Makindo Medical Notes

🧠 In acute liver failure, elevated blood ammonia levels have major prognostic value. Ammonia crosses the blood–brain barrier → astrocytes convert it into glutamine. Although glutamine is not directly toxic, it is osmotically active, causing astrocyte swelling → cerebral oedema & raised ICP. This explains why hyperammonaemia is so dangerous in liver failure.

⚡ Aetiology & Physiology

• Ammonia (NH₃) is formed during protein metabolism (from amino acids).
• The liver detoxifies ammonia via the urea cycle → excreted by the kidneys.
• Failure of this process (hepatic, genetic, or acquired) → accumulation in blood → neurotoxicity.

🚨 Causes of Hyperammonaemia

• Hepatic Encephalopathy: Triggered by constipation, infection, GI bleed, electrolyte imbalance, or sedatives.
• Portosystemic Shunts: Blood bypasses the liver → ammonia not metabolised.
• Drugs: Sodium valproate, salicylates, TPN, steroids.
• Genetic: Urea cycle disorders (e.g. Ornithine transcarbamylase deficiency).
• Reye’s Syndrome: Rare post-viral liver injury linked to aspirin in children.
• Sampling Errors: Prolonged tourniquet/fist clenching → false high values.

🩺 Clinical Features

• Early: Forgetfulness, irritability, mild confusion, sleep–wake disturbance.
• Progressive: Memory loss, poor concentration, ataxia, tremor (± asterixis).
• Severe: Seizures, coma, cerebral oedema, raised ICP → risk of herniation.

🔬 Investigations

• Arterial ammonia >200 µg/dL → strongly linked with cerebral herniation in acute liver failure.
• Venous samples are acceptable if taken into EDTA tubes and transported on ice quickly.
• Other labs: FBC, U&E, LFTs, INR/PT, albumin.
• Imaging: Liver US; CT/MRI brain if neurological decline.
• EEG may show triphasic waves (encephalopathy).

💊 Management Principles

• 🔹 Supportive ABC care (airway protection, ventilation, fluids).
• 🔹 Treat the underlying cause (e.g. stop valproate, manage sepsis, treat GI bleed).
• 🔹 Prevent sampling artefacts: send ammonia on ice, EDTA tube.
• 🔹 Specifics in hepatic encephalopathy:
  • Lactulose (reduce ammonia absorption).
  • ± Rifaximin for recurrent HE.
  • Correct precipitants (bleeding, infection, electrolyte imbalance).
• 🔹 In inherited urea cycle defects: consider sodium benzoate, sodium phenylbutyrate, or haemodialysis if severe.

📚 Reference

• Andersen LW et al. Etiology and therapeutic approach to elevated lactate and ammonia. Mayo Clin Proc. 2013.