What's the deal with ... Gilbert's syndrome?
Unconjugated bilirubin deserves its own #tweetorial
Featuring:
🟨Why?
🟨Is it bad or...PLOT TWIST...good!?
🟨What to do about it?
🏆The most 🍌🍌trials ever conducted
#livertwitter #meded #MedTwitter
1/
Unconjugated bilirubin deserves its own #tweetorial
Featuring:
🟨Why?
🟨Is it bad or...PLOT TWIST...good!?
🟨What to do about it?
🏆The most 🍌🍌trials ever conducted
#livertwitter #meded #MedTwitter
1/
What is Gilbert's?
1⃣Healthy person gets labs. Bili 2.4, >80% indirect
2⃣Student studies all🌙, forgets 2 eat.
In AM,👀slightly 🟨
Turns out:
👉3% of🌎has bili>1.4mg/dL (fig1)
Many things⬆️indirect bili:
👉Only 1⃣ makes bili⬆️w/fasting (Fig2)
It's...
2/
1⃣Healthy person gets labs. Bili 2.4, >80% indirect
2⃣Student studies all🌙, forgets 2 eat.
In AM,👀slightly 🟨
Turns out:
👉3% of🌎has bili>1.4mg/dL (fig1)
Many things⬆️indirect bili:
👉Only 1⃣ makes bili⬆️w/fasting (Fig2)
It's...
2/
GILBERT'S SYNDROME
Who?1⃣Described c1901. Hilarious paper
(🙏google translate, my🇨🇦franglish education)
Why?2⃣Familial⬇️UDPGT protein
(the thing that 'conjugates' bili)
Why?3⃣Base pair insertion in UGT1A1 promoter
(#TATAbox, the gene that makes UDPGT)
3/
Who?1⃣Described c1901. Hilarious paper
(🙏google translate, my🇨🇦franglish education)
Why?2⃣Familial⬇️UDPGT protein
(the thing that 'conjugates' bili)
Why?3⃣Base pair insertion in UGT1A1 promoter
(#TATAbox, the gene that makes UDPGT)
3/
But ...why is Gilbert's even a thing?
Why so common?
let's back up
Where does unconjugated bili come from?
1⃣Rusty🩸cells give up heme
2⃣Heme-oxygenase➡️Biliverdin➡️unconj bili
3⃣Liver takes bili➡️conjugates, dumps in bile
(👍fig from my old pal Sush Jangi)
4/
Why so common?
let's back up
Where does unconjugated bili come from?
1⃣Rusty🩸cells give up heme
2⃣Heme-oxygenase➡️Biliverdin➡️unconj bili
3⃣Liver takes bili➡️conjugates, dumps in bile
(👍fig from my old pal Sush Jangi)
4/
Biliverdin:
non-toxic,🚰soluble, 🟩pigment
Unconjugated Bilirubin:
toxic,🚫soluble,🟨pigment, needs energy 2make,
AND needs 2b conjugated 2b excreted
Why bother?
Why does every mammal make bilirubin?
Why is Gilbert's super common?
!!WHY!!
5/
non-toxic,🚰soluble, 🟩pigment
Unconjugated Bilirubin:
toxic,🚫soluble,🟨pigment, needs energy 2make,
AND needs 2b conjugated 2b excreted
Why bother?
Why does every mammal make bilirubin?
Why is Gilbert's super common?
!!WHY!!
5/
Could unconjugated bilirubin...
...be good?
The birth of an idea:
In a 100% 🍌🍌 1938 paper:
🤔Hench saw improved RA symptoms after jaundice
💉So he injected ppl w/bili
😢No benefit
But!
Turns out bili IS an antioxidant with immunomodulating properties
6/
...be good?
The birth of an idea:
In a 100% 🍌🍌 1938 paper:
🤔Hench saw improved RA symptoms after jaundice
💉So he injected ppl w/bili
😢No benefit
But!
Turns out bili IS an antioxidant with immunomodulating properties
6/
⬆️bilirubin levels or Gilbert mutation associated with
🫁⬇️resp disease
♥️⬇️heart disease
🦀⬇️cancer, particularly colon
and lower risks of RA, crohn's, lupus, and MS
Bring on the bili?
7/
🫁⬇️resp disease
♥️⬇️heart disease
🦀⬇️cancer, particularly colon
and lower risks of RA, crohn's, lupus, and MS
Bring on the bili?
7/
Obviously too much bili is no good
1⃣+ immune associations lost when bili⬆️⬆️
2⃣Absent UDPGT? Keyword: Kernicterus.
That's crigler-najjar.
Type 1: Fatal without☀️therapy♾ or liver transplant
Type 2: 🤏UDPGT activity, induced by phenobarb
8/
1⃣+ immune associations lost when bili⬆️⬆️
2⃣Absent UDPGT? Keyword: Kernicterus.
That's crigler-najjar.
Type 1: Fatal without☀️therapy♾ or liver transplant
Type 2: 🤏UDPGT activity, induced by phenobarb
8/
Many things alter UDPGT activity
💊phenobarb induces
💊rifampin suppresses
🚬induces
🥃🍷induces, surprisingly
And the time has come!
The most🍌🍌🍌trial I have read
To prevent neonatal jaundice...
...🥃🍷was given to⬆️UDPGT activity in
... pregnant women
9/
💊phenobarb induces
💊rifampin suppresses
🚬induces
🥃🍷induces, surprisingly
And the time has come!
The most🍌🍌🍌trial I have read
To prevent neonatal jaundice...
...🥃🍷was given to⬆️UDPGT activity in
... pregnant women
9/
If you find an isolated,⬆️unconjugated bili,
how do you congratulate the patient on their Gilbert's?
1⃣You could order the gene test
But then you'd have to wear a top hat qTuesday
Dont @ me. I dont make the rules
Or
2⃣you can follow these pathways (Fig1-2)
10/
how do you congratulate the patient on their Gilbert's?
1⃣You could order the gene test
But then you'd have to wear a top hat qTuesday
Dont @ me. I dont make the rules
Or
2⃣you can follow these pathways (Fig1-2)
10/
This concludes a #tweetorial on Gilbert's!
Summary:
🟨Isolated hi indirect bili
🟨Common
🟨Unconjugated bili is antioxidant
🟨conjugation🔃by fasting, 💊🚬🥃
🟨A little extra bili may be good
Thank you for reading. Hope you enjoyed
11/11
Summary:
🟨Isolated hi indirect bili
🟨Common
🟨Unconjugated bili is antioxidant
🟨conjugation🔃by fasting, 💊🚬🥃
🟨A little extra bili may be good
Thank you for reading. Hope you enjoyed
11/11
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