Thread by @Gastronaut___

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My understanding of Hepatic encephalopathy (HE)–nutrition–muscle–ammonia in Cirrhotics
#MedTwitter

1/n Simple picture :-

•Ammonia is produced in the gut and must be detoxified.

•The LIVER is the main detox organ (urea cycle); MUSCLE is the backup (converts ammonia to glutamine via glutamine synthetase).

•In cirrhosis, liver capacity falls → the muscle has to help more. If muscle is lost (sarcopenia), ammonia rises and HE worsens.

2/ Normal vs Cirrhosis : who detoxifies ammonia?

•Normal: Liver clears the vast majority (≈80–90%); extrahepatic tissues including skeletal muscle handle the rest (≈10–20%).

•Cirrhosis: Hepatic clearance drops (less hepatocyte mass, shunting). Muscle steps up and can account for a large share (up to ~40–50%) but only if there’s muscle to do it.
• With sarcopenia, this compensatory sink collapses → ammonia builds up → HE.

3/n Why protein is therapy in Cirrhotics :-

•Cirrhotics have low glycogen stores.
Even short fasting pushes them into “accelerated starvation” → gluconeogenesis from amino acids.

( whereby 10 hours of fasting in cirrhotics approximates to 3 days of starvation in a healthy individual.)

•If dietary protein is restricted, the body breaks down muscle to supply amino acids → sarcopenia.

•Less muscle = less ammonia detoxification capacity → higher ammonia → more HE.

•Therefore, adequate protein (1.2–1.5 g/kg/day) is essential to protect muscle and support ammonia disposal.
Late-night carb/protein snacks (LES) help prevent nocturnal catabolism.

4/n AAA vs BCAA ? why protein quality matters in cirrhotics

•Two key amino-acid groups:

•AAA (aromatic amino acids ): phenylalanine, tyrosine, tryptophan - normally cleared by liver.
•BCAA (branched-chain): leucine, isoleucine, valine - primarily used by muscle.

•In cirrhosis:
•The diseased liver can’t clear AAA → plasma AAA rise.
•Muscle uses more BCAA (as fuel and for ammonia handling) → plasma BCAA fall.

•At the blood–brain barrier, AAA and BCAA compete for the same LAT1 transporter.
High AAA/low BCAA lets more AAA enter the brain → “false neurotransmitters” (octopamine, phenylethanolamine) → disturbed neurotransmission → HE features.

5/ •Clinical translation:

•Dairy/vegetable proteins (relatively BCAA-rich, AAA-lighter) are better tolerated.
•BCAA supplements can help sarcopenic patients or those with recurrent HE by improving the BCAA:AAA balance and supporting muscle synthesis.

6/ The vicious cycle

Cirrhosis → Low glycogen → Early gluconeogenesis → Muscle breakdown → Sarcopenia → ↓ Muscle glutamine-synthetase capacity → ↑ Ammonia → HE → Poor intake/immobility/hospitalizations → More sarcopenia → …. Vicious cycle continues

7/ How to break the cycle in practice

•Never restrict protein in HE; target 1.2–1.5 g/kg/day (favor dairy/vegetable protein).

•Small, frequent meals + late-night snack to blunt catabolism.

•Consider BCAA supplementation in sarcopenia or recurrent HE.

•Treat precipitants (infection, bleed, constipation, dehydration, sedatives).

•Lactulose (titrate to 2–3 soft stools/day) + rifaximin for prevention of recurrence.

•Early mobilization + resistance exercises to rebuild muscle (multidisciplinary with nutrition/physio).

•If refractory/recurrent HE, escalate care and consider transplant referral early.

@UnrollHelper