Components of the circulation

The cardiovascular system consists of a muscular pump, the heart, and two functionally distinct circulations, systemic and pulmonary (Fig. 34). Blood flow through the systemic circulation depends on contraction of the left ventricle of the heart, which forces blood into the aorta. Large arteries branch off this to supply different areas of the body, forming regional circulations which are effectively in parallel with one another. Within each tissue, smaller and smaller arterial vessels are arranged in series, terminating in the arterioles, which supply the tissue capillaries. These act as the sites of gas and nutrient exchange between blood and the interstitial fluid. Capillaries drain through venules into veins, which empty in turn into the superior and inferior venae cavae. It is these large venous vessels which return systemic blood to the right atrium of the heart.

Fig. 34 Diagrammatic representation of the cardiovascular system (see text).

The right side of the heart drives blood through the pulmonary circulation. The right ventricle fills from the right atrium and then contracts, driving blood into the pulmonary trunk, which supplies the pulmonary arteries. Pulmonary capillaries lie in close contact with the air-filled alveoli of the lung and are involved in the gaseous diffusion which oxygenates the blood (Section 4.3). The pulmonary veins return this oxygenated blood to the left atrium, which empties into the left ventricle, thus completing the double circulation.

Cardiac structure

The heart is a double pump arranged as a muscular cone with its apex directed downwards and to the left and its base behind the upper sternum. Each pumping unit consists of two chambers, with a thin-walled atrium opening into a more muscular ventricle. Endocardium lines the inner surface of the muscular myocardium, which is covered in turn by the epicardium. The whole heart is surrounded by a tough, fibrous sac, the pericardium. Atrioventricular valves prevent back flow of blood from ventricles to atria (Fig. 35). On the right side, this valve has three cusps and is known as the tricuspid valve, while on the left it has two cusps and is called the mitral valve. There are also one-way semilunar valves at the ventricular outlets, where blood flows into the pulmonary trunk (pulmonary valve) or aorta (aortic valve). The chambers on the right and left sides of the heart are separated by shared dividing walls known as the atrial and ventricular septa.

Fig. 35 The functional anatomy of the heart including the main electrical conducting pathways.

Cardiac muscle cells

The muscle cells (also known as cardiac myocytes or cardiac fibres) of the heart contain contractile proteins, as described in Section 1.6. Cardiac muscle is rich in mitochondria, reflecting its dependence on aerobic metabolism, and the cells contain only one nucleus. The fibres may branch at either end and they connect with the next cell in series through a region of close cellular association known as an intercalated disc (Fig. 36). Desmosomes link the membranes of adjacent cells at these sites. There are also special transmembrane channel proteins, which form gap junctions connecting the cytoplasm of the cells on either side of the intercalated discs. This provides electrical continuity from cell to cell allowing easy transmission of action potentials. Because of this the heart behaves as a functional syncytium, with rapid conduction of electrical signals leading to well-coordinated contraction.

Fig. 36 Uninucleate, branching cardiac muscle cells make close contact with each other via the intercalated discs. Desmosomes link adjacent cell membranes at these sites while gap junction channels provide low electrical resistance pathways from cell to cell.

Cardiac action potentials

Intracellular recordings from ventricular cells show that the resting membrane potential is similar to that in skeletal muscle, but more negative than that in nerve, at about −90 mV. As with any excitable cell, depolarization of the membrane to threshold leads to the production of an ‘all or none’ action potential with a characteristic shape (Fig. 37). There is an initial rapid depolarization to about +20 mV followed by an initial, partial repolarization of some 5–10 mV. Further repolarization is very slow indeed and this produces an action potential plateau in which membrane potential remains close to 0 mV for some 150–300 ms. After this, the membrane repolarizes rapidly, returning to the resting potential.

Fig. 37 Action potential and contractile response for a ventricular cell. The prolonged refractory period ensures that relaxation occurs before further contraction can be generated.

It is the plateau which distinguishes cardiac action potentials from those in skeletal muscle and nerve, as it greatly prolongs the action potential. This has important functional consequences for the mechanical activity of the heart. Cardiac cells are absolutely refractory to stimulation for the whole duration of the action potential and show a high degree of relative refractoriness for an additional 50 ms (Section 1.4). Therefore, a second action potential cannot be generated for a period of up to 350 ms after stimulation in ventricular cells. Contraction and relaxation are complete within this time (Fig. 37) and so it is impossible to get summation of contractions, or continuous tetanic contractions, as are commonly seen in skeletal muscle at higher frequencies of stimulation (Section 1.6). Since effective cardiac pumping depends on cyclical contraction and relaxation, the prolonged action potential protects against pump failure caused by sustained contraction, which would prevent the heart from refilling. It also sets an upper limit on the rate of contraction, which cannot exceed about 3–4 beats s⁻¹ in the ventricle. Atrial rates can be considerably higher, however, because the atrial action potential, and, therefore, the refractory period, is shorter (less than 200 ms).

Mechanism of the cardiac action potential

The mechanisms underlying the cardiac action potential are similar to those in nerve, i.e., they depend on transmembrane ion gradients and voltage-sensitive changes in membrane permeability, or conductance, to those ions (Section 1.4). Three ions, Na⁺, Ca²⁺ and K⁺, are involved (Fig. 38).

Fig. 38 The flow of ions across the cardiac cell membrane (A) and the changes in ion conductance during the action potential (B).

Sodium channels. Depolarization first opens (activates) Na⁺ channels, increasing Na⁺ conductance. This leads to an inward Na⁺ current which causes further depolarization. The resulting positive feedback accounts for the initial rapid depolarization phase, as in nerve. Sodium conductance then declines again because of depolarization-induced inactivation of Na⁺ channels. The cell remains refractory to stimulation until these have returned to their resting, closed state following repolarization.

Calcium channels. There are also Ca²⁺ channels in the membrane, which open in response to depolarization. They activate more slowly than the Na⁺ channels but once open they allow Ca²⁺ to flow into the cell (Fig. 38). This inward Ca²⁺ current keeps the membrane depolarized and thus maintains the plateau in the action potential.

Potassium channels. The conductance changes to K⁺ in cardiac cells are more complicated than those described for nerve. Potassium conductance first decreases following depolarization, so that during the plateau there is actually less outward K⁺ current than normal. This makes it easier for the inward Ca²⁺ current to maintain depolarization, since there is very little current flowing in the opposite direction. After 200 ms or so, however, K⁺ conductance rises, increasing the outward current. This K⁺ current repolarizes the membrane. Repolarization is assisted by the reduction in the opposing, inward Ca²⁺ current which also occurs in the latter part of the action potential (Fig. 38). The fact that K⁺ conductance first decreases and then increases in response to the initial depolarization reflects the fact that there is more than one type of K⁺ channel in these cells and each type responds differently to voltage changes.

Spontaneous electrical activity (automaticity)

An isolated heart beats regularly without any extrinsic stimulation from nerves or hormones. This mechanical automaticity reflects the fact that the action potentials which are conducted throughout the heart (the signals which lead to contraction) are generated spontaneously within the cardiac muscle itself. Such activity is said to be myogenic (unlike action potentials in skeletal muscle which are neurogenic, i.e., they are only produced in response to nervous stimuli). The cells responsible for spontaneous action potential production are often referred to as pacemaker cells because they determine the rate at which the heart beats. Electrical recordings from such cells show that, instead of a constant resting membrane potential between action potentials, there is a steadily depolarizing potential known as a pacemaker potential (Fig. 39). When threshold is reached an action potential fires, and then the cycle of events is repeated.

Fig. 39 Electrical activity in cardiac pacemaker cells from the sino-atrial node. The rate of spontaneous action potential production increases as the slope of the depolarizing pacemaker potential increases.

Several cell types in the heart are capable of pacemaker activity, but in the intact organ it is the fastest pacemaker which drives the rest of the heart. Once an action potential is generated at one site, it is rapidly conducted throughout the cardiac muscle and will trigger an action potential in slower pacemaker regions before they can reach the threshold potential spontaneously. Normally the pacemaking frequency is highest in a group of specialized cells called the sino-atrial node, which also have a different shape of action potential (Fig. 39). These cells dictate the rate of electrical events in the rest of the heart. This produces a resting heart rate of 60–70 beats min⁻¹, and the regular pattern of excitation and contraction which results is called sinus rhythm.

Conducting pathways in the heart

Cardiac action potentials normally originate in the pacemaker cells of the sino-atrial node, which is located in the wall of the right atrium close to the superior vena cava (Fig. 35). Action potentials are conducted away from the sino-atrial node through the normal atrial fibres. This is made possible by the interbranching structure of cardiac cells and the easy transmission of action potentials from one cell to another via the low-resistance gap junctions in the intercalated discs (Fig. 36). The conduction velocity through the atrial muscle is 0.3 m s⁻¹ and this is rapid enough to produce a coordinated atrial contraction which forces blood into the ventricles.

The atrioventricular node is located on the atrial septum in the lower half of the right atrium. It consists of specialized conducting tissue which is capable of pacemaker activity but is normally driven by conducted action potentials from the sino-atrial node. Conduction through the atrioventricular node is slow (about 0.05 m s⁻¹) and this delays transmission of the action potential to the ventricle, ensuring that ventricular contraction will not commence until atrial contraction is completed. Action potentials are conducted from the atria to the ventricles by the atrioventricular bundle, or bundle of His. This divides into right and left bundle branches, and these carry the impulses down either side of the ventricular septum towards the apex of the heart. These branches are continuous with the Purkinje fibres, which ramify through the ventricular muscle itself. Conduction through the atrioventricular bundle, the bundle branches and the Purkinje fibres is rapid (2–4 m s⁻¹) and this promotes synchronized contraction throughout the muscle of the ventricles. Local conduction from one ventricular cell to the next is much slower (0.5 m s⁻¹).

Electrocardiogram (ECG)

Because action potentials do not fire simultaneously in all cardiac cells but are conducted across the myocardium from one region to another, extracellular potential differences are generated between one area of the heart and the next. These can be recorded from the skin as very small potential differences (approximately 1 mV) and such a record is known as an electrocardiogram (ECG). This is an important clinical tool, used both in the diagnosis of abnormal cardiac rhythms (arrhythmias) or defects in the conduction pathways and when investigating possible damage to the bulk of the myocardium, e.g., caused by ischaemia.

To understand the principle underlying the ECG, let us consider an area of myocardium with two surface electrodes being used to record any potential differences from the overlying skin (Fig. 40A). At rest there will be zero potential difference between the electrodes, but as the depolarizing phase of an action potential spreads across the heart, the transmembrane potential will be reversed in one area while other areas remain polarized. This generates a potential difference which is recorded as a positive deflection, assuming the electrodes are attached to the positive and negative poles of the voltmeter as shown (reversing this connection would reverse the sign of the recorded potential difference but would not alter the shape of the ECG). Eventually, all the local myocardium will be depolarized, so the potentials at the two surface electrodes will be identical, giving zero potential difference again. Once repolarization starts to spread, however, a negative potential will be recorded until the whole tissue returns to the resting potential again.

Fig. 40 (A) The principles underlying the electrocardiogram (ECG). (B) Sample trace showing the form of real ECGs.

A typical ECG recording consists of three different waves (Fig. 40B). There is an initial positive deflection known as the P wave. This is generated by the spread of depolarization across the atria. It is followed by the QRS complex, which is produced by the spread of depolarization across the ventricles. These contain more muscle and so generate larger surface potentials. The final T wave is the result of repolarization of the ventricles. The T wave is usually smaller than the QRS wave because repolarization spreads over the surface of the ventricles more slowly than does depolarization. The same is true for the atria, and this explains why no ECG wave attributable to repolarization of the atria is seen. The exact shape of the ECG depends on which points on the body surface are used for recording. Different electrode combinations (different recording leads) can give information about different parts of the heart.

Fig. 41 Mechanical and electrical events of the cardiac cycle. Valve closure generates the heart sounds (HS). The ventricular volume record (bottom graph) can be divided into five phases: passive filling (A); atrial ejection (B); isovolumetric contraction (C); ventricular ejection (D); and isovolumetric relaxation (E).

The simplest piece of information which can be determined from the ECG is heart rate. The beat to beat interval can be measured between equivalent points on consecutive waves, e.g., from the peak of one P wave to the next. The total time for 10 beats is often measured from the ECG and divided to give an average beat to beat interval. This is then used to calculate an average heart rate, e.g., distance from first P wave to 11th P wave (10 × P–P intervals) = 208 mm; average = 20.8 mm = 0.83 s (standard ECG chart speed = 25 mm s⁻¹). Heart rate = 60 ÷ 0.83 = 72 beats min⁻¹.

Mechanical events

Electrical events

The electrical signals in the heart act as stimuli for the mechanical responses and so each wave on the ECG is associated with the onset of the relevant pressure change (Fig. 41). The P wave indicates depolarization of the atria and comes at the start of the pressure wave caused by atrial contraction. Similarly, the spread of depolarization over the ventricles, recorded as the QRS complex, marks the onset of ventricular contraction. This is followed by ventricular repolarization and the resulting T wave overlaps the drop in pressure caused by ventricular relaxation.

Measurement of cardiac output

Fick’s method

The Fick technique for the estimation of cardiac output is a specific application of Fick’s principle, which states that the rate of addition or removal of a substance in any part of the circulation equals the blood flow multiplied by the resulting change in concentration. We can apply this to the pulmonary circulation where there is a continuous uptake of O₂ from the alveoli and, as a result, [O₂] in blood increases (Fig. 42). The relationship between the magnitude of the change in [O₂] and the pulmonary blood flow can be derived from the considerations outlined in Box 8.

Fig. 42 Application of Fick’s principle to the measurement of cardiac output.

Box 8 Background mathematics: Cardiac output from Fick’s method

Each minute, the amount of O₂ entering the lungs in pulmonary arterial blood = (Pulmonary blood flow) × (Pulmonary arterial [O₂]).

Each minute the amount of O₂ leaving the lungs in the pulmonary venous blood = (Pulmonary blood flow) × (Pulmonary venous [O₂]).

The difference between these two values must equal the rate at which O₂ is absorbed from the alveoli into the pulmonary capillaries.

∴ (Pulmonary blood flow × Pulmonary venous [O₂])− (Pulmonary blood flow × Pulmonary arterial [O₂])= Rate of alveolar O₂ absorption.

Since pulmonary blood flow equals cardiac output we can simplify this to:

Cardiac output × (Pulmonary venous [O₂] − Pulmonary arterial [O₂]) = Rate of O₂ absorption.

Or:

Cardiac output

Since it is easier to take systemic than pulmonary blood samples, we can rewrite this expression in the usual form of Fick’s equation:

Cardiac output

(7)

In practice, the rate of O₂ absorption is measured using a device called a spirometer and is about 200 ml min⁻¹ at rest. Systemic arterial [O₂] can be measured from any peripheral artery and usually equals 200 ml L⁻¹. Systemic venous [O₂] cannot be measured from a peripheral vein, however, since venous [O₂] varies for different organs. A mixed venous sample must be obtained instead, either from the right ventricle or the pulmonary trunk. Such samples give an [O₂] of 160 ml L⁻¹. Inserting these values into Fick’s equation (Eq. 7) gives a value of 5 L min⁻¹ for the resting cardiac output (Fig. 42).

Indicator dilution technique

Following injection of a known amount (Y mg) of a measurable dye (the indicator) into the central venous system close to the heart, indicator concentration (c) in systemic arterial blood rapidly rises to a peak and then declines again (Fig. 43). Recirculation of the indicator leads to secondary peaks on the concentration curve, but extrapolation of the initial decline gives an estimate of what the concentration curve would have been like in the absence of such recirculation. Box 9 shows how cardiac output can be calculated from these studies.

Fig. 43 Measurement of cardiac output by the indicator dilution technique. The area A is measured and used to calculate cardiac output (see Box 9).

Box 9 Background mathematics: Cardiac output using indicator dilution

Figure 43 shows the changes in dye concentration (c). The area under the curve (A) produced by extrapolating the initial decline can be used to calculate the average concentration of indicator for the time of one circulation (t).

(8)

In theory, we could also calculate the average indicator concentration using the expression:

The indicator is dissolved in the total volume of blood flowing through the heart in time t, i.e., cardiac output × t

(9)

By equating Eq. 8 and Eq. 9 we get:

(10)

In choosing an indicator, one requires a physiologically inert substance which is retained in the circulation and is not metabolized. An adaptation of the method which fulfils all of these criteria uses injections of warm or cold saline into the pulmonary trunk and the resulting change in blood temperature is measured a few centimetres further on. This is referred to as the thermodilution technique.

Control of cardiac output

Since cardiac output is determined by heart rate and stroke volume, relevant control mechanisms must regulate one or both of these variables. These mechanisms may be divided into two groups; those which depend on intrinsic properties of the heart itself and extrinsic controls which modify cardiac performance.

Intrinsic control of cardiac function

The most important intrinsic mechanism involved in the control of cardiac output is usually referred to as Starling’s law of the heart, or the Frank–Starling mechanism, after the two physiologists who first described it. They observed an increase in the force of contraction as the resting length of the cardiac muscle fibres was increased. This resulted in increases in stroke volume and, therefore, in cardiac output, as the volume of the ventricle immediately before contraction (the end diastolic volume) was increased (Fig. 44A). This is independent of any extrinsic nervous and hormonal controls. Similar results are obtained if some other measure of the degree of ventricular filling is used, e.g., venous return (the total rate of blood flow into the atrium from the veins) or atrial pressure. One way of summarizing the overall effect of the Frank–Starling mechanism on cardiac function is as a plot of cardiac output against atrial pressure, which demonstrates clearly that increased ventricular filling leads to increased output across the normal range of atrial pressures (Fig. 44B).

Fig. 44 Starling’s law of the heart. (A) As ventricular volume increases so does the force of contraction, increasing stroke volume. (B) The effect of this on cardiac output can be plotted using atrial pressure, venous return, or end diastolic volume on the x axis, since these variables are all interrelated.

Starling’s law helps explain two important features of cardiac function, namely that cardiac output equals venous return and that the average outputs from the two ventricles are equal. If venous return suddenly rises above ventricular output, blood will accumulate in the ventricle, increasing the end diastolic volume. Starling’s law predicts that this will lead to an increase in both stroke volume and cardiac output until a new steady state is reached in which cardiac output equals venous return again. Since the output from one ventricle is responsible for the venous return to the other side of the heart in the intact circulation, this mechanism will also ensure that the cardiac output from the two ventricles remains equal. For example, if the cardiac output from the left ventricle increases, this will increase right venous return and right ventricular output will rise as a consequence.

Preload and afterload As in any muscle, the contractile performance of the heart is influenced by the mechanical forces, or loads, which it experiences. Preload refers to the level of stretch in the relaxed muscle immediately before it contracts. In the heart this is largely dictated by the venous return. Increases in venous return increase the preload, i.e., they increase the stretch in the muscle fibres before contraction. This increases contractile force and, therefore, cardiac output, as described by Starling’s law (Fig. 44).

Afterload refers to the force that the muscle must generate during contraction and this is most obviously affected by changes in arterial pressure. In a normal heart, however, increasing the systemic arterial pressure (left ventricular afterload) has little effect on cardiac output, at least over the range of pressures likely to be experienced. Therefore, it is the preload, effectively the rate of venous return, which is most important in determining cardiac output.

Nervous control

Both the sympathetic and parasympathetic divisions of the autonomic nervous system help regulate the heart’s activity (Section 7.6). They can alter the heart rate (chronotropic effects) or the strength of ventricular contraction (inotropic effects) but are not under conscious control. Instead, they are reflexly regulated by inputs from cardiovascular and other receptors, e.g., from the baroreceptors, which help regulate arterial pressure, or through connections with higher centres in the brain, e.g., in response to emotions such as anger or fear.

Sympathetic nerves Sympathetic nervous activity to the heart is controlled from a number of regions in the central nervous system (CNS), including the medulla oblongata. The postganglionic nerves release the neurotransmitter noradrenaline (norepinephrine) and supply both pacemaking and contractile cells throughout the atria and ventricles. Stimulation of these nerves leads to increases both in heart rate (positive chronotropic effect) and in myocardial contractility (positive inotropic effect). This increases the cardiac output at any given atrial filling pressure, pushing the relationship between cardiac output and atrial pressure upwards and to the left (Fig. 45A). There is a limit to the benefits of increasing heart rate, however, since the time available for diastolic filling between contractions decreases, and rates over 200 beats min⁻¹ may lead to a decline in cardiac output.

Fig. 45 Effects of autonomic nervous control on cardiac function. (A) Increased stimulation. (B) Reduced activity also alters cardiac output because there is a basal level of tonic activity in these nerves.

Parasympathetic nerves These come from the medulla oblongata in the brain and reach the heart via the vagus nerve. They supply the sino-atrial and atrioventricular nodes, releasing acetylcholine when stimulated, and this slows the heart (a negative chronotropic effect) through its influence on pacemaker activity. Maximal parasympathetic activity can reduce the heart rate to 30–40 beats min⁻¹ (vagal brake). The result is a reduction in cardiac output, pushing the cardiac function curve down and to the right (Fig. 45A). Parasympathetic nerves are not distributed to ventricular muscle and so they have no appreciable effect on contractility (i.e., no inotropic effect).

Resting nervous tone Under resting conditions, there is activity in both the sympathetic and parasympathetic nerves supplying the heart. This is referred to as resting nervous tone and cardiac function can be altered by either decreasing or increasing the frequency of stimulation by either set of nerves. For example, heart rate and cardiac output may be doubled by completely blocking the resting parasympathetic tone (Fig. 45B).

Exercise and cardiac function

During exercise, cardiac output rises to meet the increased blood flow requirements of skeletal muscle. The maximal output is about 25–30 L min⁻¹ in normal individuals. Several factors contribute to this.

Venous return. This rises as a result of compression of the veins by contracting skeletal muscle and, therefore, increases cardiac output through the Starling mechanism. Unidirectional venous valves ensure that blood is forced towards the right atrium (see Fig. 56).

Fig. 56 Venous return is assisted by contractions of skeletal muscle provided that venous valves are competent.

Sympathetic nervous activity increases both in response to higher centres involved in initiating exercise and reflexly by receptors in the exercising muscles themselves. Heart rate and myocardial contractility are increased as a result, helping boost cardiac output. In practice, the rise in heart rate is the dominant effect and there is usually little change in stroke volume. Sympathetic stimulation also leads to active constriction of the smooth muscle in the walls of veins (venoconstriction), further enhancing venous return.

Parasympathetic (vagal) activity to the heart. This is inhibited during exercise and this also contributes to the increase in heart rate.

Cardiac hypertrophy. This is seen as a response to prolonged periods of exercise over months or years in trained athletes. This increases the muscle bulk of the left ventricle through enlargement of the individual cardiac fibres, thus raising the stroke volume. As a result, the maximum cardiac output achieved during strenuous activity is considerably higher than in untrained individuals, reaching values up to 35–40 L min⁻¹. Resting cardiac output is normal, however, since athletes also have a lower than normal resting heart rate (40–50 min⁻¹) due to increased parasympathetic (vagal) tone.

Measurement of blood pressure

Pressure may be measured directly by inserting a cannula into an artery, but this is only appropriate for experimental or intensive care situations. Indirect measurement makes use of an inflatable cuff which can be wrapped around the upper arm, over the biceps area. Cuff pressure is recorded using a device known as a sphygmomanometer. The pressure is raised well above the normal arterial pressure, to approximately 200 mmHg, and then the cuff is slowly deflated. At the same time a stethoscope is used to listen, or auscultate, over the brachial artery distal to the cuff. This method is sometimes referred to as the auscultatory method. Initially there is silence because the high pressure in the cuff completely collapses the artery, but as cuff pressure falls, a short tapping sound, known as the first Korotkoff sound, is heard. This occurs when the highest pressure achieved in the artery (the systolic pressure) is slightly greater than the cuff pressure, and so a brief jet of blood is forced through in each cardiac cycle. This turbulent flow vibrates the arterial walls and produces the Korotkoff sounds. As the cuff deflates further, arterial pressure exceeds cuff pressure for longer and longer in each cycle, allowing blood to flow through for longer and with less turbulence. As a result, the Korotkoff sounds become longer and quieter. Eventually the sound disappears completely (the fifth and last Korotkoff sound) as blood flow becomes continuous and nonturbulent because the cuff pressure is below arterial diastolic pressure. The sphygmomanometer pressures corresponding with the first and last Korotkoff sounds are recorded as the systolic and diastolic arterial pressures.

Arterial pressures are normally reported in terms of the systolic/diastolic pressures, with normal values of 120/80 mmHg in systemic arteries. (Equivalent values in pulmonary arteries are considerably lower; about 25/10 mmHg under resting conditions.) Sometimes mean arterial pressure (MAP) is calculated:

(11)

A simple (arithmetic) average of systolic and diastolic values is not used for the mean pressure because diastole normally lasts twice as long as systole (Fig. 41).

Blood pressure and peripheral resistance

For fluid to flow through a pipe, there must be a pressure gradient between the two ends of the pipe (Fig. 46). The size of that gradient (ΔP) equals the rate of fluid flow (Q) times the resistance to flow (R), i.e.

Fig. 46 The main physical variables controlling flow in the circulation.

(12)

Applying this to the systemic circulation, ΔP is the pressure gradient between the aorta and the right atrium. Since atrial pressure (approximately 1 mmHg) is negligible in comparison with arterial pressure (normally 120/80 mmHg), ΔP effectively equals arterial blood pressure. The total blood flow through the systemic circulation, i.e., the cardiac output, is Q. Thus:

(13)

This is an important relationship because it indicates that blood pressure may be regulated through changes in either cardiac output or peripheral resistance.

Pressures and resistances in different types of blood vessel

Using Equation 12 we can see that if Q is constant, then the pressure difference between two points in the circulation will be proportional to the resistance of the blood vessels between those two points. The total blood flow through any class of systemic blood vessel (e.g., all arteries or all veins) must be equal to the cardiac output, so the drop in pressure along any type of blood vessel is proportional to the total resistance to blood flow offered by all vessels of that type. Blood pressure measurements can be made at different sites around the systemic circulation and the overall pressure profile determined (Fig. 47). The pressure in the aorta and large arteries is high and pulsatile (about 120/80 mmHg), and there is only a small drop in pressure along their length. Both the mean pressure and the amplitude of the pulse pressure (systolic pressure − diastolic pressure) decrease somewhat more in the small arteries but the largest pressure drop occurs within the arterioles. This tells us that the single largest contribution to the peripheral resistance comes from the arterioles (about 55% of total resistance). Arterioles have a considerable amount of smooth muscle in their walls and peripheral resistance can be actively controlled by constriction or dilatation of these vessels (vasoconstriction and vasodilatation, respectively). The resulting changes in arteriolar diameter dramatically affect their resistance since the resistance (R) of a single vessel is inversely proportional to the fourth power of the radius (r), i.e.

Fig. 47 Pressure profile of the systemic circulation. The pressure drop (ΔP) along each vascular element reflects its resistance since the total flow through each class of vessel equals the cardiac output.

(14)