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1/ #medtwitter #tweetorial Raise your hand if you have ever inappropriately checked an ammonia level.
1. Why is ammonia
in liver failure and how is this connected w/ encephalopathy?
2. When should levels be checked?
3. Aside from cirrhosis, what other conditionsammonia?
1. Why is ammonia
in liver failure and how is this connected w/ encephalopathy?2. When should levels be checked?
3. Aside from cirrhosis, what other conditions
ammonia?
2/ Ammonia is primarily produced by bacteria w/ urease enz in intestines but is also produced in muscle and the kidneys.
Table source: https://www.ccjm.org/content/76/4/252
Table source: https://www.ccjm.org/content/76/4/252
3/ 85% of ammonia is cleared by the liver through the urea cycle. 15% is cleared by muscle/kidneys. If the ammonia (/other nitrogenous waste) not metabolized it passes through the blood brain barrier glutamate>glutamine> astrocyte swelling and free radicals>encephalopathy.
4/ Ammonia can build up though production, 
clearance, or combo. In both acute or chronic liver failure, urea cycle ammonia production. Portosystemic shunting can also ammonia since less passes though liver (why TIPS risk of encephalopathy).
production, clearance, or combo. In both acute or chronic liver failure, urea cycle ammonia production. Portosystemic shunting can also ammonia since less passes though liver (why TIPS risk of encephalopathy).
5/ You might be thinking based on above that if a patient comes in with cirrhosis, you should check an ammonia level to evaluate for HE However, there are several reasons why HE is a clinical diagnosis.
6/I will discuss some of the reasons outlined in these two articles which I highly suggest reading:
https://www.journalofhospitalmedicine.com/jhospmed/article/143598/hospital-medicine/ammonia-levels-and-hepatic-encephalopathy-patients-known https://jamanetwork.com/journals/jama/article-abstract/1895229
https://www.journalofhospitalmedicine.com/jhospmed/article/143598/hospital-medicine/ammonia-levels-and-hepatic-encephalopathy-patients-known https://jamanetwork.com/journals/jama/article-abstract/1895229
7/Ammonia is a difficult test to obtain. You may have tried to add this lab test on and been dismayed when you saw it required a new draw. Using a tourniquet can falsely values as can time prior to processing. The collected sample also has to be place on ice.
values as can time prior to processing. The collected sample also has to be place on ice.
8/ In this study from 2003, arterial and venous ammonia levels where obtained to assess correlation with samples and degree of encephalopathy. There was a correleation between venous/arterial sample and degree of encephalopahy r = 0.56 for venous. https://pubmed.ncbi.nlm.nih.gov/12637132/
9/ The problem? The ULN for ammonia was 47 in this study. I used a cut off of 50 for ease. If you look at the sample a significant amount of pts with HE had normal ammonia levels and a significant amount w/o HE had ammonia levels.
ammonia levels.
10/Another paper found that blood ammonia levels had a diagnostic accuracy of 59%, sensitivity 47%, specifity 78%. It certainly should not be used as a screening test as you would miss over 1/2 of cases of HE. https://pubmed.ncbi.nlm.nih.gov/23293201/
11/A recent propensity matched study showed that in cirrhotic pts w/ HE that lactulose dose was the same regardless of ammonia level. This points to the fact we likely are not using ammonia level to guide mng. Why check a lab you don't need? https://pubmed.ncbi.nlm.nih.gov/31658104/
12/ Although not helpful in cirrhosis, checking ammonia levels can be helpful in acute liver failure as levels are associated with worse prognosis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856380/
levels are associated with worse prognosis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856380/
13/There are situations aside from liver failure in which ammonia
1. Drug toxicity including valproic acid & chemo meds
2. Urea cycle disorder
3. Glycerin toxicity- historically caused TURP syndrome (now rarely used)
Table source: https://pubmed.ncbi.nlm.nih.gov/29551609/
1. Drug toxicity including valproic acid & chemo meds
2. Urea cycle disorder
3. Glycerin toxicity- historically caused TURP syndrome (now rarely used)
Table source: https://pubmed.ncbi.nlm.nih.gov/29551609/
4. SIBO with dehydration
14/ 4. SIBO with dehydration
5. Urease producing organisms including Ureaplasma urealyticum in an immunocompromised host https://academic.oup.com/ofid/article/6/3/ofz033/5371475
Mnemonic source: https://theindianmedicalstudent.com/3-mnemonics-for-urease-positive-organisms-tonic-mnemonics-for-clonic-teens/
5. Urease producing organisms including Ureaplasma urealyticum in an immunocompromised host https://academic.oup.com/ofid/article/6/3/ofz033/5371475
Mnemonic source: https://theindianmedicalstudent.com/3-mnemonics-for-urease-positive-organisms-tonic-mnemonics-for-clonic-teens/
15/Checking an ammonia level in these situations is helpful because it may guide specific treatment. Valproic acid can cause ammonia leading to AMS w/o liver failure or supratherapeutic levels. Being aware of it is important b/c treated w/ carnitine . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536406/
ammonia leading to AMS w/o liver failure or supratherapeutic levels. Being aware of it is important b/c treated w/ carnitine . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536406/
16/Conclusions:
1. While ammonia is common in cirrhosis, HE is a clinical diagnosis. Ammonia has poor sensitivity/specificity and diagnostic accuracy and has not been shown to change treatment of HE in cirrhosis.
2.Ammonia can have prognostic implications in ALF.
1. While
ammonia is common in cirrhosis, HE is a clinical diagnosis. Ammonia has poor sensitivity/specificity and diagnostic accuracy and has not been shown to change treatment of HE in cirrhosis. 2.
Ammonia can have prognostic implications in ALF.
17/ 3. Other conditions such as drug toxicity (especially valproic acid), urea cycle disorder, and certain bacterial infections can also cause ammonia. It may be helpful to check ammonia levels in these conditions b/c it may change managment. /end
ammonia. It may be helpful to check ammonia levels in these conditions b/c it may change managment. /end
On related note, just saw this case report of 3 cases of non-hepatic hyperammonaemia with this great diagram.
https://pmj.bmj.com/content/77/913/717
https://pmj.bmj.com/content/77/913/717
