Lying almost at the centre of the body, and at 1.5-2 kg weight in ay adult the body’s largest organ, the liver is also at the centre of the body’s metabolism. It is a chemical factory and processing plant of enormous complexity, playing an indespensible role in many metabolic processes. The liver deals with the varied raw products of digestion; it processes, stores and distributes nutrients; it manufactures and breaks down proteins – the body’s basic building-blocks; it manufactures bile in order to remove wastes; and it generally acts as a reservoir, cleaner, filter and detoxi-fier for the . Scientists are still discovering functions of this amazing organ.
The liver lies at the top of the abdomen, directly under the right side of the diaphragm ; the upper surface is smooth and rounded to mould into the diaphragmatic cavity. The liver functions as one unit but it develops from a bud that divides into two halves; although fused, these two halves can function independently. The division between them is impossible to detect from the outside, and in fact peritoneal attachments, called the falciform ligament, divide the liver into an artificial right and left lobe. There are two smaller lobulations of the liver: the quadrant lobe in the front, and the caudate lobe behind. There are also indentations in the liver’s surface accommodating the inferior vena cava, the large vein draining blood from the lower half of the body, and the gall bladder tucked underneath it. Apart from a small area directly under the diaphragm, the liver is completely covered by the peritoneum, the membrane that lines other abdominal contents. The structure and function of the liver is based on the hepatic (liver) lobules. Each of the hundreds of thousands of lobules has its own arterial and portal blood supply, and each has its own bile drainage. Inside each lobule are hundreds of liver(hepato-cytes), the basic responsible for the majority of the liver’s functions.
Blood reaches the liver by two routes. First there is an arterial supply, rich in oxygen, from the hepatic artery. Second the portal vein brings blood from the abdominal digestive tract. This portal blood contains most of the absorbed products of digestion and represents 80 per cent of the blood reaching the liver, which is in total approximately 1.5 litres every minute.
Blood leaves the liver along the hepatic veins which empty into the inferior vena cava. With such a massive blood flow it is no wonder that damage to the liver can result in life-threatening blood loss.
The multifold functions of the liver run in excess of 500. However these functions can be divided into several broad but seperate areas: secretion of bile; metabolic functions; haematological (blood) functions; and detoxification.
Secretion of bile
Bile is made in the liver, stored in the gall bladder and released via the bile ducts, into the duodenum. The liver secretes 600 to 800 ml of bile daily, although the fluid content is decreased by absorption as bile is concentrated in the gall bladder. Bile is mostly water but contains dissolved minerals, bile salts, bile pigments and mucin, together with some cholesterol and other fats. The main bile pigment is bilirubin, a brownish-yellow breakdown product of haemoglobin, the oxygen-carrying substance contained within red blood. Bilirubin is not water-soluble and is carried in the bloodstream by protein molecules. Bilirubin is joined, within the liver, on to glucuronic acid, which makes it water-soluble, and is then excreted in the bile. If the bile ducts are blocked, by a gallstone for instance, conjugated bilirubin spills over into the bloodstream, making the skin yellow (jaundiced), and into the urine, making it dark; the faeces, normally brown because of bilirubin, turn pale.
Bile salts are derivatives of cholesterol, which is transformed in the liver cells. They are secreted in the bile to emulsify fat when they arrive in the small intestine. They are reabsorbed, along with fat, by the small intestine and thereby return to the liver.
The metabolic functions of the liver are numerous and some are exceedingly complex. The portal blood carries virtually all the water-soluble products of digestion to the liver. These are then processed by the hepatocytes for further distribution or storage. One product common to all metabolic processes, as with most other chemical reactions, is heat. The temperature of blood leaving the liver along the hepatic veins is measurably higher than that of blood entering the liver. This heat is distributed by the blood throughout the body.
Carbohydrates are digested and absorbed mostly as the sugars galactose and fructose, which are not useable by body cells. One of the liver’s functions is to convert these sugars into glucose, which is useable by body cells as an energy source. If there is a more than adequate amount of glucose present for immediate body requirements, the excess is converted and stored in the liver in the form of glycogen (animal starch). When too little glucose is available, and there is an excess of amino acids or glycerol (one of the breakdown products of fats), these may be converted to glucose in the liver by the process of gluconeogenesis. Thus the liver maintains the level of glucose in the blood so that all cells have a readily available resource of energy.
Although fat is stored in adipose (fat) tissue, most of the body’s fat metabolism takes place in the liver.
Large fat molecules, triglycerides, are broken down into glycerol and fatty acids. The fatty acids are further broken down into smaller energy-rich compounds, which are either utilized in the liver or passed on to other energy-consuming. Fat can also be synthesized in the liver from carbohydrate or protein, after which it is transported to the adipose tissue for storage. Approximately only five per cent of the liver is fat, but this proportion increases as a result of diseases such as those caused by abuse.
The liver is also concerned with the synthesis of the fatty substance cholesterol. 80 per cent of this is used to form bile salts; the remainder is excreted in the bile or enters the circulation in combination with protein. Protein metabolism is one of the most important functions of the liver. Unlike fat, there is no storage pool of protein, apart from the body itself in structural components of cells such as skeletal muscle. Proteins in the diet are broken down into amino acids which are absorbed.
Excess amino acids need to be deami-nated (removal of the nitrogen-containing portion) before they can be converted into carbohydrate or fat for subsequent storage or energy production. Ammonia (a nitrogen-containing molecule) is one of the breakdown products of protein metabolism, and is potentially poisonous if allowed to accumulate. It is converted in the liver to urea, which is excreted in urine by the kidneys. If the liver fails these processes break down, causing confusion, coma or death.
The liver produces 95 per cent of all proteins circulating in the blood plasma. These have numerous important functions, and a deficiency of any of them is usually an indicator of liver disease or starvation. The liver is also the site for transamination. This is the process whereby the nitrogen-containing part of an amino acid is transferred to another molecule – a keto acid – thus forming a new keto-acid and a new amino acid. The enzyme that catalyzes this transfer is normally released into the blood serum as a result of damage to the hepatic cells caused by disease. The liver plays a vital role in vitamin metabolism and storage. Vitamin A is stored in large quantities in the liver – usually enough for up to two years. Vitamins D and Bi2 are also stored in the liver, but in smaller quantities. Vitamin K is used by the liver to help produce prothrombin and other chemicals necessary for blood clotting.
Manyare broken down in the liver, so that their actions do not continue for ever. The decreased destruction of hormone that occurs as a result of liver failure produces a potentially dangerous increase in the amount of hormone in the body. This may cause fluid retention, sexual changes – growth of breast-tissue and impotence in males, and lack of periods in females – and other signs of endocrine disease.
The liver and blood
The liver acts as a reservoir which is able to store excess blood, or supplys extra blood to the circulation, according to the body’s needs. The liver of the foetus and young baby is an important site for the manufacture of red and white blood cells. After this time the liver is used merely to destroy damaged or old blood cells.
Liver cells also contain a protein called apoferritin. Any excess of iron, which is not immediately needed to make haemoglobin in red cells, is absorbed by liver cells and combined with apoferritin to produce ferritin. This is stored and utilized if for any reason bodily supplies of iron run low.
The blood-filled spaces or sinuses of the liver are lined with kupffer cells, which are also present in the spleen, bone marrow and lymph nodes. These cells ‘eat’ (phagocytose) damaged red cells and bacteria which have entered the portal blood from the intestinal tract. This extremely efficient filter system prevents gut micro-organisms from entering the general circulation and causing an infection.
By various chemical methods the liver breaks down or excretes potentially toxic substances, as has been described for urea. It is also the site of drug metabolism in many cases, and the actions of some drugs are enhanced in liver failure. Alcohol is one of the major poisons dealt with by the liver. It is broken down to harmless constituents and removed from the blood. The liver is extremely resilient in this respect but, put under strain by too high an alcohol intake, liver cells die and are replaced by scar tissue. The result is cirrhosis of the liver.
Bile ducts and gall bladder
As mentioned above, the lobules of the liver secrete bile fluid into small channels, called bile canaliculi. These come together to form large ducts, eventually becoming the right and left hepatic ducts. These two finally fuse, usually just outside the liver, to form the common hepatic duct. This joins the cystic duct, which drains the gall bladder, to form the common bile duct that empties into the duodenum. The pancreatic duct usually empties into the duodenum at the same place as the common bile duct, although in some people it may open separately into the duodenum. A large amount of bile is secreted by the liver and some of it passes directly into the duodenum; most of this, however, is stored in a greatly concentrated form in the gall bladder as a result of absorption of water and dissolved minerals. The capacity of the gall bladder is in the region of 50 to 60ml, which means it can store the end product of up to 12 hours of the liver’s biliary secretions.
The gall bladder empties when it detects the presence of food, particularly fatty food, in the stomach and small intestine. This is effected by two means; by nerve stimulation from the vagus nerve, and more effectively by the secretion of the gut hormone chole-cystokinin from the wall of the duodenum into the bloodstream. This acts directly on the gall bladder, causing it to contract and empty. Gallstones may be formed from excess cholesterol or pigment in the bile, but usually by a combination of the two. They are prevented from leaving the gall bladder by a spiral valve in the cystic duct. Although they can cause pain or inflammation in the gall bladder (cholecystitis), they causeonly when they manage to get past the valve and stick in the common bile duct, normally at the lower end.