The Liver: Our Unsung Hero and Guardian of Life

Is the liver the most amazing organ? Yes. It turns food into usable molecules. It makes proteins, bile, and hormones. It filters dangerous drugs and toxins. Without it, you would die within minutes. Also, the liver can regenerate (like a lizard's tail!), which is basically magic. The liver is estimated to have over 500 individual functions and interacts with most body systems. This article will look at the liver, zooming in from basic facts to its cellular units. Then will explore the functions of the liver.

If you were to guess the largest organ in the body, would you guess the liver? I hope not, because it's the skin. But the liver is in second place! It makes up around 2% of your body weight and usually contains about 10% of your blood. It's located under the ribs, right below the diaphragm that inflates the lungs. It's smooth and reddish brown when healthy (note: if you can see your livers color you are probably having a bad day). The liver can be divided into four parts called lobes and thousands of sub-parts called lobules. These are hexagonal columns of cells arranged so that blood can travel through carrying nutrients in and toxins and waste out.

Four types of cells make up the liver: hepatocytes, epithelial cells, Kupffer cells, and stellate cells. Most of the liver is composed of hepatocytes. These are the workhorses of the liver. Hepatocytes convert fats (called lipids), sugars (called carbohydrates), and proteins (called proteins) into usable forms. They detoxify dangerous things and excrete bile and cholesterol. The barrier epithelial cells line the walls (including blood vessel walls) inside the liver and do some filtering of small particles. It is thought that these may also do some clearance of viruses. Kupffer cells are the resident immune cells. These large cells eat bacteria and debris that enter lobules. They are always touching these dangerous particles and exhibit constant, low-level inflammation. Disruption of these cells can result in widespread, damaging liver inflammation. Finally, stellate cells store vitamin A, a critical vitamin. They are critical for promoting the liver's amazing ability to regenerate. They form temporary scars that allow for healing. When they are damaged, however, they lose vitamin A. Damaged stellate cells can activate and run amok, secreting a lot of collagen that causes fibrosis and permanent scarring called cirrhosis.

To understand the liver's major functions, let's first look at our body cells. Cells need to have a balance of chemicals to function properly. Normally cells control what goes in and out of them using special proteins. To keep unwanted things out, cells are separated from the environment around them. This separation is done by a membrane made of phospholipids. The -lipid at the end is another word for fat. Since the borders of our cells are made of fats, things that can pass through fats (called fat-soluble) can easily pass through the cell membranes. Cells cant control this very well, so we use the liver instead. The liver controls the storage and release of fat-soluble vitamins. It detoxifies dangerous drugs and converts food into usable items. The liver also creates several molecules that help body systems function.

Let's run through the liver's major functions of storage, conversion, and creation.

Storage is fairly simple. The liver stores fat-soluble vitamins and converts some of them into usable forms. It stores a quick supply of energy in the form of glycogen. Blood is stored in large quantities in the liver. This makes sense because the liver is filtering the blood. Usually, it holds a little more than 10% of the body's blood, but the liver can expand to hold much more if needed. It can also squeeze blood out if the body is bleeding profusely. This probably isn't great for the liver, but then again neither is bleeding out and dying.

The liver converts a huge amount of material from one form into another. It acts as a psychopomp for nearly all the blood in the body, including blood directly from the digestive tract. This includes tasty nutrients like fat and sugar, and dangerous toxins, like alcohol and methamphetamine. Blood is carried across the lobules and filtered through the hepatocytes and Kupffer cells. The liver doesn't just remove dangerous particles, however, it metabolizes them! Metabolism is the conversion of chemicals from one form to another. One of the most important metabolic functions is detoxification. To make drugs and toxins less dangerous, the liver converts them from being fat-soluble (able to pass through cell membranes) to being water-soluble (able to be released through urine but much harder to enter cells). Carbohydrates are converted to glycogen for storage. The liver changes fats into energy for use. Proteins are broken into building blocks and waste products are removed. Remnants of dead blood cells called bilirubin are turned into bile and used for digestion.

The conversion of materials into component parts helps the liver's third broad function, creation. The liver creates, or synthesizes, many molecules that are used all around the body. It creates important hormones like angiotensin and thyroxine. It makes chemicals for the blood like prothrombin, fibrinogen, and clotting factors. It also makes the aforementioned bile, which is critical for digesting fats.

The liver is the ultimate hero. Through all of these functions, the liver acts in the best interest of the body. It takes the hit from dangerous chemicals and sacrifices its own blood when we need it most. The liver is a team player of the highest degree. When it goes wrong we suffer throughout our whole body. Take care of that liver!

References:

Eng, F. J.,  Friedman, S. L. (2000). Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex. American Journal of Physiology-Gastrointestinal and Liver Physiology, 279(1), G7-G11. https://doi.org/10.1152/ajpgi.2000.279.1.G7

Geerts, A. (2001). History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. In Seminars in liver disease (Vol. 21, No. 03, pp. 311-336). https://doi.org/10.1055%2Fs-2001-17550

Kalra, A., Yetiskul, E., Wehrle, C. J.,  Tuma, F. (2018). Physiology, liver. https://europepmc.org/article/nbk/nbk535438

Lautt, W. W. Hepatic Circulation: Physiology and Pathophysiology. San Rafael (CA): Morgan  Claypool Life Sciences; 2009. Chapter 2, Overview. https://www.ncbi.nlm.nih.gov/books/NBK53069/

Ozougwu, J. C. (2017). Physiology of the liver. International Journal of Research in Pharmacy and Biosciences, 4(8), 13-24.

Vaja, R.,  Rana, M. (2020). Drugs and the liver. Anaesthesia  Intensive Care Medicine, 21(10), 517-523. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508170/

Yin, C., Evason, K. J., Asahina, K.,  Stainier, D. Y. (2013). Hepatic stellate cells in liver development, regeneration, and cancer. The Journal of clinical investigation, 123(5), 1902-1910. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635734/