Take your right hand and place your palm over your belly button. Move about three-four inches to the right and then upwards until you feel your ribs under your index finger. Right hand, say “hello” to the largest organ inside of you: your liver!

Our regular readers will know that our skin is our largest organ over all. However, our largest internal organ is our liver! (You’re going to ace your next trivia quiz.)

What is a liver actually made of? What does it do? Why is it so important? Can it really regenerate? Let’s dive into this squishy, meaty blob and find out! 

Q1: What does the liver do?

In a nutshell, your liver has a wide range of jobs:

  • Filtering your blood to clean out toxins (including alcohol and other poisons), pathogens and cellular debris.
  • Assisting in digestion through the secretion of bile.
  • Metabolizing drugs.
  • Storing glycogen.
  • Synthesizing non-essential amino acids, plasma proteins and blood clotting factors.
  • Mediating systemic inflammation.
  • Hosting 70’s disco nights. (I have that last one on good authority by a kidney who likes to dish.)

Q2: What is the liver made of?

The main cells you hear about with respect to the liver are hepatocytes (hepato- meaning liver and -cyte meaning cell, someone must’ve been working on that one for a while). These make up a fair chunk of the cells of the liver, about 70-85%. The remaining 15-30% is composed of endothelial cells, many immune cells, stem cells, pericytes (contractile cells that wrap around blood vessels).

Q3: How does the liver keep it’s cool?

The total blood volume of the human body circulates through the liver approximately 360 times each day (!!!!). Consequently, the liver is continually exposed to pathogenic stresses, dietary and bloodborne antigens, and immunological signals, from the GI tract and the systemic circulation. Holy smoke, why is it not constantly infected with horrible pathogens?! Why don’t we spend days sick to our stomach (or liver) after eating a meal?

Like the CNS, eyes and lungs, the liver’s immune cells maintain an immunosuppressed bias. What does this mean? Where other parts of the body will get all up in a tizzy when they encounter an attacking invader like a bacterium, the liver’s default is to maintain it’s calm unless severely provoked. This, of course, raises even more questions!

The liver’s cells must be able to recognize “true threats” to the body versus everyday bugs that come in. If you cut your finger, a local immune response is trigger. If this infection reaches a certain level or is caused by a more vicious bug, your liver gets involved. A classic example is the common cold. What may start off as an upper respiratory infection turns into a low grade fever with all the awful symptoms we all know so well. When an infection is restricted to one area, the infected area recruits immune cells from local lymphs nodes and the blood supply. In the case of a cold or even the ‘flu, the body reacts much more strongly. This is as a result of involvement of the liver. The liver is in charge of systemic inflammation, such as inducing a fever. It’s like the army general that sends in the national troops when the local branch gets overwhelmed.

The exact mechanism by which the liver is able to decide when to switch from a T regulatory cell-induced immunosuppressed state to an proinflammatory one isn’t fully understood. One theory is that pathogen-associated molecular patterns, or PAMPs, must be accompanied by a sufficient amount of danger-associated molecular patterns, or DAMPs. Both DAMPs and PAMPs are immunogenic (immune-triggering capability) molecules, such as nucleic acids or cell proteins. While PAMPs, like LPS (lipopolysaccharide), are derived from pathogens like bacteria, DAMPs, like ATP (adenosine triphosphate), are endogenous molecules released by our cells. Seeing everyday bugs may not be anything for the liver to worry about, much seeing more than the every day amount plus a lot of cell debris would be a cause for alarm and may induce an all out battle with the liver leading the way. This is a theory combines Janeway’s Stranger model (refers to the role played by PAMPs) and Matzinger’s Danger model  (refers to the role played by DAMPs) (Kuroda et al. 2011, Janeway 1989 and Kono and Rock 2008). Stranger danger anyone?

Q4: How does your liver avoid getting infections?

The liver itself has an impressive battalion of immune cells, mainly innate immune cells, that can gobble up pathogens in a thrice. This helps avoid infection. The entire structure of the liver is also designed in such a way as to limit the ability of pathogens to “latch on” and invade. We’ll go more into this in future articles.

Q5: How can the liver regrow itself? How can we donate half our liver and survive?

Unlike all the other gut organs, the liver is capable of regeneration. Not just healing but full-on reconstruction! Depending on the age and size of the person who needs a liver donation, as much as 60% of a liver may be needed. This can be done (although it’s risky) from a live donor who themselves will be fine with less than half a liver.

Hold your applause…

Even with only 25% left, a liver can regrow back to it’s full size. Isn’t that amazing?!

Now you might be asking, why can the liver regenerate itself but other organs can’t? Well, actually your skin can also regenerate. Why can’t other structures recover in the same way? Why can’t you regrow a heart or chunk of brain tissue? To regenerate, a tissue two things: differentiating stem cells and dividing tissue cells. Even with these, if you get one lobe of the liver, either left or right, while it will grow, it will never appear normal under an ultrasound. You’ll end up with one larger lobe that isn’t the same shape a regular liver would be. The same is true of the skin. I’m sure you’ve got at least one scar where the skin looks different from the surrounding tissue.

The exact mechanism by which the liver and organs in other organisms regrow is being intensely studied as if we can trigger this in other organs, like neurons, we could offer new treatments for conditions such as Alzheimer’s Disease, Spinal Cord Injury and Multiple Sclerosis.

Q6: Why do transplanted livers only have one lobe?

There are two main types of transplants. Live donor where a part of a liver is given and a deceased donor liver transplant. In the case of the live donor, often a family member, only a small portion is given (depending on the needs of the recipient and the ability of the donor). This is owing to the ability of the liver to regenerate so only a small portion is required to seed the growth of the rest of the organ. In the case of a deceased donation, usually only a portion is used even then as this enables the donor liver save the lives of several people rather than just one. Share the love!

Conclusion

The liver is awesome!

I’m sure you agree!

Did you learn something new? Any questions for us? Tweet us @TempoBioscience or leave a comment below!


Article by Olwen Reina. Contact Olwen at olwen@tempobioscience.com.
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