Somehow the liver has the incredible capacity to both heal itself after toxic injury and regrow after resection. No other solid organ in the body can regenerate like this.
2/ It's assumed that the ancient Greeks knew of the liver's unique regenerative capacity, based on the myth of Prometheus (his liver regrew daily after an eagle ate it).
At the same time, scholars have found no other ancient evidence of this knowledge.
7/ To understand how the liver accomplishes regeneration after injury or resection, we need to review the microscopic structural units of the liver, known as hepatic lobules...
8/ Each lobule is composed of 3 zones - containing hepatocytes, small bile ducts and capillaries - and is bordered by a series of portal triads.
Blood flows through the lobule, from portal triads in zone 1 to the central vein in zone 3.
9/ So how does the liver regenerate? Let's first look at cell turnover and toxic injuries.
Studies in mice suggest zone 2 hepatocytes (at the center of the lobule) = main source of regenerated liver cells, both w/ normal homeostasis and toxic injury.
10/ Exactly what drives zone 2 regeneration isn't clear.
But the same mouse study from tweet #9 found that knocking out Insulin-like growth factor binding protein 2 (IGFBP2) led to loss of hepatocyte repopulation after injury, suggesting a central role of this signaling axis.
11/ The regenerative role of mid-lobule, zone 2 hepatocytes makes teleological sense.
Zone 1 hepatocytes do oxidative metabolism eg gluconeogenesis; zone 3 hepatocytes do more drug detox.
Zone 2 = regenerative reservoir w/ injury to other zones.
17/ Animal studies suggest this hemodynamic shift may act as a trigger for regeneration.
A rat PHx model found that when blood flow to the remnant liver was kept constant after resection, and not allowed to increase, regeneration didn't occur.
20/ Finally, let's look at platelets as a type of regenerative mediator.
Amazingly, living donor liver transplant recipients who received peri-operative platelet transfusion had enhanced graft regeneration at 2 weeks post-op.
21/ But why would platelets enhance hepatic regeneration?
The main proposed mechanism involves platelet migration into the liver ➡️ direct contact w/ hepatocytes ➡️ growth factor activation ➡️ stimulation of hepatocyte proliferation.
24/SUMMARY
💥The liver = only solid organ that regenerates
💥Regeneration after toxic injury = zone 2 hepatocyte proliferation
💥Regeneration after PHx is triggered by increased portal vein blood flow and mediated by growth factors, cytokines and platelet contact w/ hepatocytes
Post script:
HUGE thank you to the inimitable @ebtapper for providing peer review of this tweetorial!
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1/ Why can multiple sclerosis symptoms worsen with heat exposure, something known as the Uhthoff phenomenon?
This question is especially relevant in the era of record-breaking heat waves and climate change.
#tweetorial #medtwitter
2/ In 1890, Wilhelm Uhthoff noted multiple sclerosis (MS) patients having a “marked deterioration of visual acuity during exercise" or after a hot bath, which ⬆️ body temperature.
1 patient lost vision just by walking vigorously in Uhthoff's clinic.
3/ The Uhthoff phenomenon is now recognized as exceedingly common in MS.
Up to 80% of patients experience ⬆️ neurological symptoms w/ even small body temp increases. These can include diminished physical (eg gait) and cognitive (eg mental fog) function.
1/THREAD
Has it ever occurred to you that Graves' disease presents a conundrum?
Graves' involves an autoimmune antibody that ACTIVATES a receptor, which is relatively unique in the landscape of human disease.
Let's unpack this fascinating mechanism.
#medtwitter #tweetorial
2/ Graves’ disease was first described by English physician Caleb Parry in 1786, when he noted an association between thyroid enlargement, tachyarrythmias, and exopthalmos in 8 patients.
Parry’s son posthumously published his description in 1825.
I ask teams to focus on efficiency, ⬆️ time for teaching/ discussion
⏳⬇️ transitions b/w patients by alerting next RN
⏳Enter orders on rounds, w/ clearly defined roles as to who will do that
⏳Present from memory (if possible), focusing on critical issues
2️⃣ Education
🧠I ❤️ to teach but avoid overwhelming residents by teaching high yield points on 2-3 patients max. I supplement w/ PM chalk talks after lunch and notes are done
🧠 I also ask each learner to share one learning point from rounds, and do so myself as well