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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2/ Pseudomonas was first isolated in 1882 by the French pharmacist Carle Gessard, after he cultured it from the blue-green pus on bandages of injured soldiers.
Ketogenic diets have ⬆️ fat and ⬇️ carbohydrates. This leads to ⬆️ serum free fatty acids and ketone body production by the liver (acetoacetate, acetone, beta-hydroxybutyrate) for use as cellular fuel.
3/ A 2009 case series described 25 patients who developed red meat allergies 1-6 months after tick bites. Reactions to meat again ranged from urticaria to full anaphylaxis.
🔑There seemed to be a clear association b/w tick bites and meat allergy onset.
3/ Not until 1978 was the association made between antibiotic-associated colitis and C.Diff, after its isolation from a patient w/ post-clindamycin colitis.
The authors noted that a toxin was crucial for virulence of the bacteria.
2/ The association between "rheumatism" and heart disease was first noted in the the late 1700s.
By 1832, the British physician James Hope observed that rheumatic heart disease (RHD) patients had valvular involvement, w/ loud cardiac murmurs on exam.