Introduction to hyperammonemia and disorders of the urea cycle
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The treatment of the patient with hyperammonemia has many common features relevant to states of elevated ammonia, regardless of cause. Therapy must not be delayed because coma duration of less than 1.5 days [8] and timely start of treatment are the most important determinants of outcome. Specialized pediatric hospitals should have first-line medications, consensus-based treatment-protocols and should act according or similar to the following principles of a recently published guideline [9]: Nothing by mouth. Stop protein intake. Immediately start infusion of 10% glucose.Tailor i.v. fluid and glucose substitution (see Table 25.1).Start first-line medication (see Table 25.2).Collect plasma and urine for diagnostic purposes without delaying therapy.
Posttransplantation critical care management
Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell in LUNG Transplantation, 2016
Early hyperammonemia and associated coma are well-described, potentially fatal complications after lung transplantation. Typically, hyperammonemia is characterized by encephalopathy, psychomotor agitation, seizures, or coma. The pathophysiology remains elusive. Treatment is supportive, and a high caloric intake is recommended. Discontinuation of exogenous nitrogen, increased caloric intake to suppress catabolism, alternative waste nitrogen agents (such as sodium benzoate or phenyl acetate), and hemodialysis to remove brain ammonia and glutamine are considered reasonable interventions in patients with secondary hyperammonemic coma. Aggressive management is pivotal to improving clinical outcomes because of the apparent existence of a point of irreversibility, after which efforts to decrease ammonia levels are ineffective.
Experimental and Clinical States of Hyperammonia: Alterations in Glutamate and Glutamine
Elling Kvamme in Glutamine and Glutamate in Mammals, 1988
Most states of hyperammonemia are due either to specific defects in the urea cycle or to severe liver disease, in which all liver functions, including urea synthesis, are decreased. Indeed, hyperammonemia and encephalopathy in cirrhosis were inversely correlated with the maximal rate of urea synthesis.94 There is some evidence that liver ammonia metabolism may be altered by portacaval shunts. Glutamine synthetase activity declined by two thirds 3 to 4 weeks after rats had an end-to-side portacaval shunt.95 The small fraction of ammonia converted to glutamine in the liver may thus be even less after this procedure. In hepatic failure, the pattern of hepatocyte damage may determine the disposition of ammonia in the liver. Glutamine synthetase was shown to be localized in the area surrounding the central vein in the rat.96 When pericentral hepatocyte damage was produced in rats with carbon tetrachloride, urea synthesis remained normal, while glutamine production fell.97
Schizandrin ameliorates behavioral disorders in hepatic injury mice via regulation of oxidative stress and neuroinflammation
Published in Immunopharmacology and Immunotoxicology, 2021
Tingxu Yan, Bing Liu, Fuyuan Li, Bo Wu, Feng Xiao, Bosai He, Ying Jia
Chronic liver disease (CLD) is the progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis [1]. The mortality of CLD patients remains high not only due to irreversible cirrhosis, but also multiple complications such as mental disease, especially depression [2]. Clinical studies have shown that some patients with CLD have more severe depressive tendencies [3]. Hyperammonemia is a common event that occurs in CLD and characterized by an elevated level of ammonia [4]. Ammonia is the best identified central nervous system toxin, which triggers a variety of neurological complications. Hyperammonemia can alter the mitochondrial function and neurotransmission and induce oxidative stress [5]. Ammonia-induced oxidative stress occurs due to increased production of reactive oxygen species (ROS), malondialdehyde (MDA), and subsequent damage of proteins, lipids, and DNA. In addition, hyperammonemia is usually accompanied by a significant increase in peripheral inflammatory cytokines, including TNF-α and IL-1β, which will amplify the cascade of inflammatory responses and then induce neuroinflammation [6]. It was reported that chronic exposure of d-galactose (d-GaIN) induced hyperammonemia and liver damage [7], and ammonia overload speeds up the production of ROS and increase of inflammation response. Therefore, d-GaIN-induced CLD model has been commonly used for the anti-oxidative stress and anti-inflammation study.
Hyperammonemia in the setting of Roux-en-Y gastric bypass presenting with osmotic demyelination syndrome
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Carly Rosenberg, Michael Rhodes
Hyperammonemia is most commonly associated with liver disease. It can cause a multitude of neurotoxic effects such as cerebral edema, brain herniation and ultimately death. Multiple case reports have now shown that Roux-en-Y gastric bypass (RYGB) can be a causative factor of hyperammonemia in the absence of liver disease [1–4]. The exact underlying mechanism is not entirely clear, but due to alteration of the gut microbiome in association with nutritional deficiencies, these are thought to be the two main reasons for increased ammonia level [1]. Although more commonly hyperammonemia neurotoxicity would be expected to cause cerebral edema, we present a case of a patient with a history of RYGB who unfortunately developed osmotic demyelination syndrome. Osmotic demyelination syndrome was speculated to be secondary to hyperammonemia. Few case reports have made this association previously; however, there is a possible underlying relationship between the two [5,6].
Phytochemical constituents and protective efficacy of Schefflera arboricola L. leaves extract against thioacetamide-induced hepatic encephalopathy in rats
Published in Biomarkers, 2022
Ali M. El-Hagrassi, Abeer F. Osman, Mostafa E. El-Naggar, Noha A. Mowaad, Sahar Khalil, Manal A. Hamed
Hepatic encephalopathy (HE) is one of the most dangerous side effects of liver diseases. It is a neuropsychiatric syndrome that develops as a result of acute or chronic liver failure. Anxiety, shorter attention span, sleep problems, personality change, impaired consciousness levels that eventually progresses to coma may appear as a result of HE and depending on the original cause of the existing liver injury (Lopez-Franco et al. 2021). Patients with HE have an exceedingly high death rate, ranging from 50 to 90% (Allampati and Mullen 2019). The pathophysiology of HE is complicated and the variables that link hepatic and neural system damage are still unknown (Wijdicks 2016). Hyperammonemia, on the other hand, is widely accepted as the cause of HE’s clinical, pathological, and neurochemical alterations. Others have suggested that HE development is influenced by inflammation (Sun et al. 2020) and oxidative stress (Montes-Cortes et al. 2018). Therefore, finding and testing effective techniques to treat and protect against acute liver and brain injury is a challenge.