Hyperammonaemia in hepatic failure

[Phloston]

---

Members don't see this ad.

UWorld says that hyperammonaemia secondary to hepatic failure is due to increased ammonia absorption by the gut. They give a vignette of a guy with haematemesis, and then they say that his hepatic encephalopathy was secondary to the increased absorption of ammonia due to his haematemesis. My question is: why would haematemesis increase ammonia absorption in the gut?

 

[Phloston]

Since lactulose (Tx for hyperammonaemia) normally acidifies intestinal NH3, thereby preventing its absorption as NH4+, then the only way increased NH3 absorption could occur would be if luminal pH is somehow increased during haematemesis. But why would that happen?

 

[Ronin786]

What I got from that question was that the decreased conversion of ammonia by the liver into urea, leads to a build up in the intestine and that buildup is absorbed. Basically an overload type of thing.

 

[thehundredthone]

Ah, I got this one wrong and it was a facepalm moment.

GI bleeding increases the protein load in the gut, hence increasing NH3 generation. It also causes hypovolaemia which can precipitate hepatic encephalopathy.

Lactulose acts by acidifying colonic contents, which will trap the NH3 as NH4. GI bleeding does not have to generate a high pH to have the NH3 absorbed, the pH in the colon is 5.5-7.

http://www.medsafe.govt.nz/profs/datasheet/a/Alphalactulosesyrup.htm

The therapeutic action of lactulose in ameliorating the symptoms of hepatic encephalopathy is considered to be a result of the following:

- Reduction of faecal pH leading to a reduced ammonia absorption via nonionic diffusion and/or diffusion of ammonia from the blood into the gut. The trapped ammonia is then excreted in the stools.
- Suppression of urase producing organisms
- Induction of an osmotic type of diarrhoea which diminishes faecal statis with reduction of nitrogenous substances for ammonia production. Decreased absorption of ammonia from the gut also results from shortening intestinal transit time.

 

[Leon22]

UWorld says that hyperammonaemia secondary to hepatic failure is due to increased ammonia absorption by the gut. They give a vignette of a guy with haematemesis, and then they say that his hepatic encephalopathy was secondary to the increased absorption of ammonia due to his haematemesis. My question is: why would haematemesis increase ammonia absorption in the gut?

i think ammonia and hemetamesis should be separated for better understanding

haemetemesis here mostly like due to esophageal varice which is complication of cirrhosis,portal hypertension

increase in ammonia is due to loss of liver function of carrying out urea cycle(amonnia to urea) and oso due to portal hypertension the portal blood shunted away from liver and anastamose with systemic blood directly(exp.at esophagus,anus,periunbilical

 

[Phloston]

i think ammonia and hemetamesis should be separated for better understanding

haemetemesis here mostly like due to esophageal varice which is complication of cirrhosis,portal hypertension

increase in ammonia is due to loss of liver function of carrying out urea cycle(amonnia to urea) and oso due to portal hypertension the portal blood shunted away from liver and anastamose with systemic blood directly(exp.at esophagus,anus,periunbilical

UWorld specifically said that the hepatic encephalopathy (in the particular patient in the vignette) was likely precipitated by his haematemesis.

They also said there was increased NH3 absorption.

-----

Moreover, important points I've grabbed regardless:

Serum BUN is decreased in liver disease because arginase synthesis is decreased, so the urea cycle is impaired. This is what causes inability to process excess NH3, although it is not the reason for the increased NH3; increased gut absorption of NH3 causes the hyperammonaemia.

Increased NH3 shunts alpha-KG to produce H2O + glutamate. This shuts down the TCA cycle, thereby causing the Sx of hepatic encephalopathy due to neurotoxicity.

Increased GABA synthesis occurs, since glutamate is the precursor of GABA and glutamate is increased.

 

[aspiringmd1015]

why is glutamate increased? bc nh3 cant be metabolized by the urea cycle so it backs up?