From Big Medical Encyclopedia

BILIRUBIN (C 33 H 36 O 6 N 4  ; lat. bilis bile + ruber red) — one of bilious pigments of yellow-red color. In B.'s structure, as well as in structure bilious pigments (see), four pyrrol rings which are linearly connected by metinovy bridges enter.


Pier. the weight (weight) of B. — 584,68. Represents the crystal substance consisting of rhomboidal prisms and plates, light orange or red-brown color, it is difficult rastvorimo in water, in glycerin and ether, poorly alcohol-solublly, it is better — in chloroform, benzene chloride and in divorced solutions of alkalis. Existence of two carboxyl groups in side chains causes acid properties B. and ability to form its salts. Alkaline salts B. of a rastvorima, salt of bivalent metals are insoluble.

B.'s education happens hl. obr. from hemoglobin of blood in reticuloendothelial system (in cells of marrow, cells of a spleen, in kupferovy cells of a liver, etc.)» and also in histiocytes of connecting fabric of any body. However the most important role in processes of education of B. of hemoglobin is played by a liver. Disintegration of hemoglobin (Hb) begins with formation of a complex with gaptoglobiny (Hp). Gemoglobin-gaptoglobinovy the complex (Hb — Hp) is exposed to enzymic oxidation, to-rogo the rupture of system of porphyrinic rings of hemoglobin (see Hemoglobin) with loss of one metinovy group (= results from CH —), edges are connected by two pyrrol rings (I and II) bearing vinyl groups (— CH = CH 2 ). The formed complex of a ferrobiliverdinglobin which because of the green coloring received the name of verdohemoglobin, or choleglobin consists of a proteinaceous component — a globin and green prosthetic group. The last contains the broken-off system of porphyrinic rings and trivalent iron. Process of transformation of Hb-HP into verdohemoglobin is carried out by the oxidase found in a hyaloplasma of hepatic cells of different types of animals. This enzyme was called afterwards gemalfameteniloksigenazy, edge for manifestation of activity demands presence of NADF-N and ions of bivalent iron and the activator of a nuclear origin. From verdohemoglobin, apparently, the globin and atom of iron is spontaneously chipped off and the pigment of green color — the biliverdin consisting of four pyrrol rings connected by three metinovy bonds in an open chain is formed. As a result of enzymatic influence the metinovy group between III and IV pyrrol rings of biliverdin is recovered to CH 2 also bilirubin is formed. Such transformation happens first of all in a liver, however in a significant amount can happen also in other bodies. In a blood plasma biliverdin does not meet.

The bilirubin which is formed out of a liver is transported in a blood plasma in the form connected with a seralbumin. Bilirubin of plasma is intercepted by a liver and, like the bilirubin which is formed in a liver in the reaction depending on UDF in the presence of UDF-glyukuroniltransferaza's enzyme generally communicates with glucuronic to - that. At the same time one or two molecules of a glyukuronat from the rest propiono are etherified howl to - you are B. Glyukuronovaya to - that reacts not in a free form, and in the form of uridindifosfatglyukuronovy to - you.

The clinic usually distinguishes B. giving at once red coloring during the processing diazotized sulphanilic to - that (with Ehrlich's diazoreactant), from B. which gives the same coloring only after after-treatment by ethanol, urea and other connections. Conditionally the first B. was called «direct bilirubin» - it is B. in the form of a bilirubinglyukuronid, the second — «indirect», or free, is the B. adsorbed on proteins of a blood plasma.

Direct and indirect B.'s definition has great clinical value since allows to diagnose various forms of jaundices. Indirect B. is found in blood in patients with hemolitic jaundice. Normal indirect (free) B. makes 75% of the general B. of blood. In blood of healthy people of size of maintenance of B., according to different authors, are not identical and fluctuate from 0,2 — 0,8·10 - 3  % to 1,5·10 - 3  %. Normal at children and adults blood serum contains from 0,2 to 0,5 — 0,8 mg of % of indirect B. (on Wang - den - to Berg). At newborn children without fiziol, jaundice contents is normal of it slightly above — to 1 — 2 mg of %.

Hod of synthesis and disintegration of hemoglobin, scheme

The most part of B. in the form of a bilirubinglyukuronid and a small part of free B. is allocated with bile in intestines. In intestines there is a rupture of glyukuronidny communication, and free B. with the participation of microbic flora is exposed to consecutive recovery with formation of the following colourless connections: mesobilirubin, mezobilinogen and stercobilinogen. Formation of stercobilinogen can happen only in a large intestine. Mezobilinogen and stercobilinogen spontaneously are oxidized oxygen in connections of yellowy-brown color — mesoblin and stercobilin which are allocated with a stake, and is preferential allocated stercobilin (see). All course of synthesis and disintegration of hemoglobin can be presented in the form of the general scheme (fig).

A part of a mezobilirubinogen from a small intestine is soaked up in blood, gets into a liver and again comes with bile to intestines.

A small part of stercobilinogen after absorption in a large intestine, passing a liver, gets to a big circle of blood circulation and it is brought out of an organism through kidneys with urine. This product of recovery of B. is called usually urobilinigen though its structure is identical to stercobilinogen. In the emitted urine urobilinigen under the influence of light and air easily is oxidized in urobilin (see).

With urine it is removed no more than 4 mg of urobilinigen a day are normal.

B. it is allocated to cookies not only connected with glucuronic to - that, but also with sulfates and other substances. Isselbakher and IAC Carti (Isselbacher, McCarty, 1959), conducting a research of bile, found in it 75% of B. in the form of bilirubinglyukuronid, apprx. 15% of a bilirubinsulfat. The residual fraction — 9 — 10% — remained not identified.

As well as for other bilious pigments, are characteristic of direct B. Gmelin's reaction (see. Gmelina test ) and its modifications for urine (Rozenbakh's reaction). B. in urine define by Fouchier's reactant (see. Garrison test ), and also Rozin's reactions: on urine layer 1% spirit of iodine; in the presence of B. on border of two liquids the greenish ring is formed. In blood serum B. Wang - den - Berg is defined by method (see. Wang - den - Berg reaction ) with use of reaction of Ehrlich. There are modifications of a method Wang - den - Berg when instead of alcohol add the substances having property to carry out reaction between indirect B. and a diazoreactant to serum. At a method of Malloya and Ivlin (N. of J. Malloy, To. A. Evelyn) is applied methyl alcohol; Endrashik, Klegkhorn and Grof (L. Endrassik, R. Cleghorn, P. Grof) offer caffeine and sodium benzoate as the catalyst; Powell — sodium benzoate and urea; Eberleyn (1960) offered a micromethod of separate definition of a bilirubinmonoglyukuronid and a bilirubindiglyukuronid and indirect B. in small volumes of blood serum. In blood determine fotokolorimetrichesk by Ivanov and Pokrovsk B.'s micromethod (add a caffeine reactant to blood serum, under influence-rogo to B. passes into a soluble state and with mix of diazoreactants gives the pink-violet coloring which is giving in to a fotometrirovaniye).

Micromethods of definition of B. matter for its definition at newborns, napr, at hemolitic disease of newborns (see).

See also Bilirubinurea , Hyperbilirubinemia , Bilious pigments .

Bibliography: Biochemical methods of a research in clinic, under the editorship of A. A. Pokrovsky, page 342, etc., M., 1969; The Reference book on clinical laboratory methods of a research, under the editorship of E. A. Kost, page 271, etc., M., 1968; Tabolin V. A. Bilirubinovy exchange and jaundices of newborns, M., 1967; Todorov Y. Clinical laboratory trials in pediatrics, the lane with bolg., page 953, etc., Sofia, 1968; Eberlein W. R. A simple solvent-partition method for measurement of free and conjugated bilirubin in serum, Pediatrics, v. 25, p. 878, 1960, bibliogr.; F 1 e i-s with h n e r G. and. A r i a s J. M. Recent advances in bilirubin formation, transport, metabolism and excretion, Amer. J. Med., v. 49, p. 576, 1970, bibliogr.; I s s e 1 b a-c h e r Κ. J. a. M with With a r t h at E. A. Studies on bilirubin sulfate and other nonglu-curonide conjugates of bilirubin, J. clin. Invest., v. 38, p. 645, 1959, bibliogr.; L ο n d ο n J. M. a. o. On origin of bile pigment in normal man, J. biol. Chem., v. 184, p. 351, 1950; Schmid R. Direct — reacting bilirubin, bilirubin glucu-ronide, in serum, bile and urine, Science, v. 124, p. 76, 1956; TalafantE. Properties and composition of the bile pigment giving a direct diazo reaction, Nature (Lond.), v. 178, p. 312, 1956.

V. A. Tabolin.