“What does the liver actually do?” So began a fascinating discussion in a science group that led on to fundamental questions of energy storage and waste management in the body. One good reason for feeling you don’t understand the liver is because it performs so many diverse functions that it has no brand presence. We know about the heart: it pumps blood; the lungs take in oxygen the bladder fills with urine. Simple.
But one look at the list of functions of the liver shows just what an extraordinary organ it is. It processes blood, clears out toxins, stores up energy, produces bile,stores nutrients, regulates blood clotting and supports the immune system, to name just a few of its many hundreds of functions.
Key to all these functions is the blood which flows steadily through the organ. Blood is, of course the great transport system, carrying almost everything the body needs to survive – and its waste products, too. Glucose providing energy from the food you eat, immune cells protecting you from infection, proteins building your cells, hormones signalling changes in your metabolism, fats, vitamins, minerals, drugs… all get to where they’re needed, thanks to the flow of blood. Of particular importance is the blood that flows through the blood vessels of the digestive system, as it picks up everything you get from the food you eat. An once it’s picked up this energy-rich blood moves immediately to the nearby liver where it’s carefully filtered.
Filtering
Nutrients from the food you’ve eaten are broken down in the stomach and intestines into smaller molecules which are able to pass out of the intestines through their porous walls. These same molecules then pass directly through the equally porous walls of blood vessels which are immediately adjacent to the intestines. By passing through these two sets of walls these small molecules, extracted from the food you eat, finally enter the bloodstream. Going with the flow, this great mixture of molecules then passes into the nearby liver carrying the nutrients you need, but also toxins you could do without.
The cells of the liver contain enzymes capable of identifying molecules of toxin and rendering them non-toxic. They then deliver these detoxified waste products to the bile fluid that’s flowing through the liver cells. The bile carries them safely away for excretion either via the intestines into the bowels or kidneys into the bladder. This disposal system is, of course, essential to protect us from toxins, but for the chemists that design drugs it also presents a headache. They have to ensure that any active ingredient they create in a pill has to be able to survive the anti-toxin processes of the liver if it is to avoid being eliminated before reaching its goal.
Storing energy
Filtering is thus one crucial role of the liver. Another, equally important one, is enabling your body to survive from one meal to the next. All the cells of the body need energy to flow into them continuously 24/7; they can’t wait till you have your next meal.
The vital molecule that carries energy to your cells is a type of sugar molecule called glucose. It’s the end-product of the process of digesting carbohydrates. After eating a meal, glucose floods the bloodstream and your ‘blood sugar’ level rises. Some of this is used immediately by the organs and muscles of the body but much of it needs to be stored, for later use between meals.
Figure 1 Model of a glucose molecule
The liver achieves this by ‘clicking’ together individual glucose molecules into chains, which are then linked together in giant branching molecules named glycogen (see figures 1 and, ignoring the colourful ribbons in the middle).
figure 2 Model of a glycogen molecule made up of thousands of glucose molecules
Your blood sugar level is constantly monitored internally and special cells in the pancreas respond when glucose levels fall in the bloodstream. When it does, they release a hormone that signals to the liver to break down more glycogen molecules in its store into the glucose units of which they are composed. In this way, glucose is released back into the bloodstream to maintain the supply of energy to cells all over the body.
At the same time, other specialised cells in the brain are also monitoring glucose levels. When the level begins to fall, these brain cells release a special kind of hormone that gives you the sensation of hunger thereby encouraging you to seek out more food to keep up the supply of glucose. What an amazing interconnected system to ensure we don’t fade away between meals!
Making proteins
As well as filtering out toxins and storing energy, another fundamental function of the liver is producing some of the proteins we need to survive.
Protein molecules are long chains of smaller molecules called amino acids. The human body uses twenty different varieties of amino acid to make its proteins. Some of these are produced within the body but others come from food. (no need to worry about the names in tiny print).
Figure 1 the twenty varieties of amino acid used in human proteins
When our digestive system breaks down the proteins in our food, the end-product is the amino acids of which they were composed. The liver uses the amino acids it receives from the digestive system to build some of the proteins the body needs. Amongst these are ones that prevent blood from leaking out of its vessels, others that transport fats through the bloodstream to where they are needed, some that assist our immune response to infection and yet others that enable our blood to clot. All play essential roles in our day-to-day survival. These proteins are produced inside specialised cells unique to the liver called hepatocytes. These remarkable cells also produce and store the energy-rich glycogen mentioned above.
Structure
The cells that do the business in the liver (hepatocytes) are organised into sheets within the structures that make up liver tissue, known as lobules.
A lobule is an amazing well organised structure.
It is roughly hexagonal with the ‘exit’ vein where blood passes out at its centre (the bright blue blob in figure 3). Radiating out from this are sheets of liver cells (hepatocytes) forming a kind of stellar burst looked at in cross section. Blood arrives from two sources at each vertex of the hexagon – bringing nutrients from the intestines (hepatic portal vein, purple) and oxygen from the heart (hepatic artery, red). Bile also passes out from the cells where it is made via ducts (green).
Figure 3 A lobule in cross section
Blood and bile flow through the lobule toward the central vein washing through all the cells on the way. This enables nutrients and oxygen to enter the cells and waste to be removed and sent away via the central vein: a beautiful, intricate system.
The hepatic portal vein (purple) brings energy-rich nutrients from the digestive system, ready for filtering and storing; the hepatic artery (red) brings equally vital oxygen direct from the heart to sustain the liver cells while they do their filtering and storing. These two inputs join together, mixing energy-rich but oxygen-poor blood from the digestive system with oxygen-rich blood from the heart.
Blood flows through tiny channels between the liver cells in an intimate network, enabling molecules from food to enter into the liver cells for processing, and the products of processing inside the cells to pass out for distribution around the body (or elimination, if unwanted).
The network of tiny channels for bile (green) run between the main liver cells. Bile is produced in the liver cells (hepatocytes) and contains cholesterol and bile salts which helps enzymes in the intestines break down molecules of the fats we have digested – an essential part of fat digestion. The bile then flows out of these tiny channels into a larger duct which leads to the gall bladder. This small organ stores the bile, ready to inject into the intestines the next time your digestives system encounters some fats.
Helen in the discussion group had heard that ammonia is somehow produced in this process – “that sounds pretty alarming to me” she interjected. She was right: ammonia is an important waste product of the breakdown of proteins into their component amino acids. This process, which takes place mainly in the intestines produces the toxic substance as a by-product. The body needs to get rid of this quickly and the liver achieves this by a cycle of chemical reactions facilitated by enzymes that convert it into the harmless substance urea. This exits the liver via its central vein and enters the nearby kidneys. Here, urea and other unwanted substances are separated out from the blood stream and combined together with large quantities of water to form urine. This passes out via the bladder, ensuring that toxic ammonia and other undesirable materials are expelled from the system.
Overall shape
Although the liver appears at first sight to be a single entity, it is actually divided into a number of separate pieces called ‘lobes’. The two main ones – right and left are shaped to fit neatly under the diaphragm and above the stomach.
Figure 4 Animation of the liver showing its two main lobes and lesser ones
A completely different kind of tissue – connective tissue – forms ligaments that separate the two main lobes and connect them to the neighbouring diaphragm and stomach. The main blood vessels that service the liver run in between the two main lobes which suggests that the the advantge of a two part structure is that it shortens the distance from the farthest parts of the liver to the central blood vessels, making the filtration process more efficient.
Damage and regeneration
One thing the discussion group did know about the liver was its ability to regenerate itself – Jean had a friend who had had half her liver removed surgically and was perfectly OK. This feat – unique amongst human organs – happens when liver cells are damaged or a section is removed in surgery. The remaining healthy cells simply get a message to reproduce themselves. The whole structure of the lobule is recreated under the control of enzymes and hormones. In effect the healthy part simply extends itself. Amazingly, a healthy liver can be regenerated even if 70 – 80 % of its mass is removed.
Members of the discussion group also knew that the liver is subject to various kinds of disease. Hepatitis is an inflammation response by the liver cells, caused by infection or injury. Fibrosis involves scarring, in which some liver cells are replaced by scar tissue. Cirrhosis is a more severe and permanent development of scar tissue, impairing the function of the liver cells. Alcohol is processed primarily by enzymes in the hepatocyte cells, and too much alcohol can overwhelm its processing capacity. As a consequence, some harmful chemicals that are created at intermediate stages of the filtering process build up to excess. If this persists over time this causes scarring of the liver and ultimately cirrhosis.
Conclusion
The standout point from this brief story of the liver is just how many roles it plays. In this blog we have selected three or four to focus on but left many others unexplored – in blood clotting and combatting infection, for example. But what it has shown is just how intricate its structure is, and just central it is to dealing with both the desirable and undesirable molecules that flow through our bloodstream. Not only an absolutely vital part of our basic functioning, but also a self-repairing part when damaged. What an asset!
Getting to Grips with Science 