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 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, severe diseases 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) of substances, the breakdown of which releases a large amount of energy, others are the most important structural components 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 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, 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)
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, ischemic heart disease, acute myocardial infarction, hypertension, endocrine disorders, chronic alcoholism, glycogenosis type I, obesity (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, respiratory sarcoidosis, 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 basic 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 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 glycogenosis type I, 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. To this end, in last years Lipid thin layer chromatography methods are widely used.
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 predominantly by non-polar compounds, mainly triacylglycerols and cholesterol esters), delimited from water by a surface layer of protein, phospholipids and free cholesterol.
Physical Features 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, 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). Determined 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.
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 is usually understood as the ability of lipid-protein complexes to introduce (transmit) free cholesterol contained in the drug into tissues.
HDL competes with LDL for cell membrane receptors, 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 known manifestation 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 in vascular wall(and other tissues) a balance is maintained between the rates of inflow and outflow of cholesterol. 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 Scale for assessing the likelihood of developing coronary artery disease and other manifestations of atherosclerosis
(Komarov F.I., Korovkin B.F., 2000)
– a group of substances that are heterogeneous in chemical structure and physical and chemical properties. 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, acts as an antioxidant. About 10% of the Russian population have high blood cholesterol levels. This condition is asymptomatic and can lead to serious illnesses(atherosclerotic vascular lesions, coronary disease hearts).
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 lipoproteins high density(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.
Indications
Increased concentrationcholesterol has diagnostic value for primary familial hyperlipidemia (hereditary forms of the disease); 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.
Methodology
The determination is carried out on the “Architect 8000” biochemical analyzer.
Preparation
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.
It is advisable to take the medication in the morning 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 there was still minor physical activity, you need to rest for at least 15 minutes before donating blood.
Lipid testing is not performed when infectious diseases, since there is a decrease in the level of total cholesterol and HDL-C, regardless of the type of infectious agent or the clinical condition of the patient. The lipid profile should be checked only after the patient has fully recovered.
It is very important that the specified recommendations are strictly followed, since only in this case will the reliable results blood tests.
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, respiratory sarcoidosis, 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 significance 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). Determined 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 with LDL for cell membrane receptors, 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 diagnosis IHD uses another indicator - 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 defense of the body”
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 prerequisites for the formation, accelerated development and aggravation of the severity of various diseases of vital organs: lungs, heart , liver, kidneys, etc. Characteristic feature This so-called free radical pathology involves damage to membranes, which is why it is also called membrane pathology.
The deterioration of the environmental situation noted in recent years, associated with long-term exposure to people 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 the course of 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-oxygen radical. 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 oxygenation), which explains the toxic effects of oxygen.
Two installed lipid peroxidation pathways:
1) non-enzymatic, ascorbate dependent activated by metal ions variable valence; 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 cellular elements tissues there were no substances (enzymes and non-enzymes) that counteract its flow. 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.
When enough high content Alpha-tocopherol in the body produces only a small amount of lipid peroxidation products, 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, and 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 increased formation of free radicals and activation of lipid peroxidation, may be independent, largely similar in pathobiochemical and clinical manifestations diseases ( vitamin deficiency E, radiation damage, some poisonings 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.
Apples, wheat germ, wheat flour, potatoes, and beans have a relatively high alpha-tocopherol content.
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 injury, some chemical poisoning;
2) somatic diseases associated with damage to internal organs. These include, first of all: chronic ischemic heart disease, diabetes, malignant neoplasms, inflammatory lung diseases (tuberculosis, nonspecific inflammatory processes a lungs), liver diseases, cholecystitis, burn disease, peptic ulcer of the 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.
Hyperlipidemia (hyperlipemia) - an increase in the concentration of total plasma lipids as a physiological phenomenon can be observed 1-4 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:
Nephrotic syndrome, lipoid nephrosis, acute and chronic nephritis;
Biliary cirrhosis of the liver, acute hepatitis;
Obesity - atherosclerosis;
Hypothyroidism;
Pancreatitis, etc.
The study of cholesterol (CH) levels reflects only the pathology of lipid metabolism in the body. Hypercholesterolemia is a documented risk factor for coronary atherosclerosis. CS is an essential component of the membrane of all cells; the special physicochemical properties of CS crystals and the conformation of its molecules contribute to the orderliness and mobility of phospholipids in membranes when temperature changes, which allows the membrane to be in an intermediate phase state (“gel - liquid crystal”) and maintain physiological functions . CS is used as a precursor in the biosynthesis of steroid hormones (gluco- and mineralocorticoids, sex hormones), vitamin D 3, and bile acids. Conventionally, we can distinguish 3 pools of cholesterol:
A - quickly exchanging (30 g);
B – slowly exchanging (50 g);
B – very slowly exchanging (60 g).
Endogenous cholesterol is synthesized in significant quantities in the liver (80%). Exogenous cholesterol enters the body as part of animal products. Transport of cholesterol from the liver to extrahepatic tissues is carried out
LDL. The removal of cholesterol from the liver from extrahepatic tissues into the liver is produced by mature forms of HDL (50% - LDL, 25% HDL, 17% VLDL, 5% -CM).
Hyperlipoproteinemia and hypercholesterolemia (Fredrickson classification):
Type 1 – hyperchylomicronemia;
type 2 - a - hyper-β-lipoproteinemia, b - hyper-β and hyperpre-β-lipoproteinemia;
type 3 – dys-β-lipoproteinemia;
type 4 – hyper-pre-β-lipoproteinemia;
Type 5 – hyper-pre-β-lipoproteinemia and hyperchylomicronemia.
The most atherogenic are types 2 and 3.
Phospholipids are a group of lipids containing, in addition to phosphoric acid (an essential component), alcohol (usually glycerol), fatty acid residues and nitrogenous bases. In clinical and laboratory practice, there is a method for determining the level of total phospholipids, the level of which increases in patients with primary and secondary hyperlipoproteinemia IIa and IIb. A decrease occurs in a number of diseases:
Nutritional dystrophy;
Fatty liver degeneration,
Portal cirrhosis;
Progression of atherosclerosis;
Hyperthyroidism, etc.
Lipid peroxidation (LPO) is a free radical process, the initiation of which occurs with the formation active forms oxygen - superoxide ion O 2 . ; hydroxyl radical HO . ; hydroperoxide radical HO 2 . ; singlet oxygen O 2 ; hypochlorite ion ClO - . The main substrates of LPO are polyunsaturated fatty acids found in the structure of membrane phospholipids. The strongest catalyst is iron metal ions. LPO is a physiological process that is important for the body, as it regulates membrane permeability, affects cell division and growth, begins phagosynthesis, and is a pathway for the biosynthesis of certain biological substances(prostaglandins, thromboxanes). The level of lipid peroxidation is controlled by the antioxidant system (ascorbic acid, uric acid, β-carotene, etc.). Loss of balance between the two systems leads to the death of cells and cellular structures.
For diagnostic purposes, it is customary to determine the content of lipid peroxidation products (diene conjugates, malondialdehyde, Schiff bases) and the concentration of the main natural antioxidant - alpha-tocopherol in plasma and red blood cells with the calculation of the MDA/TF coefficient. An integral test for assessing LPO is determining the permeability of erythrocyte membranes.
2. Pigment exchange a set of complex transformations of various colored substances in the human and animal body.
The most well-known blood pigment is hemoglobin (a chromoprotein that consists of the protein part of globin and a prosthetic group represented by 4 hemes, each heme consists of 4 pyrrole nuclei, which are interconnected by methine bridges, in the center there is an iron ion with an oxidation state of 2 +) . The average lifespan of an erythrocyte is 100-110 days. At the end of this period, destruction and destruction of hemoglobin occurs. The decay process begins already in the vascular bed and ends in the cellular elements of the system of phagocytic mononuclear cells (Kupffer cells of the liver, connective tissue histiocytes, bone marrow plasma cells). Hemoglobin in the vascular bed binds to plasma haptoglobin and is retained in the vascular bed without passing through the renal filter. Due to the trypsin-like action of the beta chain of haptoglobin and the conformational changes caused by its influence in the porphyrin ring of the heme, conditions are created for easier destruction of hemoglobin in the cellular elements of the phagocytic mononuclear system. The resulting high-molecular green pigment verdoglobin(synonyms: verdohemoglobin, choleglobin, pseudohemoglobin) is a complex consisting of globin, a broken porphyrin ring system and ferric iron. Further transformations lead to the loss of iron and globin by verdoglobin, as a result of which the porphyrin ring unfolds into a chain and a low molecular weight green bile pigment is formed - biliverdin. Almost all of it is enzymatically restored into the most important red-yellow pigment of bile - bilirubin, which is a common component of blood plasma. It undergoes dissociation on the surface of the plasma membrane of the hepatocyte. In this case, the released bilirubin forms a temporary associate with the lipids of the plasma membrane and moves through it due to the activity of certain enzyme systems. Further passage of free bilirubin into the cell occurs with the participation of two carrier proteins in this process: ligandin (it transports the main amount of bilirubin) and protein Z.
Ligandin and protein Z are also found in the kidneys and intestines, therefore, in case of insufficient liver function, they are free to compensate for the weakening of detoxification processes in this organ. Both are quite soluble in water, but lack the ability to move through the lipid layer of the membrane. By binding bilirubin to glucuronic acid, the inherent toxicity of free bilirubin is largely lost. Hydrophobic, lipophilic free bilirubin, easily dissolving in membrane lipids and consequently penetrating into mitochondria, uncouples respiration and oxidative phosphorylation in them, disrupts protein synthesis, the flow of potassium ions through the membrane of cells and organelles. This negatively affects the state of the central nervous system, causing a number of characteristic symptoms in patients. neurological symptoms.
Bilirubin glucuronides (or bound, conjugated bilirubin), unlike free bilirubin, immediately react with the diazo reagent (“direct” bilirubin). It should be borne in mind that in the blood plasma itself, bilirubin that is not conjugated with glucuronic acid can either be associated with albumin or not. The last fraction (bilirubin not associated with albumin, lipids, or other blood components) is the most toxic.
Bilirubin glucuronides, thanks to membrane enzyme systems, actively move through them (against the concentration gradient) into the bile ducts, being released along with bile into the intestinal lumen. In it, under the influence of enzymes produced by intestinal microflora, the glucuronide bond is broken. The released free bilirubin is reduced to form first mesobilirubin and then mesobilinogen (urobilinogen) in the small intestine. Normally, a certain part of mesobilinogen is absorbed in the small intestine and upper section thick, through the portal vein system it enters the liver, where it is almost completely destroyed (by oxidation), turning into dipyrrolic compounds - propent-diopent and mesobileucane.
Mesobilinogen (urobilinogen) does not enter the general circulation. Part of it, together with the products of destruction, is again sent into the intestinal lumen as part of bile (enterohepotic circulation). However, even with the most minor changes in the liver, its barrier function is largely “removed” and mesobilinogen enters first into the general blood circulation and then into the urine. The bulk of it is sent from the small intestine to the large intestine, where, under the influence of anaerobic microflora (Escherichia coli and other bacteria), it undergoes further reduction with the formation of stercobilinogen. The resulting stercobilinogen (daily amount 100-200 mg) is almost completely excreted in the feces. In air, it oxidizes and turns into stercobilin, which is one of the pigments of feces. Small part Stercobilinogen is absorbed through the mucous membrane of the large intestine into the inferior vena cava system, delivered in the blood to the kidneys and excreted in the urine.
So in the urine healthy person There is no mesobilinogen (urobilinogen), but it contains some stercobilin (which is often incorrectly called “urobilin”)
To determine the content of bilirubin in blood serum (plasma), mainly chemical and physicochemical research methods are used, among which are colorimetric, spectrophotometric (manual and automated), chromatographic, fluorimetric and some others.
One of the important subjective signs of a disorder of pigment metabolism is the appearance of jaundice, which is usually noted when the level of bilirubin in the blood is 27-34 µmol/l or more. The causes of hyperbilirubinemia can be: 1) increased hemolysis of red blood cells (more than 80% of total bilirubin is represented by unconjugated pigment); 2) impaired liver cell function and 3) delayed bile outflow (hyperbilirubinemia is of hepatic origin if more than 80% of total bilirubin is conjugated bilirubin). In the first case, they talk about the so-called hemolytic jaundice, in the second – about parenchymal jaundice (can be caused by hereditary defects in the processes of transport of bilirubin and its glucuronidation), in the third – about mechanical (or obstructive, congestive) jaundice.
With parenchymal form of jaundice destructive-dystrophic changes are noted in the parenchymal cells of the liver and infiltrative ones in the stroma, leading to an increase in pressure in the liver bile ducts. Stagnation of bilirubin in the liver is also facilitated by a sharp weakening of metabolic processes in affected hepatocytes, which lose the ability to normally perform various biochemical and physiological processes, in particular, transfer bound bilirubin from cells into bile against a concentration gradient. An increase in the concentration of conjugated bilirubin in the blood leads to its appearance in the urine.
The most “subtle” sign of liver damage in hepatitis is the appearance mesobilinogen(urobilinogen) in the urine.
With parenchymal jaundice, the concentration of bound (conjugated) bilirubin in the blood increases mainly. The content of free bilirubin increases, but to a lesser extent.
The pathogenesis of obstructive jaundice is based on the cessation of bile flow into the intestine, which leads to the disappearance of stercobilinogen from the urine. With congestive jaundice, the content of conjugated bilirubin in the blood increases mainly. Extrahepatic cholestatic jaundice is accompanied by a triad of clinical signs: discolored stool, dark urine and itchy skin. Intrahepatic cholestasis is clinically manifested by skin itching and jaundice. A laboratory study reveals hyperbilirubinemia (due to associated), bilirubinuria, increased alkaline phosphatase with normal values of transaminases in the blood serum.
Hemolytic jaundice are caused by hemolysis of red blood cells and, as a consequence, increased formation of bilirubin. An increase in free bilirubin is one of the main signs of hemolytic jaundice.
In clinical practice, congenital and acquired functional hyperbilirubinemia is distinguished, caused by a violation of the elimination of bilirubin from the body (the presence of defects in enzyme and other systems for the transfer of bilirubin through cell membranes and its glucuronidation in them). Gilbert's syndrome is a hereditary benign chronic disease that occurs with moderate non-hemolytic unconjugated hyperbilirubinemia. Post-hepatitis hyperbilirubinemia Kalka - acquired enzyme defect leading to an increase in the level of free bilirubin in the blood, congenital familial non-hemolytic jaundice of Crigler - Nayjar (absence of glucuronyltransferase in hepatocytes), jaundice with congenital hypothyroidism (thyroxine stimulates the enzyme glucuronyltransferase system), physiological jaundice of newborns, drug jaundice, etc. .
Disturbances in pigment metabolism can be caused by changes not only in the processes of heme decomposition, but also in the formation of its precursors - porphyrins (cyclic organic compounds based on a porphin ring consisting of 4 pyrroles connected by methine bridges). Porfiria – group hereditary diseases, accompanied by a genetic deficiency in the activity of enzymes involved in the biosynthesis of heme, in which an increase in the content of porphyrins or their precursors is detected in the body, which causes a number of clinical signs (excessive formation of metabolic products, causes the development of neurological symptoms and (or) increased photosensitivity of the skin).
The most widely used methods for the determination of bilirubin are based on its interaction with a diazoreagent (Ehrlich's reagent). The Jendrassik-Grof method has become widespread. In this method, a mixture of caffeine and sodium benzoate in acetate buffer is used as a “liberator” of bilirubin. The enzymatic determination of bilirubin is based on its oxidation by bilirubin oxidase. It is possible to determine unconjugated bilirubin by other methods of enzymatic oxidation.
Currently, the determination of bilirubin using “dry chemistry” methods is becoming increasingly widespread, especially in rapid diagnostics.
Vitamins.
Vitamins are essential low-molecular substances that enter the body with food from the outside and are involved in the regulation of biochemical processes at the enzyme level.
Similarities and differences between vitamins and hormones.
Similarities– regulate metabolism in the human body through enzymes:
· Vitamins are part of enzymes and are coenzymes or cofactors;
· Hormones or regulate the activity of existing enzymes in the cell, or are inducers or repressors in the biosynthesis of necessary enzymes.
Difference:
· Vitamins– low-molecular organic compounds, exogenous factors regulating metabolism and come from food from the outside.
· Hormones– high-molecular organic compounds, endogenous factors synthesized in the endocrine glands of the body in response to changes in the external or internal environment of the human body, and also regulate metabolism.
Vitamins are classified into:
1. Fat soluble: A, D, E, K, A.
2. Water-soluble: group B, PP, H, C, THFA (tetrahydrofolic acid), pantothenic acid (B 3), P (rutin).
Vitamin A (retinol, antixerophthalmic) – the chemical structure is represented by a β-ionone ring and 2 isoprene residues; The body's need is 2.5-30 mg per day.
The earliest and most specific sign of hypovitaminosis A is hemeralopia (night blindness) - impaired twilight vision. It occurs due to a lack of visual pigment - rhodopsin. Rhodopsin contains retinal (vitamin A aldehyde) as an active group - located in the retinal rods. These cells (rods) perceive low-intensity light signals.
Rhodopsin = opsin (protein) + cis-retinal.
When rhodopsin is excited by light, cis-retinal, as a result of enzymatic rearrangements inside the molecule, transforms into all-trans-retinal (in the light). This leads to a conformational rearrangement of the entire rhodopsin molecule. Rhodopsin dissociates into opsin and trans-retinal, which is a trigger that excites an impulse at the optic nerve endings, which is then transmitted to the brain.
In the dark, as a result of enzymatic reactions, trans-retinal is converted back into cis-retinal and, combining with opsin, forms rhodopsin.
Vitamin A also affects the processes of growth and development of the integumentary epithelium. Therefore, with vitamin deficiency, damage to the skin, mucous membranes and eyes is observed, which manifests itself in pathological keratinization of the skin and mucous membranes. Patients develop xerophthalmia - dryness of the cornea of the eye, as the lacrimal canal becomes blocked as a result of keratinization of the epithelium. Since the eye ceases to be washed with tears, which have a bactericidal effect, conjunctivitis, ulceration and softening of the cornea - keratomalacia - develop. With vitamin A deficiency there may also be damage to the gastrointestinal mucosa, respiratory and genitourinary tract. The resistance of all tissues to infections is impaired. With the development of vitamin deficiency in childhood, growth retardation occurs.
Currently, the participation of vitamin A in protecting cell membranes from oxidants has been shown - that is, vitamin A has an antioxidant function.
Studies of lipid and lipoprotein (LP) metabolism, cholesterol (CH), unlike other diagnostic tests, are of social importance, since they require urgent measures for the prevention of cardiovascular diseases. The problem of coronary atherosclerosis has shown a clear clinical significance of each biochemical indicator as a risk factor for coronary heart disease (CHD), and in the last decade, approaches to assessing disorders of lipid and lipoprotein metabolism have changed.The risk of developing atherosclerotic vascular lesions is assessed using the following biochemical tests:
Determination of TC/HDL-C, LDL-C/HDL-C ratios.
Triglycerides
TG are neutral insoluble lipids that enter the plasma from the intestine or liver.
In the small intestine, TGs are synthesized from exogenous dietary fatty acids, glycerol and monoacylglycerols.
The formed TGs initially enter lymphatic vessels, then in the form of chylomicrons (CM) through the thoracic lymphatic duct enter the bloodstream. The lifetime of chemical substances in plasma is short; they enter the fat depots of the body.
The presence of CM explains the whitish color of the plasma after administration fatty foods. ChMs are quickly released from TGs with the participation of lipoprotein lipase (LPL), leaving them in adipose tissues. Normally, after a 12-hour fast, CMs are not detected in plasma. Due to the low protein content and high amount of TG, CMs remain at the starting line in all types of electrophoresis.
Along with TGs supplied with food, endogenous TGs are formed in the liver from endogenously synthesized fatty acids and triphosphoglycerol, the source of which is carbohydrate metabolism. These TGs are transported by the blood to the body's fat depots as part of very low-density lipoproteins (VLDL). VLDL is the main transport form of endogenous TG. The content of VLDL in the blood correlates with an increase in TG levels. When VLDL levels are high, the blood plasma appears cloudy.
To study TG, blood serum or plasma is used after a 12-hour fast. Storage of samples is possible for 5-7 days at a temperature of 4 °C; repeated freezing and thawing of samples is not allowed.
Cholesterol
CS is an integral part of all cells in the body. It is part of cell membranes, LP, and is a precursor of steroid hormones (mineral and glucocorticoids, androgens and estrogens).
CS is synthesized in all cells of the body, but the bulk of it is formed in the liver and comes with food. The body synthesizes up to 1 g of cholesterol per day.
CS is a hydrophobic compound, the main form of transport of which in the blood is protein-lipid micellar complexes of drugs. Their surface layer is formed by hydrophilic heads of phospholipids, apolipoproteins; esterified cholesterol is more hydrophilic than cholesterol, therefore cholesterol esters move from the surface to the center of the lipoprotein micelle.
The bulk of cholesterol is transported in the blood in the form of LDL from the liver to peripheral tissues. The apolipoprotein of LDL is apo-B. LDL interacts with apo-B receptors on the plasma membranes of cells and is captured by them through endocytosis. The cholesterol released in cells is used to build membranes and is esterified. CS from the surface of cell membranes enters a micellar complex consisting of phospholipids, apo-A, and forms HDL. The cholesterol in HDL undergoes esterification under the action of lecithin cholesterol acyl transferase (LCAT) and enters the liver. In the liver, cholesterol received as part of HDL undergoes microsomal hydroxylation and is converted into bile acids. It is excreted both in bile and in the form of free cholesterol or its esters.
A study of cholesterol levels does not provide diagnostic information about a specific disease, but characterizes the pathology of lipid and lipid metabolism. The highest levels of cholesterol occur with genetic disorders of lipid metabolism: familial homo- and heterozygous hypercholesterolemia, familial combined hyperlipidemia, polygenic hypercholesterolemia. In a number of diseases, secondary hypercholesterolemia develops: nephrotic syndrome, diabetes mellitus, hypothyroidism, alcoholism.
To assess the state of lipid and lipid metabolism, the values of total cholesterol, TG, HDL cholesterol, VLDL cholesterol, and LDL cholesterol are determined.
Determining these values allows you to calculate the atherogenicity coefficient (Ka):
Ka = TC - HDL cholesterol / VLDL cholesterol,
And other indicators. For calculations, you also need to know the following proportions:
VLDL cholesterol = TG (mmol/l) /2.18; LDL cholesterol = TC – (HDL cholesterol + VLDL cholesterol).
