Ammonia

Ammonia

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Adult: 10-80 mcg/dL or 6-47 μmol/L (SI units)

Child: 40-80 mcg/dL

Newborn: 90-150 mcg/dL

Ammonia: < 50 mcg/dL paracentesis fluid

Ammonia cerebrospinal fluid (CSF) level: 10-35 mg/dL (5.87-20.5 mmol/L)^[1]

Conditions associated with “high” ammonia levels include the following^[2]:

Hemolytic disease in infants (erythroblastosis fetalis)

Reye syndrome

Liver disease, cirrhosis

Hepatic coma (not reflective of degree of coma)

Gastrointestinal (GI) hemorrhage

Renal disease

HHH syndrome: hyperornithinemia, hyperammonemia, homocitrullinuria

Transient hyperammonemia of newborn

Certain inborn errors of metabolism of urea (which the exception of argininosuccinic aciduria)

Total parenteral nutrition (TPN)

Ureterosigmoidostomy

GI tract infection with distention and stasis

Asparagine intoxication

Portal hypertension

Severe heart failure with congestive hepatomegaly

GI bleeding with mild liver disease

GI obstruction with mild liver disease^[1]

Disseminated Ureaplasma bacteria^[3]

Conditions associated with “low” ammonia levels include the following:

Essential or malignant hypertension

Use of certain antibiotics (eg, neomycin)

Hyperornithinemia

Hypothyroidism (rare)^[4]

Other states that can affect ammonia levels include the following:

Severe GI bleeding

Muscle activity

Excessive tourniquet use to collect blood samples

Hemolysis

Cigarette smoking^[1]

Cannabis intake^[5]

Delays in transportation to the laboratory after collection or before completion of analysis^[6]

Drugs that can increase ammonia levels include the following:

Alcohol

Barbiturates

Diuretics

Valproate

Narcotics

Smoking

Drugs that may cause decreased levels include the following^[1]:

Broad-spectrum antibiotics

Lactobacillus

Lactulose

Levodopa

Potassium salts

Specifics regarding collection and panels are as follows:

Specimen type: Blood plasma; serum not acceptable, urine ammonia

Container: Vacutainer (chilled heparin tube)

Collection method: Venipuncture

Blood should be brought on ice within 10 minutes to the laboratory for testing.

Panels: Urine analysis

Related test: Liver panel

Ammonia is a compound produced by intestinal bacteria and cells during the digestion of protein. It is transported through the portal vein to the liver, where the ammonia is converted to glutamine that is then metabolized by the kidneys into the final product, urea, which is excreted. If the liver is diseased, the ammonia, instead of being broken down, will build up in the blood. It can pass through the blood-brain barrier, ultimately causing hepatic encephalopathy, a condition that produces mental and neurologic changes that manifest as confusion, disorientation, and sleeplessness. Untreated patients may experience seizures and breathing difficulty and may lapse into a coma.^{[7, 8, 9, 10]}

Hyperammonemia causes hyperbilirubinemia, as it inhibits cell growth, induces apoptosis, and damages the mitochondria of the hepatocytes. This results in reduced energy synthesis, which in turn impacts the expression of enzymes associated with bilirubin metabolism.^[11]

Moreover, hyperammonemia mediates increased skeletal muscle autophagy and may contribute to sarcopenia of cirrhosis.^[12]

Metabolic recycling of ammonia via glutamate dehydrogenase 2 increases glutamate production, which supports breast cancer biomass and cancer cell proliferation under glutamine depletion.^{[13, 14]}

The test is used to help determine the cause of changes in behavior and consciousness, to confirm a diagnosis of Reye syndrome or hepatic encephalopathy caused by liver disease, to evaluate a urea cycle defect, or to investigate the cause of coma of unknown origin.

Indications for the test in newborns include the following:

Irritability

Vomiting

Lethargy

Seizures in the first few days following birth

Indications for the test in children in whom Reye syndrome is suspected include the following:

Irritability

Vomiting

Lethargy

Seizures following a viral illness

Infection

Cold

Indications for the test in adults include the following:

Mental changes

Sleepiness

Coma

An acute change for the worse in patients with liver disease

TPN use (hyperalimentation)

Causes of problems in metabolizing/breaking down ammonia include the following:

Liver disease

Decreased blood flow to the liver

Reye syndrome (increased ammonia and decreased glucose)

Renal failure

Inherited defects in the urea cycle enzyme deficiency

Hemolytic disease of the newborn

Causes of increased ammonia levels in patients with advanced liver disease include the following:

High protein intake

Gastrointestinal bleeding

Hypokalemia

Metabolic alkalosis

High-dose chemotherapy

TPN

Renal insufficiency

Shock

Ureterosigmoidostomy

Note: In hepatic encephalopathy, brain levels of ammonia may be much higher than blood ammonia levels.

The test measures the amount of ammonia in the blood. Patients should not smoke before collection of the sample.

Because other waste products can result in changes in mental and neurological performance, the ammonia level may not correlate accurately with the patient’s symptoms.

Hemolysis should be avoided and the specimen should be sent promptly to the laboratory.^[1]

Glucose levels over 500 mg/dL may interfere with the test.

Deska Pagana K, Pagana TJ, Pagana TN. Ammonia. Mosby’s Diagnostic and Laboratory Test Reference. 13th ed. St. Louis, Mo: Elsevier; 2017.

Talaska Fischbach F, Dunning MB III. Manual of Laboratory and Diagnostic Tests. 9th ed. Wolters Kluwer Health/Lippincott Williams & Wilkins; 2015.

Bharat A, Cunningham SA, Scott Budinger GR, et al. Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans. Sci Transl Med. 2015 Apr 22. 7 (284):284re3. [Medline]. [Full Text].

Diaz-Fontenla F, Castillo-Pradillo M, Diaz-Gomez A, et al. Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism. World J Gastroenterol. 2017 Jul 28. 23 (28):5246-52. [Medline]. [Full Text].

Abulseoud OA, Zuccoli ML, Zhang L, Barnes A, Huestis MA, Lin DT. The acute effect of cannabis on plasma, liver and brain ammonia dynamics, a translational study. Eur Neuropsychopharmacol. 2017 Jul. 27 (7):679-90. [Medline]. [Full Text].

Hashim IA, Cuthbert JA. Elevated ammonia concentrations: potential for pre-analytical and analytical contributing factors. Clin Biochem. 2014 Nov. 47 (16-17):233-6. [Medline].

Siracusa A, De Blay F, Folletti I, Moscato G, Olivieri M, Quirce S, et al. Asthma and exposure to cleaning products – a European Academy of Allergy and Clinical Immunology task force consensus statement. Allergy. 2013 Oct 16. [Medline].

Jazan E, Mirzaei H. Direct analysis of human breath ammonia using corona discharge ion mobility spectrometry. J Pharm Biomed Anal. 2013 Sep 10. 88C:315-320. [Medline].

Sathyamoorthy S, Chandran K, Ramsburg A. Biodegradation and Cometabolic Modeling of Selected Beta Blockers during Ammonia Oxidation. Environ Sci Technol. 2013 Oct 10. [Medline].

Zhang FY, Tang NH, Wang XQ, Li XJ, Chen YL. Simultaneous recovery of dual pathways for ammonia metabolism do not improve further detoxification of ammonia in HepG2 cells. Hepatobiliary Pancreat Dis Int. 2013 Oct. 12(5):525-32. [Medline].

Wang Q, Wang Y, Yu Z, et al. Ammonia-induced energy disorders interfere with bilirubin metabolism in hepatocytes. Arch Biochem Biophys. 2014 Aug. 555-6:16-22. [Medline].

Qiu J, Tsien C, Thapalaya S, et al. Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab. 2012 Oct 15. 303 (8):E983-93. [Medline]. [Full Text].

Spinelli JB, Yoon H, Ringel AE, Jeanfavre S, Clish CB, Haigis MC. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass. Science. 2017 Nov 17. 358 (6365):941-6. [Medline]. [Full Text].

Takeuchi Y, Nakayama Y, Fukusaki E, Irino Y. Glutamate production from ammonia via glutamate dehydrogenase 2 activity supports cancer cell proliferation under glutamine depletion. Biochem Biophys Res Commun. 2018 Jan 1. 495 (1):761-7. [Medline].

Noiret L, Baigent S, Jalan R. Arterial ammonia levels in cirrhosis are determined by systemic and hepatic hemodynamics, and organs function: a quantitative modelling study. Liver Int. 2013 Oct 17. [Medline].

Burtis CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th edition. WB Saunders: Philadelphia, PA; 2012.

PDR: Physicians’ Desk Reference. 2018.

Sridevi Devaraj, PhD, DABCC, FACB Medical Director of Clinical Chemistry and POCT, Texas Children’s Hospital; Professor of Pathology and Immunology, Baylor College of Medicine; Associate Director of Translation, Texas Children’s Microbiome Center

Disclosure: Nothing to disclose.

Sameh Gomaa, MBBS Physician, Al-Tonsy Al-Hadary Family Medicine Unit, Egypt

Sameh Gomaa, MBBS is a member of the following medical societies: Egyptian Medical Syndicate

Disclosure: Nothing to disclose.

Catherine Anastasopoulou, MD, PhD, FACE Associate Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Attending Endocrinologist, Department of Medicine, Albert Einstein Medical Center

Catherine Anastasopoulou, MD, PhD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Society for Bone and Mineral Research, Endocrine Society, Philadelphia Endocrine Society

Disclosure: Nothing to disclose.

Thomas M Wheeler, MD Chairman, Department of Pathology and Immunology, WL Moody, Jr, Professor of Pathology, Professor of Urology, Baylor College of Medicine

Thomas M Wheeler, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Medical Association, American Society for Clinical Pathology, American Society of Cytopathology, American Thyroid Association, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Harris County Medical Society