RU2757156C1 - Method for studying the metabolism of bilirubin - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine and is intended to assess the metabolism of bilirubin. The method for studying the metabolism of bilirubin is as follows: in the evening before going to bed and in the morning on an empty stomach in the blood plasma, the content of total and direct bilirubin, the volume of circulating blood and hematocrit are determined, after which the coefficient of metabolism of bilirubin (K) is calculated according to the formula. Then the state of bilirubin metabolism is assessed, its decrease is noted in men at K<1.32; and in women at K<1.26.EFFECT: use of the method makes it possible to increase the reliability of the assessment of the state of the metabolism of bilirubin.1 cl, 2 ex

Description

The invention relates to medicine, biochemistry, hepatology, laboratory diagnostics and, directly, to the assessment of bilirubin metabolism.

Bilirubin, a yellow blood pigment formed by the breakdown of hemoglobin, myoglobin and cytochromes. As a result of the gradual catabolism of hemoglobin in the cells of the reticuloendothelial system, indirect bilirubin is formed (bilirubin is not conjugated, free). Bilirubin (free, unbound, indirect) is a toxic, fat-soluble substance that can uncouple oxidative phosphorylation in cells. Nervous tissue cells are especially sensitive to it. Having entered the blood, free bilirubin combines with albumin and enters the liver with the blood stream.

In the liver, unbound (indirect, fat-soluble, toxic) bilirubin binds to organic acid (glucuronic acid) by liver cells; at the same time, it loses its toxicity and acquires solubility. Such bilirubin is called direct (linked, conjugated).

Total bilirubin combines direct and indirect bilirubin. Normal values for total bilirubin are 3.4 - 17.1 μmol / L. In this case, the content of direct (bound) bilirubin in the blood plasma is 25%.

It should be noted that sometimes normal values of total bilirubin are considered to be values reaching 20.5 μmol / L, and direct 5.6 μmol / L. At the same time, there is an opinion that normal values of direct bilirubin can reach 7.9 μmol / l (1. Biochemistry of metabolism. Textbook / EA Bessolitsyna. - 2016. - 310 p. ISBN: 9785448336638;

2. Blood biochemistry: Laboratory workshop / E. S. Barysheva, K.M. Burov // Orenburg State University. - Orenburg: OSU, 2013 .-- 141 p.)

Thus, the metabolism of bilirubin plays an important role in the metabolism at the organismal level. Moreover, the accumulation in the body of indirect, unbound bilirubin, which has toxic properties, creates the prerequisites for neurointoxication. At the same time, a decrease in the level of bilirubin in the blood, from the standpoint of clinical pathology, is not considered.

There is a known method for studying the metabolism of bilirubin, which consists in determining the content of total and direct bilirubin in the blood plasma in the morning on an empty stomach (Severin E.S., Aleinikova T.L., Osipov E.V., Silaeva S.A. / Biological chemistry . - M .: LLC "Medical Information Agency", 2008. - 364p.). In this case, the normal indicators are considered indicators of total bilirubin 3.4 - 17.1 μmol / l, and direct 0.6 - 4.2 μmol / l.

However, this technique is not very informative, since it allows assessing the content of bilirubin in blood plasma only at a specific point in time, but does not allow assessing the metabolism of bilirubin and daily fluctuations of its fractions, taking into account such indicators as circulating blood volume (BCC) and hematocrit (Ht).

Of particular importance is the assessment of the state of bilirubin metabolism in the absence of liver pathology, after hepatitis, or chronic hepatitis in the stage of clinical and laboratory remission. Since it is quite often with normal indicators of each of the parameters, but evaluating them autonomously, and not in combination with other indicators, the interpretation of the general state at the organismal level may be erroneous. Moreover, changes in the studied parameters during the day are not taken into account, which make it possible to assess the peculiarities of bilirubin metabolism in each specific case.

The objective of the present invention is to improve the reliability of assessing the state of metabolism of bilirubin.

This is achieved by the fact that a method for studying the metabolism of bilirubin is used, including determining in the morning on an empty stomach in the blood plasma the content of total and direct bilirubin, the volume of circulating blood and hematocrit, blood and hematocrit, after which the metabolic rate of bilirubin (K) is calculated according to the formula:

where: K - coefficient of the state of metabolism of bilirubin;

B _pr.utr - the content of direct bilirubin in the blood plasma in the morning;

B _{general morning} - the content of total bilirubin in the blood plasma in the morning;

BCC in the _morning - the volume of circulating blood in the morning;

Ht _morning - morning hematocrit;

B _ave. - the content of direct bilirubin in the blood plasma in the evening;

B _{obsh.vech ..} - the content of total bilirubin in the blood plasma in the evening;

BCC _vech - the volume of circulating blood in the evening;

Ht _vech - hematocrit in the evening,

assessing the state of the metabolism of bilirubin, note its decrease in men at K <1.32; and in women at K <1.26.

The method improves the reliability of the assessment of the state of the metabolism of bilirubin.

In the daytime, the main resources of the body are aimed at satisfying vital processes in conditions of increased daily activity of the body, which, according to the dominant of Ukhtomsky, are currently priority. Accordingly, the supply of energy to other functions of the body. At the same time, the traditional single study of the content of various fractions of bilirubin in the blood plasma in the morning on an empty stomach does not reflect their daily fluctuations in indicators due to the more intense formation of indirect, unbound (toxic) bilirubin during the period of daytime activity (hemolysis, more intense cleavage of myoglobin and the active use of cytochromes for oxidative recovery reactions), as well as the intake of a large amount of direct bilirubin with bile into the digestive tract during a meal, which leads to a decrease in its content in blood plasma.

Accordingly, at night, the body is restored, endotoxins are utilized and neutralized, anabolic processes prevail, in particular, a more active synthesis of direct bilirubin, which is formed when toxic unbound bilirubin is converted into a bound non-toxic form.

Moreover, often when interpreting the results, first of all, attention is paid to the content of total bilirubin, without a targeted analysis of indicators of direct bilirubin and its specific gravity in the composition of total bilirubin. So, for example, at the upper limit of the norm of total bilirubin and the lower limit of the norm of direct bilirubin, the interpretation of the analysis is performed as normal, while there is a decrease in the neutralization of free toxic indirect bilirubin and its translation into the bound non-toxic form of direct bilirubin.

The method for studying the metabolism of bilirubin differs from the known one in that in the evening before going to bed, the content of total and direct bilirubin, the volume of circulating blood and hematocrit are determined in the blood plasma, after which the coefficient of metabolism of bilirubin (K) is calculated according to the formula:

where:

K - coefficient of the state of metabolism of bilirubin;

B _pr.utr - the content of direct bilirubin in the blood plasma in the morning;

B _{general morning} - the content of total bilirubin in the blood plasma in the morning;

BCC in the _morning - the volume of circulating blood in the morning:

Ht _morning - morning hematocrit;

B _ave. - the content of direct bilirubin in the blood plasma in the evening;

B _{obsh.vech ..} - the content of total bilirubin in the blood plasma in the evening;

BCC _vech - the volume of circulating blood in the evening;

Ht _vech - hematocrit in the evening;

assessing the state of the metabolism of bilirubin, note its decrease in men at K <1.32; and in women at K <1.26.

The proposed method for studying the metabolism of bilirubin makes it possible to assess the state of the metabolism of bilirubin, taking into account the daily fluctuations of its fractions and restoring the balance in the current time mode.

The method is carried out as follows: in the evening before going to bed and in the morning on an empty stomach, the content of total and direct bilirubin, the volume of circulating blood and hematocrit are determined in the blood plasma, after which the coefficient of metabolism of bilirubin (K) is calculated according to the formula:

where:

K - coefficient of the state of metabolism of bilirubin;

B _pr.utr - the content of direct bilirubin in the blood plasma in the morning;

B _{general morning} - the content of total bilirubin in the blood plasma in the morning;

BCC in the _morning - the volume of circulating blood in the morning:

Ht _morning - hematocrit in the morning

B _ave. - the content of direct bilirubin in the blood plasma in the evening;

B _{obsh.vech ..} - the content of total bilirubin in the blood plasma in the evening;

BCC _vech - the volume of circulating blood in the evening;

Ht _vech - hematocrit in the evening;

assessing the state of the metabolism of bilirubin, note its decrease in men at K <1.32; and in women - at K <1.26.

The method for studying the protein-synthesizing function of the liver was developed by evaluating biochemical blood tests in 148 apparently healthy volunteers in the absence of liver pathology, aged from 24 to 43 years. The studies in each subject were carried out 3 times at weekly intervals. Of these, there were 73 men and 75 women.

All participants signed an informed consent to participate in the study and a confidentiality agreement.

According to the survey results, the conditionally normal indicators (K) for men were 1.32 and more; and for women - 1.26 or more.

The method for studying the metabolism of bilirubin was applied in dynamics in 34 patients with liver pathology (chronic hepatitis in remission). Of these, 21 are men and 13 are women. During the initial examination, there was a decrease in the metabolic rate of bilirubin K in men to 1.12-1.23. In the course of maintenance therapy, there was a tendency towards a gradual normalization of the K coefficient to 1.32-1.41, that is, there was a positive trend in the state of bilirubin metabolism.

Example: Patient S., 41 years old. Diagnosis: Chronic hepatitis in the stage of clinical and laboratory remission. During the initial examination: the content of total bilirubin in the blood in the evening - 19.8 μmol / l; direct bilirubin 3.2 μmol / l, bcc - 4.8 l. Ht - 48%. When re-examining in the morning, the total bilirubin is 18.1 μmol / l; direct bilirubin - 3.7 μmol / l, bcc - 4.7 l, Ht - 49%. Coefficient K = 1.21, which indicated a decrease in the metabolism of bilirubin. After the maintenance therapy, the general condition of the patient improved, the total bilirubin content of 18.4 μmol / l was noted in the evening; direct bilirubin 3.7 µmol / l, BCC - 4.8 l, Ht - 47% At the next examination in the morning, the total bilirubin content in the blood is 17.4 µmol / l; direct bilirubin - 4.9 μmol / l, bcc - 4.6, Нt - 48%. Coefficient K = 1.32. The positive dynamics of the metabolic rate of bilirubin K coincided with the positive dynamics of other biochemical parameters (total protein, creatinine, urea, uric acid, total protein alkaline phosphatase, thymol test, leukocyte formula).

Similar results were obtained in women, in whom the metabolic rate of bilirubin K decreased to 1.11 -1.17 on admission. Against the background of the treatment, there was a positive trend and the indices of the bilirubin K coefficient increased to 1.24 -1.36.

Example: Patient E., 36 years old. She had a history of acute viral hepatitis complicated by liver failure. She underwent a comprehensive examination before the planned pregnancy. Laboratory indicators are within the standard values. During the initial examination of the state of the metabolism of bilirubin: the content of total bilirubin in the blood in the evening - 18.2 μmol / l; direct bilirubin 3.4 µmol / l, BCC - 4.2 l, Ht - 48. When reexamined in the morning, total bilirubin is 18.4 µmol / l; direct bilirubin - 3.9 μmol / l, BCC 4.3 l, Ht - 49%. Coefficient K = 1.13, which indicated a decrease in the metabolism of bilirubin. After the maintenance corrective therapy, the general condition of the patient improved, the total bilirubin content of 19.1 μmol / l was noted in the evening; direct bilirubin 3.6 μmol / l, bcc - 4.3 l, Ht - 46%. When re-examining in the morning, the total bilirubin content in the blood is 18.2 μmol / l; direct bilirubin - 4.6 g / l, bcc - 4.2 l. Ht - 47. Coefficient K = 1.28. In parallel with the normalization of the indices of the metabolic rate of bilirubin K, there was a positive trend in other biochemical indices (ALAT, ASAT, alkaline phosphatase, thymol test, nitrogen balance, leukocyte formula).

The results obtained indicated that the use of the proposed method for studying the metabolism of bilirubin allows not only to assess its state at the current time, but can also be a criterion for the effectiveness of treatment in liver pathology.

The determination of laboratory parameters in the study of blood in the morning and in the evening was carried out according to the same method and expressed in the same units of measurement (urea - mmol / l; total protein - g / l). In addition, during the study, the hematocrit and the volume of circulating blood were determined, while the dynamics of these values had a significant effect on the results of the study of the metabolism of bilirubin. It should be noted that the results in the morning and in the evening were expressed in the same units of measurement. When carrying out calculations, the units of measurement in the numerator and denominator are mutually canceled, which makes it possible to obtain the coefficient K in numerical terms.

Thus, the method for studying the metabolism of bilirubin makes it possible to solve the set task, namely, to increase the reliability of the assessment of the metabolism of bilirubin.

Claims (12)

A method for studying the metabolism of bilirubin, including determining in the morning on an empty stomach in the blood plasma the content of total and direct bilirubin, the volume of circulating blood and hematocrit, characterized in that in the evening before going to bed, the content of total and direct bilirubin, the volume of circulating blood and hematocrit are determined in the blood plasma, after which calculate the metabolic rate of bilirubin (K) by the formula

where K is the coefficient of the state of the metabolism of bilirubin; B _pr.utr - the content of direct bilirubin in the blood plasma in the morning; B _{general morning} - the content of total bilirubin in the blood plasma in the morning; BCC in the _morning - the volume of circulating blood in the morning; Ht _morning - morning hematocrit; B _pr.vech - the content of direct bilirubin in the blood plasma in the evening; B _obsh.vech - the content of total bilirubin in the blood plasma in the evening; BCC _vech - the volume of circulating blood in the evening; Ht _vech - hematocrit in the evening, When assessing the state of the metabolism of bilirubin, its decrease was noted in men with K <1.32, and in women with K <1.26.