Liver topics

Question 1

What is the normal metabolism of ammonia?

Answer 1

Liver normally metabolises ammonia.
- 50% of ammonia arises from endogenous glutamine conversion in enterocytes. 50% is from the gut lumen by degradation of nitrogen substrate from diet or gut bacteria.
In hepatocytes ammonia is converted yo urea or glutamine.

Question 2

Why does ammonia rise in liver failure?

Answer 2

The loss of viable hepatocytes leads to impaired metabolism of ammonia

Question 3

What effects do raised ammonia have?

Answer 3

1. It accumulates in astrocytes which can lead to hepatic encephalopathy, cerebral oedema, intracranial hypertension and brain herniation.
2. It also contributes to immune dysfunction and infection

Question 4

What’s the prognostic value of ammonia?

Answer 4

> 150 in ALF is associated with increased complications
In ACLF the risk of cerebral oedema is lower but raised ammonia is a/w increased risk of extra-hepatic organ failure and death.

Question 5

How to measure ammonia?

Answer 5

Arterial samples better reflect acute changes in nitrogen metabolism.
Sample needs to be fresh.
Serial measurements are more useful that a single time point

Question 6

What are the potential therapeutic strategies to modulate serum ammonia?

Answer 6

1. Lactulose
2. Rifaximin
3. Metabolic scavengers e.g. LOLA
4. RRT
5. Liver support dialysis e.g MARS
6. Plasma exchange

Question 7

What are the mechanisms of action of lactulose in managing ammonia?

Answer 7

1. Colonic acidification promotes conversion of NH3 (ammonia) to non-absorbable NH4+ (ammonium)
2. Inhibits ammoniagenic bacteria growth
3. Inhibition of intestinal glutamine absorption
4. Decreased ammonia absorption time and increased nitrogen excretion