Facts About Liver

1- Human liver is a very vital organ. It is so important that if it stops functioning even for a single day, a person will simply die. Unfortunately, it is one of the least thought about organs. So, it is time that we change our view and start giving it the much deserved attention. Here are some 25 interesting facts about human liver.

2- The size of the liver increases with age, from an average span of 5 cm at the age of five years, to 15 cm in adulthood. The normal liver weighs 1.4 to 1.5 kg in men and 1.2 to 1.4 kg in women and is reddish-brown in color. The liver has two parts – the right lobe and the left lobe. The right lobe is bigger than the left lobe.

3- ‘Hepar’ is the Greek term for liver. It is because of this Greek name that most liver related medical terms actually start with ‘hepatic or hepato’.

4- Liver protects our body from harmful substances or toxin that we put in our body either deliberately or unintentionally through food we eat or drink.

5- The liver also protects our body from the toxins by cleaning the blood from chemicals that are spontaneously within our body because of day to day activities.

6- The chemicals removed from the blood are sent into our intestines in form of bile. These chemicals are then removed in form of feces or stool. These chemicals may also be sent into the kidneys where they are filtered out from the body in form of urine.

7- Liver is responsible for producing bile. Bile is very important because it helps in digesting food. Of course, without bile the body would simply fail to remove toxins from the body.

8- The bile produced by the liver is also important because it helps to breakdown fats into smaller particles so that the pancreatic lipase can digest fat better.

9- Bile produced by liver is also responsible for the characteristic brown color of the stool.

10- Our body produces a chemical known as bilirubin. This is pretty toxic and if it goes unfiltered into the kidneys, it can damage them. The liver actually filters and makes bilirubin safe before sending it to the kidneys. The kidneys then filter out the bilirubin from the body along with urine. This is what gives the characteristic yellow color to our urine.

11- Humans are not the only living beings to have a liver. Any living creature with a spinal column or a backbone has a liver. In short every vertebrate in this world has a liver.

12- The Greeks considered the liver to be the home of all human emotions. According to Greeks, the liver was the organ which was closest to divine presence.

13- Yet another interesting fact about liver is that it never uses sugar for energy. It only stores sugar. In reality, liver is the storehouse of any excess sugar that we consume. It stores this sugar in form of a compound known as glycogen. Between meals when our body needs sugar, the liver breaks down the glycogen to form glucose. This glucose is then used by the remaining body as energy fuel.

14- Almost all medicines that we consume are processed by the liver. Because our body is not capable of using the medicines as is, the liver breaks them down in a form that the body can use.

15- The liver is responsible for producing enzymes and chemicals that helps the blood to clot in the event of bleeding due to a cut.

16- Liver is also responsible for making cholesterol. While high levels of low density lipoprotein or (bad cholesterol) is actually bad, cholesterol is also required for building cells as well as hormones. Hormones are necessary for normal functioning of the body because they can be rightly termed as the messengers in our body. Absence of hormones will lead to abnormal body functioning because they will fail to communicate properly.

17- Liver is responsible for performing over 500 different vital functions of the body.

18- At any given point in time, liver contains 10% of the total blood in the body. It filters around 1.4 liters of blood every single minute.

19- The Greeks used to practice what we today call as hepatoscopy. It is a practice where the Greeks used to sacrifice goats and oxen and examined their livers to determine whether they will earn victory in a battle or war.

20- Human liver is actually an iron warehouse. It also contains extra minerals and vitamins which allows a person to perform throughout the day.

21- Our body that is up and running is because of the blood. If blood wasn’t there right from the beginning, we would not even exist. This blood was actually made by liver even before our birth.

22- Yes, we did say that artificial liver replacement is not possible but liver transplant is possible. One very interesting fact about liver is that it can sustain and survive heavy damage. It can grow back.

23- Liver transplant usually involves cutting out a certain part of the liver from the donor and giving it to the receiver. The part of the liver that is cut out from the donor can actually grow back!

24- The first ever liver transplant in human history was carried out by Dr. Thomas E. Starzl in year 1963 at University of Colorado Medical School. The transplant was not successful because of the lack of effective immunosuppressive drugs. He made another attempt in 1967 and the transplant was successful.

Anatomy of Liver

The liver is a peritoneal organ positioned in the right upper quadrant of the abdomen. It is the largest visceral structure in the abdominal cavity, and the largest gland in the human body, weighing in at around 3 pounds.

An accessory digestion gland, the liver performs a wide range of functions; including synthesis of bile, glycogen storage and clotting factor production.

Anatomical Position

The liver is predominantly located in the right hypochondrium and epigastric areas, and extends into the left hypochondrium.

When discussing the anatomical position of the liver, it is useful to consider its external surfaces, associated ligaments, and the anatomical spaces (recesses) that surround it.

Liver Surfaces

The external surfaces of the liver are described by their location and adjacent structures. There are two liver surfaces – the diaphragmatic and visceral:

Diaphragmatic surface – the anterosuperior surface of the liver.

It is smooth and convex, fitting snugly beneath the curvature of the diaphragm.

The posterior aspect of the diaphragmatic surface is not covered by visceral peritoneum, and is in direct contact with the diaphragm itself (known as the ‘bare area’ of the liver).

Visceral surface – the posteroinferior surface of the liver.

With the exception of the fossa of the gallbladder and porta hepatis, it is covered with peritoneum.

It is moulded by the shape of the surrounding organs, making it irregular and flat.

It lies in contact with the right kidney, right adrenal gland, right colic flexure, transverse colon, first part of the duodenum, gallbladder, oesophagus and the stomach.

Coronary ligament (anterior and posterior folds) – attaches the superior surface of the liver to the inferior surface of the diaphragm and demarcates the bare area of the liver The anterior and posterior folds unite to form the triangular ligaments on the right and left lobes of the liver.

Ligaments of the Liver

There are various ligaments that attach the liver to the surrounding structures. These are formed by a double layer of peritoneum.

Falciform ligament – this sickle-shaped ligament attaches the anterior surface of the liver to the anterior abdominal wall and forms a natural anatomical division between the left and right lobs of the liver. The free edge of this ligament contains the ligamentum teres, a remnant of the umbilical vein.

Triangular ligaments (left and right):

The left triangular ligament is formed by the union of the anterior and posterior layers of the coronary ligament at the apex of the liver and attaches the left lobe of the liver to the diaphragm.

The right triangular ligament is formed in a similar fashion adjacent to the bare area and attaches the right lobe of the liver to the diaphragm.

Lesser omentum – Attaches the liver to the lesser curvature of the stomach and first part of the duodenum. It consists of the hepatoduodenal ligament (extends from the duodenum to the liver) and the hepatogastric ligament (extends from the stomach to the liver). The hepatoduodenal ligament surrounds the portal triad.

In addition to these supporting ligaments, the posterior surface of the liver is secured to the inferior vena cava by hepatic veins and fibrous tissue.

Hepatic Recesses

The hepatic recesses are anatomical spaces between the liver and surrounding structures. They are of clinical importance as infection may collect in these areas, forming an abscess.

Subphrenic spaces – located between the diaphragm and the anterior and superior aspects of the liver. They are divided into a right and left by the falciform ligament.

Subhepatic space – a subdivision of the supracolic compartment (above the transverse mesocolon), this peritoneal space is located between the inferior surface of the liver and the transverse colon.

Morison’s pouch – a potential space between the visceral surface of the liver and the right kidney. This is the deepest part of the peritoneal cavity when supine (lying flat), therefore pathological abdominal fluid such as blood or ascites is most likely to collect in this region in a bedridden patient.

Liver Lobes

The structure of the liver can be considered both macroscopically and microscopically.

The liver is covered by a fibrous layer, known as Glisson’s capsule. It is divided into a right lobe and left lobe by the attachment of the falciform ligament. There are two further ‘accessory’ lobes that arise from the right lobe, and are located on the visceral surface of liver:

Caudate lobe – located on the upper aspect of the visceral surface. It lies between the inferior vena cava and a fossa produced by the ligamentum venosum (a remnant of the fetal ductus venosus).

Quadrate lobe – located on the lower aspect of the visceral surface. It lies between the gallbladder and a fossa produced by the ligamentum teres (a remnant of the fetal umbilical vein).

Separating the caudate and quadrate lobes is a deep, transverse fissure – known as the porta hepatis. It transmits all the vessels, nerves and ducts entering or leaving the liver with the exception of the hepatic veins.

Microscopic structure of Liver

To understand the function of the liver it is necessary to understand the blood supply to the liver.  It is supplied by the hepatic artery in the typical manner but it is the only digestive organ drained by the inferior vena cava.  Other digestive organs such as the small intestine, parts of the large intestine, stomach and pancreas are drained by the hepatic portal system which takes the blood directly to the liver.  Thus, the liver receives oxygen poor, nutrient rich blood from the hepatic portal system and oxygen rich blood from the hepatic artery.

The liver consists of the following major histological components:

Stroma – which is a continuation of the surrounding capsule of Glisson. It consists of connective tissue and contains the vessels. The capsule is also covered by a layer of mesothelium, arising from the peritoneum covering the liver. The connective tissue of the stroma is type III collagen (reticulin), which forms a meshwork that provides integrity for the hepatocytes and sinusoids.

Parenchyma – which is mainly represented by hepatocytes

Hepatocytes   

The internal structure of the liver is made of around 100,000 small hexagonal functional units known as lobules. Hepatocytes are one of the primary functional cells of the liver. These large and polyhedral (six surfaces) cells make up 80% of the total cells of the liver. They can contain between two and four nuclei, which are large and spherical, occupying the centre of the cells. Each nucleus has at least two nucleoli. The typical lifespan of a hepatocyte is five months. They are located in flat irregular plates that are arranged radially like the spokes of a wheel around a branch of the hepatic vein, called the central vein or central venule since it really has the structure of a venule. The adjacent hepatocytes leave a very small space between them known as bile canaliculi which are almost 1.0-2.0 μm in diameter. The cell membranes near these canaliculi are joined by tight junctions.

These rows are one cell wide and are surrounded by sinusoidal capillaries or sinusoids. This arrangement ensures that each hepatocyte is in very close contact with blood flowing through the sinusoids, i.e. bathed in blood.

The endothelial cells lining sinusoids are fenestrated and in most species lack a basal lamina.  Gaps are also present between the endothelial cells.  Taken together these two properties make the sinusoids extremely leaky and allow for the extremely close contact between the blood and the surface of hepatocytes.  Many materials in the blood, except for whole blood cells, can pass between the spaces in the sinusoidal lining.

Although sinudoidal endothelial cells lie very close to hepatocytes, they do not actually make contact.  A narrow space is present between the surface of the hepatocyte and the surface of the endothelial cell.  This is called the space of Disse; it is filled with numerous microvilli from the hepatocytes.  As in other areas of the body, these structures serve to increase the surface area of the cell membrane that comes in contact with the blood facilitating exchange of molecules between hepatocytes and the blood.

In addition, sinusoids contain a specific cell type called Kupffer cell, containing ovoid nuclei. These monocyte derivatives of the mononuclear phagocytic system are part of the sinusoid lining from which they extend processes into the lumen. Therefore, Kupffer cells continuously sample the blood travelling through the sinusoids, phagocytosing antigens, microorganisms, and damaged red blood cells.

The cytoplasm is acidophilic in routine H&E staining, dotted with basophilic regions represented by rough endoplasmic reticulum (rER) and ribosomes. In addition, hepatocytes contain the following organelles:

1- Smooth endoplasmic reticulum (sER), which is essential in toxin degradation and conjugation, as well as cholesterol synthesis.

2- Mitochondria (up to 1000/cell)

3- Golgi network, which is composed of approximately 50 small Golgi units. They contain granules with very low density lipoprotein and bile precursors.

4- Peroxisomes, which contain oxidases and catalases. These enzymes are responsible for detoxification reactions taking place in the liver, for example, that of alcohol.

4- Glycogen deposits, which are lost in during H&E preparations, leaving irregular stained areas.

5- Lipid droplets

6- Lysosomes, which are responsible for iron storage under the form of ferritin.

7- The perisinusoidal space contains a specific type of cell called Ito, or hepatic stellate, cells. Their role is the storage of hepatic vitamin A inside lipid droplets, which is subsequently released as retinol. However, Ito cells are also responsible for hepatic fibrosis, since they are the ones secreting large amounts of collagen during liver injury.

Hepatic Lobules

In histological terms, the liver consists of a large number of microscopic functional units that work in unison to ensure the overall, proper activity of the entire organ. There are three possible ways of describing one such unit, as given below:

Classic Hepatic lobule

The classic lobule is the traditional description and the one that you have most likely heard of the most. It consists of hexagonal plates of hepatocytes stacked on top of each other. Within each plate, the hepatocytes radiate outwards from a central vein. As they extend towards the periphery, the hepatocytes are arranged into strips, similar to the spokes of a cartwheel. Hepatic sinusoids travel between the strips of hepatocytes, draining into the central vein.

One portal canal is located at each corner of the hexagonal classic lobule, making a total of six for each lobule. These portal canals are composed of the portal triads, which are surrounded by loose stromal connective tissue. A periportal space (space of Mall), where lymph is produced, is sandwiched between the connective tissue of the portal canals and the hepatocytes.

While connective tissue is present around the portal canals, the interlobular quantity is very small in humans. This can make routine histological visualizations of the classic lobule difficult.

Portal lobule 

While the classic lobule view focuses on the blood supply and hepatic mass arrangement, the portal lobule view underlines the exocrine function of the liver i.e. bile secretion. In this case, each functional unit is a triangle, having a central axis through a portal canal and the imaginary vertices through the three different but closest portal canals surrounding it. The area covered by the triangle represents the hepatic regions that secrete bile into the same bile duct.

Liver acinus

The focus of this description is the perfusion, metabolism and pathology of hepatocytes, providing a more accurate description of the physiology of the liver. A liver acinus functional unit is in the shape of an oval. The short axis is represented by a shared border between two adjacent lobules together with the portal canals. The long axis is an imaginary line between two adjacent central veins.

Each liver acinus can be divided into three zones:

Zone 1 – It is the one closest to the short axis, hence to the portal canals and supply of arterial blood. The hepatocytes in zone 1 receive the highest amount of oxygen.

Zone 2 – It is the one located between zones 1 and 3.

Zone 3 – It is the one furthest from the short axis but closest to the central vein, hence the hepatocytes receive the least amount of oxygen.

Portal canal:  Three structures are found grouped together in the loose connective tissue surrounding the plates of hepatocytes.  These include branches of the hepatic artery, the hepatic portal vein (venule) and the intralobular bile ductule.  This group of three structures has been called a portal triad but now is called a portal canal. It also contains lymphatic vessels and vagus nerve (parasympathetic) fibres.

Arterial Supply and Venous Drainage

The liver has a unique dual blood supply:

Hepatic artery proper (25%) – supplies the non-parenchymal structures of the liver with arterial blood. It is derived from the coeliac trunk.

Hepatic portal vein (75%) – supplies the liver with partially deoxygenated blood, carrying nutrients absorbed from the small intestine. This is the dominant blood supply to the liver parenchyma, and allows the liver to perform its gut-related functions, such as detoxification.

Venous drainage of the liver is achieved through hepatic veins. The central veins of the hepatic lobule form collecting veins which then combine to form multiple hepatic veins. These hepatic veins then open into the inferior vena cava.

Nerve Supply

The parenchyma of the liver is innervated by the hepatic plexus, which contains sympathetic (coeliac plexus) and parasympathetic (vagus nerve) nerve fibres. These fibres enter the liver at the porta hepatis and follow the course of branches of the hepatic artery and portal vein.

Glisson’s capsule, the fibrous covering of the liver, is innervated by branches of the lower intercostal nerves. Distension of the capsule results in a sharp, well localised pain.

Lymphatic Drainage

The lymphatic vessels of the anterior aspect of the liver drain into hepatic lymph nodes. These lie along the hepatic vessels and ducts in the lesser omentum, and empty in the colic lymph nodes which in turn, drain into the cisterna chyli.

Lymphatics from the posterior aspect of the liver however, drain into phrenic and posterior mediastinal nodes which join the right lymphatic and thoracic ducts.

Physiology of the Liver

Digestion

The liver plays an active role in the process of digestion through the production of bile. Bile is a mixture of water, bile salts, cholesterol, and the pigment bilirubin. Hepatocytes in the liver produce bile, which then passes through the bile ducts to be stored in the gallbladder. When food containing fats reaches the duodenum, the cells of the duodenum release the hormone cholecystokinin to stimulate the gallbladder to release bile. Bile travels through the bile ducts and is released into the duodenum where it emulsifies large masses of fat. The emulsification of fats by bile turns the large clumps of fat into smaller pieces that have more surface area and are therefore easier for the body to digest.

Bilirubin present in bile is a product of the liver’s digestion of worn out red blood cells. Kupffer cells in the liver catch and destroy old, worn out red blood cells and pass their components on to hepatocytes. Hepatocytes metabolize hemoglobin, the red oxygen-carrying pigment of red blood cells, into the components heme and globin. Globin protein is further broken down and used as an energy source for the body. The iron-containing heme group cannot be recycled by the body and is converted into the pigment bilirubin and added to bile to be excreted from the body. Bilirubin gives bile its distinctive greenish color. Intestinal bacteria further convert bilirubin into the brown pigment stercobilin, which gives feces their brown color.

Metabolism

The hepatocytes of the liver are tasked with many of the important metabolic jobs that support the cells of the body. Because all of the blood leaving the digestive system passes through the hepatic portal vein, the liver is responsible for metabolizing carbohydrate, lipids, and proteins into biologically useful materials.

Our digestive system breaks down carbohydrates into the monosaccharide glucose, which cells use as a primary energy source. Blood entering the liver through the hepatic portal vein is extremely rich in glucose from digested food. Hepatocytes absorb much of this glucose and store it as the macromolecule glycogen, a branched polysaccharide that allows the hepatocytes to pack away large amounts of glucose and quickly release glucose between meals. The absorption and release of glucose by the hepatocytes helps to maintain homeostasis and protects the rest of the body from dangerous spikes and drops in the blood glucose level. 

Fatty acids in the blood passing through the liver are absorbed by hepatocytes and metabolized to produce energy in the form of ATP. Glycerol, another lipid component, is converted into glucose by hepatocytes through the process of gluconeogenesis. Hepatocytes can also produce lipids like cholesterol, phospholipids, and lipoproteins that are used by other cells throughout the body. Much of the cholesterol produced by hepatocytes gets excreted from the body as a component of bile.

Dietary proteins are broken down into their component amino acids by the digestive system before being passed on to the hepatic portal vein. Amino acids entering the liver require metabolic processing before they can be used as an energy source. Hepatocytes first remove the amine groups of the amino acids and convert them into ammonia and eventually urea. Urea is less toxic than ammonia and can be excreted in urine as a waste product of digestion. The remaining parts of the amino acids can be broken down into ATP or converted into new glucose molecules through the process of gluconeogenesis.

Detoxification

As blood from the digestive organs passes through the hepatic portal circulation, the hepatocytes of the liver monitor the contents of the blood and remove many potentially toxic substances before they can reach the rest of the body. Enzymes in hepatocytes metabolize many of these toxins such as alcohol and drugs into their inactive metabolites. And in order to keep hormone levels within homeostatic limits, the liver also metabolizes and removes from circulation hormones produced by the body’s own glands.

Storage

The liver provides storage of many essential nutrients, vitamins, and minerals obtained from blood passing through the hepatic portal system. Glucose is transported into hepatocytes under the influence of the hormone insulin and stored as the polysaccharide glycogen. Hepatocytes also absorb and store fatty acids from digested triglycerides. The storage of these nutrients allows the liver to maintain the homeostasis of blood glucose. Our liver also stores vitamins and minerals – such as vitamins A, D, E, K, and B12, and the minerals iron and copper – in order to provide a constant supply of these essential substances to the tissues of the body.

Unfortunately, one common hereditary disorder called hemochromatosis causes the liver to store too much iron, potentially leading to liver disease. Modern DNA health testing can help you find out if you are genetically at higher risk of acquiring this condition or others like Gaucher disease ad alpha-1 antitrypsin deficiency, all of which increase your risk of developing liver disease.

Production

The liver is responsible for the production of several vital protein components of blood plasma: prothrombin, fibrinogen, and albumins. Prothrombin and fibrinogen proteins are coagulation factors involved in the formation of blood clots. Albumins are proteins that maintain the isotonic environment of the blood so that cells of the body do not gain or lose water in the presence of body fluids.

Immunity

The liver functions as an organ of the immune system through the function of the Kupffer cells that line the sinusoids. Kupffer cells are a type of fixed macrophage that form part of the mononuclear phagocyte system along with macrophages in the spleen and lymph nodes. Kupffer cells play an important role by capturing and digesting bacteria, fungi, parasites, worn-out blood cells, and cellular debris. The large volume of blood passing through the hepatic portal system and the liver allows Kupffer cells to clean large volumes of blood very quickly.