Video
Pathophysiology of HE
Author(s):
Experts in hepatology discuss the pathophysiology of HE and how certain factors influence the brain in HE.
Arun B. Jesudian, MD: Our patients, usually all of them who have this advanced degree of liver disease, have sarcopenia and are in a state of catabolism, muscle breakdown. And that skeletal muscle breakdown can be a source of nitrogen, which leads us into the pathophysiology of hepatic encephalopathy. Could you connect the dots for us between bacteria and ammonia and how those influence the brain?
Kimberly A. Brown, MD: I wish I could. I think we’ve struggled forever to understand what are the factors that get to the brain that can cause this phenomenon to occur. We certainly know that there’s likely a role of the microbiome and the translocation of bacteria across the gut. The first place it goes is into the portal vein and then into the liver. And if they’re shunting, it just goes right back to the brain.
Ammonia’s interesting though, right? We historically measure ammonia. First of all, we measure it incorrectly. It has to be measured in an unoccluded arm, and it has to go on ice and be run very quickly. We don’t do any of those things. So first of all, we measure it wrong, and it doesn’t correlate with anything. I can’t even remember the last time as a liver physician that I measured ammonia. But we do know that’s probably in part what happens when somebody has a bacterial infection, those factors worsen encephalopathy or precipitate an event of encephalopathy. But measuring ammonia has never been helpful, although it seems to be what we were all taught.
Arun B. Jesudian, MD: It’s very true. When I teach medical students or residents, I use the word ammonia repeatedly when talking about the pathophysiology of hepatic encephalopathy. It’s among the toxins that we know can escape liver detoxification in the setting of hepatic insufficiency and portosystemic shunting, and can cause cognitive dysfunction. But then I always have to follow that with [saying], but please don’t send a venous serum ammonia [test], or use that clinically because it’s such an unreliable test for the reasons you mentioned.
Kimberly A. Brown, MD: It is interesting because I often pose this question to my fellows. Let’s say the patient is looking at you, and they’re perfectly happy and they can answer all the questions, and their ammonia is 79 µ/dL. What are you going to do? On the other hand, if the patient is confused and disoriented, and their ammonia is 53 µ/dL, what are you going to do? So we treat the patient clinically based on their symptoms, not based on what their ammonia level is.
Arun B. Jesudian, MD: Absolutely. We still see it checked frequently, but I think we’re hopefully succeeding a bit in the messaging about hepatic encephalopathy [being] a clinical diagnosis, and grading its severity is also clinical, and you can’t rely on that blood test at least.
Kimberly A. Brown, MD: I agree.
Transcript edited for clarity
