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[Conditions](https://durgical.com/en/conditions/) · [Metabolism: amino acids and the urea cycle](https://durgical.com/en/conditions/)

# 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.

- [Liver](https://durgical.com/en/anatomy/liver/)
- [White matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/)
- [Portal vein](https://durgical.com/en/anatomy/hepatic-portal-vein/)
- [Frontal lobe](https://durgical.com/en/anatomy/superior-frontal-gyrus/)
- [Thalamus](https://durgical.com/en/anatomy/thalamus/)

## In biochemistry

- [Urea cycle: Entry · Carbamoyl phosphate synthetase I (CPS-I)](https://durgical.com/en/biochemistry/pathways/urea-cycle/#paso-0)
- [Urea cycle: Step 2 · Argininosuccinate synthetase (ASS)](https://durgical.com/en/biochemistry/pathways/urea-cycle/#paso-2)
- [Urea cycle: Step 3 · Argininosuccinate lyase (ASL)](https://durgical.com/en/biochemistry/pathways/urea-cycle/#paso-3)
- [Urea cycle: Step 4 · Arginase 1](https://durgical.com/en/biochemistry/pathways/urea-cycle/#paso-4)
- [Malate–aspartate shuttle: Step 5 · Aspartate–glutamate carrier (aralar SLC25A12, citrin SLC25A13)](https://durgical.com/en/biochemistry/pathways/malate-aspartate-shuttle/#paso-5)
- [Ammonia (ammonium)](https://durgical.com/en/biochemistry/molecules/ammonia/)
- [Urea](https://durgical.com/en/biochemistry/molecules/urea/)
- [Glutamine](https://durgical.com/en/biochemistry/molecules/glutamine/)
- [Carbamoyl phosphate synthetase I (CPS-I)](https://durgical.com/en/biochemistry/enzymes/carbamoyl-phosphate-synthetase-i/)
- [Ornithine transcarbamylase (OTC)](https://durgical.com/en/biochemistry/enzymes/ornithine-transcarbamylase/)
- [Argininosuccinate synthetase (ASS)](https://durgical.com/en/biochemistry/enzymes/argininosuccinate-synthetase/)
- [Argininosuccinate lyase (ASL)](https://durgical.com/en/biochemistry/enzymes/argininosuccinate-lyase/)
- [Arginase 1](https://durgical.com/en/biochemistry/enzymes/arginase-1/)
- [Glutamate dehydrogenase (GDH)](https://durgical.com/en/biochemistry/enzymes/glutamate-dehydrogenase/)
- [Glutamine synthetase](https://durgical.com/en/biochemistry/enzymes/glutamine-synthetase/)
- [Transamination and deamination](https://durgical.com/en/biochemistry/topics/transamination-and-deamination/)

## In physiology

- [Functions of the liver](https://durgical.com/en/physiology/functions-of-the-liver/)

## 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

## Red flags

- Altered consciousness with very high ammonia
- Signs of cerebral oedema (bradycardia, hypertension, abnormal pupils)
- A lethargic newborn without a clear cause

## Diagnosis

**Clinical**
Unexplained encephalopathy at any age, especially with vomiting or with [liver](https://durgical.com/en/anatomy/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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/conditions/hyperammonaemia/)

## Related conditions

- [Ornithine transcarbamylase (OTC) deficiency](https://durgical.com/en/conditions/ornithine-transcarbamylase-deficiency/)
- [Propionic acidaemia](https://durgical.com/en/conditions/propionic-acidaemia/)
- [Methylmalonic acidaemia](https://durgical.com/en/conditions/methylmalonic-acidaemia/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Portal hypertension](https://durgical.com/en/conditions/portal-hypertension/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Ammonia Levels: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/ammonia-levels/) (MedlinePlus, US National Library of Medicine, 2026); [Hereditary urea cycle abnormality: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000372.htm) (MedlinePlus, US National Library of Medicine, 2026); [Loss of brain function - liver disease: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000302.htm) (MedlinePlus, US National Library of Medicine, 2026).

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Source: https://durgical.com/en/conditions/hyperammonaemia/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/hyperammonaemia/