Pyruvic acid in the blood
Clinical diagnostic value research
Normal: 0.05-0.10 mmol/l in the blood serum of adults.
Contents of the PVK increases in hypoxic conditions caused by severe cardiovascular, pulmonary, cardiorespiratory failure, anemia, malignant neoplasms, acute hepatitis and other liver diseases (most pronounced in terminal stages liver cirrhosis), toxicosis, insulin-dependent diabetes mellitus, diabetic ketoacidosis, respiratory alkalosis, uremia, hepatocerebral dystrophy, hyperfunction of the pituitary-adrenal and sympathetic-adrenal systems, as well as the administration of camphor, strychnine, adrenaline and during heavy physical exertion, tetany, convulsions (with epilepsy).
Clinical and diagnostic value of determining the content of lactic acid in the blood
Lactic acid(MK) is the end product of glycolysis and glycogenolysis. A significant amount of it is formed in muscles. From muscle tissue MK travels through the bloodstream to the liver, where it is used for glycogen synthesis. At the same time, part of the lactic acid from the blood is absorbed by the heart muscle, which utilizes it as an energy material.
SUA level in blood increases in hypoxic conditions, acute purulent inflammatory tissue damage, acute hepatitis, liver cirrhosis, renal failure, malignant neoplasms, diabetes mellitus (in approximately 50% of patients), mild uremia, infections (especially pyelonephritis), acute septic endocarditis, poliomyelitis, serious illnesses blood vessels, leukemia, intense and prolonged muscle loads, epilepsy, tetany, tetanus, convulsive states, hyperventilation, pregnancy (in the third trimester).
Lipids are substances of various chemical structures that have a number of common physical, physicochemical and biological properties. They are characterized by the ability to dissolve in ether, chloroform, and other fatty solvents and only slightly (and not always) in water, and also form, together with proteins and carbohydrates, the main structural component of living cells. The inherent properties of lipids are determined by the characteristic features of the structure of their molecules.
The role of lipids in the body is very diverse. Some of them serve as a form of deposition (triacylglycerols, TG) and transport (free fatty acids-FFA) substances, the breakdown of which releases a large amount of energy, others are the most important structural components of cell membranes (free cholesterol and phospholipids). Lipids take part in the processes of thermoregulation, protection of vital important organs(for example, kidneys) from mechanical stress (injuries), protein loss, in creating elasticity skin, protecting them from excessive moisture removal.
Some of the lipids are biologically active substances with modulator properties hormonal influence(prostaglandins) and vitamins (polyunsaturated fatty acids). Moreover, lipids promote the absorption of fat-soluble vitamins A, D, E, K; act as antioxidants ( vitamins A, E), largely regulating the process of free radical oxidation of physiologically important compounds; determine the permeability of cell membranes to ions and organic compounds.
Lipids serve as precursors for a number of steroids with pronounced biological effects - bile acids, vitamins D, sex hormones, and adrenal hormones.
The concept of “total lipids” in plasma includes neutral fats (triacylglycerols), their phosphorylated derivatives (phospholipids), free and ester-bound cholesterol, glycolipids, and non-esterified (free) fatty acids.
Clinical and diagnostic value of determining the level of total lipids in blood plasma (serum)
The norm is 4.0-8.0 g/l.
Hyperlipidemia (hyperlipemia) – an increase in the concentration of total plasma lipids as a physiological phenomenon can be observed 1.5 hours after a meal. Nutritional hyperlipemia is more pronounced, the lower the level of lipids in the patient’s blood on an empty stomach.
The concentration of lipids in the blood changes in a number of pathological conditions. Thus, in patients with diabetes mellitus, along with hyperglycemia, pronounced hyperlipemia is observed (often up to 10.0-20.0 g/l). With nephrotic syndrome, especially lipoid nephrosis, the content of lipids in the blood can reach even higher numbers - 10.0-50.0 g/l.
Hyperlipemia is a constant phenomenon in patients with biliary cirrhosis and in patients with acute hepatitis (especially in the icteric period). Elevated levels of lipids in the blood are usually found in individuals suffering from acute or chronic nephritis, especially if the disease is accompanied by edema (due to the accumulation of LDL and VLDL in the plasma).
The pathophysiological mechanisms that cause shifts in the content of all fractions of total lipids determine, to a greater or lesser extent, pronounced change concentrations of its constituent subfractions: cholesterol, total phospholipids and triacylglycerols.
Clinical and diagnostic significance of the study of cholesterol (CH) in blood serum (plasma)
Studying the level of cholesterol in blood serum (plasma) does not provide accurate diagnostic information about specific disease, but only reflects the pathology of lipid metabolism in the body.
According to epidemiological studies, the upper level of cholesterol in the blood plasma is almost healthy people at the age of 20-29 years it is 5.17 mmol/l.
In blood plasma, cholesterol is found mainly in the composition of LDL and VLDL, and 60-70% of it is presented in the form esters(bound cholesterol), and 30-40% is in the form of free, non-esterified cholesterol. Bound and free cholesterol make up the total cholesterol.
High risk The development of coronary atherosclerosis in people aged 30-39 and over 40 years old occurs at cholesterol levels exceeding 5.20 and 5.70 mmol/l, respectively.
Hypercholesterolemia is the most proven risk factor for coronary atherosclerosis. This has been confirmed by numerous epidemiological and clinical studies who established a connection between hypercholesterolemia and coronary atherosclerosis, the incidence of coronary artery disease and myocardial infarction.
Most high level cholesterol is observed in genetic disorders in lipid metabolism: familial homo-heterozygous hypercholesterolemia, familial combined hyperlipidemia, polygenic hypercholesterolemia.
In a number of pathological conditions, secondary hypercholesterolemia develops . It is observed in liver diseases, kidney damage, malignant tumors pancreas and prostate, gout, ischemic heart disease, acute heart attack myocardium, hypertension, endocrine disorders, chronic alcoholism, glycogenosis type I, obesity (in 50-80% of cases).
A decrease in plasma cholesterol levels is observed in patients with malnutrition, with damage to the central nervous system, mental retardation, chronic failure cardiovascular system, cachexia, hyperthyroidism, acute infectious diseases, acute pancreatitis, acute purulent-inflammatory processes in soft tissues, febrile conditions, pulmonary tuberculosis, pneumonia, sarcoidosis of the respiratory system, bronchitis, anemia, hemolytic jaundice, acute hepatitis, malignant liver tumors, rheumatism.
Determination of the fractional composition of cholesterol in blood plasma and its individual lipids (primarily HDL) has acquired great diagnostic importance for judging the functional state of the liver. By modern presentation, the esterification of free cholesterol into HDL is carried out in the blood plasma thanks to the enzyme lecithin-cholesterol acyltransferase, formed in the liver (this is an organ-specific liver enzyme). The activator of this enzyme is one of the basic components of HDL - apo - Al, constantly synthesized in the liver.
A nonspecific activator of the plasma cholesterol esterification system is albumin, also produced by hepatocytes. This process primarily reflects functional state liver. If normally the coefficient of cholesterol esterification (the ratio of the content of ester-bound cholesterol to total) is 0.6-0.8 (or 60-80%), then in case of acute hepatitis, exacerbation of chronic hepatitis, liver cirrhosis, obstructive jaundice , as well as chronic alcoholism, it decreases. A sharp decrease in the severity of the cholesterol esterification process indicates insufficiency of liver function.
Clinical and diagnostic significance of studying the concentration of total phospholipids in blood serum.
Phospholipids (PL) are a group of lipids containing, in addition to phosphoric acid (as an essential component), alcohol (usually glycerol), fatty acid residues and nitrogenous bases. Taking into account the dependence on the nature of the alcohol, PLs are divided into phosphoglycerides, phosphosphingosines and phosphoinositides.
The level of total PL (lipid phosphorus) in blood serum (plasma) increases in patients with primary and secondary hyperlipoproteinemia types IIa and IIb. This increase is most pronounced in type I glycogenosis, cholestasis, obstructive jaundice, alcoholic and biliary cirrhosis, viral hepatitis(mild course), renal coma, posthemorrhagic anemia, chronic pancreatitis, severe diabetes mellitus, nephrotic syndrome.
To diagnose a number of diseases, it is more informative to study the fractional composition of serum phospholipids. For this purpose, lipid thin layer chromatography methods have been widely used in recent years.
Composition and properties of blood plasma lipoproteins
Almost all plasma lipids are associated with proteins, which gives them good solubility in water. These lipid-protein complexes are commonly referred to as lipoproteins.
According to modern concepts, lipoproteins are high-molecular water-soluble particles, which are complexes of proteins (apoproteins) and lipids formed by weak, non-covalent bonds, in which polar lipids (PL, CXC) and proteins (“apo”) form a surface hydrophilic monomolecular layer surrounding and protecting the internal phase (consisting mainly of ECS, TG) from water.
In other words, LP are peculiar globules, inside of which there is a fat drop, a core (formed mainly by non-polar compounds, mainly triacylglycerols and cholesterol esters), delimited from water by a surface layer of protein, phospholipids and free cholesterol.
The physical characteristics of lipoproteins (their size, molecular weight, density), as well as the manifestations of physicochemical, chemical and biological properties, largely depend, on the one hand, on the ratio between the protein and lipid components of these particles, on the other hand, on the composition of the protein and lipid components, ᴛ.ᴇ. their nature.
The largest particles, consisting of 98% lipids and a very small (about 2%) proportion of protein, are chylomicrons (CM). Οʜᴎ are formed in the cells of the mucous membrane of the small intestine and are a transport form for neutral dietary fats, ᴛ.ᴇ. exogenous TG.
Table 7.3 Composition and some properties of serum lipoproteins (Komarov F.I., Korovkin B.F., 2000)
| Criteria for assessing individual classes of lipoproteins | HDL (alpha-LP) | LDL (beta-LP) | VLDL (pre-beta-LP) | HM |
| Density, kg/l | 1,063-1,21 | 1,01-1,063 | 1,01-0,93 | 0,93 |
| Molecular weight of drug, kD | 180-380 | 3000- 128 000 | - | |
| Particle sizes, nm | 7,0-13,0 | 15,0-28,0 | 30,0-70,0 | 500,0 - 800,0 |
| Total proteins, % | 50-57 | 21-22 | 5-12 | |
| Total lipids, % | 43-50 | 78-79 | 88-95 | |
| Free cholesterol,% | 2-3 | 8-10 | 3-5 | |
| Esterified cholesterol, % | 19-20 | 36-37 | 10-13 | 4-5 |
| Phospholipids, % | 22-24 | 20-22 | 13-20 | 4-7 |
| Triacylglycerols, % | ||||
| 4-8 | 11-12 | 50-60 | 84-87 |
If exogenous TGs are transported into the blood by chylomicrons, then the transport form endogenous triglycerides are VLDL. Their education is defensive reaction body, aimed at preventing fatty infiltration, and subsequently liver degeneration.
The size of VLDL is on average 10 times smaller than the size of CM (individual VLDL particles are 30-40 times smaller than CM particles). They contain 90% of lipids, of which more than half are TG. 10% of all plasma cholesterol is carried by VLDL. Due to the content of a large amount of TG, VLDL shows insignificant density (less than 1.0). It has been established that LDL and VLDL contain 2/3 (60%) of all cholesterol plasma, while 1/3 is HDL.
HDL– the densest lipid-protein complexes, since the protein content in them is about 50% of the mass of the particles. Their lipid component consists half of phospholipids, half of cholesterol, mainly ether-bound. HDL is also constantly formed in the liver and partly in the intestines, as well as in the blood plasma as a result of the “degradation” of VLDL.
In case LDL and VLDL deliver Cholesterol from the liver to other tissues(peripheral), including vascular wall, That HDL transports cholesterol from cell membranes (primarily the vascular wall) to the liver. In the liver it goes to the formation of bile acids. In accordance with this participation in cholesterol metabolism, VLDL and themselves LDL are called atherogenic, A HDL– antiatherogenic drugs. Atherogenicity is usually understood as the ability of lipid-protein complexes to introduce (transfer) free cholesterol contained in the drug into tissues.
HDL competes for cell membrane receptors with LDL, thereby counteracting the utilization of atherogenic lipoproteins. Since the surface monolayer of HDL contains a large amount of phospholipids, at the point of contact of the particle with the outer membrane of the endothelial, smooth muscle and any other cell, favorable conditions are created for the transfer of excess free cholesterol to HDL.
In this case, the latter remains in the surface HDL monolayer only for a very short time, since with the participation of the LCAT enzyme it undergoes esterification. The formed ECS, being a nonpolar substance, moves into the internal lipid phase, releasing vacancies to repeat the act of capturing a new ECS molecule from the cell membrane. From here: the higher the activity of LCAT, the more effective the antiatherogenic effect of HDL, which are considered as LCAT activators.
When the balance between the processes of the influx of lipids (cholesterol) into the vascular wall and their outflow from it is disturbed, conditions are created for the formation of lipoidosis, the most famous manifestation of which is atherosclerosis.
In accordance with the ABC nomenclature of lipoproteins, primary and secondary lipoproteins are distinguished. Primary LPs are formed by any apoprotein of one chemical nature. These include LDL, which contains about 95% apoprotein B. All others are secondary lipoproteins, which are associated complexes of apoproteins.
Normally, approximately 70% of plasma cholesterol is found in “atherogenic” LDL and VLDL, while about 30% circulates in “antiatherogenic” HDL. With this ratio, a balance in the rates of inflow and outflow of cholesterol is maintained in the vascular wall (and other tissues). This determines the numerical value cholesterol ratio atherogenicity, component of the specified lipoprotein distribution of total cholesterol 2,33 (70/30).
According to the results of mass epidemiological observations, at a concentration of total cholesterol in plasma of 5.2 mmol/l, a zero balance of cholesterol in the vascular wall is maintained. An increase in the level of total cholesterol in the blood plasma of more than 5.2 mmol/l leads to its gradual deposition in the vessels, and at a concentration of 4.16-4.68 mmol/l a negative cholesterol balance is observed in the vascular wall. The level of total cholesterol in blood plasma (serum) exceeding 5.2 mmol/l is considered pathological.
Table 7.4 Probability rating scale development of ischemic heart disease and other manifestations of atherosclerosis
(Komarov F.I., Korovkin B.F., 2000)
Pyruvic acid in the blood
Clinical and diagnostic significance of the study
Normal: 0.05-0.10 mmol/l in the blood serum of adults.
Contents of the PVK increases in hypoxic conditions caused by severe cardiovascular, pulmonary, cardiorespiratory failure, anemia, malignant neoplasms, acute hepatitis and other liver diseases (most pronounced in the terminal stages of liver cirrhosis), toxicosis, insulin-dependent diabetes mellitus, diabetic ketoacidosis, respiratory alkalosis, uremia , hepatocerebral dystrophy, hyperfunction of the pituitary-adrenal and sympathetic-adrenal systems, as well as the administration of camphor, strychnine, adrenaline and during heavy physical exertion, tetany, convulsions (with epilepsy).
Clinical and diagnostic value of determining the content of lactic acid in the blood
Lactic acid(MK) is the end product of glycolysis and glycogenolysis. A significant amount of it is formed in muscles. From muscle tissue, UA travels through the bloodstream to the liver, where it is used for the synthesis of glycogen. In addition, part of the lactic acid from the blood is absorbed by the heart muscle, which utilizes it as an energy material.
SUA level in blood increases in hypoxic conditions, acute purulent inflammatory tissue damage, acute hepatitis, liver cirrhosis, renal failure, malignant neoplasms, diabetes mellitus (in approximately 50% of patients), mild uremia, infections (especially pyelonephritis), acute septic endocarditis, poliomyelitis, severe diseases blood vessels, leukemia, intense and prolonged muscle stress, epilepsy, tetany, tetanus, convulsive states, hyperventilation, pregnancy (in the third trimester).
Lipids are substances of various chemical structures that have a number of common physical, physicochemical and biological properties. They are characterized by the ability to dissolve in ether, chloroform, other fatty solvents and only slightly (and not always) in water, and also form, together with proteins and carbohydrates, the main structural component of living cells. The inherent properties of lipids are determined by the characteristic features of the structure of their molecules.
The role of lipids in the body is very diverse. Some of them serve as a form of storage (triacylglycerols, TG) and transport (free fatty acids-FFA) of substances, the breakdown of which releases a large amount of energy, others are the most important structural components of cell membranes (free cholesterol and phospholipids). Lipids are involved in the processes of thermoregulation, protecting vital organs (for example, kidneys) from mechanical stress (injury), protein loss, creating elasticity of the skin, and protecting them from excessive moisture removal.
Some of the lipids are biologically active substances that have the properties of modulators of hormonal effects (prostaglandins) and vitamins (polyunsaturated fatty acids). Moreover, lipids promote the absorption of fat-soluble vitamins A, D, E, K; act as antioxidants (vitamins A, E), which largely regulate the process of free radical oxidation of physiologically important compounds; determine the permeability of cell membranes to ions and organic compounds.
Lipids serve as precursors for a number of steroids with pronounced biological effects - bile acids, vitamins D, sex hormones, and adrenal hormones.
The concept of “total lipids” in plasma includes neutral fats (triacylglycerols), their phosphorylated derivatives (phospholipids), free and ester-bound cholesterol, glycolipids, and non-esterified (free) fatty acids.
Clinical and diagnostic value of determining the level of total lipids in blood plasma (serum)
The norm is 4.0-8.0 g/l.
Hyperlipidemia (hyperlipemia) – an increase in the concentration of total plasma lipids as a physiological phenomenon can be observed 1.5 hours after a meal. Nutritional hyperlipemia is more pronounced, the lower the level of lipids in the patient’s blood on an empty stomach.
The concentration of lipids in the blood changes in a number of pathological conditions. Thus, in patients with diabetes mellitus, along with hyperglycemia, pronounced hyperlipemia is observed (often up to 10.0-20.0 g/l). With nephrotic syndrome, especially lipoid nephrosis, the content of lipids in the blood can reach even higher numbers - 10.0-50.0 g/l.
Hyperlipemia is a constant phenomenon in patients with biliary cirrhosis and in patients with acute hepatitis (especially in the icteric period). Elevated levels of lipids in the blood are usually found in individuals suffering from acute or chronic nephritis, especially if the disease is accompanied by edema (due to the accumulation of LDL and VLDL in the plasma).
The pathophysiological mechanisms that cause changes in the content of all fractions of total lipids, to a greater or lesser extent, determine a pronounced change in the concentration of its constituent subfractions: cholesterol, total phospholipids and triacylglycerols.
Clinical and diagnostic significance of the study of cholesterol (CH) in blood serum (plasma)
A study of cholesterol levels in blood serum (plasma) does not provide accurate diagnostic information about a specific disease, but only reflects the pathology of lipid metabolism in the body.
According to epidemiological studies, the upper level of cholesterol in the blood plasma of practically healthy people aged 20-29 years is 5.17 mmol/l.
In blood plasma, cholesterol is found mainly in LDL and VLDL, with 60-70% of it in the form of esters (bound cholesterol), and 30-40% in the form of free, non-esterified cholesterol. Bound and free cholesterol make up the total cholesterol.
A high risk of developing coronary atherosclerosis in people aged 30-39 and over 40 years old occurs when cholesterol levels exceed 5.20 and 5.70 mmol/l, respectively.
Hypercholesterolemia is the most proven risk factor for coronary atherosclerosis. This has been confirmed by numerous epidemiological and clinical studies that have established a connection between hypercholesterolemia and coronary atherosclerosis, the incidence of coronary artery disease and myocardial infarction.
The highest level of cholesterol is observed with genetic disorders in lipid metabolism: familial homo-heterozygous hypercholesterolemia, familial combined hyperlipidemia, polygenic hypercholesterolemia.
In a number of pathological conditions, secondary hypercholesterolemia develops . It is observed in liver diseases, kidney damage, malignant tumors of the pancreas and prostate, gout, coronary heart disease, acute myocardial infarction, hypertension, endocrine disorders, chronic alcoholism, type I glycogenosis, obesity (in 50-80% of cases).
A decrease in plasma cholesterol levels is observed in patients with malnutrition, damage to the central nervous system, mental retardation, chronic failure of the cardiovascular system, cachexia, hyperthyroidism, acute infectious diseases, acute pancreatitis, acute purulent-inflammatory processes in soft tissues, febrile conditions, pulmonary tuberculosis, pneumonia, sarcoidosis of the respiratory system, bronchitis, anemia, hemolytic jaundice, acute hepatitis, malignant liver tumors, rheumatism.
Determination of the fractional composition of cholesterol in blood plasma and its individual lipids (primarily HDL) has acquired great diagnostic importance for judging the functional state of the liver. According to modern concepts, the esterification of free cholesterol into HDL occurs in the blood plasma thanks to the enzyme lecithin-cholesterol acyltransferase, which is formed in the liver (this is an organ-specific liver enzyme). The activator of this enzyme is one of the main components of HDL - apo-Al, which is constantly synthesized in the liver.
A nonspecific activator of the plasma cholesterol esterification system is albumin, also produced by hepatocytes. This process primarily reflects the functional state of the liver. If normally the coefficient of cholesterol esterification (i.e. the ratio of the content of ether-bound cholesterol to total) is 0.6-0.8 (or 60-80%), then in acute hepatitis, exacerbation of chronic hepatitis, liver cirrhosis, obstructive jaundice, and It also decreases in chronic alcoholism. A sharp decrease in the severity of the cholesterol esterification process indicates insufficiency of liver function.
Clinical and diagnostic significance of studying the concentration of total phospholipids in blood serum.
Phospholipids (PL) are a group of lipids containing, in addition to phosphoric acid (as an essential component), alcohol (usually glycerol), fatty acid residues and nitrogenous bases. Depending on the nature of the alcohol, PLs are divided into phosphoglycerides, phosphosphingosines and phosphoinositides.
The level of total PL (lipid phosphorus) in blood serum (plasma) increases in patients with primary and secondary hyperlipoproteinemia types IIa and IIb. This increase is most pronounced in glycogenosis type I, cholestasis, obstructive jaundice, alcoholic and biliary cirrhosis, viral hepatitis (mild), renal coma, posthemorrhagic anemia, chronic pancreatitis, severe diabetes mellitus, nephrotic syndrome.
To diagnose a number of diseases, it is more informative to study the fractional composition of serum phospholipids. For this purpose, lipid thin layer chromatography methods have been widely used in recent years.
Composition and properties of blood plasma lipoproteins
Almost all plasma lipids are bound to proteins, which makes them highly soluble in water. These lipid-protein complexes are commonly referred to as lipoproteins.
According to modern concepts, lipoproteins are high-molecular water-soluble particles, which are complexes of proteins (apoproteins) and lipids formed by weak, non-covalent bonds, in which polar lipids (PL, CXC) and proteins (“apo”) form a surface hydrophilic monomolecular layer surrounding and protecting the internal phase (consisting mainly of ECS, TG) from water.
In other words, lipids are peculiar globules, inside of which there is a fat droplet, a core (formed predominantly by non-polar compounds, mainly triacylglycerols and cholesterol esters), delimited from water by a surface layer of protein, phospholipids and free cholesterol.
The physical characteristics of lipoproteins (their size, molecular weight, density), as well as the manifestations of physicochemical, chemical and biological properties, largely depend, on the one hand, on the ratio between the protein and lipid components of these particles, on the other hand, on the composition of the protein and lipid components, i.e. their nature.
The largest particles, consisting of 98% lipids and a very small (about 2%) proportion of protein, are chylomicrons (CM). They are formed in the cells of the mucous membrane of the small intestine and are a transport form for neutral dietary fats, i.e. exogenous TG.
Table 7.3 Composition and some properties of serum lipoproteins (Komarov F.I., Korovkin B.F., 2000)
| Criteria for assessing individual classes of lipoproteins | HDL (alpha-LP) | LDL (beta-LP) | VLDL (pre-beta-LP) | HM |
| Density, kg/l | 1,063-1,21 | 1,01-1,063 | 1,01-0,93 | 0,93 |
| Molecular weight of drug, kD | 180-380 | 3000- 128 000 | - | |
| Particle sizes, nm | 7,0-13,0 | 15,0-28,0 | 30,0-70,0 | 500,0 - 800,0 |
| Total proteins, % | 50-57 | 21-22 | 5-12 | |
| Total lipids, % | 43-50 | 78-79 | 88-95 | |
| Free cholesterol,% | 2-3 | 8-10 | 3-5 | |
| Esterified cholesterol, % | 19-20 | 36-37 | 10-13 | 4-5 |
| Phospholipids, % | 22-24 | 20-22 | 13-20 | 4-7 |
| Triacylglycerols, % | ||||
| 4-8 | 11-12 | 50-60 | 84-87 |
If exogenous TGs are transported into the blood by chylomicrons, then the transport form endogenous triglycerides are VLDL. Their formation is a protective reaction of the body aimed at preventing fatty infiltration, and subsequently liver degeneration.
The size of VLDL is on average 10 times smaller than the size of CM (individual VLDL particles are 30-40 times smaller than CM particles). They contain 90% of lipids, of which more than half are TG. 10% of total plasma cholesterol is carried by VLDL. Due to the content of a large amount of TG, VLDL shows insignificant density (less than 1.0). It has been established that LDL and VLDL contain 2/3 (60%) of total cholesterol plasma, while 1/3 is HDL.
HDL– the densest lipid-protein complexes, since the protein content in them is about 50% of the mass of the particles. Their lipid component consists half of phospholipids, half of cholesterol, mainly ether-bound. HDL is also constantly formed in the liver and partly in the intestines, as well as in the blood plasma as a result of the “degradation” of VLDL.
If LDL and VLDL deliver Cholesterol from the liver to other tissues(peripheral), including vascular wall, That HDL transports cholesterol from cell membranes (primarily the vascular wall) to the liver. In the liver it goes to the formation of bile acids. In accordance with this participation in cholesterol metabolism, VLDL and themselves LDL are called atherogenic, A HDL– antiatherogenic drugs. Atherogenicity refers to the ability of lipid-protein complexes to introduce (transmit) free cholesterol contained in the drug into tissues.
HDL competes for cell membrane receptors with LDL, thereby counteracting the utilization of atherogenic lipoproteins. Since the surface monolayer of HDL contains a large amount of phospholipids, at the point of contact of the particle with the outer membrane of the endothelial, smooth muscle and any other cell, favorable conditions are created for the transfer of excess free cholesterol to HDL.
However, the latter remains in the surface HDL monolayer only for a very short time, since it undergoes esterification with the participation of the LCAT enzyme. The formed ECS, being a nonpolar substance, moves into the internal lipid phase, releasing vacancies to repeat the act of capturing a new ECS molecule from the cell membrane. From here: the higher the activity of LCAT, the more effective the antiatherogenic effect of HDL, which are considered as LCAT activators.
If the balance is disturbed between the processes of the influx of lipids (cholesterol) into the vascular wall and their outflow from it, conditions can be created for the formation of lipoidosis, the most famous manifestation of which is atherosclerosis.
In accordance with the ABC nomenclature of lipoproteins, primary and secondary lipoproteins are distinguished. Primary LPs are formed by any apoprotein of one chemical nature. These can conditionally include LDL, which contains about 95% apoprotein B. All others are secondary lipoproteins, which are associated complexes of apoproteins.
Normally, approximately 70% of plasma cholesterol is found in “atherogenic” LDL and VLDL, while about 30% circulates in “antiatherogenic” HDL. With this ratio, a balance in the rates of inflow and outflow of cholesterol is maintained in the vascular wall (and other tissues). This determines the numerical value cholesterol ratio atherogenicity, component with the indicated lipoprotein distribution of total cholesterol 2,33 (70/30).
According to the results of mass epidemiological observations, at a concentration of total cholesterol in plasma of 5.2 mmol/l, a zero balance of cholesterol in the vascular wall is maintained. An increase in the level of total cholesterol in the blood plasma of more than 5.2 mmol/l leads to its gradual deposition in the vessels, and at a concentration of 4.16-4.68 mmol/l a negative cholesterol balance is observed in the vascular wall. The level of total cholesterol in blood plasma (serum) exceeding 5.2 mmol/l is considered pathological.
Table 7.4 Scale for assessing the likelihood of developing coronary artery disease and other manifestations of atherosclerosis
(Komarov F.I., Korovkin B.F., 2000)
Lipids are called fats that enter the body with food and are formed in the liver. Blood (plasma or serum) contains 3 main classes of lipids: triglycerides (TG), cholesterol (CS) and its esters, phospholipids (PL).
Lipids are able to attract water, but most of them do not dissolve in the blood. They are transported in a protein-bound state (in the form of lipoproteins or, in other words, lipoproteins). Lipoproteins differ not only in composition, but also in size and density, but their structure is almost the same. The central part (core) is represented by cholesterol and its esters, fatty acids, and triglycerides. The shell of the molecule consists of proteins (apoproteins) and water-soluble lipids (phospholipids and non-esterified cholesterol). The outer part of apoproteins is capable of forming hydrogen bonds with water molecules. Thus, lipoproteins can be partially dissolved in fats and partially in water.
Chylomicrons, after entering the blood, break down into glycerol and fatty acids, resulting in the formation of lipoproteins. Cholesterol-containing chylomicron residues are processed in the liver.
Cholesterol and triglycerides are formed in the liver into very low-density lipoproteins (VLDL), which release some of the triglycerides to peripheral tissues, while the remainder goes back to the liver and is converted into low-density lipoproteins (LDL).
L PN II are transporters of cholesterol for peripheral tissues, which is used to build cell membranes and metabolic reactions. In this case, non-esterified cholesterol enters the blood plasma and binds to lipoproteins high density(HDL). Esterified cholesterol (bound to esters) is converted into VLDL. Then the cycle repeats.
The blood also contains intermediate density lipoproteins (IDL), which are remnants of chylomicrons and VLDL and contain cholesterol in large quantities. DILI in liver cells with the participation of lipase are converted into LDL.
Blood plasma contains 3.5-8 g/l of lipids. An increase in blood lipid levels is called hyperlipidemia, and a decrease is called hypolipidemia. The indicator of total blood lipids does not provide a detailed picture of the state of fat metabolism in the body.
Quantitative determination of specific lipids is of diagnostic importance. The lipid composition of blood plasma is presented in the table.
| Lipid fraction | Normal indicator | |
| General lipids | 4.6-10.4 mmol/l | |
| Phospholipids | 1.95-4.9 mmol/l | |
| Lipid phosphorus | 1.97-4.68 mmol/l | |
| Neutral fats | 0-200 mg% | |
| Triglycerides | 0.565-1.695 mmol/l (serum) | |
| Non-esterified fatty acids | 400-800 mmol/l | |
| Free fatty acids | 0.3-0.8 µmol/l | |
| Total cholesterol (there are age-specific norms) | 3.9-6.5 mmol/l (unified method) | |
| Free cholesterol | 1.04-2.33 mmol/l | |
| Cholesterol esters | 2.33-3.49 mmol/l | |
| HDL | M | 1.25-4.25 g/l |
| AND | 2.5-6.5 g/l | |
| LDL | 3-4.5 g/l | |
| Type | Increased blood levels | |
| Lipoproteins | Lipids | |
| I | Chylomicrons | Cholesterol, triglycerides |
| On | LDL | Cholesterol (not always) |
| Type | Increased blood levels | |
| Lipoproteins | Lipids | |
| Nb | LDL, VLDL | Cholesterol, triglycerides |
| III | VLDL, LPPP | Cholesterol, triglycerides |
| IV | VLDL | Cholesterol (not always), triglycerides |
| V | Chylomicrons, VLDL | Cholesterol, triglycerides |
– a group of heterogeneous chemical structures and physical and chemical properties substances. In blood serum they are represented mainly by fatty acids, triglycerides, cholesterol and phospholipids.
Triglycerides are the main form of lipid storage in adipose tissue and lipid transport in the blood. A study of triglyceride levels is necessary to determine the type of hyperlipoproteinemia and assess the risk of developing cardiovascular diseases.
Cholesterol performs the most important functions: it is part of cell membranes, is a precursor of bile acids, steroid hormones and vitamin D, and acts as an antioxidant. About 10% of the Russian population have increased level cholesterol in the blood. This condition is asymptomatic and can lead to serious illnesses(atherosclerotic vascular lesions, coronary heart disease).
Lipids are insoluble in water, so they are transported by blood serum in combination with proteins. Lipid+protein complexes are called lipoproteins. And proteins that are involved in lipid transport are called apoproteins.
Several classes are present in blood serum lipoproteins: chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL).
Each lipoprotein fraction has its own function. synthesized in the liver and transport mainly triglycerides. Play an important role in atherogenesis. Low-density lipoproteins (LDL) rich in cholesterol, deliver cholesterol to peripheral tissues. Levels of VLDL and LDL promote the deposition of cholesterol in the vascular wall and are considered atherogenic factors. High density lipoproteins (HDL) participate in the reverse transport of cholesterol from tissues, taking it away from overloaded tissue cells and transferring it to the liver, which “utilizes” it and removes it from the body. A high level of HDL is considered an anti-atherogenic factor (protects the body from atherosclerosis).
The role of cholesterol and the risk of developing atherosclerosis depends on which lipoprotein fractions it is included in. To assess the ratio of atherogenic and antiatherogenic lipoproteins, it is used atherogenic index.
Apolipoproteins- These are proteins that are located on the surface of lipoproteins.
Apolipoprotein A (ApoA protein) is the main protein component of lipoproteins (HDL), which transports cholesterol from peripheral tissue cells to the liver.
Apolipoprotein B (ApoB protein) is part of lipoproteins that transport lipids to peripheral tissues.
Measuring the concentration of apolipoprotein A and apolipoprotein B in blood serum provides the most accurate and unambiguous determination of the ratio of atherogenic and antiatherogenic properties of lipoproteins, which is assessed as the risk of developing atherosclerotic vascular lesions and coronary heart disease over the next five years.
To the study lipid profile includes the following indicators: cholesterol, triglycerides, VLDL, LDL, HDL, atherogenicity coefficient, cholesterol/triglycerides ratio, glucose. This profile provides complete information about lipid metabolism, allows you to determine the risks of developing atherosclerotic vascular lesions, coronary heart disease, identify the presence of dyslipoproteinemia and type it, and, if necessary, choose the right lipid-lowering therapy.
Increased concentrationcholesterol has diagnostic value for primary familial hyperlipidemia ( hereditary forms diseases); pregnancy, hypothyroidism, nephrotic syndrome, obstructive liver diseases, pancreatic diseases (chronic pancreatitis, malignant neoplasms), diabetes mellitus.
Decreased concentrationcholesterol has diagnostic value for liver diseases (cirrhosis, hepatitis), starvation, sepsis, hyperthyroidism, megaloblastic anemia.
Increased concentrationtriglycerides has diagnostic value for primary hyperlipidemia (hereditary forms of the disease); obesity, excessive carbohydrate consumption, alcoholism, diabetes mellitus, hypothyroidism, nephrotic syndrome, chronic renal failure, gout, acute and chronic pancreatitis.
Decreased concentrationtriglycerides has diagnostic value for hypolipoproteinemia, hyperthyroidism, malabsorption syndrome.
Very low density lipoproteins (VLDL) used to diagnose dyslipidemia (types IIb, III, IV and V). High concentrations of VLDL in the blood serum indirectly reflect the atherogenic properties of the serum.
Increased concentrationlow density lipoprotein (LDL) has diagnostic value for primary hypercholesterolemia, dislipoproteinemia (types IIa and IIb); for obesity, obstructive jaundice, nephrotic syndrome, diabetes mellitus, hypothyroidism. Determination of LDL level is necessary for prescribing long-term treatment, the purpose of which is to reduce lipid concentrations.
Increased concentration has diagnostic value for liver cirrhosis and alcoholism.
Decreased concentrationhigh density lipoprotein (HDL) has diagnostic value for hypertriglyceridemia, atherosclerosis, nephrotic syndrome, diabetes mellitus, acute infections, obesity, smoking.
Level determination apolipoprotein A indicated for early assessment of the risk of coronary heart disease; identifying patients with a hereditary predisposition to atherosclerosis at a relatively young age; monitoring treatment with lipid-lowering drugs.
Increased concentrationapolipoprotein A has diagnostic value for liver diseases and pregnancy.
Decreased concentrationapolipoprotein A has diagnostic value for nephrotic syndrome, chronic renal failure, triglyceridemia, cholestasis, sepsis.
Diagnostic valueapolipoprotein B- the most accurate indicator of the risk of developing cardiovascular diseases, is also the most adequate indicator of the effectiveness of statin therapy.
Increased concentrationapolipoprotein B has diagnostic value for dyslipoproteinemia (IIa, IIb, IV and V types), coronary heart disease, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver diseases, Itsenko-Cushing syndrome, porphyria.
Decreased concentrationapolipoprotein B has diagnostic value for hyperthyroidism, malabsorption syndrome, chronic anemia, inflammatory joint diseases, myeloma.
The determination is carried out on the “Architect 8000” biochemical analyzer.
to study the lipid profile (cholesterol, triglycerides, HDL-C, LDL-C, Apo-proteins of lipoproteins (Apo A1 and Apo-B)
It is necessary to refrain from physical activity, drinking alcohol, smoking and medicines, dietary changes for at least two weeks before blood collection.
Blood is taken only on an empty stomach, 12-14 hours after the last meal.
Preferably morning appointment medicines carry out after drawing blood (if possible).
The following procedures should not be performed before donating blood: injections, punctures, general body massage, endoscopy, biopsy, ECG, X-ray examination, especially with the introduction of a contrast agent, dialysis.
If it was still insignificant physical activity– You need to rest for at least 15 minutes before donating blood.
Lipid testing is not performed for infectious diseases, since there is a decrease in the level of total cholesterol and HDL-C, regardless of the type of infectious agent, clinical condition patient. The lipid profile should be checked only after the patient has fully recovered.
It is very important that these recommendations are strictly followed, since only in this case will reliable blood test results be obtained.
Lipids are substances of various chemical structures that have a number of common physical, physicochemical and biological properties. They are characterized by the ability to dissolve in ether, chloroform, other fatty solvents and only slightly (and not always) in water, and also form, together with proteins and carbohydrates, the main structural component of living cells. The inherent properties of lipids are determined by the characteristic features of the structure of their molecules.
The role of lipids in the body is very diverse. Some of them serve as a form of deposition (triacylglycerols, TG) and transport (free fatty acids - FFAs) of substances, the breakdown of which releases a large amount of energy, ...
others are the most important structural components of cell membranes (free cholesterol and phospholipids). Lipids are involved in the processes of thermoregulation, protecting vital organs (for example, kidneys) from mechanical stress (injury), protein loss, creating elasticity of the skin, and protecting them from excessive moisture removal.
Some of the lipids are biologically active substances that have the properties of modulators of hormonal effects (prostaglandins) and vitamins (polyunsaturated fatty acids). Moreover, lipids promote the absorption of fat-soluble vitamins A, D, E, K; act as antioxidants (vitamins A, E), which largely regulate the process of free radical oxidation of physiologically important compounds; determine the permeability of cell membranes to ions and organic compounds.
Lipids serve as precursors for a number of steroids with pronounced biological effects - bile acids, vitamins D, sex hormones, and adrenal hormones.
The concept of “total lipids” in plasma includes neutral fats (triacylglycerols), their phosphorylated derivatives (phospholipids), free and ester-bound cholesterol, glycolipids, and non-esterified (free) fatty acids.
Clinical and diagnostic value of determining the level of total lipids in blood plasma (serum)
The norm is 4.0-8.0 g/l.
Hyperlipidemia (hyperlipemia) - an increase in the concentration of total plasma lipids as a physiological phenomenon can be observed 1.5 hours after a meal. Nutritional hyperlipemia is more pronounced, the lower the level of lipids in the patient’s blood on an empty stomach.
The concentration of lipids in the blood changes in a number of pathological conditions. Thus, in patients with diabetes mellitus, along with hyperglycemia, pronounced hyperlipemia is observed (often up to 10.0-20.0 g/l). With nephrotic syndrome, especially lipoid nephrosis, the content of lipids in the blood can reach even higher numbers - 10.0-50.0 g/l.
Hyperlipemia is a constant phenomenon in patients with biliary cirrhosis and in patients with acute hepatitis (especially in the icteric period). Elevated levels of lipids in the blood are usually found in individuals suffering from acute or chronic nephritis, especially if the disease is accompanied by edema (due to the accumulation of LDL and VLDL in the plasma).
The pathophysiological mechanisms that cause changes in the content of all fractions of total lipids, to a greater or lesser extent, determine a pronounced change in the concentration of its constituent subfractions: cholesterol, total phospholipids and triacylglycerols.
Clinical and diagnostic significance of the study of cholesterol (CH) in blood serum (plasma)
A study of cholesterol levels in blood serum (plasma) does not provide accurate diagnostic information about a specific disease, but only reflects the pathology of lipid metabolism in the body.
According to epidemiological studies, the upper level of cholesterol in the blood plasma of practically healthy people aged 20-29 years is 5.17 mmol/l.
In blood plasma, cholesterol is found mainly in LDL and VLDL, with 60-70% of it in the form of esters (bound cholesterol), and 30-40% in the form of free, non-esterified cholesterol. Bound and free cholesterol make up the total cholesterol.
A high risk of developing coronary atherosclerosis in people aged 30-39 and over 40 years old occurs when cholesterol levels exceed 5.20 and 5.70 mmol/l, respectively.
Hypercholesterolemia is the most proven risk factor for coronary atherosclerosis. This has been confirmed by numerous epidemiological and clinical studies that have established a connection between hypercholesterolemia and coronary atherosclerosis, the incidence of coronary artery disease and myocardial infarction.
The highest level of cholesterol is observed with genetic disorders in lipid metabolism: familial homo- and heterozygous hypercholesterolemia, familial combined hyperlipidemia, polygenic hypercholesterolemia.
In a number of pathological conditions, secondary hypercholesterolemia develops . It is observed in liver diseases, kidney damage, malignant tumors of the pancreas and prostate, gout, coronary heart disease, acute myocardial infarction, hypertension, endocrine disorders, chronic alcoholism, type I glycogenosis, obesity (in 50-80% of cases).
A decrease in plasma cholesterol levels is observed in patients with malnutrition, damage to the central nervous system, mental retardation, chronic failure of the cardiovascular system, cachexia, hyperthyroidism, acute infectious diseases, acute pancreatitis, acute purulent-inflammatory processes in soft tissues, febrile conditions, pulmonary tuberculosis, pneumonia, sarcoidosis of the respiratory system, bronchitis, anemia, hemolytic jaundice, acute hepatitis, malignant liver tumors, rheumatism.
Determination of the fractional composition of cholesterol in blood plasma and its individual lipids (primarily HDL) has acquired great diagnostic importance for judging the functional state of the liver. According to modern concepts, the esterification of free cholesterol into HDL occurs in the blood plasma thanks to the enzyme lecithin-cholesterol acyltransferase, which is formed in the liver (this is an organ-specific liver enzyme). The activator of this enzyme is one of the main components of HDL - apo - Al, constantly synthesized in the liver.
A nonspecific activator of the plasma cholesterol esterification system is albumin, also produced by hepatocytes. This process primarily reflects the functional state of the liver. If normally the coefficient of cholesterol esterification (i.e. the ratio of the content of ether-bound cholesterol to total) is 0.6-0.8 (or 60-80%), then in acute hepatitis, exacerbation of chronic hepatitis, cirrhosis of the liver, obstructive jaundice, and It also decreases in chronic alcoholism. A sharp decrease in the severity of the cholesterol esterification process indicates insufficiency of liver function.
Clinical and diagnostic value of concentration studies
total phospholipids in blood serum.
Phospholipids (PL) are a group of lipids containing, in addition to phosphoric acid (as an essential component), alcohol (usually glycerol), fatty acid residues and nitrogenous bases. Depending on the nature of the alcohol, PLs are divided into phosphoglycerides, phosphosphingosines and phosphoinositides.
The level of total PL (lipid phosphorus) in blood serum (plasma) increases in patients with primary and secondary hyperlipoproteinemia types IIa and IIb. This increase is most pronounced in glycogenosis type I, cholestasis, obstructive jaundice, alcoholic and biliary cirrhosis, viral hepatitis (mild), renal coma, posthemorrhagic anemia, chronic pancreatitis, severe diabetes mellitus, nephrotic syndrome.
To diagnose a number of diseases, it is more informative to study the fractional composition of serum phospholipids. For this purpose, lipid thin layer chromatography methods have been widely used in recent years.
Composition and properties of blood plasma lipoproteins
Almost all plasma lipids are bound to proteins, which makes them highly soluble in water. These lipid-protein complexes are commonly referred to as lipoproteins.
According to modern concepts, lipoproteins are high-molecular water-soluble particles, which are complexes of proteins (apoproteins) and lipids formed by weak, non-covalent bonds, in which polar lipids (PL, CXC) and proteins (“apo”) form a surface hydrophilic monomolecular layer surrounding and protecting the internal phase (consisting mainly of ECS, TG) from water.
In other words, lipids are peculiar globules, inside of which there is a fat droplet, a core (formed predominantly by non-polar compounds, mainly triacylglycerols and cholesterol esters), delimited from water by a surface layer of protein, phospholipids and free cholesterol.
The physical characteristics of lipoproteins (their size, molecular weight, density), as well as the manifestations of physicochemical, chemical and biological properties, largely depend, on the one hand, on the ratio between the protein and lipid components of these particles, on the other hand, on the composition of the protein and lipid components, i.e. their nature.
The largest particles, consisting of 98% lipids and a very small (about 2%) proportion of protein, are chylomicrons (CM). They are formed in the cells of the mucous membrane of the small intestine and are a transport form for neutral dietary fats, i.e. exogenous TG.
Table 7.3 Composition and some properties of serum lipoproteins
| Criteria for assessing individual classes of lipoproteins | HDL (alpha-LP) | LDL (beta-LP) | VLDL (pre-beta-LP) | HM |
| Density, kg/l | 1,063-1,21 | 1,01-1,063 | 1,01-0,93 | 0,93 |
| Molecular weight of drug, kD | 180-380 | 3000- 128 000 | — | |
| Particle sizes, nm | 7,0-13,0 | 15,0-28,0 | 30,0-70,0 | 500,0 — 800,0 |
| Total proteins, % | 50-57 | 21-22 | 5-12 | |
| Total lipids, % | 43-50 | 78-79 | 88-95 | |
| Free cholesterol,% | 2-3 | 8-10 | 3-5 | |
| Esterified cholesterol, % | 19-20 | 36-37 | 10-13 | 4-5 |
| Phospholipids, % | 22-24 | 20-22 | 13-20 | 4-7 |
| Triacylglycerols, % | ||||
| 4-8 | 11-12 | 50-60 | 84-87 |
If exogenous TGs are transported into the blood by chylomicrons, then the transport form endogenous triglycerides are VLDL. Their formation is a protective reaction of the body aimed at preventing fatty infiltration, and subsequently liver degeneration.
The size of VLDL is on average 10 times smaller than the size of CM (individual VLDL particles are 30-40 times smaller than CM particles). They contain 90% of lipids, of which more than half are TG. 10% of total plasma cholesterol is carried by VLDL. Due to the content of a large amount of TG, VLDL shows insignificant density (less than 1.0). It has been established that LDL and VLDL contain 2/3 (60%) of total cholesterol plasma, while 1/3 is HDL.
HDL– the densest lipid-protein complexes, since the protein content in them is about 50% of the mass of the particles. Their lipid component consists half of phospholipids, half of cholesterol, mainly ether-bound. HDL is also constantly formed in the liver and partly in the intestines, as well as in the blood plasma as a result of the “degradation” of VLDL.
If LDL and VLDL deliver Cholesterol from the liver to other tissues(peripheral), including vascular wall, That HDL transports cholesterol from cell membranes (primarily the vascular wall) to the liver. In the liver it goes to the formation of bile acids. In accordance with this participation in cholesterol metabolism, VLDL and themselves LDL are called atherogenic, A HDL– antiatherogenic drugs. Atherogenicity refers to the ability of lipid-protein complexes to introduce (transmit) free cholesterol contained in the drug into tissues.
HDL competes for cell membrane receptors with LDL, thereby counteracting the utilization of atherogenic lipoproteins. Since the surface monolayer of HDL contains a large amount of phospholipids, at the point of contact of the particle with the outer membrane of the endothelial, smooth muscle and any other cell, favorable conditions are created for the transfer of excess free cholesterol to HDL.
However, the latter remains in the surface HDL monolayer only for a very short time, since it undergoes esterification with the participation of the LCAT enzyme. The formed ECS, being a nonpolar substance, moves into the internal lipid phase, releasing vacancies to repeat the act of capturing a new ECS molecule from the cell membrane. From here: the higher the activity of LCAT, the more effective the antiatherogenic effect of HDL, which are considered as LCAT activators.
If the balance is disturbed between the processes of the influx of lipids (cholesterol) into the vascular wall and their outflow from it, conditions can be created for the formation of lipoidosis, the most famous manifestation of which is atherosclerosis.
In accordance with the ABC nomenclature of lipoproteins, primary and secondary lipoproteins are distinguished. Primary LPs are formed by any apoprotein of one chemical nature. These can conditionally include LDL, which contains about 95% apoprotein B. All others are secondary lipoproteins, which are associated complexes of apoproteins.
Normally, approximately 70% of plasma cholesterol is found in “atherogenic” LDL and VLDL, while about 30% circulates in “antiatherogenic” HDL. With this ratio, a balance in the rates of inflow and outflow of cholesterol is maintained in the vascular wall (and other tissues). This determines the numerical value cholesterol ratio atherogenicity, component with the indicated lipoprotein distribution of total cholesterol 2,33 (70/30).
According to the results of mass epidemiological observations, at a concentration of total cholesterol in plasma of 5.2 mmol/l, a zero balance of cholesterol in the vascular wall is maintained. An increase in the level of total cholesterol in the blood plasma of more than 5.2 mmol/l leads to its gradual deposition in the vessels, and at a concentration of 4.16-4.68 mmol/l a negative cholesterol balance is observed in the vascular wall. The level of total cholesterol in blood plasma (serum) exceeding 5.2 mmol/l is considered pathological.
Table 7.4 Scale for assessing the likelihood of developing coronary artery disease and other manifestations of atherosclerosis
For differential diagnostics of ischemic heart disease another indicator is used - cholesterol atherogenic coefficient . It can be calculated using the formula: LDL cholesterol + VLDL cholesterol / HDL cholesterol.
More often used in clinical practice Klimov coefficient, which is calculated as follows: Total cholesterol – HDL cholesterol / HDL cholesterol. In healthy people, the Klimov coefficient Not exceeds "3" The higher this coefficient, the higher the risk of developing IHD.
System “lipid peroxidation – antioxidant protection organism"
In recent years, interest in the clinical aspects of studying the process of free radical lipid peroxidation has increased immeasurably. This is largely due to the fact that a defect in this metabolic link can significantly reduce the body’s resistance to the effects of unfavorable factors of the external and internal environment, as well as create the prerequisites for the formation, accelerated development and aggravation of the severity of the disease. various diseases vital organs: lungs, heart, liver, kidneys, etc. A characteristic feature of this so-called free radical pathology is membrane damage, which is why it is also called membrane pathology.
The deterioration of the environmental situation noted in recent years associated with long-term exposure on people by ionizing radiation, progressive air pollution with dust particles, exhaust gases and other toxic substances, as well as soil and water with nitrites and nitrates, chemicalization of various industries, smoking, alcohol abuse led to the fact that, under the influence of radioactive contamination and foreign substances, very reactive substances began to form in large quantities, significantly disrupting metabolic processes. What all these substances have in common is the presence of unpaired electrons in their molecules, which makes it possible to classify these intermediates as so-called free radicals (FR).
Free radicals are particles that differ from ordinary ones in that in the electron layer of one of their atoms in the outer orbital there are not two electrons mutually holding each other, making this orbital filled, but only one.
When the outer orbital of an atom or molecule is filled with two electrons, a particle of substance acquires more or less pronounced chemical stability, whereas if there is only one electron in the orbital, due to the influence it exerts - the uncompensated magnetic moment and the high mobility of the electron within the molecule - the chemical activity of the substance increases sharply.
CPs can be formed by the abstraction of a hydrogen atom (ion) from a molecule, as well as the addition (incomplete reduction) or donation (incomplete oxidation) of one of the electrons. It follows that free radicals can be represented either by electrically neutral particles or by particles carrying a negative or positive charge.
One of the most widespread free radicals in the body is the product of incomplete reduction of an oxygen molecule - superoxide anion radical (O 2 -). It is constantly formed with the participation of special enzyme systems in the cells of many pathogenic bacteria, blood leukocytes, macrophages, alveolocytes, cells of the intestinal mucosa, which have an enzyme system that produces this superoxide anion radical of oxygen. Mitochondria make a major contribution to O2 synthesis as a result of the “draining” of some electrons from the mitochondrial chain and transferring them directly to molecular oxygen. This process is significantly activated under conditions of hyperoxia ( hyperbaric oxygen therapy), this explains the toxic effect of oxygen.
Two installed lipid peroxidation pathways:
1) non-enzymatic, ascorbate dependent, activated by metal ions of variable valency; since during the oxidation process Fe ++ turns into Fe +++, its continuation requires the reduction (with the participation of ascorbic acid) of oxide iron into ferrous iron;
2) enzymatic, NADPH-dependent, carried out with the participation of NADP H-dependent microsomal dioxygenase, generating O — 2 .
Lipid peroxidation occurs through the first pathway in all membranes, while through the second, it occurs only in the endoplasmic reticulum. To date, other special enzymes are known (cytochrome P-450, lipoxygenases, xanthine oxidases) that form free radicals and activate lipid peroxidation in microsomes (microsomal oxidation), other cell organelles with the participation of NADPH, pyrophosphate and ferrous iron as cofactors. With a hypoxia-induced decrease in pO2 in tissues, xanthine dehydrogenase is converted into xanthine oxidase. In parallel with this process, another is activated - the conversion of ATP into hypoxanthine and xanthine. When xanthine oxidase acts on xanthine, it forms superoxide oxygen radical anions. This process is observed not only during hypoxia, but also during inflammation, accompanied by stimulation of phagocytosis and activation of the hexose monophosphate shunt in leukocytes.
Antioxidant systems
The described process would develop uncontrollably if the cellular elements of the tissues did not contain substances (enzymes and non-enzymes) that counteract its progress. They became known as antioxidants.
Non-enzymatic free radical oxidation inhibitors are natural antioxidants - alpha-tocopherol, steroid hormones, thyroxine, phospholipids, cholesterol, retinol, ascorbic acid.
Basic natural antioxidant alpha-tocopherol is found not only in plasma, but also in red blood cells. It is believed that molecules alpha tocopherol, are embedded in the lipid layer of the erythrocyte membrane (as well as all other cell membranes of the body), protect unsaturated fatty acids of phospholipids from peroxidation. The preservation of the structure of cell membranes largely determines their functional activity.
The most common antioxidant is alpha tocopherol (vitamin E), contained in plasma and plasma cell membranes, retinol (vitamin A), ascorbic acid, some enzymes, for example superoxide dismutase (SOD) red blood cells and other tissues, ceruloplasmin(destroying superoxide anion radicals of oxygen in blood plasma), glutathione peroxidase, glutathione reductase, catalase etc., influencing the content of LPO products.
With a sufficiently high content of alpha-tocopherol in the body, only a small amount of lipid peroxidation products are formed, which are involved in the regulation of many physiological processes, including: cell division, ion transport, renewal of cell membranes, in the biosynthesis of hormones, prostaglandins, in the implementation of oxidative phosphorylation. A decrease in the content of this antioxidant in tissues (causing a weakening of the body's antioxidant defense) leads to the fact that the products of lipid peroxidation begin to produce a pathological effect instead of a physiological one.
Pathological conditions, characterized advanced education free radicals and activation of lipid peroxidation, may be independent, largely similar in pathobiochemical and clinical manifestations diseases ( vitamin deficiency E, radiation injury, some poisoning chemicals ). At the same time, the initiation of free radical oxidation of lipids plays an important role in formation of various somatic diseases associated with defeat internal organs.
LPO products formed in excess cause disruption not only of lipid interactions in biomembranes, but also of their protein component - due to binding to amine groups, which leads to disruption of the protein-lipid relationship. As a result, the accessibility of the hydrophobic layer of the membrane for phospholipases and proteolytic enzymes increases. This enhances the processes of proteolysis and, in particular, the breakdown of lipoprotein proteins (phospholipids).
Free radical oxidation causes changes in elastic fibers, initiates fibroplastic processes and aging collagen. In this case, the most vulnerable are the membranes of erythrocyte cells and arterial endothelium, since they, having a relatively high content of easily oxidized phospholipids, come into contact with a relatively high concentration of oxygen. Destruction of the elastic layer of the parenchyma of the liver, kidneys, lungs and blood vessels entails fibrosis, including pneumofibrosis(for inflammatory lung diseases), atherosclerosis and calcification.
The pathogenetic role is beyond doubt activation of sex in the formation of disorders in the body under chronic stress.
A close correlation has been found between the accumulation of lipid peroxidation products in the tissues of vital organs, plasma and erythrocytes, which makes it possible to use blood to judge the intensity of free radical oxidation of lipids in other tissues.
The pathogenetic role of lipid peroxidation in the formation of atherosclerosis and coronary heart disease, diabetes mellitus, malignant neoplasms, hepatitis, cholecystitis, burn disease, pulmonary tuberculosis, bronchitis, and nonspecific pneumonia has been proven.
The establishment of LPO activation in a number of diseases of internal organs was the basis for use with therapeutic purpose antioxidants of various natures.
Their use gives a positive effect in chronic ischemic heart disease, tuberculosis (also causing the elimination adverse reactions on antibacterial drugs: streptomycin, etc.), many other diseases, as well as chemotherapy for malignant tumors.
Antioxidants are increasingly used to prevent the consequences of exposure to certain toxic substances, weaken the “spring weakness” syndrome (believed to be caused by intensified lipid peroxidation), prevent and treat atherosclerosis, and many other diseases.
Relatively high content alpha-tocopherol is found in apples, wheat germ, wheat flour, potatoes, and beans.
To diagnose pathological conditions and evaluate the effectiveness of treatment, it is customary to determine the content of primary (diene conjugates), secondary (malondialdehyde) and final (Schiff bases) LPO products in blood plasma and erythrocytes. In some cases, the activity of antioxidant enzymes is studied: SOD, ceruloplasmin, glutathione reductase, glutathione peroxidase and catalase. Integral test for assessing gender is determination of the permeability of erythrocyte membranes or the osmotic resistance of erythrocytes.
It should be noted that pathological conditions, characterized by increased formation of free radicals and activation of lipid peroxidation, can be:
1) an independent disease with a characteristic clinical picture, for example, vitamin E deficiency, radiation damage, some chemical poisoning;
2) somatic diseases associated with damage to internal organs. These include, first of all: chronic ischemic heart disease, diabetes mellitus, malignant neoplasms, inflammatory diseases lungs (tuberculosis, nonspecific inflammatory processes lungs), liver diseases, cholecystitis, burn disease, peptic ulcer stomach and duodenum.
It should be borne in mind that the use of a number of well-known drugs (streptomycin, tubazide, etc.) in the process of chemotherapy for pulmonary tuberculosis and other diseases can itself cause activation of lipid peroxidation, and consequently, aggravation of the severity of the disease.
