liver

liver The concept that certain organs, such as the liver, brain, and heart, enjoyed a higher status than others was first proposed and accepted in the earliest days of medical thought. Indeed, the Babylonians considered the liver to be the seat and mirror of the soul and, as a consequence, this organ became the focus of divination ceremonies, in which the livers of sacrificial animals were carefully inspected by priests for signs of damage prior to being offered as gifts to the gods. The observed condition of the excised organ was taken to portend the future and, especially, to predict whether or not conditions were favourable for battle. Prayers at these solemn ceremonies were even inscribed on tablets shaped like livers, many of which were subsequently recovered from countries bordering the Mediterranean, far beyond the limits of Babylon.

It was the Greeks who first abandoned superstition in favour of an approach to the understanding of the body based on anatomy and physiology, and it is in the writings of Aristotle where the first attempts to describe animals' livers based on dissection are to be found. However, because of his great influence, Aristotle also helped to perpetuate the notion that human emotions were controlled by four cardinal ‘humours’, two of which — yellow bile and black bile — emanated from the liver. These liver-derived humours were held to be responsible for choleric and melancholic moods, respectively. The coming of the Renaissance age and the scientific revolution put paid to the notion that body organs exist under a hierarchical structure, and the fallacy of the four humour theory was exposed. Rather than denigrate the importance of the liver, however, advances in anatomy and physiology over the years have instead highlighted how important the liver is for normal bodily function.

Anatomy

The liver — the largest internal organ of the body — weighs approximately 1200–1500 g or, on average, one fiftieth of the total adult body weight. It is relatively larger in the infant, comprising approximately one twentieth of the birth weight. Situated in the upper abdomen, beneath the right rib cage and separated from the chest cavity by the diaphragm, the upper border of the liver lies approximately at the level of the nipples. Largely composed of cells known as hepatocytes, which are involved in a multiplicity of synthetic, metabolic, and biotransformatory processes, the liver is unusual in that it is perfused with a dual blood supply. The portal vein carries blood from the spleen and intestines and accounts for approximately 75% of the liver's blood supply, whilst the hepatic artery, which arises indirectly from the aorta, delivers the remaining 25%. Owing to the higher oxygen content of arterial blood, oxygen delivery to the liver is about equally derived from the portal vein and hepatic artery. There is continuous exchange between hepatocytes and the perfusing blood, as various chemicals delivered to the liver from elsewhere in the body by the bloodstream are taken up for degradation and further metabolism, whilst others produced by the liver are, conversely, exported from it. An alternative pathway for dispersal of substances produced in the liver is through secretion into an extensive system of minute canals which eventually form the bile ducts draining into the intestine.

Functions

A multitude of functions of the liver have already been well described, and there are many more of which relatively little is currently known. One of the most important — and easily recognizable when deranged — is the metabolism of the pigment, bilirubin, a chemical predominantly derived from products released during the normal destruction of senescent red blood cells. Yellow discolouration of the eyes and the skin (jaundice) ensues when overproduction of bilirubin exceeds the liver's metabolic capability or when hepatic metabolism of bilirubin is impaired.

Another important function of the liver is the synthesis of bile acids, which are then transported via the bile ducts into the intestine to aid in the digestion of fatty foods and the absorption of certain fat-soluble vitamins, particularly vitamins A, D, E, and K. These vitamins are important for night vision, building strong bones and maintaining normal skin integrity and nerve function, as well as for ensuring normal clotting of the blood. Cholesterol and phospholipids — each of which are important constituents of all cell membranes — and triglycerides — which contain a variety of fatty acids and act as an important storage form of energy — are also synthesized in the liver.

The liver is the main site for the metabolism of a vast range of chemical substances produced as a result of the digestion of food in the intestine. For example, ammonia, produced by digestive processes and by the action of intestinal bacteria on dietary protein, is absorbed into the bloodstream. Ammonia in high quantities interferes with normal brain function — an eventuality prevented by its conversion in the liver to the non-toxic compound, urea. Many other amino acids — the building blocks for protein synthesis — which are derived from the diet and from tissue degradation, are also carried by the bloodstream to the liver. Once there they are metabolized to various proteins with a wide range of important functions, including the prevention of fluid accumulation within the tissues and the binding of potentially toxic compounds, such as copper and iron. The liver has a remarkable capacity for such tasks. Under experimental conditions, at least 85% of the liver must be removed or damaged before protein synthesis is substantially impaired.

The liver also plays a key role in carbohydrate metabolism, resulting in the synthesis of glucose for energy and the generation of body heat. Excess quantities are stored as glycogen, which can subsequently be mobilized as required. There is also a complex system of enzymes which function to convert a myriad of drugs and other toxins, including alcohol, to non-toxic metabolites. The activity of these enzyme systems may be modified by various factors. For example, the capacity of the liver to metabolize alcohol is increased by a steady high level of drinking but markedly impaired by alcohol binges.

Another important function of the liver is performed by so-called ‘phagocytic’ Kupffer cells, which line the vascular networks. These cells play an important role in the prevention of systemic infection and inflammation, by extracting and destroying particulate matter, such as pro-inflammatory bacterial cell walls, as it passes through the liver via the bloodstream.

Advancing age has various effects on the liver. Liver weight and blood supply are each reduced in the healthy elderly subject, but most functions of the liver are well maintained. However, the metabolism of certain drugs may be impaired and this may be at least partly responsible for the increased sensitivity to drugs and possibly also for the high prevalence of adverse drug reactions in this group, especially when multiple drugs are ingested.

Disorders

Any or all of the various liver functions outlined above may be disturbed to varying extents in acute liver disorders, such as acute viral hepatitis. Most such episodes resolve spontaneously without sequelae, owing to the great capacity of liver cells to regenerate. Chronic liver disorders, such as cirrhosis, in which fibrosis and nodule formation occur as the common end result of many disorders causing destruction of hepatocytes, may have more serious consequences. Over the past thirty-five years, liver transplantation has grown from a largely experimental procedure to become a well-established treatment option, not only for that subgroup of patients who have advanced cirrhosis and an otherwise poor prognosis, but also for those patients with the less commonly encountered acute liver failure or liver-based metabolic disorders. Over 650 liver transplantations are performed annually in the UK alone, with over 70% of recipients making a full recovery.

It is clear that, even though ancient cultures were mistaken as to the functions of the liver, they were certainly correct in attaching so much importance to it. Indeed, the maxim that ‘life depends on the liver’ is as pertinent today as ever before.

Stephen M. Riordan, and Roger Williams

See alimentary system.See also bile; gall bladder; jaundice.