from gastrointestinal bleeding. Hyperammonemia can also be caused by a catabolic state, such as severe malnutrition. Muscle is an important extrahepatic site of ammonia metabolism, and severe sarcopenia can lead to hyperammonemia. Certain drugs and toxins, including antiepileptic agents such as valproate, can cause urea-cycle dysfunction and hyperammonemia. Hyperammonemia can also be due to infections with urease-producing bacteria, including Klebsiella pneumoniae.
A: There is an increasingly recognized association between noncirrhotic hyperammonemia and a history of Roux-en-Y gastric bypass, and some experts have proposed naming this phenomenon the “gastric bypass hyperammonemia syndrome.” Case reports describe patients with hyperammonemic encephalopathy who are typically middle-aged and female and do not have clinically significant liver disease. Hyperammonemic encephalopathy may develop at various points after bypass surgery, with hallmark findings including hypoalbuminemia, nutritional deficiencies, an elevated plasma glutamine level, and a low zinc level. It has been hypothesized that undiagnosed hemizygous pathogenic variants in the gene that encodes ornithine transcarbamylase (OTC) in women could contribute to an elevated risk of urea-cycle dysfunction. A role for zinc deficiency in urea-cycle enzymatic dysfunction has also been hypothesized. Increased production of ammonia, portosystemic shunting, an altered intestinal microbiome, and a profound catabolic state after Roux-en-Y gastric bypass may all contribute to the pathogenesis of this syndrome, although more investigation is needed to understand this rare and unique disease.