Muscle contraction

Muscle contraction

The contraction of the muscular layer of the veins is also important, which in the veins of the lower half of the body, where the conditions for venous outflow is more complicated, is more developed than in the veins of the upper body. The reverse flow of venous blood is prevented by special devices of the veins – valves that make up the peculiarities of the venous wall. Venous valves consist of a fold of endothelium containing a layer of connective tissue. They face the free edge towards the heart and therefore do not prevent the blood from flowing in this direction, but keep it from returning back. Arteries and veins usually go together, with small and medium arteries accompanied by two veins, and large – one. Except for some deep veins, this rule excludes mainly superficial veins reaching the subcutaneous tissue and almost never accompanying arteries.

The walls of blood vessels have their own serving thin arteries and veins, vasa vasorum. They depart either from the same trunk, the wall of which is supplied with blood, or from the neighboring one and pass in the connective tissue layer surrounding the blood vessels and more or less closely connected with their outer sheath; This layer is called the vascular vagina, vagina vasorum. In the wall of arteries and veins there are numerous nerve endings (receptors and effectors) connected with the central nervous system, due to which the nervous regulation of blood circulation is carried out by the mechanism of reflexes. Blood vessels are extensive reflexogenic zones that play a large role in the neuro-humoral regulation of metabolism. Accordingly, the functions and the structure of the various departments and the features of innervation all the blood vessels in recent times have been divided into 3 groups:

1) the heart vessels that begin and end both circles of circulation, the aorta and the pulmonary trunk (i.e., elastic arteries), hollow and pulmonary veins;
2) the great vessels that serve for the distribution of blood throughout the body. These are large and medium sized extraorgan arteries of the muscular type and extraorgan veins;
3) organ vessels providing exchange reactions between the blood and the parenchyma of organs. These are intraorgan arteries and veins, as well as links in the microvasculature.



An arteriole differs from an artery in that its wall has only one layer of muscle cells, thanks to which it performs a regulatory function. Arteriole proceeds directly into the precapillary, in which muscle cells are scattered and do not constitute a continuous layer. The precapillary differs from arterioles in the fact that it is not accompanied by a venule.

Numerous capillaries depart from the precapillary.
Capillaries are the thinnest vessels that perform the exchange function. In this regard, their wall consists of a single layer of flat endothelial cells, permeable to substances and gases dissolved in a liquid. Anastomozirovaya widely between themselves, the capillaries form a network (capillary network), turning into postcapillary, built similarly to precapillary. Postcapillary continues into the venula, accompanying arterios. Venules form thin initial segments of the venous bed that make up the roots of the veins and pass into the veins.

Veins (lat. Vena, Greek phlebs; hence phlebitis – inflammation of the veins) carry blood in the opposite direction to the arteries, from organs to the heart. Their walls are arranged according to the same plan as the walls of the arteries, but they are much thinner and have less elastic and muscular tissue, due to which empty veins fall, and the lumen of the arteries in the transverse section gapes; veins, merging with each other, form large venous trunks – veins that flow into the heart.

Veins widely anastomose among themselves, forming venous plexus.
The movement of blood through the veins is due to the activity and the suctioning action of the heart and chest cavity, in which negative pressure is created during inhalation due to the pressure difference in the cavities and also due to the reduction of the skeletal and visceral muscles of the organs and other factors.

Circulatory system.

Circulatory system.

Arteries. The wall of the arteries. Capillaries Veins. The circulatory system consists of a central organ – the heart – and closed tubes of various calibers in conjunction with it, called blood vessels (Latin vas, Greek angeion – vessel; hence, angiology). With its rhythmic contractions, the heart drives the whole mass of blood, contained in the vessels.

Arteries. The blood vessels that go from the heart to the organs and carry blood to them are called arteries (aeg – air, tereo – contain; arteries on corpses are empty, which is why they used to be considered as air tubes).

The wall of the arteries consists of three shells. Inner shell, tunica intima. lined on the lumen of the vessel by the endothelium, under which the subendothelium and the inner elastic membrane lie; medium, tunica media, built from loose muscle fibers, myocytes, alternating with elastic fibers; the outer sheath, tunica externa, contains connective tissue fibers. The elastic elements of the arterial wall form a single elastic frame that acts as a spring and determines the elasticity of the arteries.

As they move away from the heart, arteries divide into branches and grow smaller and smaller. The arteries closest to the heart (the aorta and its large branches) perform mainly the function of conducting blood. In them to the fore the anti-stretching of a mass of blood, which is thrown out by a heart beat, comes forward. Therefore, in their wall structures of a mechanical nature are relatively more developed, i.e., elastic fibers and membranes. Such arteries are called elastic type arteries. In medium and small arteries, in which the inertia of the cardiac impulse weakens and requires its own contraction of the vascular wall for further blood advancement, the contractile function prevails. It is provided with a relatively large development in the vascular wall of muscle tissue. Such arteries are called muscular arteries. Individual arteries supply blood to entire organs or parts of them.

In relation to the organ, there are arteries that go beyond the organ, before entering it – extraorgan arteries, and their continuations that branch out inside it – intraorgan, or ingraorganic arteries. Lateral branches of the same stem or branches of different trunks can be connected to each other. Such a combination of vessels before disintegration of them into the capillaries is called anastomosis, or fistula (stoma – mouth). The arteries that form the anastomoses are called anastomosing (most of them). Arteries that do not have anastomoses with adjacent trunks before moving into the capillaries (see below) are called end arteries (for example, in the spleen). The terminal, or terminal, arteries are more easily blocked with a blood stopper (thrombus) and predispose to the formation of a heart attack (local organ death). The last branchings of the arteries become thin and small and therefore stand out under the name of arterioles.


Eye: structure

The eyes are located in the depressions of the skull, called the eye sockets, the eye is strengthened here with the help of four direct and two oblique muscles that control its movements. The human eyeball has a diameter of about 24 mm and weighs 6 to 8 g. The eyeball is formed by three membranes of the eyeball and is covered with conjunctiva in front.

The wall of the eye consists of three concentric layers:

1. sclera and cornea. Outside the cornea protects the conjunctiva – a thin transparent layer of cells, transient in the epithelium of the eyelids. Conjunctiva does not enter the corneal area covering the iris. The eyelids protect the cornea from mechanical damage, and the retina from too bright light. The outer surface of the cornea is covered with a thin layer of tear fluid.

2. choroid, ciliary body, lens and iris.

3. the retina. The retina is the inner lining containing photoreceptor cells (rods and cones), as well as the body and axons of the neurons that form the optic nerve. In the place where the optic nerve comes out of the eye, the retina does not contain any rods or cones, this place is called a blind spot of the retina. The most sensitive area of ​​the retina, containing only cones, is the central fossa fossa. The beam of light is focused on it most accurately.

The shape of the eye is maintained by hydrostatic pressure (25 mm Hg) of aqueous humor and vitreous.

The outer shell of the eyeball, the sclera, is under conjunctiva. It consists mainly of collagen fibers, usually affected by autoimmune diseases.

Medium, vascular, shell provides the production and outflow of aqueous humor. The defeat of the choroid is most often caused by immunocomplex allergic reactions and allergic reactions of the delayed type.

The inner shell of the eyeball, the retina, consists of nerve elements and is a peripheral part of the visual analyzer.

The conjunctiva is the mucous lining the posterior surface of the eyelids and the anterior surface of the sclera. It consists of epithelium and connective tissue basis. Normally, mast cells (about 6000 / mm-3) lymphocytes and granulocytes are detected only in the stroma of the conjunctiva, directly under the epithelium. When inflammation occurs, for example, in spring conjunctivitis, conjunctivitis with papilla hyperplasia, these cells appear in the epithelium.

Conjunctiva is rich in lymphatic vessels. The lymph flows from the lateral part of the conjunctiva to the parotid lymph nodes located in front of the auricle trestle, from the medial lymph node to the submandibular lymph nodes. The membranes of the eyeball are devoid of lymphatic vessels.

The vascular membrane and its derivatives – the iris and ciliary body – contain a dense network of vessels. The ciliary body produces aqueous humor, which, like urine and CSF, is a plasma filtrate.

In allergic diseases of the eye can affect any of the membranes of the eyeball. Conjunctiva and tear film on its surface are the first barrier to infection, airborne allergens, organic and inorganic compounds.

Eyes: ophthalmologic examination

First examine the eyelids, then the conjunctiva.

When conjunctivitis is defined: edema, hyperemia, hypertrophy of the papillae and follicles on the conjunctiva of the eyelids and the eyeball. The follicles are larger than the papillae, have the appearance of colorless, grayish or yellow grains ranging from tenths to a few millimeters, do not have their own blood vessels. In the center of each papilla, on the contrary, there is a vessel. When conjunctivitis necessarily palpate the parotid and submandibular lymph nodes: their increase is characteristic of infectious conjunctivitis and is not found in allergic conjunctivitis. Then, tearing, presence and character of discharge from the eyes are evaluated. With uveitis and cataract ophthalmoscopy.

Uveitis is often observed in autoimmune diseases, cataracts – in allergic diseases and long-term treatment with corticosteroids.

In the study of the anterior chamber of the eye assess the nature of the aqueous humor. The watery moisture may contain blood, which is evenly distributed in the anterior chamber or settles at its bottom, or pus, which usually settles at the bottom of the chamber. If the anterior chamber is shallow, glaucoma should be suspected. In this case, mydriatics are contraindicated. A rough estimate of the depth of the anterior chamber of the eye is possible with side lighting with a pen-flashlight.

Eyes: diseases, symptoms of diseases

Trichiasis – the growth of eyelashes in the direction of the eyeball – is caused by the deformation of the cartilage of the upper or lower eyelid, which leads to the twisting of the eyelid.
Constant contact of the eyelashes with conjunctiva leads to conjunctivitis, possibly corneal damage.

Tearing can be a consequence of increased production of tear fluid in case of allergies or obstruction of the tear ducts. The latter is often observed in chronic sinusitis and rhinitis. If you suspect a violation of the outflow of tear fluid in the eye instilled 2% solution of fluorescein. Normally, the dye disappears after 1 min.

Subconjunctival hemorrhage occurs with severe friction of the eyelids, vomiting, coughing, straining, often occurs without cause. With frequent subconjunctival hemorrhages, it is necessary to examine the blood coagulation system.

Pingvecula is a yellowish plaque on the conjunctiva of the eyeball, often located medially from the cornea. It occurs as a result of subepithelial deposition of collagen and proliferation of connective tissue, usually asymptomatic. With age, the pingvecula increases. The pinguecula is often confused with pterigia, which is a triangular proliferation of the conjunctiva that crawls onto the cornea from the medial side.

Flicheng – a small infiltrate in the form of a grayish node of a rounded shape, located in the region of the limbus, is often observed with tuberculosis, a staph infection, exhaustion.

Blepharitis is an inflammation of the eyelids.

Chalazion is a chronic granulomatous inflammation of the meibomian gland.

Barley – a small abscess on the conjunctiva or the skin of the eyelid, occurs as a result of purulent inflammation of the sebaceous gland.

Episcleritis and scleritis – inflammation of the outer membrane of the eyeball – sclera.

The amarotic cat’s eye, the white pupil, is observed in cataracts, Chediak-Higashi syndrome, retinoblastoma and retrolental fibroplasia.

Eyes: diseases, side effects of drugs

Side effects of agents used to treat eye diseases.

Beta-blockers for local use prescribed for glaucoma. It is assumed that they reduce the production of aqueous humor in the anterior chamber of the eye, which, in turn, leads to a decrease in intraocular pressure. Betaxolol is used as beta1-adrenergic blockers, – and nonselective beta-adrenergic blockers – levobunolol, metipranolol and timolol.
All beta-blockers for local use can cause bronchospasm, as they, bypassing the liver, immediately enter the lungs. However, beta1-blockers cause this complication much less frequently than non-selective beta-blockers.

Adverse reactions to the on / in the introduction of fluorescein during fluorescein angiography develop in 5% of patients. In 50% of them, these reactions develop repeatedly. Since the frequency of deaths in fluorescein angiography is 1: 220,000, and more than 200,000 such studies are conducted in the United States each year, an average of at least 1 person dies from fluorescein in the United States. When on / in the introduction of fluorescein anaphylactoid reaction develops, which in 2.9% of patients is accompanied by nausea, in 1.2% – vomiting, in 0.2% – hyperemia of the skin and urticaria and can lead to shock. It has been shown that with on / in the introduction of fluorescein increases the level of histamine in serum.

Skin tests to identify patients with a high risk of reaction to fluorescein are not informative. Avoid repeated reactions to fluorescein, using schemes for the prevention of anaphylactoid reactions to radiopaque substances, as a rule, fails.

Glaucoma: causes, symptoms, diagnosis and treatment of glaucoma

The term glaucoma implies an extensive group of diseases that are characterized by:

  • increased intraocular pressure (IOP)
  • damage to the optic nerve head, as well as retinal ganglion cells
  • narrowing the field of view

Glaucoma may occur regardless of age, but is most common in the elderly or senile.

Glaucoma is considered one of the main causes of irreversible blindness in the world according to the World Health Organization (WHO).

Intraocular fluid and ways of its outflow

Intraocular fluid (hereinafter VGZH) plays a huge role in maintaining the level of intraocular pressure. It is one of the sources of nutrition for intraocular structures (lens, cornea, trabecular apparatus, vitreous humor).

It is produced by the VGZH processes of the ciliary body, located behind the iris, and is collected in the back chamber of the eye. Next, most of the liquid, washing the lens, flows through the pupil, enters the anterior chamber and passes through the eye drainage system (trabecula and Schlemm’s canal), which is located in the corner of the anterior tail chamber. From the drainage system of the eye, the VGZH enters the output collectors (graduates), and then into the superficial veins of the sclera.

In this way, about 85% of the intraocular fluid flows, but there is another way of outflow, which flows about 15%.

The HAH may exit the eye, seeping through the stroma of the ciliary body and the sclera into the veins of the choroid and sclera. This outflow pathway is called uveoscleral.

There is a certain equilibrium between the production of IGL and its outflow. If this balance is disturbed, the level of intraocular pressure changes, which is a prerequisite for the development of glaucoma.

Causes and mechanisms of development of glaucoma

Glaucoma is a multifactorial disease, for the development of which a number of causes (risk factors) are needed:

  • heredity
  • individual anatomical features or abnormal structures of the eye
  • pathology of the cardiovascular, nervous and endocrine systems.

Various combinations of these risk factors trigger the mechanism for the development of glaucoma, which can be represented as stages:

  • increased production of intraocular fluid and / or deterioration of its outflow from the cavity of the eyeball;
  • an increase in intraocular pressure (IOP) is higher than the tolerant (tolerable) for the optic nerve;
  • ischemia (impaired blood supply) and hypoxia (lack of oxygen) of the optic nerve head;
  • development of glaucomatous optic neuropathy followed by
  • atrophy (death) of the optic nerve.

Forms of glaucoma

The following main types (forms) of glaucoma are distinguished:

  • congenital glaucoma:
  • primary early congenital glaucoma,
  • infantile congenital glaucoma,
  • juvenile glaucoma,
  • concomitant congenital glaucoma
  • Adult primary glaucoma:
  • primary open angle glaucoma (POAG) – multifactorial disease associated with involutional and age-related changes in the eye)
  • primary angle-closure glaucoma (PZUG) – (the main cause of the disease is the closure of the anterior chamber angle, where the drainage system of the eye is located, by the iris root)
  • secondary glaucoma in adults: (a consequence of other ocular or somatic diseases, in which there is an involvement of structures involved in the production or outflow of IGL)

Symptoms of glaucoma

Predominantly, glaucoma is asymptomatic, and the patient notes a decrease in vision, when already 50% of the optic nerve fibers are permanently damaged.

Non-specific symptoms of glaucoma are:

  • blurred vision
  • pain
  • rez
  • feeling of heaviness in the eyes
  • narrowing of the field of view
  • blurred vision in the dark
  • “rainbow circles” before the eyes when looking at the source of light

Nonspecific symptoms are called because they may be characteristic of other ophthalmologic diseases.
In case of closed-angle glaucoma and the onset of an acute attack, the symptoms are severe: severe eye pain, headache, redness of the eye, nausea, vomiting.

But if any of the above symptoms appear, you should immediately consult a doctor.

Diagnosis of glaucoma

For the diagnosis of glaucoma and determine the method of treatment of glaucoma, it is necessary to conduct a thorough diagnostic examination, which should include:

  • visometry (determination of visual acuity)
  • refractometry (determination of the optical power of the eye – refraction)
  • perimetry (definition of peripheral vision)
  • tonometry (determination of intraocular pressure)
  • biometrics (determining the depth of the anterior chamber, the thickness of the lens, the length of the eye)
  • biomicroscopy (examination of tissues and media of the eye with a slit lamp)
  • gonioscopy (study of the structure of the anterior chamber angle)
  • ophthalmoscopy (fundus examination with assessment of the state of the optic nerve and retina)

Glaucoma treatment

Conservative treatment of glaucoma includes drugs that reduce the production of intraocular fluid and / or improve its outflow, hemodynamic (improves blood flow) and neuroprotective (protecting nerve fibers) drugs.

These drugs are prescribed only after a diagnostic examination by an ophthalmologist.

With insufficient effectiveness of conservative therapy (increased IOP, narrowing of the visual field, progression of optical neuropathy), surgical treatment is indicated.

Surgical treatment of glaucoma is aimed at eliminating intraocular blocks (obstacles) in the path of intraocular fluid movement or at creating a new outflow path.

There are many types of operations for glaucoma, but the most successful are:

non-penetrating deep sclerectomy

– with drainage of the anterior chamber angle

– without drainage of the anterior chamber angle

After cutting the conjunctiva and the formation of superficial and deep scleral flaps, the Schlemm canal’s outer wall is removed, thus enhancing the outflow of intraocular fluid through the drainage system of the eye. Sometimes, in the area of ​​excision of the Schlemm’s external wall, drainage is implanted to enhance the effectiveness of the operation.

The advantages of this operation:

  • painlessness
  • local drip anesthesia
  • atraumatic
  • performed without penetration into the cavity of the eye, which allows to avoid a number of complications (a sharp decrease in IOP, bleeding, detachment of the choroid, etc.)

Non-penetrating deep sclerectomy is a highly effective method for the surgical treatment of open-angle glaucoma.

penetrating deep sclerectomy

– with drainage of the anterior chamber angle

– without drainage of the anterior chamber angle

– with valve implantation

After cutting the conjunctiva and forming a superficial scleral flap, deep scleral layers are excised, then the anterior chamber is opened and part of the iris is excised, which allows the intraocular fluid to circulate freely in the anterior and posterior chambers of the eye. To enhance the efficiency of the outflow of IHL from the eye, a drainage or valve is implanted in the area of ​​the operation.

Penetrating deep sclerectomy is a more traumatic operation, but its effectiveness is indisputable with angle-closure glaucoma and with the ineffectiveness of a previously non-penetrating operation.

It is worth remembering that timely diagnosis and the appointment of adequate conservative or surgical treatment allows you to maintain high vision in patients with glaucoma for a long period.



In reptiles with a final exit to land and the development of a pulmonary type of respiration, completely displacing the branchial branch, the further development of the pulmonary circulation occurs, so that 2 circles of circulation develop: pulmonary and corporal. Accordingly, the ventricle begins to divide the incomplete septum into two sections – the right and left ventricles. In birds, mammals and humans, there is a complete separation of the heart by a septum into 2 ventricles, respectively, in two circles of blood circulation. Because of this, they have completely separated venous and arterial blood: the venous blood flows into the right heart, and the arterial blood flows to the left.

By the nature of the circulating fluid, the vascular system of humans and vertebrates can be divided into two sections: 1) the circulatory system — a system of tubes through which blood circulates (arteries, veins, microcirculatory sections and the heart), and 2) the lymphatic system — a system of tubes, but which is moving colorless liquid – lymph. In the arteries, blood flows from the heart to the periphery, to the organs and tissues, and in the veins to the heart.

The movement of fluid in the lymphatic vessels occurs in the same way as in the veins, in the direction from the tissues to the center. There are, however, significant differences between the nature of the discharge of substances by the venous and lymphatic vessels. Dissolved substances are absorbed mainly by the blood vessels, solids – lymphatic. Absorption through the blood is much faster. In the clinic, the entire system of blood vessels is called cardiovascular, in which the heart and blood vessels are isolated.

Vascular system.

Vascular system.

The vascular system is a system of tubes through which fluids (blood and lymph) circulate through them, on the one hand, supplying the nutrients necessary for them to the cells and tissues of the body, on the other hand, removal of the waste products of cellular elements and transferring of these products to the excretory organs (kidneys). In the intestinal cavity, the digestive cavity gives numerous outgrowths from itself, which facilitates the delivery of nutrients to certain parts of the body. But already in nemertin (a subtype of worms) there appear three separate blood vessels. The lancelet has a closed circulatory system, which is, however, still devoid of heart; the movement of the colorless blood of the lancelet is caused by the pulsation of the vessels themselves. In the circulatory system of vertebrates, the heart appears as a pulsating organ, gradually becoming more complex in its structure during phylogenesis.

The heart of fish consists of two chambers: the blood receptor – the atria, in front of which is the venous sinus, sinus venosus, and the expulsion – the ventricle, followed by the arterial cone, conus arteriosus. Through the whole heart venous blood flows, which flows further through the gill arteries to the gills, where it is enriched with oxygen (gill breathing). In amphibians, due to the beginning of the emergence from water and the emergence along with the gill and pulmonary type of respiration, the formation of the pulmonary circulation begins: the pulmonary artery develops from the last gill artery, which carries blood from the heart to the lungs, where gas exchange takes place. In this regard, the perceiving part of the heart – the atrium – is divided by a septum into two separate atria (right and left), as a result of which the heart becomes three-chambered. At the same time, venous blood flows in the right atrium, arterial blood flows in the left, and mixed blood in the common ventricle. In the larval state, the gill blood circulation functions, in the adult – pulmonary circulation, which reflects the beginning of the transition from the aquatic environment to the air.

Lipids of blood and dyslipidemia

Atherosclerosis of the heart vessels is handled by cardiologists, brain vessels – neurologists ( angioneurologists ), atherosclerosis of the aorta, arteries of the lower extremities – vascular surgeons. In the diagnosis of atherosclerosis, a large role belongs to the instrumentalists who own methods of duplex scanning of vessels, electrocardiography, radiography (magnetic resonance imaging, angiography, contrast research methods, positron emission tomography).

Thus, there are no universal specialists on this issue. There are doctors who are well-versed in the issues of atherosclerosis of one or another vascular region, but in matters of biochemistry of lipids they often have amateurish knowledge. In connection with the above, it becomes clear that patients with atherosclerosis require amultidisciplinary approach and in most cases should be supervised collegially by physicians of different profiles.

To reveal the latent forms of IHD, the samples from the population were sampled on a treadmill and a bicycle ergometer with scrupulous study of ECG features.

The subsequent long-term work at the Institute of the Human Brain of the Russian Academy of Sciences forced to face patients with cerebrovascular disease (CEH).And at them on the first place as the reason of illness acted an atherosclerosis and an arterial hypertensia (AH). This meant the need to delve into the questions of duplex scanning of brachiocephalic arteries, analyze the results of magnetic resonance angiography of cerebral vessels, the data of positron emission tomography of the brain, not to mention the study of the lipid profile of blood in these patients.

In parallel, for many years, we had to be clinically examined for patients with familial hypercholesterolemia, along with geneticists from the Institute of Experimental Medicine

All this allowed us to gain experience that combined individual problems of cardiology, angioedema , lipidology , genetics, to study the clinical, genetic and clinical-biochemical features of patients with dyslipidemia and atherosclerosis.

The concept of lipids, the classification of dyslipidemia

Lipids – fat-like compounds – are part of the blood plasma; for normal functioning they are necessary for every cell of the body. The concept of ” dyslipidemia ” (DLP) appeared in medical literature in the last quarter of the 20th century. Until this time, when describing the lipid composition of the blood, they were most often referred to as ” hyperlipidemia ” (GLP), ie,   that is, o   high cholesterol (CH) or triglycerides (TG). About other deviations from the norm in the lipid composition of the blood at that time was little known.

In addition to cholesterol and TG, lipids include phospholipids (PL) and free (non-esterified) fatty acids (FFA).

ChS, TG, FL in the aqueous medium, which is the blood, are insoluble. To circulate in the plasma (and in these compounds almost all cells are constantly in need), the lipids must have acquired the ability to dissolve in the aquatic environment. This was possible after the combination of cholesterol, TG and PL into complexes with proteins, resulting in the formation of lipoprotein particles – lipoproteins or lipoproteins.

FFA is easier to transport, because they are easily combined with blood albumins and are transferred with them.

J. Gofman et al . (1949) proposed a classification of lipoproteins depending on their behavior in a solution of a certain density under ultracentrifugation . Since that time, lipoproteins (LP) have been divided into classes: chylomicra (CM)   – the largest and least dense particles, very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL). These physical properties of LPs reflect the features of their chemical structure.

The LP particle has a spherical shape, its core is formed by cholesterol- esters and TG, and its environment is made up of molecules of phospholipids and free cholesterol. One end of these molecules is apolarized and facing the nucleus, the other (outer) end of the molecule has a charge, so that it is immediately surrounded by polar water molecules, due to which the LP particles acquire solubility in the aqueous medium, transportability and the ability to be delivered to any cell.

We present a schematic representation of a low density lipoprotein particle – LDL

Apo B-100 is a protein particle, phospholipids, triglycerides, cholesterol esters and unesterified cholesterol are also shown .

Different density of LPs is explained by unequal relations between the content of cholesterol, TG and PL in LP particles, as well as by the quantitative and qualitative characteristics of the specialized proteins, apoproteins, that make up them .

The largest LPs are chylomicrons with a diameter of 80 to 1000 nanomycrons , 95% of which consist of TG and have the lowest density, they remain at the start with electrophoresis in a polyacrylamide gel.

VLDL have a diameter of 30-80 nanomecrons and 60   % consist of TG, contain up to 15   % XC- esters and the same amount of PL, their apoproteins ( apoB , apoS ,apoE ) are 5-7%, with the key protein being apoprotein B-100.

LDL are formed from VLDL under the influence of enzymes, their diameter is less – 20-25 nanomycrons , 40   %   they consist of HS- esters , at 25   % – fromapoproteins , and their main apoprotein – apoprotein B-100 (is 95   %), in small amounts in LDL there are apoproteins apos and apoE . LDL also contain some free cholesterol and 6   % TG. LDL are the main transporter of cholesterol from the liver to the periphery.

Not so long ago, LDLs began to differentiate into separate subfractions (the most atherogenic are small, dense particles), the same applies to VLDL [R Krauss , 1995;Yu.I. Ragino , 2004].

HDL are characterized by the smallest diameter (13 nanomecrons ) and 45   % consist of proteins. The key protein of HDL is apoprotein A-I, it is 65   %, 20   % ofapoproteins represent A-II. The composition of HDL is 20   % Of HS- esters and PL. The main function of HDL is the delivery of cholesterol from the periphery (from the surface of somatic cells) to the liver. At present, several subfractions of HDL (depending on the degree of their maturity) are distinguished : HDL- 2a , HDL-2b and HDL-3, their functional differences are not fully understood.

The most important mission of HDL is not only the capture of cholesterol on the periphery and its transfer to the liver, but also the protection of LDL from peroxidation. It is known that LDL acquire atherogenicity only after its modification (peroxidation and other changes). These most important properties of HDL are proved by the work of AN Klimov and his colleagues and won universal recognition. Since that time, the definition of an antiatherogenic fraction of lipids has been fixed for HDL.

It is necessary to mention separately one more thing about the special fraction of LP-LP (a). It includes LDL, in which apo B-100 is connected by a disulfide bridge with a special protein – apo (a), homologous to plasmin [B. Nordesgaard et al ., 2011]. The elevated plasma content of lipoprotein (a) leads to its accumulation in the vascular wall and is complicated quite quickly by atherosclerosis.

It is necessary to distinguish   primary and secondary GLP.   As for secondary HLP, they are symptomatic and are caused by a certain initial disease. Most often it is diabetes mellitus, hypothyroidism, chronic nephrosis- nephritis or biliary cirrhosis. In most people, GLP can be induced artificially, if the daily diet includes excessive amounts of eggs and animal fats (alimentary GLP). We do not dwell on secondary GLP here.

Under   primary GLP (DLP)   implies genetically caused violations of the lipid composition of the blood, in the genesis of which a greater or lesser role can still play the features of nutrition, physical conditions, and certain concomitant diseases.

Classification of the GLF Frederickson   [D. Fredrickson & R. Lees , 1965] distinguishes 6 types of GLP:   I type – hyperhylomicronemia ,   at which the blood serum acquires a milky white color due to a large number of chylomicrons containing many TG (up to 800-1000   mg / dL and more). When the tube with blood is standing in the refrigerator, XM float up, so that the upper third of the tube forms a creamy layer. Type I GLP is rare, manifested from early childhood, accompanied by severe pancreatitis and hepatolenal syndrome.

IIa type      hypercholesterolemia (HCS)   – characterized by a sharply increased content of LDL, while the content of TG remains normal; at   IIb type (HCS in combination with moderate hypertriglyceridemia )   there is a high level of blood cholesterol, but at the same time the content of not only LDL cholesterol but also cholesterol is increased.

A distinctive feature of type III HLP is a very high level of both cholesterol and TG, as well as the presence of beta-fraction of VLDL.   This fraction of lipoproteins behaves at electrophoresis as LDL, and with ultracentrifugation – like VLDL [A. N. Klimov, N.G. Nikulcheva , 1999]. This type of GLP leads to widespread atherosclerosis, affecting the aorta and most of its branches, so that it can be characterized by aortic aneurysm, intermittent claudication syndrome, ischemic heart and brain disease.

IIa and IIL types of HLP occur in 15-20   % of the adult population in Europe and the US, patients with type III HLP are very rare.

IV type of GLP   is relatively widespread and is mainly manifested by hypertriglyceridemia (significantly increases the level of VLDL); this type of GLP can be complicated by cerebrovascular disease and / or coronary heart disease. Very often in these cases, a violation of tolerance to carbohydrates, and often diabetes mellitus type 2.

Occasionally you can face V   type of GLP.   On the composition of the blood, it resembles type I GLP, but the degree of CGM is less. This pathology is onlydeveloped to 35-40 years and is also characterized by hepatolienal syndrome (although less pronounced than in type I), pancreatitis, and impaired glucose tolerance or type II diabetes mellitus.

Since the end of the 20th century, it became clear that the classification of Fredrickson does not exhaust the whole variety of violations of the lipid composition of the blood, based on the definition of XM, XC, TG, LDL, VLDL. Increasingly, they began to describe such forms of DLP, in which there is no increase in lipid levels, but a decrease in the content of HDL is detected (according to old terminology – alpha lipoproteins). As mentioned above, HDL is the only form of LP, aimed at capturing cholesterol from the surface of peripheral cells and transporting it to the liver for further “processing”. As it turned out, the deficit of HDL is conducive to the retention of cholesterol in the tissues,   it leads to the development of atherosclerosis without HCS.

This form of DLP – a selectively low level of HDL in the absence of GLP – is quite common. This means that a more general definition of lipid lipid abnormalities – DLP – is more correct than GLP, since it covers all variants of these disorders. Thus, Fredrickson’s phenotypic classification should be supplemented by another type of lipid content disorder :   selective lowering of the level of HDL ( hypoalphalipino-proteinemia ).

If we use the term   ” Atherogenicity “   in relation to the types of DLP, that is,   that is, the ability to be complicated by atherosclerosis, the third type of HLP should be considered the most atherogenic, then the Pa, IIL types of HLP (DLP) and the low level of HDL cholesterol (selective reduction of the alpha fraction of lipoproteins) occupy almost equal positions; Step IV is below the type of GLP, and the last place is occupied by the V type.

I type of GLP is not taken into account here,   c. in   mainly found in children and is associated not with heart lesions, but other internal organs (pancreas, liver, spleen).

It should be noted that although such large lipid particles as VLDL characteristic of IV and V types of GLP are not able to penetrate through the interendothelialspaces into the inner shell of the vessels, but after enzymatic cleavage they are transformed into smaller particles – remnants , which too can infiltrate into the intima vessels.

Standard guidelines for lipid composition of blood

It is necessary to distinguish between the norm of lipid parameters characteristic of a healthy person and the target level of the same indicators that should be sought in patients with clinical manifestations of atherosclerosis or with a complex of risk factors for IHD or CEH. In these latter cases, the approach to lipid standards should be more stringent, otherwise it will be difficult to stop the progression of the disease.

When talking about normal blood lipids in healthy people, you also need to take into account gender, age, blood pressure, the Quetelet index , the habit of smoking , hereditary complication of atherosclerosis and its complications. If there are several risk factors for atherosclerosis in an even healthy person, the approach to the lipid profile should also be more stringent. Thus, in healthy, but smoking men with hereditary burden of IHD, leading a sedentary lifestyle, with excessive body weight, blood lipid levels should be more stringent than in a healthy person without these risk factors.

Women, if they do not smoke and do not suffer from diabetes, are much less prone to atherosclerosis, so they will admit a higher level of blood lipids.

With this in mind, the normal limits of lipid blood counts can be defined as “sliding.”

Take, for example, a healthy non-smoker, a man of 40 years of age, of a regular physique (height 180   cm, body weight – 82   kg), leading an active lifestyle, without a hereditary burden of atherosclerosis. For him, the following parameters may be considered normal: total cholesterol – 5.2 mmol / l, TG – 1.3 mmol / l and HDL-C – 1.3mmol / l, LDL – 3.2 mmol / l, wherein the ratio of atherogenic will be 3 units.   . In this series of indicators, only HDL cholesterol corresponds to the ideal norm for a middle-aged man. For patients with risk factors for IHD or CEH or with manifestations of these diseases, it is desirable to have a lower level of total cholesterol than indicated in the previous example,   e. in the presence of signs of atherosclerosis and its complications, lower LDL cholesterol and the atherogeniccoefficient should be achieved .

In women, as indicated, the upper limit of the norm for total cholesterol and LDL cholesterol is higher than in men, but they should have a lower limit for the anti-atherogenic fraction of LP (HDL-C), which is defined as 53   mg / dl or 1.35 mmol / l (in men, this figure should be not less than 1.05 mmol / l or 41   mg / dL ).

In the last decade, lipid and other biochemical indices in millimoles / liter have been estimated , although in the English literature, the concentration of lipids in plasma is still often indicated in mg / dL. There are coefficients of transfer of some units to others. To translate the cholesterol values ​​from mg / dl into mmol / l, their value should be divided by 39, for example, 250   mg / dl corresponds to 5.4 mmol / l (if reverse translation is required, then the cholesterol content in mmol / L should be multiplied by 39). When translating TG from one calculation to another, the coefficient “89” is used. Values ​​of VLDL (Ch VLDL) and LDL (LDL-C) are derived by calculations after biochemical determination of total cholesterol, TG and HDL cholesterol.

If the TG value is given in mg / dl , one-fifth of the TG is taken to obtain the VLDL value: for example, at TG = 250   mg / dL value of VLDL = 50   mg / dl. If the TG determination was carried out in mmol / l, then the fission factor is “2.2,” ie,   ie at TG = 2.8 mmol / l – VLDL content = 1.3 mmol / l.

To calculate the content of LDL (more precisely, LDL cholesterol), it is necessary to subtract the sum of HDL cholesterol and cholesterol LP from the value of total cholesterol. Thus, for a general XC = 250   mg / dL , HDL cholesterol = 40   mg / dL and VLDL cholesterol = 50   mg / dL Calculation of LDL cholesterol is as follows: 250 – (40 + 50) = 160   mg / dl. In calculations in mmol / l, if the total cholesterol content is 6.4 mmol / L, HDL cholesterol = 1.03 mmol / L, and VLDLP cholesterol 1.3 mmol / L, then LDL cholesterol is 6.4 – (1.03 + 1.3) = 4.1 mmol / l.

To assess the atherogenicity of the lipid spectrum of blood, it is convenient to use an additional criterion – the coefficient of atherogenicity . Calculation of this coefficient according to AN Klimov is very simple: we need to take the difference between the values ​​of total cholesterol and cholesterol and cholesterol and divide it by the HDL cholesterol. For example, with a total cholesterol level of 6.4 mmol / L and a cholesterol ratio of 1.03 mmol / L, the atherogenicity coefficient is calculated as a fraction with a difference (6.4-1.03) in the numerator and 1.03 in the denominator, which will be expressed as 5.2 units. Normally, this figure should not exceed 2.5 units.

Mechanisms of development of primary GLP or DLP

Modern ideas about the mechanism of the development of hyperlipidemia would have been impossible without the brilliant works of J. Goldstein & M. Brown (1974-1977), for which they were awarded the Nobel Prize 1985   in

The authors discovered the main pathway for the cellular uptake of LDL: they described specialized LDL receptors that can be incorporated into the membranes of liver and other somatic cells and actively capture LDL from their blood washing. These receptors are synthesized in cellular organelles, transported to the surface of the cell membrane, where, by capturing LDL, they form the “LDL-LDL receptor” complex. With the help of a special transport protein, the newly formed complex moves from the cell membrane inwards, to its organoids, and undergoes processing and utilization therein.

The synthesis of LDL receptors is a self-regulating process. If the cell is in need of cholesterol, the synthesis of LDL receptors is stimulated, and if there is no need for cholesterol in a given time period in the cell, the synthesis of LDL receptors is inhibited or terminated. In other words, the number of LDL receptors on the surface of cells is not constant and depends on the saturation of the CS cell. This is how the physiological process of cholesterol metabolism proceeds with the normal functioning of LDL receptors, intracellular transport proteins that move the LDL receptors to the cell membrane, and the “LDL + LDL” receptor complexes, transported from the membrane to the interior of the cell.

If the synthesis of LDL receptors or the proteins that transport them is disrupted, problems will arise with the capture of LDL from the peripheral blood, which will result in the accumulation of LDL in the blood plasma, ie , will cause HCS.

It should be noted that the normal uptake of LDL by their receptors is only ensured if the structure of the LDL itself is correct. If the LDL structure turns out to be wrong (nonstandard), then the connection with normal receptors is extremely difficult, which will also lead to HCS.

It is necessary to touch here and antiatherogenic fraction of lipids – HDL, which are synthesized in the liver and in the wall of the small intestine. The newly synthesized ( nascent ) HDL are disc-shaped and contain only unesterified or free cholesterol. Under the action of the enzyme lecithin-cholesterol acyltransferase (LHAT), free cholesterol in these particles is converted to esterified . As the cholesterol is esterified, the HDL particles mature and assume a spherical shape, after which they are designated as HDL-2 and HDL-3. Only at this stage, the HDL acquire the ability to take the cholesterol from the peripheral cells and transport it to the liver.

With a sufficient number of normally functioning HDL particles and a physiological process of entrapping these particles with the liver (in harmony with properly functioning LDL receptors) , a normal cholesterol exchange is provided between the liver, blood plasma and peripheral tissues.

Types of genetically determined dyslipidemia

All primary DLPs have a genetically determined nature. However, it is necessary to differentiate the classical family forms of HCV or DLP (monogenic GLP)and such forms of HCV or DLP that are associated only with a hereditary predisposition to this pathology (polygenic DLP). The development of the latter largely depends on environmental factors – nutritional conditions, physical activity, certain concomitant diseases (metabolic syndrome, diabetes, obesity, etc.).

Classical family forms of DLP (monogenic), as a rule, appear from childhood, when one or both parents bear the “main” mutant gene for this pathology. A similar gene plays a leading role in the “ensemble” of genes involved in the exchange of lipoproteins. These genes are designed to regulate the production and structure of one of the core lipoproteins (LP) or the structure and function of specialized lipoprotein receptors, or protein transporters, sometimes enzymes that perform their synthesis or cleavage.

The mutant gene is often transmitted from one of the parents, i.e. , the defect is of a heterozygous character Much less common are cases where a mutant gene is inherited from both parents, that is , the defect has a homozygous nature. In this case, the pathology manifests itself in early childhood and proceeds very hard.

To understand the laws of inheritance, one must imagine that for some genetic defects, dominant inheritance is characteristic for others – recessive. Passed to the heir, the dominant gene sooner or later will manifest itself, although it is inherited from one of the parents. The recessive gene manifests itself as a violation in full force if it is inherited from both parents. If the recessive gene is transmitted to the offspring only from one of the parents, then the heir becomes only the carrier of the pathological gene. For such a gene to manifest itself clinically, a “conjugal meeting” of this person with another carrier (carrier) of the same recessive gene is necessary. Only then in a part of their descendants the disease manifests itself clinically. Homozygous “heirs” in such families are born with a frequency of 25          %, heterozygous – (carriers of one mutant gene) – with a frequency of 50 %, finally, 25 % of offspring in such a marriage can not get a pathological gene and does not differ from individuals from a healthy population.

We present figure 2 (schematic diagram of the hereditary transmission of familial HCV), which shows the path of transmission of a heterozygous dominant mutation (male faces are designated by squares, female faces are circles). Carriers of the mutant gene of the family HCS in this figure have a two-color characteristic.

In families where one of the parents has a dominant mutant gene (causing HCS), and the second parent has a healthy set of genes, the probability of inheriting a pathological dominant gene, as mentioned, is 50   %. In other words, half of the descendants in such a marriage can expect the birth of ” heterozygotes ” with family HCV.

So, primary DLP can be caused by one “main” mutant gene (monogenic family DLP), and the mutations of this gene may be different, that is , they are heterogeneous.

In most cases, birefringence is the primary consequence of the interaction of several nucleotide polymorphisms in the ensemble of secondary polygenes , involved in the regulation of lipid metabolism.    it   polygenic DLP in families with a hereditary predisposition to DLP, to which unfavorable environmental factors (for example, excess animal fats and cholesterol in the diet, etc.) or aggravating co-morbidities (metabolic syndrome, diabetes, obesity) are added.

If the appearance of DLP with monogenic family inheritance is unavoidable, the development of DLP with the inheritance of nucleotide polymorphisms does not necessarily occur.

Monogenic (Family) WCT

Let us first consider specific types of monogenic DLPs.

For our latitudes, the most common family HCS is due to deficiency or defect in LDL receptors in liver and other somatic cells or their low functional activity (due to structural defect). The consequence of this is the accumulation of LDL particles, the main carriers of cholesterol, in the circulating blood.

With relatively frequent heterozygous forms of familial HCV (1 case per 500 population), the blood cholesterol level in these individuals usually ranges from 8-10 mmol / l (350-500 mg / dl ). In rare cases of homozygous familial HCV (1 case per 1 million inhabitants), the blood cholesterol level reaches 15-20 mmol / l (650-1000 mg / dL ).

The nucleotide chain of the gene for the LDL receptor consists of approximately 45,000 nucleotides. It is necessary to assume that in its construction the probability of “error” or mutation is quite high, and these “failures” can occur in different parts of the nucleotide chain, are able to “fix” and be inherited. About 1500 variants of mutations leading to familial HCV and causing disruption of the activity of LDL receptors are described.

One of the variants of this mutation is quite widespread among the Eastern European Jews – “Ashkenazi”, whose ancestors were from Lithuania, because of what the mutation was called “Lithuanian”. Interestingly, among the Jews of Spanish descent – long-established inhabitants of the Mediterranean ( Sephardic Jews ) – a “Lithuanian” mutation is not found.

Among French-Canadians and residents of South Africa with Dutch roots, the frequency of this disease is very high (1 case per 100-300 people), which was called the “effect of the founder.” This is explained by the fact that in a relatively limited population there are mainly only “internal” marriages, that is , this ethnic group almost does not mix with the wider population, which increases the chance of genetically determined pathology.

Mutations of familial HCV associated with a defect in the gene for LDL receptors arise in one of the genetic loci of the 19th chromosome.

Another variant of familial HCG is characterized by a breakdown in the structure of apoprotein B-100, a key protein of LDL. In this case, normal LDL receptors poorly recognize LDL and bind to them poorly, since apo B-100 is a ligand (linker) of LDL receptors. The gene that controls the structure of apo B-100 is located in the 2 nd chromosome. The mutation of this gene entails a defect apo B-100, which will lead to a bad evacuation of LDL from the circulating blood. This is another version of the family HCH. This type of mutation is most often found among peoples inhabiting the countries of Western Europe.

Both described variants of familial HCC have the character of dominant mutations.

A third (rare) species of familial HCV is described, which is autosomal recessive (ARH). The mutation was discovered in one Lebanese family and was called “Lebanese”. The mutation is localized in one of the genes of the 1 st chromosome. This gene is “responsible” for the synthesis of the transport protein that carries the LDL + LDL receptor complex from the surface of the hepatic cells inwards to the organoids that must be utilized for LDL. If the transport protein is not capable of transferring the LDL + LDL receptor complexes into the cell, they accumulate on the membrane and block further LDL binding. A consequence of this will be a delay in LDL in peripheral blood, i.e. HCS.

Recently opened one more – the 4th       type of monogenic autosomal dominant mutation, also leading to familial HCV. This is the result of a mutation in one of the genes of the 1 st chromosome, which controls the synthesis of the enzyme ” subtilisin-kexin- type 9 -protein-convertase ,” designated as PCSK-9. Depending on the nature of its structure, this enzyme can either inhibit or stimulate the activity of LDL receptors. In the case where PCSK-9 is produced with increased affinity for LDL receptors, the activity of these receptors will be inhibited, which will lead to HCS.

Interestingly, the mutation of this enzyme may also be directly opposite to that described above. As a result, the affinity of PCSK-9 for LDL receptors will decrease, they (LDL receptors) will be very active, which will cause a decrease in the level of LDL and cholesterol. In this case, we can talk about a mutation with a positive sign, which will provide resistance to the development of atherosclerosis.

There is also a monogenic mutation associated not with GLP, but with dyslipidemia (DLP) without HCS, leading to widespread atherosclerosis due to the very low content of anti-atherogenic fraction – HDL in blood plasma. This rare endemic disease is the Tangier disease, which is common in one of the islands in the Western Atlantic. The disease develops as a result of a homozygous mutation of a gene located in the 9th chromosome and encoding the synthesis of the transport protein ABCA-1. This protein serves as a specialized intracellular carrier of free cholesterol to the key apoprotein of HDL – apo    A1. If an ABCA deficiency occurs in the body, the formation of mature, functionally active forms of HDL is blocked. In addition to the shortage of transport protein (ABCA-1), the content of the A-1 and A-II apoproteins , the key HDL proteins, is also significantly reduced when Tangier disease , without which their synthesis is impossible.

Deficiency of HDL-3 and HDL-2 dramatically reduces the reverse transport of cholesterol from the surface of peripheral cells to the liver. Cholesterol is delayed in tissues, including accumulation in the vascular wall, which leads to the formation of atherosclerotic plaques, although HCS does not develop in this case.

In the literature, other homozygous mutations associated with defects in other sterol transport proteins are described , such as ABCG-5, ABCG-8. With the broken structure of these proteins, the release of sterols from cells is greatly hindered [K. Berge et al ., 2000].

As a rule, such defects are accompanied by increased absorption of plant sterols [J. Horton et al ., 2002], which leads to sitosterolemia , although HCS is absent. Since the necessary protein carriers of sterols are small, the ability of the sterols to be released in the body, which gradually accumulates in the liver, is impaired. This entails suppressing the synthesis of LDL receptors, which in the future can also cause HCS.

Dyslipidemic states characterized by a selective decrease in HDL level (without HCV and without GTG) are quite common in all regions of the world, although they are not related to Tangier disease. When heterozygous carriers of the defective gene ABCA-1 Tangier disease does not develop, but the HDL-fraction content is clearly reduced, which makes these people vulnerable to atherosclerosis [MU Mandelstam, VB Vasiliev, 2008]. Even one pathological allele of the gene that controls the synthesis of the protein ABCA-1 can have a negative effect on this transport protein and make it insufficiently functional.

In some cases, the deficit of HDL is developed as a result of an anomaly in the structure of the genes controlling the synthesis of lecithin-cholesterol acyltransferase (LHAT), the participation of which is necessary for the esterification of free cholesterol. This defect arises as a result of polygenic pathology with a combination of several functionally significant nucleotide polymorphisms (in several genetic loci).

Another monogenic (genetically determined) recessive defect is the cause of a rare form of dyslipidemia – abetalipoproteinemia . In this type of DLP, the synthesis of apoprotein B is disrupted , the formation of LDL particles is sharply inhibited and the level of cholesterol and blood TG is reduced. Although in this case the soil for the development of atherosclerosis disappears, serious violations from the central and peripheral nervous system develop, since the extreme deficiency of LDL primarily affects trophic nerve cells and their processes.

Of the other little-known monogenic defects associated with the development of DLP, one can point to a mutation in the gene controlling the production of the scavenger- receptors. The function of these cell formations of the liver is to capture the HDL-returning HDLs loaded with cholesterol, which they brought from the periphery. If the function of the scavenger- receptors is disrupted, HDL – PI poorly penetrate the liver, their concentration in the peripheral blood rises, but the function is paralyzed, since they are loaded with cholesterol up to the limit and can no longer perform their anti-atherogenic mission [D. Osgood et al      ., 2003]. The level of total cholesterol is increased. Thus, sometimes you have to deal with patients who have a lot of HDL, but functionally they are inactive. In other words, there are individuals with a high content of HDL particles, and their protection from atherosclerosis is at a very low level.

A similar situation occurs with genetically determined triglyceridylase deficiency , which does not cleave TG, does not release HDL from them, which greatly inhibits the anti-atherogenic function of these particles [R. Hegele et al ., 1991].

The poor performance of HDL can be associated not only with their deficiency, but with the genetically determined pathology (deficiency) of transport proteins transporting lipids. For example , if transport protein such as CETP lacks (carries cholesterol esters and TG), it is difficult to mobilize esterified cholesterol from HDL, these particles are enlarged, overloaded with cholesterol, and instead of acceptors, cholesterol becomes its donors [ILLUMINATE, 2006]. The concentration of cholesterol in the peripheral blood is up to 70 mg / dl (1.8 mmol / l) and higher. Again, with this example, one can ascertain that the not always high content of the antiatherogenic fraction of lipoproteins (HDL) in      The circulating blood guarantees protection against atherosclerosis. We observed one such patient.

We quote our observation:

Patient S., 65 years old (1995 ). In March 1995 , the patient suffered an acute myocardial infarction on the anterolateral wall of the left ventricle. When examined at home 3 days after a heart attack (the patient refused hospitalization), the patient’s condition is satisfactory, the pulse is 60 beats / min, BP = 140/80 mm Hg. Art. In the anamnesis – many years of hypertension, irregularly taking antihypertensive drugs. In 1980 (at the age of 50) suffered a first myocardial infarction. In May 1995 , when the blood lipid profile was studied, the total CH = 308 mg / dl (7.9 mmol / L), CT = 185 mg / dl (2.1 mmol / L), HDL-CI = 91 mg / dl (2 , 3 mmol              / l), LDL cholesterol = 180 mg / dL (4.6 mmol / L), the atherogenicity coefficient is 2.4 units.

SUMMARY. Despite the very high level of HDL cholesterol (91 mg / dl ) and the normal coefficient of atherogenicity , the patient suffered myocardial infarction twice. There is every reason to assume that the HDL particles in this patient do not fulfill their intended role. These particles are many, but they are functionally, apparently, inferior.

There are other forms of genetically determined dyslipidemia , for example, combined hyperlipidemia , in which the level of both cholesterol and TG is increased. This type of DLP (HLP) results from the mutation of a gene that controls the synthesis of transcriptional DNA, which is described as the Upstream Stimulatory Factor (USF-1). It is also a monogenic mutation, in which the elimination of VLDLP, and hence the TG, from the circulating blood is mainly disturbed. For the first time, this mutation was identified in Finland and, in its heterozygous variant, apparently causes THG in individuals with a metabolic syndrome. The authors who described this mutation [P. Pajukanta et al        ., 2004], consider USF-1 as a regulator of the work of other genes, which by means of RNA encodes the synthesis of a number of proteins participating in the exchange and transport of apoproteins A-2, C-3, E, ABCA-1, etc.

Special attention is required to assess the genetic determination of apoprotein E. According to researchers from South Korea [N. Oh et al ., 2008], several isoforms of apoE ( apo E-2, apo E-3, apo E-4) have been identified , which can occur in different combinations, depending on the genetically determined genotype. It was found that in the majority of practically healthy individuals who do not have DLP, the genotype E-3 / E-3 (homozygous) or the E-3 / E-2 or E-3 / E-4 (heterozygous) alleles is usually found. In some cases (due to the presence of certain nucleotide polymorphisms in some genes) genotypes E-2 / E-2 or E4 / E4 are formed, at which defective  apoproteins E [D. Betteridge & J. Morrell , 2003]. In some cases, there is a predisposition to the development of severe combined hyperlipidemia , close to type III according to Fredrickson’s classification . In the future (with age) in persons with similar disorders, there is a high probability of developing dementia or conditions close to Alzheimer’s syndrome.

At the 79th congress of the European Society for the Study of Atherosclerosis in Sweden (2011), Spanish researchers [M. Solancs et al .] Reported two mutations that they found in 9 patients with type III HLP (they designated them as R136S and AL149).

Of the monogenic mutations, one often encounters familial HCV associated with deficiency of LDL receptors or disorders in the structure of the LDL particles themselves.

Polygenic DLP

Population surveys aimed at detecting dyslipidemic conditions primarily identify primary DLPs that are polygenic, that is , caused by genetically determined nucleotide polymorphisms that create a hereditary predisposition to these conditions.

A survey of adults in cities in the European part of Russia revealed 15-20 % of individuals with such disorders, which are realized in conditions of additional unfavorable environmental factors, for example, it can be a diet containing many animal fats, sugary products; sedentary lifestyle; smoking; stress, etc.

Admittedly, controlling the lipid composition of blood with diet and medications is much easier with polygenic DLP, whereas monogenic DLPs are more difficult to treat therapeutically.

As for the manifestations of polygenic DLP, it is most often a moderate HCS or hypertriglyceridemia (THG in the range 2.0-2.5 mmol / l).

If the pathological significance of HCS is not in doubt at present, there is no single point of view regarding the harmful effect of a moderate increase in blood TG levels. In the modern literature, more and more works in which the pathological significance of postprandial THG is attached , ie , an increase in the concentration of TG in the blood plasma after 1-2 hours after eating. It should be borne in mind that the main carriers of TG are VLDL, which are the main substrate for LDL production, the main culprit in the process of lipid infiltration into the vascular wall after its modification.

Reciprocal relationships between TG and VLDLP, on the one hand, and HDL, on the other, have been established. The higher the VLDL level, the lower the HDL content. It’s not for nothing that the latest guidelines on lipidology suggest that we talk not so much about LDL cholesterol as an indicator of the risk of atherosclerosis, but about cholesterol not related to HDL. This cholesterol is calculated as the difference between the total cholesterol and the amount of cholesterol-VLDL, intermediate-density lipoprotein cholesterol (LDL), and LDL cholesterol. It is even easier to calculate this atherogenic cholesterol index as the difference between total cholesterol and HDL cholesterol [ESC / EAS Guidelines , 2011]. It is this cholesterol that is the reference criterion for assessing the pathological significance of HCV.

Clinical manifestations of dyslipidemia

The most severe homozygous monogenic forms of hypercholesterolemia usually begin to appear from the age of 5-7 when the child develops yellowish spots that rise above the skin – xanthomas – on the extensor surfaces of the hands, in the region of the elbows, and sometimes in other parts of the skin, for example, in the gluteal region . In the older age tendon xanthomas are formed in the area of ​​metacarpophalangeal joints and Achilles tendons 

There is also a deposition of cholesterol-containing formations in the eyelid region, which are known as ” xanthelasm “. Already in childhood have homozygotes with hypercholesterolemia observed lipoid arc of the cornea, which can be seen at the edge of the iris in the form of rings or poluduzhek top, sides, or bottom, being provided between the arc or semicircle cholesterol ringlet and the edge of the iris can be seen free from cholesterol rim (Fig. 3 ). All these are typical “tags” of congenital monogenic HCV.

Determination of total cholesterol in the blood plasma reveals extremely high rates – 15-20 mmol / l (600-800 mg / dL ). By the age of 15, such an adolescent often has a systolic murmur in the aortic aortic cavity, less often a carotid artery, as the cholesterol deposits begin to enter the vascular wall and atherosclerotic plaques form.

We give a rare example of family number 2, in which heterozygous GLP IIa type was in both parents (not related by kinship). The youngest daughter inherited a mutant gene from one of the parents, that is , it can be characterized as a heterozygote for a family HCV, the eldest son obtained mutant genes from both the mother and the father, ie , became the owner of a homozygous HCV.

A patient, K., born in 1935 , who underwent two myocardial infarctions, who had a high HCV (446 mg / dL ), was proband for this family, and his sister, Valentin P., was invited to the survey r. She had no complaints about her health, but the bright circular lipoid arches of the cornea attracted attention . A study of blood lipids found HCS (480 mg / dL ). The husband of Valentina – EP, 1939 b. also had lipoid arches of the cornea and was treated for intermittent claudication;          the   His blood cholesterol was determined at 450 mg / dl. He died suddenly, at the wheel of a car, at the age of 52. At the son – Konst . P., 1965 b. – There were large xanthomas on elbows, in the area of ​​metacarpophalangeal articulations and Achilles tendons, and lipoid arches of the cornea. On the aorta, a rough systolic murmur was heard, as in the stenosis of the aortic orifice.

His blood cholesterol fluctuated within the “astronomically” high values: 1500-2000 mg / dL (more than 25 mmol / l!). At the age of 18, the young man suddenly died. Autopsy revealed widespread atherosclerosis of the aorta and coronary arteries.

Daughter – Nat . P., 1975 b. had no clinical markings of HCV (it did not have either xanthoma or lipoid arches of the cornea), total blood cholesterol = 274 mg / dL (7.0 mmol / l). She developed normally, got married, gave birth to a healthy child. At mother Konst .    and   Nat . Valentine P., despite the very high level of blood cholesterol, up to 70 years of age, the state of health remained quite satisfactory.

SUMMARY . A unique family is represented here, in which husband and wife, not being relatives, had a heterozygous HCV. In the family, two children were born, of whom the son was a homozygote for the family HCS, the daughter – a heterozygote . At the son the level of HS of blood reached an incredibly high level, which gave clinical symptoms from childhood in the form of multiple xanthomas , lipoid arches of the cornea, early-formed aortic stenosis and coronary atherosclerosis. It is not surprising that this young man had a lethal outcome at the age of 18. These data are confirmed by a pathoanatomical study.

The daughter of this family, although the concentration of cholesterol in the blood plasma was elevated, the level of HCS was much lower than that of both parents and the brother, so that until the adulthood, she did not have any clinical manifestations of HCV.

It is noteworthy that men in this family (both son and father) passed away at a young age, whereas women, despite the HCV, exist quite safely and have no serious complications. The example of this family demonstrates the importance of the gender factor for the prediction of patients with heterozygous HCV, although this is not always the case. This is in part true only for heterozygous forms of HCV.

It has already been pointed out that in a certain percentage of cases where both parents have a heterozygous form of HCV, healthy children (without a pathological gene) may be born, but the probability of having children with a heterozygous form of HCS is higher (less high with a homozygous form of HCV).

It is better to learn that the child has inherited the mutant gene of HCS from an early age to start preventive activities since childhood. For this purpose, in families where one of the parents (especially both parents) has HCS, one must take the umbilical cord blood of a newborn baby to study the lipid spectrum.

If it is a heterozygous HCV, clinically it most often manifests itself after 20 years (in women – much later). In heterozygous children in such families, there are usually no typical typical HCV labels, mentioned above ( xanthoma , lipoid arches of the cornea), but they can appear in adulthood. The level of blood cholesterol in these cases varies in the range of 8-10 mmol / l. Clinical signs of developing atherosclerosis in the aorta, in the vessels of the heart, in the carotid arteries in these individuals begin to be detected by the age of 35 (with homozygous forms of HCS – from childhood).

Occasionally there are such monogenic forms of hyperlipidemia , in which not HCS acts, but other disorders, for example, GTG or hyperchylomicronemia ( CGM ).

We give an example:

In the 1980s, we observed a girl with GXM, whose parents were practically healthy, but both of them appeared to be carriers of the recessive gene of CGM. The daughter inherited from both her mother and her father one recessive gene from the CGM. The disease manifested itself from early childhood. The serum of the girl’s blood was turbid, contained a thick layer of XM, which was biochemically expressed in extremely high Tg levels, which reached several thousand mg / dl (25-30 mmol / l). Already at the age of 2, the child had acute pancreatitis, because of which children’s surgeons performed laparotomy. The girl was on a special diet, took a set of digestive enzymes and for some time felt satisfactory. When palpating the abdominal cavity, there was a significant increase in the liver and spleen. The further destiny of the girl (after 14 years) is unknown to us.

SUMMARY. The parents, each of which was the carrier of only one recessive mutant gene (heterozygous carriers of the gene), had no clinical manifestations of the disease. But their daughter inherited 2 recessive mutated GKM gene (that is, it turned out to be a homozygote for a mutant gene), so that the disease manifested itself in full force and led to repeated acute pancreatitis, hepatolienna syndrome and disability .

In cases with genetically determined STT type IV, the first clinical manifestations usually occur by the age of 40 when tolerance to carbohydrates is violated and type 2 diabetes mellitus develops, and then signs of cerebral or coronary artery atherosclerosis appear.



Cholesterol refers to organic compounds, lipids that enter the body with food, as well as synthesized liver. One of the types of natural fatty alcohols, cholesterol is needed to ensure the normal life of a person.

Excess cholesterol in the blood – the primary link in the process of atherosclerotic, or cholesterol, plaques in the blood vessels. Normally, the level of total cholesterol found in the blood as an element of lipoprotein is in the range of 3.6-5.2 mmol / l, and with age due to physiological processes the upper limit of the norm increases depending on the age and the sex of the patient. With more indicators exceeding the upper limit, the risk of atherosclerosis increases, significantly increasing when the index reaches 6.2 mmol / l and more.

Circulating in the blood, cholesterol, with its excess, has the property of sticking together and accumulating in the arteries. Clumps or plaques obstruct the movement of blood, creating obstacles to blood flow and narrowing the lumen of the vessels, which causes oxygen starvation and insufficient blood supply to tissues and organs. With the disintegration of some of the plaques contribute to the formation of a thrombus, which provokes thromboembolism, heart attacks, strokes and can lead to death.

However, also, as an excess, the lack of cholesterol is dangerous. This compound, for example, is one of the important advantages of breastfeeding: cholesterol is important for the development of the brain of infants, affects the production of essential hormones, bone-muscle, immune, reproductive systems, and in substitute compounds, its content is significantly inferior to mother’s milk. Other important functions of cholesterol include:

ensuring the strength and elasticity of cell membranes;
the necessary component of the synthesis of cortisone, vitamin D, the regulation of the balance of phosphorus and calcium in the body;
participation in the functioning of the nervous and immune system;
protection of blood cells (erythrocytes) from the effects of various types of hemolytic poisons;
the necessary component for the production of hormones of the reproductive system, etc.
A lowered level of “good” cholesterol leads to sexual and reproductive disorders, inability to conceive, loss of libido, and also to depressive states with a high probability of suicidal outcome, digestive disorders, development of osteoporosis, diabetes, hemorrhagic stroke. Because of the danger of lowering the level of total cholesterol in the blood when taking statins, experts recommend changing the diet, lifestyle and trying to lower the level of cholesterol without medications. To do this, you need to know the techniques that help reduce cholesterol without drugs, and what foods reduce cholesterol in the blood, and which, on the contrary, increase.