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Choleresis. Pigment metabolism. Types of jaundice

 

Bile is produced by the liver cells – hepatocytes. Choleresis is the synthesis and secretion of bile by hepatocytes; the secretion of water by epithelial cells of bile ducts; reabsorption of water as it moves through the ducts of bile; excretion by hepatocytes of organic and inorganic components. In the day the person is secreted from 250 to 1000 ml of bile. Choleresis occurs continuously. After the meal, secretion of bile is enhanced reflexively after 3-12 min, and one of the stimuli that affect the acceleration of the process is the bile itself.

Cleavage products, toxic compounds and drugs are excreted with the bile. Bile acids emulsify fats, allowing absorption of fatty acids, cholesterol, vitamins B, K, E, and calcium salts in the small intestine. Bile creates favorable conditions for digestion in the small intestine, improves digestion of proteins and carbohydrates, facilitates the absorption of their cleavage products, stimulates the motility of the small intestine, prevents putrefaction in the intestines, providing an antimicrobial effect, and stimulates the secretion of pancreatic juice and bile formation function of the liver.

The components of bile are bile acids, bile pigments, cholesterol, phospholipids, fatty acids, sodium, potassium, calcium, chlorine, phosphatidylcholine and water. Bile contains enzymes, vitamins, urea, uric acid, amino acids and other useless to the body compounds. Many substances, including drugs are excreted with bile. Substances secreted in the bile are divided into two groups:

- substances associated with proteins in plasma (e.g. hormones). They cannot penetrate the kidney filter and are excreted in bile;

- substances which are insoluble in water (cholesterol, steroids). In the liver they join with glucuronic acid and pass into a water-soluble state, after this they are excreted through the kidneys.

Cholesterol exists in a dissolved state in the complex with bile salts and phosphatidylcholine. With a lack of bile acids cholesterol precipitates, and the stones can be formed. Intensive formation of stones is marked in bile stasis and infection.

Bile pigments (bilirubin is the main) do not take part in digestion. Their secretion by the liver is only excretory process.

Bile removes from the body many drugs, toxins, and inorganic substances - compounds of copper, zinc and mercury.

The production of bile is controlled by nerve and humoral mechanisms. Increased level of bile components in blood stimulate choleresis. Hormones have significant impact on choleresis. Vasopressin, ACTH, and insulin stimulate it. The pineal gland hormone also stimulates secretion of bile, as a result of its direct effect on the liver parenchyma. Choleresis process is most closely associated with the cleavage of the hemoglobin in the tissues and the formation of bile pigments.

Pigment metabolism. Heme is the prosthetic group of hemoglobin and hemin enzymes; about 80% of the body’s heme is in hemoglobin. With the destruction of red blood cell hemoglobin is released. Its cleavege occurs in the liver, spleen and bone marrow. The degradation of the hemoglobin in the liver begins with α-methine linkage between rings I and II of the porphyrin ring. This process is catalyzed by NADPH- containing oxidase and leads to the formation of green pigment verdoglobin. Then verdoglobin spontaneously decomposes, iron and globin protein are released and one of the bile pigments – biliverdin - is formed. The formed biliverdin is enzymatically reduced to the main bile pigment bilirubin in the liver.



The cleavage of hemoglobin:

hemoglobin®verdoglobin®biliverdin®bilirubin.

The main part of bilirubin is formed in the cells of reticuloendothelial system of the spleen and bone marrow. From these organs bilirubin in the complex with albumin is transported by blood to the liver where its conjugation with glucuronic acid takes place. Glucuronic acid is attached to carboxyl groups of propionyl residues, forming glucuronides of bilirubin. Conjugation with glucuronic acid significantly changes the properties of bilirubin. Bilirubin is insoluble in water; that is why it is transported by blood in the complex with albumin. Bilirubinglucuronide is water-soluble and easily excreted in the bile into the intestine. Bilirubin is toxic, especially to the brain; glucuronides of bilirubin are not toxic. Thus, as a result of conjugation of bilirubin its detoxification occurs and its excretion from the body is facilitated.

Glucuronic acid is hydrolytically cleaved from bilirubinglucuronides in the intestine under the influence of bacterial enzymes. A newly formed bilirubin is reduced in some double bonds, forming two groups of products: urobilinogens and sterkobilinogens. Most of these substances (95%) is excreted in the feces, the rest is absorbed from the intestine into the blood and then re-enters the bile, and is partially eliminated through the kidneys. Urobilinogens and sterkobilinogens in the air are oxidized by oxygen, and converted into urobilins and sterkobilins, pigments having a yellow color. Conversion products of bilirubin are called bile pigments. Healthy adult excretes 200-300 mg of bile pigments in the feces and 1-2 mg in the urine daily. Bile pigments are almost always found in gallstones, and in approximately ¼ of cases, they are main components of the stones. Determination of bile pigments concentration in blood and urine is used in the differential diagnosis of jaundice.

Types of jaundice.The concentration of bilirubin in the blood of a healthy person is 1.7-17 mcmol/l. The blood contains both unconjugated bilirubin (¾), and glucuronides. Unconjugated bilirubin in this case is in the complex with blood albumin because it is insoluble in water. Bilirubin with diazo chlorosulfonic acid forms azo compound of pink-purple color; this reaction is used to detect the bilirubin in the blood and urine. Unconjugated bilirubin bound with albumin reacts only after the addition of alcohol, which frees it from its complex with albumin (indirect bilirubin); glucuronides of bilirubin are detected without adding alcohol (direct bilirubin).

With increased degradation of red blood cells, bile duct blockage or liver dysfunction concentration of bilirubin in the blood increases, and as a result skin, mucous membranes, eye sclera become yellow in color (jaundice). Yellow coloration of the skin becomes visible when the concentration of bilirubin in the blood is 2-3 mg/dl. Determination of the concentration of various bile pigments in blood and urine helps reveal the cause of jaundice.

Hemolytic jaundice. With the intense degradation of erythrocytes more bilirubin is formed and the rate of its glucuronidation in the liver, as well as the rate of excretion into the intestine increases. However, the rate of bilirubin formation can exceed the liver's ability to remove it from the blood. Consequently, in hemolytic jaundice the concentration of indirect bilirubin in the blood is increased. Liver secretes large quantities of bilirubin glucuronides in the intestine from which urobilinogens and sterkobilinogens are formed. Therefore, the excretion of urobilinogens and sterkobilinogens in the urine is increased. The content of the sterkobilinogen in feces is increased.

Neonatal jaundice. In the fetus and newborn the amount of red blood cells per unit body weight is more than in adult, as well as the concentration of hemoglobin in erythrocytes. In the weeks after the birth the amount of hemoglobin in the blood of newborn approaches the value characteristic of the adult. In this period the relative rate of erythrocytes degradation is more than in subsequent periods. On the other hand, the ability of the liver to remove bilirubin from the blood of the fetus is poorly developed (during the prenatal period bilirubin is removed through the placenta). In newborns the activity of the enzyme UDP-glucuronyl transferase is decreased. However, the rate of bilirubin excretion from the blood is increased by 3-4 times in the first hours or days after the birth. In the first days of a newborn bilirubin concentration in the blood is increased, and in some infants (approximately 20%) it is increased significantly. Neonatal jaundice can be associated with slowing down of the switch of genes encoding UDP-glucuronyl transferase. Other reasons can be low ability of the liver to extract bilirubin from the blood and reabsorption of bilirubin from the intestine. In severe cases of neonatal jaundice, when bilirubin concentration in the blood exceeds 30 mg/dl, brain functions are damaged. In such conditions, to remove bilirubin from the body massive blood transfusion is used.

Obstructive (regurgitation) jaundice. When there is biliary obstruction (gallstone, tumor, scar) bile can no longer get to the intestine, but hepatocytes continue to generate it. Under these conditions, bile pigments get into the bloodstream, thus the concentration in the blood of both direct and indirect bilirubin is increased. Direct bilirubin as a water-soluble and small molecule substance is filtered in Bowman capsule and excreted in urine. There are no urobilinogens and sterkobilinogens in urine because bilirubin does not enter the intestine. For a complete obstruction of the biliary tract feces are discolored, sterkobilin is absent, urine has the color of dark beer because it contains large amounts of bilirubin.

Hepatocellular jaundice(parenchymal jaundice). In hepatitis liver cells are damaged and, consequently, the production of bile is reduced; in addition, as a result of the liver parenchyma damage the bile enters not only the bile ducts, but also the blood. In hepatic jaundice the concentration of indirect bilirubin and direct bilirubin in the blood is increased (bile enters the blood). Conjugated bilirubin is founded in the urine.

Hereditary jaundice. Hereditary defects of glucuronyltransferase are well known. In the complete absence of enzyme activity bile pigments are not detected in the bile and there is a high concentration of unconjugated bilirubin (40 mg/dl) in the blood.


Date: 2016-04-22; view: 1097


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