Lecturer: �PhD Antsupova V.V.

PATHOPHYSIOLOGY

OF BLOOD VESSELS

Ministry of Health of Ukraine

Bohomolets National Medical University

Pathophysiology department

FUNCTIONAL CLASSIFICATION OF BLOOD VESSELS

• The compensatory vessels (aorta, arteries of elastic and muscular-elastic type);
• The resistance vessels(the arterioles and venules located in the pre- and post-capillary parts of the vascular bed);
• The exchange vessels(capillaries and venules);
• Capacitance vessels (mainly small veins)

PATHOLOGICAL CHANGES IN THE COMPENSATORY VESSELS. ATHEROSCLEROSIS�

• The concept of atherosclerosis
• Etiology and pathogenesis of atherosclerosis
• Classification
• Complications

АTHEROSCLEROSIS

Chronic disease characterized by impaired fat and protein metabolism, and is manifested by the deposition in the walls of blood vessels of elastic and elastic-muscular types of lipid complexes, complex compounds of carbohydrates, blood elements and circulating substances, connective tissue formation, calcium deposition.

АTHEROSCLEROSIS IS MULTIFACTORIAL DISEASE. �The main risk factors are:

• Age
• Gender
• Genetics
• Smoking
• High BP

• Hypercholesterolemia
• Diabetes mellitus
• Obesity
• Sedentary lifestyle
• Emotional stress

TARGET LEVELS OF LIPIDS �

Toral cholesterol < 5.0 mmol/l

LDLP < 3.0 mmol/l

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HDLP > 1.0 mmol/l

Triglycerides < 2.0 mmol/l

STRUCTURE OF LIPOPROTEIDS

Don’t impact atherogenesis significantly

Proatherogenic

Anti- atherogenic

Each increase in LDL cholesterol by 0.5 mmol/l leads to an increase in the relative risk of death due to coronary heart disease by 25%

ATHEROSCLEROSIS DEVELOPMENT

Endothilial dysfunction

Foam cells

Fatty streaks

Partial lesion

Atheroma

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Fibroatheroma

Complicated lesion

From the first decade

From the third decade

From the forth decade

Lipid accumulation

Smooth muscle cells and collagen

Thrombosis, hematoma

ARTERIAL WALL IN NORM

Endothelial cells

Smooth muscle cells

EARLY ATHEROSCLEROSIS

Lipids accumulate in the intima, which leads to disorders of endothelial cell function

Activated endothelial cells secrete adhesion molecules and cause chemotaxis of inflammatory cells, mainly monocytes

EARLY ATHEROSCLEROSIS

Monocytes penetrate the intima, are transformed into macrophages and absorb lipids with the formation foam cells

Activated macrophages secrete cytokines and growth factors that stimulate the igration of smooth muscle cells into the intima

Migrating smooth muscle cells change their phenotype from contractile to reparative: synthesize the matrix component of the fibrous capsule trying to "cure" the damage prevent rupture of plaques

ATHEROSCLEROSIS

Prelipid stage

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Stage of fatty spots and streaks

STABLE ATHEROMA

Fibrous capsule

(smooth muscle cells and matrix)

Endothelial cells

Іntimal smooth muscle cells

(reparative phenotype)

Smooth muscle cells in media

(contractile phenotype)

inflammation - macrophages,

Т- cells

Unstable plaque

Stable plaque

Oxidised LDLP

Genetically caused pathology

Іnfection (Herpesviruses, Chlamidia)?

DESTABILIZATION OF ATHEROMA

Activated macrophages cause the death of intimate smooth muscle cells and destroy the matrix in the fibrous capsule

DEVELOPED ATHEROSCLEROSIS

UNSTABLE ATHEROSCLEROTIC PLAQUE

Platelet aggregation at the site of rupture / erosion

Thrombus formation and growth in the lumen of the vessel and plaque

Growth of a plaque

The place of the previous rupture of the plaque

Thrombus under lysis

Migration of SMCs

DEVELOPED ATHEROSCLEROSIS

UNSTABLE ATHEROSCLEROTIC PLASTER

COMPLICATIONS OF ATHEROSCLEROSIS

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Aneurism of aorta formation

COMPLICATIONS OF ATHEROSCLEROSIS

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Development of an atherosclerotic defect of the aortic valve

COMPLICATIONS OF ATHEROSCLEROSIS

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Atherosclerosis of the arteries of the brain

COMPLICATIONS OF ATHEROSCLEROSIS

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Atherosclerotic wrinkled kidneys.

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Renal failure is rare.

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As a result of increase in activity of renin-angiotensin system there is a nephrogenic rterial hypertension.

COMPLICATIONS OF ATHEROSCLEROSIS

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Atherosclerosis of the intestinal arteries

Intestinal gangrene and peritonitis

COMPLICATIONS OF ATHEROSCLEROSIS

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Atherosclerosis of the arteries of the extremities

gangrene of the extremities as a result of thrombosis of the femoral artery or popliteal artery

PATHOPHYSIOLOGY OF RESISTANCE VESSELS�ARTERIAL HYPERTENSION��

Hypertensive disease - a disease of the cardiovascular system, which develops as a consequence of primary dysfunction of higher vascular control centers, neurohumoral and renal mechanisms, characterized by increased systolic and (or) diastolic blood pressure, and in severe stages - organic changes in the heart, kidneys and CNS.

FORMS OF HYPERTENSION

⭮△↓↘🢧△◢ ⭨🡙△ 🢫▽▽🢫🡘◄↓🢧↙⭰ ↑◢▲🢫△◄🢫🡘▽↓🡙🡘 ⭨⮡⭫⭦ 🡙← ▲🢫🡙▲↙🢫⭰ – ↑🢧▽ 🡘🡙 ▽↓🡘→↙🢫 ↗🡘🡙▷🡘 🢩🢧►▽🢫 🢨►◄ ▽🢫◁🢫△🢧↙ ↘🢫🢩↑🢧🡘↓▽↘▽ 🢧△🢫 ↙↓🡘↗🢫🢪 ◄🡙 🢧↙◄🢫△🢫🢪 ▲🢧◄↑▷🢧◢▽ ↓🡘 ⮒⭮ 🢩🡙🡘◄△🡙↙⭸

⌤🢫🢩🡙🡘🢪🢧△◢ ↑◢▲🢫△◄🢫🡘▽↓🡙🡘 ↓▽ ▽◢↘▲◄🡙↘ 🡙← 🡙◄↑🢫△ 🢪↓▽🢫🢧▽🢫▽

CAUSES OF SECONDARY HYPERTENSION

RISK FACTORS

Non-modifiable:

• Genetic
• Age
• Sex

Modifiable:

• Obesity and metabolic syndrome
• Excessive use of salt
• Psycho-emotional overload
• Alcohol consumption
• Low physical activity

HEMODYNAMIC TYPES �OF HYPERTENSION

Given that P=Q x R, where Q is minute blood volume,

Q=SV(stroke volume) x HR(heart rate);

R - total peripheral resistance, R=8ηl/πr4, where η – viscosity of the blood; l – the length of the blood vessel; r – radius of the blood vessel, there are the following hemodynamic types of arterial hypertension:

• hyperkinetic - increased Q, unchanged or slightly reduced R;
• eukinetic - there is an increase in both Q and R;
• hypokinetic - the value of Q is not changed or slightly reduced, R - sharply increased.

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FACTORS AFFECTING ARTERIAL PRESSURE

PATHOGENESIS �OF ESSENTIAL HYPERTENSION

The starting factor of essential hypertension development is the hyperactivity of the nerve centers of blood pressure regulation.

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Hyperactivity of these centers is expressed in the strengthening of pressor exposure through:

• activation of SAS;
• secretion of vasopressin;
• inclusion of renal factors: renin-angiotensin-aldosterone; prostaglandins.

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HOW TOTAL PERIPHERAL RESISTANCE (TPR) �INCREASES IN HYPERTENSION COURSE

• TPR rises gradually. With increasing cardiac output according to the myogenic theory of autoregulation of blood flow, there is a stretching of smooth muscle cells of the arteries and arterioles, which according to Frank-Starling law leads to their further spasm, reducing vascular radius, increasing total peripheral resistance and decreasing blood flow velocity and tension to a normal level.

HOW TPR �INCREASES IN HYPERTENSION COURSE

• The mechanism of enhanced contraction after pre-stretching of both smooth muscle and cardiomyocytes, according to modern ideas, is associated with a rapid increase in calcium current directed from the extracellular fluid into the sarcoplasm, due to the activation of mechanically dependent sarcolemma calcium channels.

HOW TPR �INCREASES IN HYPERTENSION COURSE

• Prolonged and significant increase in blood pressure damages the walls of blood vessels, which stimulates the local formation of angiotensin II and endothelin-1, which are potent vasoconstrictors and growth factors that stimulate migration and hyperplasia of smooth muscle cells and vascular wall fibroblasts, protein synthesis, synthesis , which leads to thickening of the media and intimacy.

HOW TPR �INCREASES IN HYPERTENSION COURSE

• Proliferative thickening of arterioles is significantly enhanced in the presence of insulin resistance, as hyperglycemia further damages the endothelium, and excess insulin is a growth factor.
• In addition, hypertensive endothelial damage causes adhesion to the vessel wall of platelets, neutrophils and monocytes with the development of an inflammatory process, which is accompanied by edema and proliferation of fibroblasts of the intima of blood vessels.

Angiotensin II also leads to hypertrophy and myocardial fibrosis after ischemic injury or in response to a constant increase in blood pressure.

HOW TPR �INCREASES IN HYPERTENSION COURSE

• Proliferative thickening of the media and intima leaves the arterioles permanently narrowed, regardless of the presence or absence of stimuli that cause vasoconstriction. From this point on, the total peripheral resistance remains constantly elevated, and arterial hypertension acquires signs of eukinetic, and after myocardial hypertrophy, cardiosclerosis and cardiac depletion and hypokinetic type.

ATHEROSCLEROSIS �AND ARTERIAL HYPERTENSION �– VISCIOUS CIRCLE OF VASCULAR PATHOLOGY

Chronic damage to the vascular wall

Development of atherosclerosis

Endothelial dysfunction

Violation of vascular tone regulation

Increased blood pressure

THANK YOU FOR ATTENTION!