The level blood pressure in the healthy people it is the very stable value. The stability of blood pressure is supported complicated complex by regulative systems. Hayton (1974) has divided them into two groups – hemodinamic system and regulating system.

The hemodinamic systems are represented by two parameters:

· СO – cardiac output (minute volume of blood, that is amount of blood, which heart throws out in circulation for 1 minutes);

· PR – peripheral resistance, that is resistance arterial vessels, mainly – arterioles, movement of blood.

· The level arterial pressure is determined on the basis of equation Puazel: AP = СO х PR, that is it directly proportional to an cardiac output and peripheral resistance.

In the healthy person both these values – cardiac output and peripheral resistance – stay in inversive relation. If in the certain conditions the cardiac output is increased, the peripheral resistance accordingly decreases. Owing to opposite shifts of both values average hemodinamicpressure remains within the limits of physiological boundaries. In case of decrease of an cardiac output the peripheral resistance increases, and average hemodinamic pressure is again saved normal.

The regulating systems two varieties regulative mechanisms – system of short-term operation and system of durablis action belong. The system of short-term action is represented by two mechanisms. The first from them it is baroreceptors and chemorecerptors of aortas arc and sinucarotid zones, which, devices react to acute increasing or lowering blood pressure. The impulses from receptors achieve vasomotorial centre in medulla oblongata and reticular formation. From aorta arc they go to depressor nerve of Ludvig-Cion, from sinucarotid zones the excitation gets brain through ramus sinus caroticus (nerve Hering). From brain efferent signals through cholinergic and adrenergic fibres get to periphery and regulate lumen of arterioles, frequency and force of beat veins capacity. So the correction of arterial pressure is carried out. The second outline system of short-term operation consists of three components: renin –angiotensin ІІ – arterioles. It counteracts to acute hypothension. The system of  durablis  operation is represented of two final effectors substances –angiotensin ІІ and aldosteron.

Regulation of arterial blood pressure. The kinds of arterial hypertension.

In the healthy people arterial pressure is within the limits of 100/60-139/89 mm Hg. Despite of difficult complex regulation, in many cases arterial pressure is increased or decreased. High arterial pressure is called hypertension, low – hypotension. Arterial hypertension is constant and prolonged increase arterial pressure. It is selecting two stages arterial hypertension: boundary hypertension and fixed (stable) hypertension. Boundary hypertension is called such state, when the pressure periodically achieves values of 140/90-159/94 mm Hg or constantly stays in this range. If arterial pressure achieves level of 160/95 mm Hg or exceeds these digits, it is regarded as stable, fixed hypertension.

Arterial hypertension divide on two groups – primary and secondary. Primary arterial hypertension is called still essential hypertension, or hypertonic illness. It is separate nosological unit. Its consist above 80 per cent all arterial hypertensions. The second group consist secondary hypertension. On them it is about 20 per cent of hypertensions. It is not separate nosological unit, and only symptoms of some diseases (from this one more name – symptomatic hypertension).

Etiology and pathogenesis of hypertonic disease

To  problem the disease   hypertonic  to approach easiest on the basis of the analysis already formula, known for us: AP = СO х PR.

All influences, which are capable to increase cardiac output or peripheral resistance, it is possible to consider as etiological factors of hypertonic disease. To major etiologicalfactors belong the following: increase  of plasma volume, increase cardiac output, increase activity of sympathetic nervous system, alteration  of kidneys functions, increase peripheral resistance, hereditary predisposition.

Increase of plasma  volume   is connected with accumulation of the salt in organism. It is possible in consumption plenties of salt, or in insufficient selection it by kidneys (for example, kidney insufficiency). It is considered, that the long consumption 5 g of salt per day can cause hypertension in the people, which   have hereditary predisposition.

The following scientific observations testify to a role NaCl in occurrence arterial hypertension. The Japanese population, which lives on sea coast, every day consumes salt in increased amount with water and food. Among this population is observed very high morbility by hypertension (40 % of the adult population the after 40 years). At the same time among the population, which lives in mountainous district and consumes less salt, the level of morbility from hypertonic disease does not exceed 2 %, that is in 20 times is lower. On the other hand, that lower-salt diet influences positive medical effect at the patients.

Salt promotes some mechanisms. Owing to accumulation  of sodium, volume of extracellular liquid (including – circulatting blood) is increased, follow the cardiac output increases and as a result is increased arterial pressure. Compensator response on increase of plasmas volume is the limitation blood circulation through the organs, and it is achieved by increase resistance of peripheral vessels and increase pressure. The accumulation sodium and water in walls of vessels is results of thickening the walls and decrease lumen of vessels. Finally, the accumulation of sodium in walls of vessels is results of increase sensitivity myocytes to pressor agents, in particular to  angiotensin ІІ.

Increase of cardiac output. The increase volume of plasma increases cardiac output secondaryly. However there are factors, which are capable directly to increase cardiac output. Among them – emotional stress, hyperthyroidism. All these states are accompanied by activation sympathetic nervous system. Stimulation of cardiac activity is carried out through β-adrenoreceptors   of  myocard on adrenaline acts. It increases stroke volume. In combination with increase cardiac rate  it lead to signiticant increase of cardiac output.

Increase sympathetic tonus. One of the factors responsible for development essential hypertension, can be increase of activity sympathetic nervous system. This hyperactivity has effect for functions of some organs, which can be considered as a targe sympathetic influences. To this group belong heart, arteries, veins and kidney. Heart changes the activity on the already stated above mechanism: the frequency of cardiac rate is increased, stroke volume of blood is increased and in a result the cardiacoutput is increased.

In pathogenesis of arterial hypertension the special place belongs small-sized arteries-arterioles. They are named  vessels of resistance or taps of vascular system. The most characteristic property of these vessels is the very high resistance to blood circulation, for want to it is supported the proper level of arterial pressure.

The high resistance to blood circulation in arterioles is provided with some structural and functional features them, named: а) a small lumen – 15-70 microns; b) a thick layer smooth ring muscle; c) the wall of arterioles stays in a state continuous tonus.

Regulation of peripheral resistance and arterial pressure – main function of resistance vessels.

The influence of sympathetic  nerves to arterioles is carried out by two ways –direct and mediated. From the terminations sympathetic nerves is selected  noradrenaline. It acts to α1-adrenoreceptors of vessels and narrows them. In such a way it increases peripheral resistance, and arterial pressure.

Other mechanism consists in activation of adrenal gland medullar layer, where are synthesized catecholamins – adrenaline and noradrenaline. The level of blood pressure will depend from issue them simultaneous and of different direct action of both hormones to cardio-vascular system: а) noradrenaline through α1-adrenoreceptors of resistance vessels increases them tonus, peripheral resistance and arterial pressure; b) adrenaline excites β-adrenoreceptors of myocard, increases cardiac output and in such way increases blood pressure; c) simultaneously adrenaline acts to β-adrenoreceptors vessels dilatates throught them and decrease blood pressure.

The development of arterial hypertension is possible only by following ratio to effects of noradrenaline and adrenaline: increase of pressure by stimulation vessels β-adrenoreceptors by noradrenaline plus increase of pressure, stimulated β-adrenoreceptors of myocard by adrenaline, in the sum should exceed decrease pressure connected to action adrenaline to vessels β-adrenoreceptors. But such situation develops only at 20 percent of the patients with hypertonic disease.

Noradrenaline increases tonus not only the arteries, but also the veins. In their walls is present smooth muscle too. The narrowing of veins causes redistribution of blood from venous vessels to arterial. The volume of circulatting blood is increased, the cardiac output is increased and the peripheral resistance is increased.

Kidneys functions disturbance. Long spasm of arterioles includes the renals factor of progressive and stabilization hypertonic disease. The narrowing of arterioles is results of pressure falling in renals capillaries. In the answer the synthesis and selection in blood of proteolytic enzyme rennin is increased.

Renin is synthesized by juxtaglomerular apparatus, which consists of three  structures (parts): а) endothelium of afferent arterioles of renals glomerule; b) epithelioids cells near glomerules, which surround afferent arteriole; c) the dense stain (macula densa) – epithelial cells of a segment distal  convoluted renal tubules, which envelop  afferent arteriole as cuff.

Active renin represents proteolytic enzym with molecular weight 42 KDa. It influences on α2-globulin (angiotensinogen), which is synthesized in a liver.  Renin breaks off leicin-leicinous connection in a molecule of angiotensin and transforms it in angiotensin І(decaprotein). Angiotensin І is not active absolutly. It influences  angiotensin converting enzyme, which is located, mainly, in lung. This  enzyme separate from angiotensin І histidilleicin also transforms it in  angiotensin  ІІ (octaprotein). Angiotensin ІІ – very powerful pressor agent. In blood it is not stable. Under influence enzyme of angiotensinases  it loses asparagin acid and turns in angiotensin ІІІ (hectaprotein). It occurs mainly in kidneys. The function  of angiotensinases is executed by many proteolytic enzymes – tripsin,  hemotripsin, pepsin, aminopeptidase. The activity of angiotensin ІІІ makes 30-50 percent activity angiotensin ІІ.

The  action of angiotensin ІІ is very diverse. It includes set of mechanisms, which increase blood pressure and stabilize arterial hypertension. Major of them: а) direct action to specific receptors  of vessels smooth muscles; b) mediated action through the central nervous system – some sites   of  brain trunk are sensitized to angiotensin ІІ, they stimulate vasomotorial  centre; c) through peripheral sympathetic nervous system – angiotensin ІІ is stimulates secretion of noradenalin from presynaptic endings; d) through medulla layer of adrenal glands – angiotensin ІІ stimulates libering of catecholamins; e) through  kidneys – by active reabsorbtion of sodium and delay of water irrespective of aldosterone mechanism.

Renin-angionensin-aaldosterone system

Dependent from activity of renin hypertonic disease divide on three forms:

· normoreninemal – 55-60 % of all cases, · hyporeninemal – 25-30 %, · hyperreninemal - 10-20 %.

Thus, and on this parameter hypertonic disease is not homogeneous.

It was clarified further , that the kidneys select not only renin, which eventually results in increase of blood pressure and stabilization arterial  hypertansion. They have also depressor function. The kidneys select following  depresor substances: phospholipid inhibitor of renin,antihypertension neutral lipids medullar layer of kidneys, prostaglandins,  angiotensinase,  alkalized  ethers phosphatidilholin.

The largest interest from these substances is prostaglandins. They are synthesized kidneys. Stimulators synthesis of prostaglandins in kidneys are considered angiotensin ІІ, vasopressin,  catecholamins, that is those substances, which cause narrowing renals arterioles and ischemia of kidneys. Depressor property of prostaglandins will be realized due to the following mechanisms. Prostaglandins, especially PGE2, render  natriurtic action. They dilatate renals arteries, and also directly oppress return transepithelial transport of sodium chloridum in nefrone.  Besides, prostaglandins prevent  action of antiuretic on reabsorbtion of water.

The kidneys start still one more mechanism of stabilization hypertension - hormonal. Angiotensin ІІ and ІІІ, being powerful vasocontrictors, simultaneously stimulate synthesis of aldosterone in glomerulars zone  of adrenal glands cortex.  Effect steroids of them is identical. Aldosterone enhances reabsorbtion of sodium in canaliculus, especially in distaldepartent. Sodium is accumulated in liquids of an organism and in smooth muscles of vessels.

Increase of vesseles resistance. Irrespective of first reason, in the patients with hypertonic disease almost always increases peripheral resistance. It is considered, that the essence hypertonic disease just is in increase of peripheral vessels tonus. Hyperkinetic phase, which is connected to increase of cardiac output, happens only at early stages of disease and not in all patients.

The hereditary predisposition has concrete confirmation: а) in separate families the disease meets in some times more often, than in population; b) high percent concordans monozygotes twins on hypertonic disease is installed; c) it is established, that if one of the parents suffered by hypertonic disease, for them children the risk of disease six times is higher, than for children from family not burdened by that disease.

In a basis of hereditary predisposition to essential hypertension the lay disturbances transmembran transport of ions. In  the particular, in such patients in cytozole of vessels wall  myocyte  is  accumulated calcium because of deficiency Ca2+ -ATP-ase. Calcium can not be deleted from myocytes in intracellular environment. The accumulation increases it contractive ability of vessels wall myocytes and due to stable increase of peripheral resistance. Once more possible mechanism – generical  conditioned oppression  systems endotheliocytes of enzymal, which make internal  vasodilatators  (oxid of nitrogen, prostacyclin).

Secondary hypertensions represent symptoms of such diseases. 1. Diseases of kidneys: glomerulonephritis (14 %), pielonephritis, interstitial nephritis  due to abusing analgetics, hereditary nephritis (syndrome  Alport’s),  polycytosis  kidney. 2. Stenosis of renal artery  (1 %). Hypertension arises not in each stenosis. The most often reason of stenosis, caused atheroscleroticplatelits(at 70-80 of %), which damage usually proximal third of renal artery on the one hand. Other reason of  stenosis with hypertension itsfibromuscular hyperplasia of an average third of renal artery. It, as a rule, double-side and more often happens at the women. The mechanism of hypertension in stenosis of renal artery – hyperproduction of renin. 3. Primary aldosteronism (Cоnn syndrome) – in 1 % of cases. The reasons – unilateral adenoma glomerular zone adrenal glands or double-side diffuse hyperplasia of adrenal glands. 4. Paraganglioma (1 %) –tumour from chromaffin cells of medullar layer adrenal glands or sympathetic nerves, as a rule – benighn. Inparaganglioma is increased both cardiac output, and peripheral resistance. 5. Coarctation of the aorta  is an anatomic defect, in which aorta in pectoral or abdominal department is narrowed to such extend, that it represents serious barrier for blood circulation. In all vessels, which depart from the aorta proximal of narrowing, the resistance increases and is increased arterial pressure.

Experimental models of arterial hypertension

Models confirming a role of the nervous factor in increase of arterial pressure:

1. Arterial hypertension owing to an irritation of hypothalamus nucleuses. The irritation of a back nucleus frequently results to hypertension, connected with increase of cardiac output. The irritation of a central nucleus causes hypertension due to of peripheral resistance  increase. Electricity stimulation  ventro-medial nucleus gives hypertension, which depends from simultaneously  increase of cardiac output and peripheral resistance.

2. Arterial hypertension from double-side damage nucleus  tractus solitarii to medulla oblongata of rats, where are located primary  synapsis  of sinuaorticus baroreceptors. Arterial pressure is increased immediately without change of frequency of cardiac rate. The reason of hypertension is the sharp increase of peripheral resistance

3. Reflexogenic hypertension, in dogs and rabbits  affter section depressor nerve Ludvig-Cion or sinus nerves Hering.

Models, which confirm participation renals factor in occurrence and stabilization of arterial hypertension:

1. Vasorenal hypertension, which is caused by narrowing renals arteries. Conditions of reproduction: а) arteries should be narrowed only partially, instead of are blocked completely; b) the  narrowing should be double-side; c) the variant is possible(probable): narrowing arteries of one kidney plus  removal  of the other kidney.

2. Renoprival hypertension it arises after removel both kidneys and  spending of animal on dialysis.

Models confirming a role of adrenal glands in fixing arterial hypertension:

1. Mineral-corticoids hypertension  in the case  of long introduction of aldosteron with simultaneously purpose of solution NaClinstead of water.

2. Salty hypertension.  Sodium chlorids in a fair quantity even without additional hormonal effects is capable to cause hypertension.

Model confirming role of the hereditary factor in etiology of hypertonic disease.

Exists genetic (spontaneous) hypertension in rats. In the animal with spontaneous hypertension is revealed higher, than in normal animals, permeability ions channels in membranes smoothmuscle cells of arteries. These membrane defects can have some significance in increase of arteries tonus and regulation of volume extracellular liquid. They can be considered as one of the factors pathogenesis hypertonic disease.

Hypertension (HTN) or high blood pressure, sometimes called arterial hypertension, is a chronic medical condition in which the  blood  pressurein  the  arteries is elevated. This requires the heart to work harder than normal to circulate blood through the blood vessels. Blood pressure is summarised by two measurements, systolic and diastolic, which depend on whether the heart muscle is contracting (systole) or relaxed between beats (diastole). Normal blood pressure at rest is within the range of 100-140mmHg systolic (top reading) and 60-90mmHg diastolic (bottom reading). High blood pressure is said to be present if it is persistently at or above 140/90 mmHg.

Hypertension is classified as either primary (essential) hypertension   or   secondary hypertension; about 90–95% of cases are categorized as "primary hypertension" which means high blood pressure with no obvious underlying medical cause. The remaining 5–10% of cases (secondary hypertension) are caused by other conditions that affect the kidneys, arteries, heart or endocrine system.

Hypertension is a major risk factor for stroke, myocardial infarction (heart attacks), heart failure, aneurysms of the arteries (e.g. aortic aneurysm),peripheral arterial disease and is a cause of chronic kidney disease. Even moderate elevation of arterial blood pressure is associated with a shortenedlife expectancy. Dietary and lifestyle changes can improve blood pressure control and decrease the risk of associated health complications, although drug treatment is often necessary in people for whom lifestyle changes prove ineffective or insufficient.

Signs and symptoms. Hypertension is rarely accompanied by any symptoms, and its identification is usually through screening, or when seeking healthcare for an unrelated problem. A proportion of people with high blood pressure report headaches (particularly at the back of the head and in the morning), as well as ligh the adedness, vertigo, tinnitus (buzzing or hissing in the ears), altered vision or fainting episodes. These symptoms however are more likely to be related to associated anxiety than the high blood pressure itself.

On physical examination, hypertension may be suspected on the basis of the presence of hypertensive retinopathy detected by examination of the optic fundus found in the back of the eye using ophthalmoscopy. Classically, the severity of the hypertensive retinopathy changes is graded from grade I–IV, although the milder types may be difficult to distinguish from each other. Ophthalmoscopy findings may also give some indication as to how long a person has been hypertensive.

Secondary hypertension. Some additional signs and symptoms may suggest secondary hypertension, i.e. hypertension due to an identifiable cause such as kidney diseases or endocrine diseases. For example, truncal obesity, glucose intolerance, moon facies, a "buffalo hump" and purple striae suggest Cushing's syndrome. Thyroid disease and acromegaly can also cause hypertension and have characteristic symptoms and signs. An abdominal bruit may be an indicator of renal artery stenosis (a narrowing of the arteries supplying the kidneys), while decreased blood pressure in the lower extremities and/or delayed or absent femoral arterial pulses may indicate aortic coarctation (a narrowing of the aorta shortly after it leaves the heart). Labile or paroxysmal hypertension accompanied by headache, palpitations, pallor, and perspiration should prompt suspicions of pheochromocytoma. A proportion of resistant hypertension appears to be the result of chronic high activity of the autonomic nervous system; this concept is known as "neurogenic hypertension".

Primary hypertension (essential) is the most common form of hypertension, accounting for 90–95% of all cases of hypertension. In almost all contemporary societies, blood pressure rises with aging and the risk of becoming hypertensive in later life is considerable. Hypertension results from a complex interaction of genes and environmental factors. Numerous common genetic variants with small effects on blood pressure have been identified as well as some rare genetic variants with large effects on blood pressure but the genetic basis of hypertension is still poorly understood. Several environmental factors influence blood pressure. Lifestyle factors that lower blood pressure include reduced dietary salt intake, increased consumption of fruits and low fat products (Dietary Approaches to Stop Hypertension (DASH diet)), exercise, weight loss and reduced alcohol intake. Stress appears to play a minor role with specific relaxation techniques not supported by the evidence. The possible role of other factors such as caffeine consumption, and vitamin D deficiency are less clear cut. Insulin resistance, which is common in obesity and is a component of syndrome X (or the metabolic syndrome), is also thought to contribute to hypertension. Recent studies have also implicated events in early life (for example low birth weight, maternal smoking and lack of breast feeding) as risk factors for adult essential hypertension, although the mechanisms linking these exposures to adult hypertension remain obscure.

Secondary hypertension. Pathophysiology.

In most people with established essential (primary) hypertension, increased resistance to blood flow (total peripheral resistance) accounting for the high pressure while cardiac output remains normal. There is evidence that some younger people withprehypertension or 'borderline hypertension' have high cardiac output, an elevated heart rate and normal peripheral resistance, termed hyperkinetic borderline hypertension. These individuals develop the typical features of established essential hypertension in later life as their cardiac output falls and peripheral resistance rises with age. Whether this pattern is typical of all people who ultimately develop hypertension is disputed. The increased peripheral resistance in established hypertension is mainly attributable to structural narrowing of small arteries and arterioles, although a reduction in the number or density of capillaries may also contribute. Hypertension is also associated with decreased peripheral venous compliance which may increase venous return, increase cardiac  preload and, ultimately, cause diastolic dysfunction. Whether increased  active vasoconstriction plays a role in established essential hypertension is unclear.

Pulse pressure (the difference between systolic and diastolic blood pressure) is frequently increased in older people with hypertension. This can mean that systolic pressure is abnormally high, but diastolic pressure may be normal or low – a condition termed isolated systolic hypertension. The high pulse pressure in elderly people with hypertension or isolated systolic hypertension is explained by increased arterial stiffness, which typically accompanies aging and may be exacerbated by high blood pressure.


Many mechanisms have been proposed to account for the rise in peripheral resistance in hypertension. Most evidence implicates either disturbances in renal salt and water handling (particularly abnormalities in the intrarenal renin-angiotensin system) and/or abnormalities of the sympathetic nervous system.  These mechanisms are not mutually exclusive and it is likely that both contribute to some extent in most cases of essential hypertension. It has also been suggested that endothelial dysfunction and vascular inflammation may also contribute to increased peripheral resistance and vascular damage in hypertension.

Diagnosis. Typical tests performed. Renal System - Tests - Microscopic urinalysis, proteinuria, BUN and/or creatinine; Endocrine – Serum sodium, potassium, calcium, TSH; Metabolic - Fasting blood glucose, HDL, LDL, and total cholesterol, triglycerides; Other - Hematocrit, electrocardiogram, and chest radiograph (Sources: Harrison's principles of internal medicine others).

Hypertension is diagnosed on the basis of a persistently high blood pressure. Traditionally, this requires three separate sphygmomanometer measurements at one monthly intervals. Initial assessment of the hypertensive people should include a complete history and physical examination. With the availability of 24-hour ambulatory blood pressure monitors and home blood pressure machines, the importance of not wrongly diagnosing those who have white coat hypertension has led to a change in protocols. In the United Kingdom, current best practice is to follow up a single raised clinic reading with ambulatory measurement, or less ideally with home blood pressure monitoring over the course of 7 days. Pseudohypertension in the elderly or noncompressibility artery syndrome may also require consideration. This condition is believed to be due to calcification of the arteries resulting an abnormally high blood pressure readings with a blood pressure cuff while intra arterial measurements of blood pressure are normal.


Plasma lipoproteins are synthesized and excreted by two types of cells: liver parenchyma cells and small intestine epithelial cells. There is a lipid drop inside (nucleus), containing triglycerides and cholesterol ethers. Membrane covers the nucleus; it consists of protein (apolipoprotein, or apo-), phospholipids and non-aetherificated cholesterol.

All lipids are in blood plasma in protein-binded form. Non-aetherificated fat acids are binded with albumin, others – with a- and b-globulins and make lipoprotein complexes. General amount of all lipids in blood plasma of healthy adults can changes between 4-8 g/l. Generally the lipoprotein particle is soluble in water and is transport form of lipids in blood. There are four main classes of lipoprotein: chilomicrones, very low density lipoproteins, low-density lipoproteins, high-density lipoproteins.

The richest in triglycerides are the particles (table), which are formed in the intestinal wall during absorption of exogenous triglycerides and cholesterol. At first chilomicrones go into thoracic lymphatic duct, and then – into the common blood flow (their components are 90 % of alimentary trigycerides, 4-5 % of cholesterol, 4-5 % of phospholipids, 1 % of albumin – apoprotein A, B, C, E). Very low-density lipoproteins (VLDL) are produced in the liver, and less –in bowels wall. They are basic transport form of endogenoustriglycerides. They contain 10 % ofapoprotein B, C, E, 90 % of lipids, main components of which – 60 % triglycerides, synthesized in organism, 15 % cholesterol, 15% phospholipids. Low-density lipoproteins (LDLP) contain about 25 % of apoprotein B, E and 75% of lipids. Lipids contain  mostly cholesterol  (about 50 %, major of it ischolesterol ethers), phospholipids – about 30 %, triglycerides – about 8-10 %. Low-density lipoproteins are mostly rich in cholesterol and are the most atherogenous. In healthy people two of third of all cholesterol of blood plasma is found in low-density lipoproteins, so they are the basic transport form of cholesterol in human organism.  Low-density lipoproteins are generated partially or fully due to very low-density lipoproteins disintegration in blood plasma owing to lipoproteidlipase, which are activated by heparin. High-density lipoproteins (HDLP) about 30 % of phospholipids, about 20 % of cholesterol ether and very little of triglycerides. Part of them synthesizes in liver and in the thin bowels wall, and another part forms in blood plasma from chilomicrones and very low-density lipoproteins degradation products, which were formed due to lipoproteidlipase.

Healthy people plasma, taken before meals, contains 0,8-1,5 g/l of very low-density lipoproteins, 3,2-4,5 g/l of low-density lipoproteins and 2,7-4,3 g/l of high-density lipoproteins. Women’s plasma contains more high-density lipoproteins than men’s plasma. From the chemical point of view is fatty alcohol. Natural waxy cholesterol properties allow it to execute functions of the cell “skeleton” in human and animal organism. Each cell of our body contains cholesterol. Being a point of the cell, cholesterol together withphospolipids and proteins provide the selective cell perspicacity for substances, which enter and leave. Cholesterol is source of formation of sexual and steroid hormones, and also of cholic acids. It’s indispensable for organism growth and cell division.

The low-density lipoproteins is the main transport form of cholesterol in the human organism, they carry cholesterol from liver into membranes of different cells. How dolow-density lipoproteins particles bring cholesterol into the cell? Organs and tissues cells contain specific apo-B and apo-Е-receptors for binding low-density lipoproteins particleson the surface of plasmatic and intracellular membranes. General number of receptors can go up to ten thousand per one cell. One apo-B or apo-Е-receptors binds up one apoprotein-B or apoprotein-E particle of low-density lipoproteins. This is the receptor-mediated endocytosis. This way of lipoproteins transportation is directed only to supply the internal cells’ needs in cholesterol and does not lead to lipoprotein-particles entrance into arteries’ intimae of cholesterol changes or  its  metabolites  in plasma and cells, they govern the cells interchange including the liver. When entering the cell endocytosis vesicles that contain lipoproteins particles come into contact with lysosoms where lipoproteins are slitted. The exempted cholesterol is used for own needs (for example, for membranes synthesis). This way is regulated according to the reverse mechanism: if cholesterol contentsrise in the cell amount of apo-B or apo-Е-receptors on the cell membranes diminishes, and, as the result, lipoproteins enthrallment take place; also the intracellular synthesis is being depresses.

Аpо-В-receptor  Аpо-Е-receptor

(receptor connects one apoprotein B or apoprotein E particle of LDLP, is depended to Ch needs of the cell)

Another way of cholesterol regulation is its removal from the cellular membrane. Such removal of the “fulfilled” cholesterol takes place permanently. It is realized by high-density lipoproteins rich albumen and phospolipids during their contact with the cell membrane. Cholesterol is etherificated under the influence of special lecitin-cholesterin-acetiltransferase and is transported into liver, where is partially oxidized into cholic acids and excreted out the organism.

Normally these two processes cholesterol in low-density lipoproteins from liver into cell and in removal from the cell and the reverse transportation to the liver are balanced. A thin balance between the delivery and the removal of cholesterol and other fats into the cell and from it determines vessels’ wall destiny: whether fats are accumulated in it or the wall remains normal. The process regulation in considerably depends on lipoproteins concentration and correlation in blood plasma.  10-15 % of population has got hereditary molecular deviations in cholesterol or lipoprotein metabolism: 1) some one has the heightened synthesis of cholesterol, of atherogenous lipoproteins synthesis in liver and thin bowels; 2) others have violations of atherogenous lipoproteins removal in blood flow. Examples of hereditary lipoproteins metabolism defects: а) tanjer’s illness – almost full absence of high density lipoproteins in blood, such patients, despite the very low content of general cholesterol in blood (30-125 mg/dl), have the signs of atherosclerosis in earlyage, b) family hyperlypoproteinaemia. This pathology the lack of apo-B and apo-E-receptors on cell surface of parenchymatose and connective type is genetically conditioned. Low density lipoproteins blood plasma don’t enter the cell, or enter it in considerably diminished amount, this is the reason the accumulation of low density lipoproteins to the blood and, as the consequence, to development of atherosclerosis in already early age.

There is another way – the unregulable (or non- receptor) endocytosis. Plasma low-density lipoproteins and very in endocytosevesicles penetrate via undamaged endothelial cells. These vesicles transport low-density lipoproteins from the plasmatic membrane to the basal one by means of endocytosis into the vessels’ intimae. It is assumed, that the unregulable endocytosis low-density lipoproteins enthrallment wins the main role in atherosclerosis development.

Namely word “atherosclerosis” consists of two Greek words: “atheros” –porridge, “sclerosis” – bulge. Atherosclerosis is characterized by the focal bulge and the consolidation of the vessel wall in the result of deposit of the porridge-like mass in it, that masscontaining lipids (cholesterol), complicated carbohydrates, blood elements and calcium salts.  Atherosclerosis is the variable combination of changes in arteries’ intimae, which consists of focal lipids accumulation, complicated carbohydrates, blood substances of fibrous tissue and of calcium salts accumulation, which is associated with changes in media. Precipitation takes place in intimae of big and middle caliber arteries with well-developed elastic layer (aorta, coronary vessels, cerebral arteries), that accumulation of lipids is called lipoidosis.

Pathogenesis study of this illness has started from experiments N.N.Anichkov and S.S.Khalatov, which showed that feeding of rabbits with clean cholesterol brought on the formation of atherosclerotic plaques in aorta wall. Thus a first experimental model of this illness was created.  The cholesterol atherosclerosis model for more then 90 years has being the object of numerous scientific researches because changes in animals’ arteries are principally identical to atherosclerotic changes in human being. Anichkov created the infiltrative atherosclerosis theory.  The following expression belongs to him: “There is no atherosclerosis without cholesterol”. But other scientists proved that atherosclerosis could be without the hypercholesterinaemia and, even, hypercholesterinaemia without atherosclerosis. It was shown, that hypercholesterinaemia can appear not only by alimentaryway, because two of third of cholesterol in man organism is synthesized from albumens, fats, and carbohydrates via acetyl-Co-A.

The great role was given to the disorder of lipoproteins metabolism, to the disorder of low-density lipoproteins and high-density lipoproteins fractions correlation, dyslypoproteinemias, and also to the state of the vascular wall. It was shown, that neither cholesterol, nor other lipids do not penetrate independently into arterial wall (only in lowdensity lipoproteins storage). Besides receptor-mediated endocytosis Klimov describes such lipoproteins transport ways into the arterial wall, as unspecific unregulable endocytosis.

The capture of lipoproteins particles by endothelial cells with their following transportation into subendothelial space (intimae). This way starts to function actively when the low-density lipoproteins level in blood rises and at the same time their cholesterol saturation rises. There are the next mechanisms: via intercellular channels of endothelium, through damaged gaps of endothelium monolayer. Damage of endothelium takes place permanently and during all life. Endothelium can be damaged by some chemical substances, for example by tobacco nicotine, and by autoimmune complexes.

Obesity, diabetes, smoking, hypokinesia and other risk factors influence arteries’ wall. One of damage causes is action of hemodynamic blood factors. There are hypertension, pulse wave blow and blood stream turbulence. These factors are mostly active in those arteries areas of big or middle caliber, where convexity, bifurcation, offshoot, constriction and outside squeezing of vessels are present. These are those places, where the glycocalics-supraendothelial layer is first impaired, which defends the endothelium, and then the endothelium itself is empired. In people who have hypertension, the atherosclerosis develops in 3-4 times quickly, than in people with normal blood pressure.

The second important hemodynamic factor is the so-called displacement tension, which is mostly strongly displayed on the outside side of the bend and of the arteries ramifications. There in first turn starts the formation of atherosclerotic injuries. Heart contractions induce pushing arteries’ displacement, and in the result of that, the shift straining effect on endothelium and intimae becomes stronger, that gives rise to microtearings formation in these layers of coronal arteries.

The autoimmune complexes, including lipoproteins as antigen, damage the endothelium. The thrombocytes adhesion takes place. Active thrombocytes excrete thromboxanum, which assists their adhesion and aggregation and narrows the vessels; excrete a growth factor, which stimulates proliferation of vascular wall cells. The delay of lipoproteins passing through intimae can be the result of thickening of this layer of arterial wall (age hyperplasia, hypertension, genetic factors, inflammatory processes and other).

During long stay in intimae, lipoproteins undergo different transformations (modifications – low density lipoproteins). They stimulate cholesterol precipitation in arteries walls. Modified lipoproteins are actively captured by intimae cells and primarily by macrophages, as macrophages have not only apo-B and apo-E-receptors to low-density lipoproteins, which regulate the mechanism of re-entry tie, but also unregulable intracellular cholesterol receptors, which provide enthrallment of different modification lipoproteins. These are so-called “scavenger-receptors” for modified-lipoproteins, for lipoproteins glycoseamynoglicanes complex, for very low-density lipoproteins, receptors for autoimmune complexeslipoproteins-antibody. This leads to piling up of great amount of cholesterol in macrophages, mainly cholesterol ethers and to foamy cells formation. Accumulation of modified low density lipoproteins in intimae is key moment of atherosclerosis, because low density lipoproteins induce the formation of foamy cells, the destruction of which leads to forming of atheroma and necrosis of ambient tissues of vascular wall.

The basic cellular source is the monocytes-macrophages, which are transformed into foamy cells. Unlike other cells, they have many scavenger-receptors to modified lipoproteins on their surface. The important condition which lead to monocytes migration into intimae is very low density lipoproteins in plasma, under influence of which endothelium of big vessels excretes the monocytes’ chemotaxic factor, which assists the adhesion of monocytes on endothelium surface. Fixed monocytes excrete interleukin-1, which changes superficial properties of endothelium, provides adhesion of monocytes and their active migration into intimae. Scavenger-receptor reaction of monocytes-macrophages in vascular wall is defensive and adaptive. It is directed on the removal from intimae of the surplus fixed lipoproteins in it. But unregulable capture of modified lipoproteins and their in complete catabolism in cell’s lysosoms lead to the transformation of macrophages into foamy cells. The capture of immune complexes lipoproteins-antibody by macrophages hastens the foamy cells formation.

Atherosclerosis has four stages: 1) pre-lipid or foamy cells stage (monocytes-macrophages transformation into foamy cells); 2) lipid blots; 3) fibrous plaque; 4) complicated stinging (ulceration, calcinosis, thrombosis). The first stage is characterized by formation of the foamy cells, migration of smooth muscles cells from media into the intimae due to haemotaxic factors of macrophages, endoteliocytes and smooth muscles cells proliferation under the influences of thrombocytes and endotheliocytes growth factors, interleukin 1.

The mechanism of lipid blots formation are as follows: surplus cholesterol ethers and cholesterol non ethers accumulation in foamy cells leads to their splitting, in the result of that lipids cholesterol outpour outside, forming extra cellular lipid pilings.

Lipid blots. The third stage has such mechanisms: cholesterol irritates ambient tissues, causing the corresponding reaction of connective tissue and macrophages, which is displayed by the proliferation, and then by development of fibrous tissue which like capsule surrounds the lipid mass trying to isolate it fully. A part of capsule turned to vessel clear space side is denser; it protrudes inside the vessel. Plaques, in which softening phenomena and disintegration of fatty inclusions prevail, are called atheromas. Clots and plaques havedimension from pin head to several centimeters in diameter. This stage is irrevocable.

3 stage of atherosclerosis

Fourth stage: an ulcerated plaque can be the formation place of wall thrombus, the cause of atheromatous detritus penetration into the blood and brain, coronary arteries’ embolia.

The risk factors are causally connected with illness; their influence can be evaluated in popularistic researches. Besides hypercholesterinemia, hypertriglyceridemia and hypo-α-lipoproteinemia, the role of which has already been explained in detail and which also refer to risk factors.  It is necessary to mark such factors, as age, sex (mainly males), arterial hypertension, smoking, broken tolerance to glucose (diabetes), obesity, overeating, low-movable mode of life, person’s peculiarities and conduct, heredity, gout, softness of drinking water.

Age. Atherosclerosis develops within long time, sometimes   during all human life. It is mostly expressed in old and senile age. The fighting for continuation of active human existence of period can be considered as prophylaxis method of atherosclerosis and its clinical expressions.

Sex.  Men considerably more frequently suffer from atherosclerosis, that's why belonging to masculine gender can be a risk factor.  One of causes of their raised receptivity to atherosclerosis is lower content of antiatherogenous high-density lipoproteins. In women the antiatherosclerotic action of woman’s sexual hormones is found.

Arterial hypertension is the reason of arteries’ endothelial cover damage and bulge of intimae. In such intimae lipoproteins particles stay and accumulate easier.

Smoking. Nicotine raises endothelial cells penetration for lipoproteins, causes spasms of heart and lower extremities arteries, rises the ability of thrombocytes to aggregation and, thus, contributes to formation of thrombus in arteries.

Diabetes mellitus. Patients have high level of lipoproteins (very low-density lipoproteins and triglucerides) in blood as the result oflipolysis activation. High level of blood glucose conduces of the modified lipoproteins (glucosidated low density lipoproteins) formation.Glucosidated low-density lipoproteins increase the vassal permeability, macrophages hemotaxis into the intimae, conduce monocytes and thrombocytes adhesion, stimulate of the smooth muscle cells proliferation.

Obesity (surplus body mass) conduces to lipoproteins increase in blood, and frequently to decrease of antiatherogenous high-density lipoproteins.

Low-movable mode of life (hypokinesia). People, who permanently attend to running, have the raised amount ofantiatherogenous lipoproteins in blood. Physical work generally contributes to saving the normal body mass, to lowering the arterial pressure; it prevents the development of diabetes mellitus. And this, its turn, detains the development of atherosclerosis and ischemic heart disease.

Person’s conduct and peculiarities. Contemporary man, especially in city conditions, has strained, stowed with stresses and emotions life rhythm. In response for frequent emotional situations, the adaptable reactions of cardiac-vascular system are disturbed due to the plenty secretion of catecholamines into blood. This, on one hand, causes to perspicacity rise of endothelium for plasma apo-B-lipoproteins, and on another – to lypolysis process activation in adipose tissue to reinforcement of triglycerides synthesis and very low-density lipoproteins in liver.

Heredity. Convincing data, that show the meaning of genetic factors in atherosclerosis pathogen, were received in several countries during the inspection of families’ members and relative persons of people, suffering with ischemic heart disease. It was discovered that among relatives of those women, who had myocardium infarction before 65 the death rate because of coronal insufficiency (men younger 55, women younger 65) was seven times higher, than in whole population.

Gout. Patients with atherosclerosis frequently have raised level of urinary acid in blood. And patients, ill with gout, often have atherosclerosis. There is correlation between urinary acid level and triglycerides contents in blood.

Water Softness. Regions where people use up soft water with insufficient microelements contents, atherosclerosis is more frequent and is more difficult, than in regions with hard water. Vanadium, manganese, magnesium, chrome are those microelements insufficiency of which contributes to atherosclerosis development.

All these factors act not independently, but several together. Knowledge of peculiarities of their action plays a great role for primaryprophylaxy of atherosclerosis.

Oddsei - What are the odds of anything.