QUESTIONS

1. True/False:
   
   One cannot have hepatic encephalopathy without excessive serum ammonia levels.
    
2. Where does one's body get ammonia from?
    
3. List some popular urease + bacteria.
    
4. How does lactulose work?
    
5. Whatinthehell is alpha-ketoglutarate and how does it fit into the hepatic encephalopathy story?
    
6. Whatinthehell is a mercaptan & how does it fit into the hepatic encephalopathy story?
    
7. Short Chain fatty acids are considered toxins involved in hepatic
   encephalopathy though what they exactly do that's bad is not known. Where do SCFA's come from ?
    
8. There is a lot of controversy about the ratio of branch-chained amino acids to aromatic amino acids. Which amino acids are which and what is the theory behind giving more branch-chained amino acids?
    
9. In liver failure, the skeletal muscle's uptake of branch-chain amino acids is increased.
   
   What does the skeletal muscle want with branch-chain amino acids?
    
10. Flumazeril - what is it & why might it be relevant to hepatic
    encephalopathy?
     
11. Why might L-Dopa be used in hepatic encephalopathy?
     
12. Why is constipation bad in hepatic encephalopathy?
     
13. Why might some one recommend feeding yogurt cultures in a recovering hepatic encephalopathy patient?
     
14. If you were in wild raging liver failure, why might you get cerebral
    edema?
    
    
    
    
     

ANSWERS

1. False. Ammonia levels do not even correlate with degree of encephalopathy & you get get hepatic encephalopathy without elevated ammonia levels.
   
   
   
   
    
2. COLON FLORA - urease + guys are happy to convert any urea they get into ammonia. Normally this ammonia is re-converted back to urea by the liver but the diseased liver can't cut it.
   
   RENAL TUBULAR SYNTHESIS FROM GLUTAMINE (a less important  source)
   
   NH3 comes from the catabolism of protein, urea & DNA.
   
   
   
   
    
3. Some popular urease + guys are proteus, ureaplasma & staph.  Some good antibiotic choices to keep their numbers in check are neomycin, kanamycin, vancomycin, paromomycin, & metronidazole. Remember, the evil microflora also produce mercaptans & SCFA's. Kill 'em.
   
   
   
   
    
4. Lactulose has several actions. First, it promotes catharsis so any colon flora substrate won't be hanging around as long for them to feed upon. Classically, it acidifies the colon contents thus converting NH3 to NH4+ which doesn't diffuse back into the body very well.  There is also a phenomenon called "CATABOLITE REPRESSION" which relates to the fact that lactulose is a disaccharide & thus a good CHO source for the flora. They will preferentially consume the CHO & spend less time dregrading & deaminating protein.
   
   
   
   
    
5. Alpha-ketoglutarate is a form of glutamine.  When alpha-ketoglutarate takes up an NH3 it becomes glutamate (as in MSG).  When glutamate takes up an NH3 you get glutamine.
   These forms of glutamine can happily take up NH3 for you but it costs you ATP which your brain doesn't really need to be spending frivolously.  Glutamine loaded with NH3 gets transported out of the brain where it can be found in high levels in the circulation.
   
   
   
   
    
6. Mercaptans are metabolic by-products of methionine. (DMSO is an example) We do not know why mercaptans are toxic. We do know that methionine is not toxic until it gets converted into a mercaptan by the GI Flora. DMSO is responsible for bad breath
   associated with liver failure.
   
   
   
   
    
7. SCFA's are produced by flora processing MCT's & by incomplete hepatic processing of LCFA's.
   
   
   
   
    
8. BCAAs  = leucine
                      isoleucine
                      valine
   
   AAAs   = tyrosine
                      tryptophan
                      phenylalanine
   
   The normal BCAA:AAA ration is 3:1. Both types of amino acids compete to get into the brain. AAA's seem to get converted into inhibitory neurotransmitters & false neurotransmitters.
   
   
   
   
    
9. Here I go again, asking questions when I'm only sorta sure of the answers. Normally, the liver uses all amino acids except the BCAA's which other organs (like skeletal muscle) can use.  When the liver fails & isn't using the other aa's, the periphery is still using BCAA's so there is a relative reduction in BCAA's only because there are now so many other aa's running around. I assume the skeletal muscle is burning BCAA's for fuel but I'm not sure.
   
   
   
   
    
10. Flumazeril is an experimental benzodiazepine antagonist. The GABA receptor is normally complexed with receptors for benzodiazepines & barbiturates.  In HE something happens to these receptors with increases their sensitivity greatly (part of
    why it isn't good to use valium as an appetite stimulant in HE)  Hemorrhage in the GI tract is associated with increased absorption of bacterial products with GABA-like  activity (which would normally get cleared by the liver) This drug seems to reduce the sensitivity of the aforementioned receptors.
    
    
    
    
     
11. L-Dopa (a norepi & dopamine precurser) displaces false neurotransmitters. This is the idea but it also turns out it increases renal NH3 excretion somehow & this may be the real reason why it seems to work.
    
    
    
    
     
12.  Constipation is bad because it gives the evil flora more time to eat. The more they eat, the more toxins they produce.
    
    
    
    
     
13. Lactobacilli are not urease+ and the idea was that the GI tract could be populated by them.  IT turns out that you'd need huge amounts of yogurt so forget it.
    
    
    
    
     
14. An altered Blood brain barrier in HE allows toxins & proteins to leak out of the CNS capillaries into the extracellular space.  They pull fluid with them.  This process is worsened by hypoalbuminemia. Still, if you think encephalopathy is getting worse fast, don't forget to rule out hypoglycemia before getting excited about cerebral edema.