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 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: ccjm.org/content/76/4/2…
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).
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:
journalofhospitalmedicine.com/jhospmed/artic…
jamanetwork.com/journals/jama/…
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.
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.

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.
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.
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?

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.

ncbi.nlm.nih.gov/pmc/articles/P…
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: 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 academic.oup.com/ofid/article/6…
Mnemonic source: theindianmedicalstudent.com/3-mnemonics-fo…
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 .

ncbi.nlm.nih.gov/pmc/articles/P…
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.
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
On related note, just saw this case report of 3 cases of non-hepatic hyperammonaemia with this great diagram.
pmj.bmj.com/content/77/913…

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More from @AnnKumfer

2 Sep
Really enjoyed @UnremarkableLab last night where we discussed HTN in the hospital.
You are an intern on night float and get called that a patient's BP is 195/110. You:
For anyone who participated, I found this article a really helpful read. I also would suggest listening to the Annals of Call Podcast(acpjournals.org/doi/10.7326/A1…).

the-hospitalist.org/hospitalist/ar…
Some key points the article made:
1. 72% of pts in hospital have HTN
2. 1 study the article cites- 94 pts given IV hydral (only 4 needed)>17 had adverse effects from hypotension
3. Study of pts given IV treatment for HTN- 56% had BP ⬇️ >25%, 2 hypotensive, 6 had to hold BP med
Read 10 tweets
1 Sep
What infections are on your list for infection-induced thrombosis? Why do infections predispose to thrombosis?

Source: ncbi.nlm.nih.gov/pmc/articles/P…
Here are some:
Bacterial: H. pylori, C. pneumoniae, M. pneumoniae, H. influenzae, S. pneumoniae, S.aureus, E.coli, Fusobacterium species, C burnetii
Vital: COVID-19, Influenza, EBV, CMV, HSV, VZV, HIV, Dengue, Hep A/C
What infections do you think of?
williams.medicine.wisc.edu/viral_coagulop…
The below infections are associated w/ antiphosholipid antibody + (likely through molecular mimicry), but not all infections significantly increase thrombosis risk. Risk ⬆️in HIV, Hep C, and CMV. Also ⬆️ risk with genetic predisposition. Image source: ncbi.nlm.nih.gov/pmc/articles/P…
Read 15 tweets
15 Aug
11/ What if instead the pred dose is 7.5mg ? Should pt be given stress dose steroids? A JAMA review found in in patients on chronic steroids (pred doses 5-16mg) who received their usual daily dose of steroid on day of surgery, no cases of hypotension. pubmed.ncbi.nlm.nih.gov/19075176/ Image
12/ Who should be given stress-dose steroids and how much should be given?
1. Pts w/ adrenal insufficiency on physiological dose of steroids
2. Consider if receiving major surgery (ie cardiothoracic surgery or major abdominal surgery)

Table source: pubmed.ncbi.nlm.nih.gov/11779267/ Image
13/Caveats:
1/If a patient is unable to take oral dose of steroid prior to surgery or concern for absorption, give IV formulation
2 Giving IV hydrocort in above scenario likely be sufficient to meet physiological cortisol need but easier to keep on oral dose if tolerating PO.
Read 5 tweets
15 Aug
#medtwitter You receive a pre-op request for consult asking about stress dose steroids:
A patient is on 50mg of prednisone for an inflammatory condition (started several weeks ago) & is undergoing an unrelated surgery. What steroid dose would you give on the day of surgery?
2/The first question is how much cortisol the body needs. Under normal circumstances, the body produces 10-12mg of cortisol a day (about 3 mg of prednisone). This occurs in a circadian rhythm:

Image source: slideplayer.com/slide/7644164/ Image
3/ Under stress, cortisol production increases
Mild stress- ⬆️ 2x
Moderate-severe stress- ⬆️ 3-4x
Life-threatening stress- ⬆️ as high as 10x

This is why individuals with adrenal insufficiency are told to double steroids when sick because adrenal gland ⬆️ cortisol under stress.
Read 10 tweets
28 Jul
#medstudenttwitter A review of syphilis testing
1/ Scenario 1: You are seeing a patient in clinic and obtain syphilis screening of HCM. For screening, a nontreponemaltest (RPR or VDRL) are usually sent first. What is the sensitivity of the RPR testing?
2/ RPR has on overall sens of 91, spec 95 but decreased sensitivity in primary syphilis (86%) RPR sens> VRDL (sens 78%). Nontreponemal can have false – in primary syphilis due to antibody formation or the prozone effect.
3/ What about false +? Infections, pregnancy, and SLE are some common causes of false + RPR. See table linked below:
aafp.org/afp/1999/0415/…
Read 12 tweets
14 Jul
1/Having just finished residency, I am having morning report withdrawals. Thankfully, I was able to tune in yesterday for a great case. .
Reposting my ANCA infographic below. I wanted to take some time to review drugs associated w/ vasculitis w/ + ANCA. Image
2/The morning report pearl is that with dual+ on Elisa ANCA testing (both MPO and PR3) consider a drug-induced vasculitis. When I think about dual + ANCA, levamisole-induced vasculitis comes to mind first.
3/ Levamisole is an antihelminthic agent that is present in up to 60-70% of street cocaine. It can cause a cutaneous vasculitis prominent on the extremities (especially ears and nose). Highest risk is with smoking or snorting cocaine.
Read 7 tweets

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