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Ammonia (NH3)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Plasma/Serum Ammonia – Hepatic Encephalopathy Marker)

Synonyms

  • Ammonia
  • NH₃
  • Blood ammonia
  • Plasma ammonia
  • Venous ammonia
  • Arterial ammonia (critical care)

Units of Measurement

µmol/L, µg/dL, µg/100mL, µg%, µg/mL, µg/L, mg/L

Description

Ammonia (NH₃) is a toxic nitrogenous compound produced from:

  • Amino acid metabolism
  • Bacterial activity in the intestine
  • Renal ammoniagenesis
  • Muscle protein breakdown

Normally, the liver converts ammonia → urea via the urea cycle.
When liver function is impaired or blood flow bypasses the liver, ammonia accumulates, leading to hepatic encephalopathy (HE).

Ammonia measurement is essential for evaluating:

  • Hepatic encephalopathy
  • Acute liver failure
  • Urea cycle disorders
  • Reye syndrome
  • Severe neonatal illness

Physiological Role

  • Nitrogen transport intermediate
  • Acid–base balance (kidney generates NH₄⁺ to buffer acid load)
  • Brain neurotransmission (excess ammonia disrupts astrocytes → cerebral edema)

Clinical Significance

Elevated Ammonia (Hyperammonemia)

1. Liver-Related Causes

  • Acute liver failure
  • Cirrhosis with portosystemic shunting
  • Fulminant viral hepatitis
  • Alcoholic hepatitis

2. Urea Cycle Disorders (UCD)

  • Ornithine transcarbamylase deficiency
  • CPS-I deficiency
  • ASS/ASL deficiency

(Severe elevations → neonatal coma)

3. Medications / Toxins

  • Valproate toxicity
  • Chemotherapy
  • Carbamazepine
  • Salicylates
  • Toxins causing mitochondrial dysfunction

4. Other Causes

  • GI bleeding (↑ protein load)
  • Severe infection/sepsis
  • Reye syndrome
  • Gastric bypass / portosystemic shunts
  • Total parenteral nutrition
  • Renal failure (mild–moderate)

Ammonia > 150–200 µmol/L → risk of cerebral edema, especially in acute liver failure.

Low Ammonia

Not clinically significant; occurs rarely with:

  • Overheparinized sample
  • Excessive handling delays
  • Hypothermia

Reference Intervals

(Tietz 8E + Mayo + ARUP + AASLD)

Adults (Venous Plasma)

  • 10 – 50 µmol/L
  • ≈ 17 – 85 µg/dL

Arterial Plasma

  • Lower values: ~15–45 µmol/L
    (more accurate in hepatic encephalopathy)

Newborns

  • < 100 µmol/L normal
  • >150–200 µmol/L → strongly suggests UCD

Sample Collection – CRITICAL

Ammonia is unstable. Errors are common.

To ensure accuracy:

  • Collect in pre-chilled EDTA or heparin tube
  • Place on ice immediately
  • Centrifuge within 15–30 minutes
  • Avoid use of a tourniquet
  • Avoid fist clenching
  • Avoid hemolysis
  • Analyze promptly

Delayed processing → false elevation

Unit Meanings

UnitMeaning
µmol/Lmicromole per liter
µg/dLmicrogram per deciliter
µg/100 mLsame as µg/dL
µg%microgram per 100 mL
µg/mLmicrogram per milliliter
µg/Lmicrogram per liter
mg/Lmilligram per liter

Diagnostic Uses

1. Hepatic Encephalopathy

  • Elevated ammonia supports diagnosis
  • NOT a stand-alone diagnostic tool
  • Arterial ammonia correlates better with HE grade

2. Acute Liver Failure

High ammonia → indicates:

  • Cerebral edema risk
  • Need for ICU management
  • Predicts poor prognosis

3. Inborn Errors of Metabolism

Markedly high ammonia in neonates suggests:

  • Urea cycle defects
  • Organic acidemias (propionic, methylmalonic)
  • Fatty acid oxidation disorders

4. Monitoring Therapy

Used to monitor response to:

  • Lactulose
  • Rifaximin
  • Hemodialysis (in severe hyperammonemia)

Analytical Notes

  • Venous vs arterial sample differences must be noted.
  • Capillary samples inaccurate for ammonia.
  • Protein-rich meals may increase ammonia slightly.
  • Plasma preferred over serum.

Clinical Pearls

  • Ammonia correlates poorly with mental status in chronic HE.
  • Extremely high ammonia (>200–300 µmol/L) → consider UCD, not cirrhosis.
  • GI bleeding increases ammonia due to protein breakdown.
  • Valproate inhibits carbamoyl phosphate synthetase → hyperammonemia without liver failure.
  • Ammonia rises quickly after sample mishandling — a major cause of false positives.

Interesting Fact

Ammonia was first recognized as a cause of hepatic coma in the 1950s. Despite limitations, it remains an essential biomarker in acute liver failure and inborn metabolic disorders.

References

  1. Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Ammonia Testing.
  2. Mayo Clinic Laboratories - Ammonia Test Interpretation.
  3. ARUP Consult - Hyperammonemia Diagnostic Pathway.
  4. AASLD - Hepatic Encephalopathy Guidelines.
  5. IFCC - Analytical Recommendations for Ammonia.
  6. NIH / MedlinePlus - Ammonia Overview.
  7. Emergency Medicine & Hepatology Reviews - Ammonia in Critical Care.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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