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FUNCTION OF THE LIVER

Carbohydrate metabolism. Carbohydrates, from digested food, are absorbed in the small intestine, mainly, in the form of glucose, fructose and galactose and with portal blood transported to the liver. Galactose, that may be utilized only by the liver, and fructose are transformed into glucose. The latter yields to splitting (glycolysis) to form energy or is united into a large molecule of glycogen and in such form finds itself in hepatic cells.

When small potentialities of the liver as "depot" of glycogen turn out to be used to the end, carbohydrates are being transformed into fat and deposited in various parts of the body.

In insufficient supply of carbohydrates glycogen of the liver is splitted and enters the vascular bed (glycogenolysis). If glycogen stores will be used up, glucose can be produced in the liver, in particular, from lactic acid or from amino acid (gluconeogenesis).

Protein metabolism. In the smooth endoplasmic reticulum of hepatocytes are synthetized plasma proteins (albumin, /?- and y-globulins), blood coagulation factors (fibrinogen, factors II, V, VII, IX, X). In splitting of amino acids (and, first of all, in putrefaction of protein in the intestine) ammonia is received. In the liver from ammonia and carbon dioxide a urea is obtained:

2NH₃ + C0₂ = H₂N - C - NH₂ + H₂0

Fat metabolism. The liver and small intestine produce about 90% of cholesterol contained in the organism. In the liver it is used as initial substance for synthesis of bile acids, structural material for membranes and hormones.

Fatty acids, absorbed with food, are splitted in the liver and used for obtaining the energy or for the formation of the organism's own fatty acids, steroids and phospholipids. The liver is also able to synthetize saturated and unsaturated fatty acids, first of all, from carbohydrates, amino acids and other initial organic substances.

Bile secretion. Hepatic cells excrete bile into the biliary capillaries under the pressure up to 26 cm water column. If the pressure in biliary tract exceeds 35 cm water column, bile secretion stops.

Bile includes 80-95% of water, it is isotonic to plasma and has the same pH. It contains bilirubin, bile acids, cholesterol, steroids, phospholipids, mucus, enzymes, hormones and electrolytes. 700-1200 ml of bile is produced every day.

Bilirubin gives the bile its characteristic colour. It is produced in destruction of hemoglobin and enzymes comprising heme, in reticuloendothelial system, particularly in the spleen (about 300 mg per day). So formed bilirubin is not water-soluble and must, for its transportation, bind with serum albumin. This water-insoluble bilirubin is also known under the name of nonconjugated or indirect.

In the liver, under the influence of enzymes of smooth endoplasmic reticulum of hepatocytes by means of addition of two molecules of glucuronic acid, bilirubin becomes water-soluble, conjugated and direct. In the process it loses its ability to cause a toxic lesion of cerebral cells and may be excreted from the hepatic cells into biliary capillaries, and from there through bile ducts — to the intestine. Here, it is, under the influence of enterobacteria, splitted turning into stercobilin (100-200 mg per day) that gives feces its colour, as well as into urobilin and urobilinogen. The lesser part of this stain is resorbed and with the portal blood returns to the liver. Traces of urobilinogen through a systemic circulation come into the kidneys and are excreted.

In poor excretory function of the liver an increase of urobilin quantity in the urine is established. In the organism there are about 4 g of fatty acids. Having very powerful surface activity they can form the so-called micellae grouping its hydrophilic (water-soluble) portions of the molecule outward, and hydrophobic (liposoluble) ones — inwards. Captured inside liposoluble substances become water-soluble, transportable and able to resorb in the intestine. Food that contains water-insoluble lipids (alimentary fat, cholesterol, liposoluble vitamins, medicinal agents, poisons) may, in this form, enter through mucous membrane of the intestine. Thus, fatty acids are a decisive prerequisite for resorption of liposoluble substances from the intestine. A further prerequisite is the presence of pancreatic lipase (enzyme splitting fats) that is activated by fatty acids.

Up to 99% of fatty acids supplied to the intestine with bile are reabsorbed in the small intestine and again return to the liver. From this enterohepatic circle only about 1% of fatty acids that are released daily into the intestine, get into the large intestine and removed from the organism. So, only this small amount of bile acids that is being lost, must be daily replaced. The richer is the food with fat, the more intensive and faster proceeds this enterohepatic circulation of fatty acids.

Detoxication. In hepatocytes, namely, in the smooth endoplasmic reticulum are many enzymes, taking in consideration their specificity, may detoxicate a great number of foreign substances by forming complex structures that are excreted later. Even those substances may be detoxicated that never before encountered hepatocytes. These may be medicaments, some products of nutriti on, fungal poison and the organism's own metabolytes, toxic in certain concentrati on, for example, ammonia, phenol, indole and other derivatives, hormones, etc. In accordance with Brodie's hypothesis, these enzymes were being formed gradually in the process of evolution in order to turn fat-soluble foreign substances into the opposite having raised their water solubility and having made possible their removal through the liver with bile and through the kidneys.

Biotransformation takes place in the liver in two phases. The first includes preparation of foreign substances for a further process of modification, for example, by means of insertion of necessary molecular fragments into the molecule of foreign substance. This reaction leads to a partial inactivation of the initial substance. In the second phase the process of modification ends (for example, binding with glucuronic acid) owing to which the product, of exchange becomes water-soluble and may be directly removed with bile or urine.

The above reaction may be traced by the example of morphine that binds, mainly, with glucuronic acid in the liver. Morphineglucuronide has almost no morphine effect. For 48 hours 6-10% of the dose are excreted through the kidneys in the form of unchanged morphine and about 60% of morphineglucuronide.

The rate of enzymatic reaction of biotransformation of foreign substances is individual. In one patient the same medicaments are eliminated rapidly, in the other — significantly slower. Many enzyme systems of the liver mature after human birth from a few days to one week. This explains toxicity of many medicaments in the early period after birth.

Enzymatic activity of matured hepatic cells is regulated depending on the

need (enzyme induction) that reflects a well-known mechanism of adaptability. At present, more than 200 foreign substances are known that can stimulate formation of hepatic enzymes taking part in the destruction of corresponding foreign substances. Phenobarbital may serve as an example. Administering this preparation in the course of several days, we stimulate synthesis of the whole number of enzymes participating in its exchange.

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