"Mo sinusoidal pressure, mo lymph"
- Ernest H. Starling MD, personal communication
4/
Lymph production in #cirrhosis is:
1⃣Proportional to portal pressure
2⃣Massive. Nearly 10 times normal
Thoracic duct flow goes from 120cc/hr to up to 1.2L/hr!
😀Fig2: Splenorenal shunt surgery ⬇️lymph production
🥸Fig3: Drain the thoracic duct & eliminate ascites
5/
As portal hypertension worsens (as the HVPG rises past 10mmHg), the lymphatics are stressed, then overwhelmed, and ascites develops
6/
But WHERE does the ascites actually come from?
The weeping liver!
Check this 1955 paper out:
Method: clamped IVC in dogs
Result: Ascites beaded on the liver surface. Covering the liver with a bag collects all the ascites, keeps the gut dry
7/
Hold up!
We dont yet understand where the extra fluid is coming from
The secret lies between two seemingly conflicting facts:
People with #cirrhosis and ascites have: 1. Peripheral fluid overload 2. Low central blood volume
8/
The reason for low central blood volume in #cirrhosis:
1⃣Despite ⬆️lymph return, 🫀is underfilled
2⃣All the blood is trapped in vasodilated gut arteries
3⃣Arterial vasodilation is proportional to disease severity
9/
If blood is trapped, return to the heart is low, and so is delivery to the pesky kidney
As a result:
1⃣ALL THE TOOLS are revved: Renin, aldosterone, ADH, norepi
2⃣Renal tubules respond: sodium & free H20 excretion plummets
3⃣Plasma volume increases
1⃣The peritoneum absorbs 0.5-1L/day
2⃣Diuretics do NOT speed this up
3⃣Diuretics drop plasma volume!
12/
1⃣Diuretics work by Starling forces!
They⬇️pressure gradient between portal & hepatic veins (HVPG)
How?
2⃣They drop HVPG proportional to⬇️plasma volume
How?
3⃣Spironolactone addresses the cause: high aldo
13/
Final summary
1⃣Ascites=a trick the liver plays on the 🫀/kidney
2⃣Sinusoidal htn⬆️⬆️lymph production
3⃣Arterial vasodilation traps blood in the gut
4⃣Cardiac return suffers
5⃣RAAS en fuego
6⃣⬆️Plasma volume
7⃣Ascites forms
8⃣Diuretics⬇️plasma volume; spiro⬇️RAAS
/End
This concludes a #tweetorial on ascites formation/treatment. Thank you for reading. I hope you enjoyed.
If interested, please see below for my 'ascites' menu
Correction in the first figure: "Total blood volume is high" is correct. But that is addressed in the next tweet. This figure shows that central blood volume is low, proportional to portal pressure.
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👋Described~60 yrs ago by Adams/Foley
👋Methods:60pts w/impending hepatic coma vs controls
👋Flapping flexion/extension, best @ the🤚but happens even 2 the 👁️lids! Has intervening tremor (mini-asterixis)
Look 4 it while checking handgrip! #livertwitter 1/4
Why asterixis?
1⃣Adams/Foley:🤷
2⃣Ammonia? Unlikely!(fig1)
3⃣Precipitating factors? Asterixis, like HE itself, is a biomarker of badness: bleeding, infection, sedatives(Fig2)
4⃣They looked @🧠; swollen astrocytes! Particularly in the basal ganglia!(Fig3) #livertwitter 2/4
Why asterixis part 2
A study using magnetoencephalography showed:
1⃣There is 'excessive corticomuscular motor coherence' 2⃣Diseased basal ganglia fail to select and pace the motor areas
This seems to confirm what Adams/Foley found in the brain
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)