The Liver

The liver is the second largest organ in the human body. It lies in the abdominal cavity, just under the diaphragm to which it is attached. It is divided into lobes. When sectioned the liver is seen to be made up of many adjacent lobules which are very indistinctly defined in most mammals. In the pig the lobules are more clearly defined. Each lobule consists of a number of radially arranged columns of liver cells (hepatocytes) with channels between them. The channels are called sinusoids and bile canaliculi. The sinusoids carry blood from branches of the hepatic portal vein and the hepatic artery to a central branch of the hepatic vein (see page 5 of the nutrition section for information on the blood supply of the liver). The liver is covered by a connective tissue coating called Glisson’s capsule.

The structure of the liver lobules places a huge surface area of hepatocytes in close contact with the blood and this allows the liver to carry out its blood content alterations effectively. Many of the liver cells are tetraploid as a result of chromosome duplication without subsequent cell division (a process called endomitosis). This gives the cells increased ability to synthesise mRNA and thus more proteins can be produced.

Functions of the liver

Metabolism of Carbohydrates

Sugars enter the blood stream from the gut and these occur in variable amounts. The liver must maintain the glucose blood sugar level at approximately 90 mg glucose 100cm^-3 blood. This is particularly important for the brain cells which cannot store glucose. The various hexose sugars are converted into glucose for storage as glycogen. About 100g of glycogen is stored in the liver. The conversion of glucose to glycogen is known as GLYCOGENESIS and it is stimulated by the presence of insulin.

Breaking glycogen down into glucose is known as GLYCOGENOLYSIS. The hormone glucagon stimulates the activity of a phosphorylase to initiate the glycogen breakdown process and the glucose produced is released into the blood. Adrenaline and noradrenalin can also stimulate this action during times of cold or stress. The muscles also store glycogen but cannot convert it back directly to glucose.

Lactic acid conversion. When the muscles have produce lactic acid by anaerobic respiration the liver cells convert some of this back to glucose using energy derived from the aerobic breakdown of some of the lactate.

If the glycogen stores run out it is essential to maintain glucose supplies and a process called GLUCONEOGENESIS occurs. When blood sugar levels stay too low the adrenal gland releases adrenocorticotropic hormone which results in the release of glucocorticoids from the adrenal glands. These hormones stimulate the release of amino acids, fatty acids and glycerol from body tissues into the blood and also stimulate the production of the enzymes in the liver for the conversion of these substances into glucose. If the supply of glucose in the body exceeds it’s storage capabilities then it is converted to fats and stored in the adipose tissues spread around various body organs, especially under the skin.

Proteins and amino acids

Deamination - Excess amino acids cannot be stored by mammals and must be converted to sugar molecules for respiratory purposes, or for gluconeogenesis. The amino group (-NH₂) is stripped off of the amino acid along with another hydrogen atom to produce ammonia (NH₃).

2 amino acids + oxygen = 2 keto acids + ammonia

The ammonia is highly toxic and is immediately converted to urea by the ORNITHINE CYCLE.

Three amino acids in the cycle accept two ammonia molecules, a carbon dioxide molecule and a water molecule to create a urea molecule.

Transamination

Certain non-essential amino acids can be manufactured by the liver from other amino acids and keto acids. Basically the amino group is transferred from the amino acid onto the keto acid which then becomes an amino acid.

Plasma protein production

Most of the plasma proteins are manufactured from amino acids by the hepatocytes. The commonest types are albumins which have an osmotic potential balancing effect, resisting water loss from capillaries due to the hydrostatic pressure of the blood. They also act as transport molecules for substances which could be easily lost from the blood or which could have side effects, calcium, tryptophan, some steroid hormones and aspirin.

Plasma globulins are large proteins. The a and b types transport lipids, hormones, cholesterol, the vitamins B12, A, D, and K, and the mineral iron.

Fats

Fat storage is not one of the jobs normally performed by the liver. The deposition of fats in the liver could disrupt blood flow and seriously restrict the efficiency of the liver. The liver’s main role in fat metabolism is conversion of excess glucose to fats for storage elsewhere and the removal and breakdown of cholesterol and phospholipids from the blood.

Red blood cell manufacture and destruction

During embryonic development the liver produces the first crop of red blood cells. Later when the red marrow is formed it stops carrying out their manufacture.

Old red blood cells or those which show signs of damage are trapped by the Kupffer cells in the sinusoids and are intracellularly digested. The products are passed to the hepatocytes which convert the globin molecules into amino acids while the haem is converted to biliverdin and bilirubin, the bile pigments. The iron is converted to ferritin for storage. the bile pigments are passed into the bile canaliculi to be excreted via the gut.

Bile production

The bile is a dilute solution of bile salts (0.8%), bile pigments (0.2%), mineral salts (0.7%) and cholesterol (0.6%). The bile salts are produced from cholesterol by the hepatocytes. Sodium glycholate and Sodium taurochlorate are the commonest bile salts and their function is to emulsify fats, acting much like a detergent does.

Hormone production and destruction

Although not usually considered as an endocrine gland the liver does produce growth hormones referred to as somatomedins under the influence of the hormone somatotrophin from the pituitary gland.

Many hormones are broken down by the hepatocytes but at different rates, for example testosterone and aldosterone are rapidly destroyed while oestradiol, ADH and thyroxine are broken down quite slowly. The action of the liver regulates to some extent the amount of hormone left active in the system.

Detoxification

The Kupffer cells collect and destroy bacteria and viruses from the blood in the sinusoids, but the toxins released by these pathogens and the substances entering through the gut are acted upon by the hepatocytes. The toxins are rendered less active by either, oxidation, methylation (adding a CH₃ group), combination with organic or inorganic molecules or molecular degradation. This tends to be very effective for naturally occurring toxins but the liver’s attempts at detoxification can result in certain substances becoming even more toxic than before, paracetamol is a good example.

Heat production

It is now considered unlikely that the liver acts as a sort of internal heating system for the body. The balance of endothermic and exothermic reactions tends to be fairly equal so that heat output is rather low.