Kardiovaskulárny systém

Physiology of the circulation

Blood is circulated by the continuous pumping action of the heart within a closed system. In the normal circulatory system, the blood flow rate or velocity varies inversely with the total cross-sectional area of the blood vessels. This means that the velocity is inversely proportional to the cross-sectional area and directly proportional to the blood flow in the blood vessel. As the total cross-sectional area increases, the flow velocity decreases. All tissues and cells in the body need oxygen and nutrients; however, the demand varies by tissue type (neurons and cardiac muscle cells require a continuous supply of oxygen). 

The function of circulation are as follows:

• To deliver oxygen, nutrients, and hormones to the cells
• To remove wastes, carbon dioxide, and excess ions from the cells, and to eliminate the heat generated by cellular metabolism
• To establish connections between the body’s afferent systems (such as the gastrointestinal tract and the lungs) and efferent systems (including the kidneys, gastrointestinal tract, lungs, and skin)

The primary function of the heart is to pump blood through the vessels and maintain circulation. The heart output or cardiac output (CO), expressed in litres/minute, is the volumetric flow rate the heart pumps out in one minute. This amount is equal to the product of stroke volume (approximately 5–5.5 L) and the number of beats per minute (heart rate)​.

Pressure differences in the systemic circulation

Contraction of the ventricles causes dilation of the large arteries and provides kinetic energy, thus contributing to blood flow. (Since fluids, as well as the blood itself, are compressed.) 

Friction develops in the blood flow between circulating blood particles, and the blood frictionally interacts with the vessel walls. Friction produces heat. Thus, the energy from a heart contraction is transformed into thermal energy. Friction is the resistance to relative motion or flow, which is essential for pressure changes within blood vessels.  

Perfusion pressure is inversely proportional to resistance: an increase in resistance decreases flow, and a decrease in resistance increases flow. 

Blood flow: laminar versus turbulent

In physics, particularly in fluid dynamics, the volumetric flow rate (also known as the volume flow rate or volume velocity) is not uniform across a cross-section. Fluid layers that adhere to the vessel wall move more slowly, while the velocity is highest at the centre of the flow.

Blood flow in the body is typically laminar in most blood vessels (the layers of blood cells move parallel to the long axis of the blood vessel). If the volume velocity increases (e.g., in a narrowed or obstructed vessel), turbulent flow occurs, and blood particles move forward and in different directions. Blood particles create small whirlpools, eddies, and swirls in the blood that make an audible sound. A stethoscope can hear this noise over a blood vessel during blood pressure measurement.

Korotkoff sounds

Laminar flow depends on the following factors: the diameter of the blood vessel, the velocity, and the viscosity of the liquid. The Poiseuille-Hagen formula describes the characteristics of laminar flow through a pipe, where the fluid moves steadily and all particles stream along the same flow line in parallel layers. The equation of steady, laminar, Newtonian flow through circular tubes is Q=πΔPr⁴/8ηl, where Q is the volumetric flow rate, r and l are the tube radius and length, ΔP is the pressure drop in the direction of low, and η is the fluid viscosity. With the roles of Q and η interchanged, this is the basic equation of capillary viscometry. In laminar flow, the flow rate is directly proportional to the pressure difference/perfusion pressure (P1-P2=ΔP), the 4th power of the radius of the pipe, and it is inversely proportional to the length of the pipe and viscosity.

This means that, in a specific section of a blood vessel, resistance is directly proportional to the length of the vessel and its viscosity. At the same time, it is inversely proportional to the 4th power of the blood vessel's radius. Thus, in the case of a short vessel length, a large vessel diameter, and low viscosity, the vascular conductance of the specific blood vessel will be increased. Among many factors that affect circulation, vessel diameter is the most important that can be changed.

Poisseuille-Hagen formula

The connection between the flow rate and the cross-sectional area

As the total cross-sectional area of the vessels increases, the flow velocity decreases (aorta ⟶ , larger arteries ⟶ , small arteries). The cross-sectional area of each capillary is small compared to the aorta; the total cross-sectional area of all the capillaries is much greater than the cross-sectional area of the aorta. From the muscular arteries, blood is distributed into arterioles, which then become terminal arterioles. The capillary bed contains metarterioles and real capillaries. Precapillary sphincters regulate the number of opened capillaries needed for adequate tissue perfusion. Exchange across capillary walls is essential to the survival of the cells and tissues.

Exchange of nutrients and waste products

Microcirculation is the circulation of terminal arterioles, metarterioles, precapillary sphincters, capillaries, and the smallest postcapillary venules. Its primary function is nutrient and waste exchange between the vessels and the surrounding environment. 

The exchange occurs in capillaries and postcapillary venules; in capillaries, the precapillary sphincters control pressure and blood flow. This means that 1 red blood cell “spends" about 1 second in a certain capillary; this is the exchange time of gases and other materials. In addition to that, at rest, blood flows only in some of the capillaries (as precapillary sphincters are closed and open only in metabolically “active” tissues).

The endothelial cell structure in the wall of capillaries is permeable to lipid-soluble materials (such as gases: O2, CO2, alcohol, and lipids). The vessel wall's water permeability depends on the number of aquaporins, while most solute particles traverse the membrane via transport mechanisms.

Aquaporins or water channels

The Starling Principle

According to Starling's hypothesis, the movement of extracellular fluid between blood and tissues is determined by the differences in hydrostatic pressure and colloid osmotic (oncotic) pressure between blood plasma in the microvessels and interstitial fluid. Hydrostatic pressure within a blood vessel is determined by where resistance to flow occurs; constriction of the arterioles raises pressure, while vasodilation decreases it. The larger the venule's diameter is, the higher the pressure in the capillaries becomes. Meanwhile, venous dilatation decreases pressure.  

Colloid osmotic pressure of the blood (Пk= ~25 mmHg) occurs due to albumin that attracts positively charged molecules and, ultimately, water into the intravascular compartment. Hydrostatic pressure (the opposite of colloid osmotic pressure) is the force exerted by the fluid inside the blood capillaries against the capillary wall: ~35 mmHg, and in the veins: ~17 mmHg. 

Fluid is reabsorbed into the venules and returns to the heart via venous circulation. In contrast, excess interstitial fluid is absorbed by lymph capillaries and drained into the larger lymphatic vessels. When the lymphatic system fails, venous insufficiency or malfunctioning blood vessels cause excess fluid to accumulate in the interstitial space. This is called oedema.

Intravascular hydrostatic pressure (P_c) is the principal force driving fluid out of the vasculature into the interstitial space. Proteins cannot pass through most capillary walls; thus, ultrafiltrate is produced in the tissue space.  

Interstitum is mainly composed of collagen, elastin, and glycosaminoglycans, which are mechanically entangled and cross-linked to form a gel-like material. Matrix proteins (e.g., glycosaminoglycans and collagen) determine the composition and organisation of the interstitium's mechanical properties, such as its strength, elasticity, and hydration. The volume of interstitial fluid in the tissues varies (e.g., ~10–12% of the muscle tissue and ~35% of the skin consists of interstitial fluid). 

In the microcirculation, 2‒4 litres of fluid circulate daily upon entering the lymphatic capillary, and the collected fluid becomes lymph. Lymph eventually drains into larger lymphatic vessels, which are filtered by lymph nodes or tonsils (secondary lymphatic organs). 

Following that, lymph drains into larger lymphatic ducts (e.g., the thoracic duct and the right lymphatic duct), and then it reaches the left and the right venous angles (angulus venosus sinister et dexter), where it flows with carbon dioxide-rich blood in the circulation. (See previous chapters in The hematopoietic system and the blood

‒ Secondary (peripheral) lymphoid organs)  

Lymph flow is managed by the movements of organs, such as the intestines and skeletal muscles, which exert external pressure on the lymphatic walls (extrinsic forces). The rhythmic contractions of smooth muscles lining the lymphatic vessels (intrinsic forces) also play a major role in lymph circulation.

Luminal valves in larger lymphatic vessels also ensure the forward flow of lymph. Inhalation decreases intrathoracic pressure and dilates the thoracic vena cava, which facilitates lymphatic circulation.    

Central and local control of blood flow and volume

In the wall of arterioles and precapillary resistance arteries, the structure of smooth muscles is homogenous. These arteries have basal vascular tone (in a quiescent state, smooth muscles are partially constricted, i.e., the contractile filaments are partially activated). 

Basal vascular tone may differ in the parallel blood vessels. Local circulatory control mechanisms rely heavily on changes in myogenic tone, which is influenced by the stretch state of muscles. 

In most blood vessels and organs, blood flow is proportional to perfusion pressure. When intravascular pressure increases (as occurs following systole), the resulting stretch on muscle cells leads to contraction and increased myogenic tone. Nevertheless, blood flow is relatively independent of perfusion pressure in some organs, known as flow autoregulation.  

In vascular beds with high myogenic tone, pressure changes do not significantly affect vessel diameter, maintaining stable blood flow. This is known as arterial autoregulation, and it is observed in the cerebral and coronary arteries. 

As a result of cerebral autoregulation, the cerebral vasculature maintains stable blood flow between 60 and 160 mmHg despite changes in mean arterial pressure.

Vessels in the splanchnic area, skeletal muscle, and pulmonary and cutaneous vessels have low basal tone. In response to pressure changes, the diameter of blood vessels can change significantly.

At rest, sympathetic nerves release noradrenaline, which acts on the walls of blood vessels (i.e., vasoconstrictor), leading to a neurogenic tone. Cerebral and coronary vessels have some degree of autonomic innervation, although it is not as extensive as that of other blood vessels. Therefore, their blood flow regulation is primarily influenced by local factors rather than neurogenic tone, while splanchnic and skeletal muscle vessels have some degree of neurogenic tone.  

The basal “resting” tone, or sympathetic tone, is the normal tone of the vascular wall. (As shown in figure „Regulation of blood pressure”, point I.)

The sympathetic nervous system controls blood flow in vascularized areas with low basal tone (e.g., in splanchnic areas and cutaneous blood vessels). These areas respond with marked vasoconstriction to noradrenaline/adrenaline released in response to sympathetic action.    

Regulation of blood pressure

Summary of the local regulation of blood flow

If capillary resistance decreases, blood flow in metabolically active tissues rises above the normal or basal vascular tone. This is called functional hyperemia. Functional hyperemia (increased blood flow) can be observed in active skeletal muscles, in response to increased metabolic demands of the heart and digestive system, and in neuronal activity in specific areas of the brain. In case the resistance of the capillaries decreases, blood flow in the metabolically active tissues rises above the “resting” or basal vascular tone.

During metabolic activity, chemical products are produced, including hydrogen ions (H⁺), carbon dioxide (CO₂), adenosine, and potassium ions (K⁺). These act as vasoactive mediators that cause vasodilation. These chemical factors act on the smooth muscle cells in the precapillary resistance vessel walls, causing relaxation and an increase in local blood flow.

Reactive hyperemia occurs when blood flow decreases in a specific blood vessel (e.g., a limb). If ischemia resolves, blood vessel resistance decreases and blood flow increases.

The role of vascular endothelium in the regulation of blood flow

The tunica intima is the inner layer of a blood vessel wall. It comprises endothelial cells that produce and secrete vasoactive substances (vasoconstrictors and vasodilators). Nitric oxide (NO) and prostacyclin are two important vasodilator molecules. 

Neural control of the cardiovascular system

Mechanisms through which the body regulates systemic arterial pressure: cardiovascular reflexes

The cardiovascular system rarely operates in a resting state, as circulation must adjust to constantly changing conditions (e.g., body position, physical activity, and stress).

In addition, in specific nonphysiological situations, e.g., when the body loses blood and fluids (hypovolemia) or experiences oxygen (O₂) deprivation (hypoxia), the circulatory system must adapt and take corrective measures to keep organs functioning.

The autonomic nervous system and the medulla oblongata of the brainstem control the cardiovascular and respiratory systems and regulate blood pressure. 

The circulatory system provides information by regulating the cardiovascular system: baroreceptors are mechanoreceptors or stretch receptors in the walls of the heart and blood vessels, while chemoreceptors are sensory receptors that detect changes in the chemical composition of blood.

Aortic, carotid and cardiopulmonary baroreceptors

High-pressure baroreceptors are found in the aortic body (glomus aorticum), within the aortic arch, and in the internal carotid arteries (carotid sinus – sinus caroticus). These receptors are mechanosensitive nerve endings located in the walls of certain blood vessels that have a range of sensitivity to changes in blood pressure. Typically, baroreceptors are sensitive to changing pulsatile arterial pressure; above 60 mmHg, the action potential frequency also increases. Baroreceptors generate action potentials when arterial pressure is low. In normotensive subjects, the frequency of baroreceptor action potentials reaches a maximum when arterial blood pressure is about 200 mmHg. 

Baroreceptors in the carotid sinus are connected to sensory nerve fibres that travel through the glossopharyngeal nerve (CN IX); the aortic body sends sensory information to the brain via the vagus nerve (glomus aorticum). The nucleus tractus solitarii (a part of the medulla oblongata in the brainstem) receives sensory input from the vagus and glossopharyngeal nerve and is the primary integrative centre for cardiovascular control. 

An increase in mean arterial blood pressure increases baroreceptor activity, which activates the medulla (nuclei of the CN X). As the medulla processes this incoming (afferent) information about the increased stretch of the vessel wall, this centre sends efferent signals via the parasympathetic nervous system to the heart, decreasing heart rate. This ultimately results in a decrease in blood pressure. 

The role of high-pressure receptors is an essential mechanism for the short-term stabilisation of arterial blood pressure, specifically for controlling blood pressure between systoles. When blood pressure increases, vagal nerve activity increases as well. The vagus nerve is responsible for parasympathetic control of the heart, which includes slowing the heart rate and reducing cardiac output. An increase in vagal tone can lead to a decrease in heart rate and, subsequently, a reduction in blood pressure through decreased total peripheral resistance and cardiac output. A fall in blood pressure inhibits the activity of the vagus nerve, and increased sympathetic tone raises cardiac output and total peripheral resistance, which helps raise blood pressure. (In individuals with hypertension, the sensitivity of baroreceptors may decrease and adapt to the higher blood pressure ranges and continue to function, albeit with reduced sensitivity.)

Cardiopulmonary baroreceptors

Low-pressure volume or cardiopulmonary receptors are located within the atria, ventricles, and pulmonary vasculature. They regulate blood pressure and blood volume. 

These receptors are sensitive to changes in the stretch or distension of the blood vessel wall (or blood volume). They are innervated by the vagus nerve (a sensory nerve). Suppose blood volume becomes excessive or the vessel wall stretches. In that case, the reflexes initiated by the cardiopulmonary receptors may become overwhelmed, leading to tachycardia, as the sympathetic nervous system can quickly and effectively increase heart rate.

Cardiopulmonary receptors play an essential role in long-term blood pressure regulation by controlling blood volume. Signals from cardiopulmonary receptors can influence the release of vasopressin and the amount of renin produced by the kidneys, thereby influencing the effects of angiotensin and aldosterone. These hormonal effects occur in different ways, resulting in increased blood volume. This happens in hypovolemia and hypotension. These hormonal mechanisms are inhibited by increased atrial stretch (as in hypervolemia). 

Cardiovascular reflexes in upright posture

Sudden changes from lying to an upright posture can cause problems, as the hydrostatic pressure in the arterial vessels increases rapidly in the lower body regions (up to ~80 mmHg).

Increasing blood pressure dilates veins, pooling up to 500 ml of blood in the vessels below the heart. As a result, venous return decreases, and cardiac output and stroke volume decrease as well (in the upright position, the stroke volume can be up to 20–25% lower than in the lying position). In such cases, mean arterial pressure should decrease, but baroreceptors exert controlling mechanisms to keep it in normal ranges.   

Cardiopulmonary receptors sense the decrease in central venous pressure and increase the tone of sympathetic nerve fibres in the precapillary resistance arteries and veins. In addition, they activate the secretion of vasopressin and renin, raising blood pressure and blood volume. 

From the supine to the upright position, nerve impulses from baroreceptors in the carotid sinus decrease because anatomically, the carotid sinus is located approximately 30 cm above the heart; thus, a blood pressure of 90 mmHg measured in the lying position drops to 75 mmHg when standing up. Increased vasoconstriction mediated by the sympathetic nervous system, heightened sympathetic stimulation that elevates the heart rate, and enhanced secretion of catecholamines by the adrenal glands all contribute to maintaining normal mean arterial pressure.

If homeostatic regulation in the upright position is impaired, mean arterial pressure may fall significantly, reducing cerebral blood flow and causing fainting (orthostatic or postural hypotension). Syncope usually resolves spontaneously, as lying down restores normal blood flow to the brain.

Arterial chemoreceptors

Sensory fibres of CN IX and X work as chemoreceptors in the area of the aortic body (glomus aorticum) and carotid body (glomus caroticum). At normal O2 levels, the firing rate of arterial chemoreceptors decreases. In hypoxia or when blood metabolite levels (CO2, H+, K+) are high, the firing rate increases. 

The firing rate of chemoreceptors can increase in circulatory failure or following significant blood loss. Activation of CN IX and X stimulates the sympathetic system to constrict peripheral blood vessels. The key function of chemoreceptors is to facilitate breathing. Chemoreceptors maintain circulation in case of very low blood pressure (60‒80 mmHg).

1. Short-term (1‒30 sec): neural regulation  

• Carotid sinus reflex (baroreceptors located in the carotid sinus)  
• Chemoreceptors stimulate breathing 
• Cerebral ischemia reflex leads to marked activation of the sympathetic nervous system.

• Renin-angiotensin-aldosterone system: vasoconstriction, retention of sodium
• Vasopressin: vasoconstriction, water retention
• The kidneys regulate circulatory volume by controlling sodium and water balance, thus maintaining homeostasis of extracellular fluid volume (ECFV). Increased sodium and water intake raise ECFV and blood volume.

Hormones involved in blood pressure control