Conditions · Metabolism: amino acids and the urea cycle
Hyperammonaemia !
Hyperammonaemia is too much ammonia in the blood. It can come from a genetic defect or a diseased liver and is an emergency for the brain.
Updated 2026-11-01
Structures involved
Tap one to see what it is and open it in 3D.
In biochemistry
- Urea cycle: Entry · Carbamoyl phosphate synthetase I (CPS-I)
- Urea cycle: Step 2 · Argininosuccinate synthetase (ASS)
- Urea cycle: Step 3 · Argininosuccinate lyase (ASL)
- Urea cycle: Step 4 · Arginase 1
- Malate–aspartate shuttle: Step 5 · Aspartate–glutamate carrier (aralar SLC25A12, citrin SLC25A13)
- Ammonia (ammonium)
- Urea
- Glutamine
- Carbamoyl phosphate synthetase I (CPS-I)
- Ornithine transcarbamylase (OTC)
- Argininosuccinate synthetase (ASS)
- Argininosuccinate lyase (ASL)
- Arginase 1
- Glutamate dehydrogenase (GDH)
- Glutamine synthetase
- Transamination and deamination
In physiology
What it is
A rise in plasma ammonia from more production or less removal. It is a feature shared by many diseases.
Who gets it
In adults the most common cause is cirrhosis with hepatic encephalopathy; in newborns, urea cycle disorders and organic acidaemias.
Causes
- Urea cycle disorders (CPS-I, OTC, ASS, ASL, arginase, NAGS)
- Organic acidaemias (propionic, methylmalonic)
- Cirrhosis, acute liver failure and portosystemic shunts
- Drugs such as valproic acid
- Hyperinsulinism–hyperammonaemia syndrome
Risk factors
- GI bleeding, infection, constipation or dehydration in cirrhosis
- Fasting, fever or childbirth in genetic defects
- Very high-protein diet
Pathophysiology
Ammonia crosses the blood–brain barrier. Astrocytes fix it as glutamine with glutamine synthetase; glutamine draws in water and causes cerebral oedema. It also disturbs neurotransmitters and uses up α-ketoglutarate, lowering neuronal energy.
Classification
- Primary: urea cycle defects
- Secondary: organic acidaemias, fatty acid oxidation defects, drugs
- Acquired: liver disease
Symptoms and signs
- Vomiting and refusal of food
- Drowsiness, confusion and behaviour change
- Asterixis in liver disease
- Seizures and coma
Diagnosis
- Clinical
- Unexplained encephalopathy at any age, especially with vomiting or with liver disease.
- Tests
- Plasma ammonia drawn without a tourniquet, on ice and processed fast; arterial gases, glucose, lactate and ketones; plasma amino acids, urine organic acids and orotic acid to find the cause; liver tests.
- Imaging
- Brain CT or MRI to rule out other causes and assess oedema; liver Doppler ultrasound in adults.
Treatment
- Acute
- Stop protein, give glucose to halt catabolism and correct the trigger
- Acute
- Haemodialysis when ammonia is very high or does not fall
- Medical
- Nitrogen scavengers (sodium benzoate and phenylacetate), arginine or carglumic acid depending on the genetic cause
- Medical
- In hepatic encephalopathy: lactulose and rifaximin
Complications
- Cerebral oedema and herniation
- Permanent neurological damage
- Death
Prognosis
It depends on the cause and how long ammonia stayed high; fast treatment improves the neurological outcome.
Test yourself
Think of the answer, then tap the question to see it.
How does ammonia harm the brain?
Astrocytes turn it into glutamine, which draws in water and causes oedema; it also uses up α-ketoglutarate and disturbs neurotransmitters.
Which test helps separate an OTC defect from a CPS-I defect?
Urinary orotic acid: high in OTC deficiency and normal in CPS-I or NAGS deficiency.
Why is lactulose used in hepatic encephalopathy?
It acidifies the colon, turning NH₃ into NH₄⁺ that is not absorbed, and speeds transit.
Related conditions
- Ornithine transcarbamylase (OTC) deficiency
- Propionic acidaemia
- Methylmalonic acidaemia
- Cirrhosis
- Portal hypertension
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Ammonia Levels: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Hereditary urea cycle abnormality: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Loss of brain function - liver disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.
