Blood flow and the Circulatory System Blood will only flow through the CVS system if the

pressure in one part of the s ystem is higher than in another part. The heart contracts, generates the increase in pres sure in the arterial side of the vascular system and causes the flow of blood from the a rea of high pressure to the area of low pressure. As blood flows down the blood vessel, pressure decreases. The highest pressure is in the aorta and systemic arteries, en the lowest pressure is in the vena cava. Blood flow (F) refers to the amount or volume of blood that moves past a point i n the CVS (eg aorta)]. Blood flow in the CVS is influenced and determined by blood pressure and the resistance against flow. Flow (F) is directly proportional to the pressure difference (D P) between two p oints, ie. F D P, where D P = P1 - P2 . (1) This basically means that the higher the pressure difference between two points in the CVS (eg aorta versus venae cavae) the greater the volume of blood that flows bet ween them. Flow is inversely proportional to the resistance in the vessels, ie. F = 1/R(2) This basically means that the higher the resistance to flow, the more difficult or slow blood would flow through the vessel (or CVS). Resistance is the sum total of all the frictional forces that resist flow in the system. The resistance to blood flow is influenced by: The length of the blood vessel (L) the radius of the blood vessel (r) the viscosity of the blood (h ) These factors are summarized in Poiseuilles law: R= 8 h L p r 4 Where: 8 is a constant h = blood viscosity L = Length of tube p = constant r = radius of the tube The length of the blood vessel is dependent on the anatomy of the system and rem ains constant. Thus the longer a blood vessel, the higher the resistance, but blood v essel length does not alter to change the flow of blood. Yet, the influence of length of a vessel or tube plays an important role in vascular resistance is the shorter len gth of the pulmonary circulatory system vs the systemic circulatory system, which is the re ason for the lower blood pressure in the pulmonary system than systemic. The viscosity of the blood is determined by the ratio of RBC to plasma and is no rmally constant. If the RBC and protein concentration rises, so the viscosity of the bl ood will rise (polycythemia) and the blood resistance to flow will increase. It will in t urn increase

the blood pressure (hypertension). A decrease in viscosity (eg. Anemia or blood loss) will decrease the resistance to flow and the blood pressure. A change in the radius of blood vessels makes the biggest contribution to resist ance to blood flow. If vessel A has a radius that is half that of vessel B, the resis tance to flow will be 16x more in A than in B (because r4). A decrease in blood vessel ra dius is called vasoconstriction and will cause a decrease in flow, while an increase blo od vessel radius is called vasodilatation and will cause an increase in blood flow in the vessel. Blood flow through parts of the circulation that is in series is the same. E.g. Blood flow through the heart and aorta is the same as the flow through the lungs, systemic circulation and the left and right side of the heart. The individual vascular be ds that make up the systemic circulation are however linked in parallel. Only a part of the total systemic blood flow moves through each of these vascular beds. The resistance to flow in the vascular beds is however lower in the parts that are linked in series. Th is is because the total surface area of all vessels linked in parallel is larger. Blood flow is not uniform over the whole radius of the blood vessel. The blood c ells near the wall of the blood vessel tend to stick to the vessel and each other and flow is therefore slower here. In the middle of the blood vessel flow is straight and fa ster. This is called laminar flow. Interruption of laminar flow by obstructions in the blood vessel causes turbulent flow that can often be heard as a murmur with the aid of a stethoscope. Blood flow in the ventricles and aorta is normally turbulent which assists with the mixing of blood before it enters the systemic circulation. Turbulent bl ood flow in blood vessels is undesirable and could cause blood clot formation in the vess el. Flow velocity of blood Flow velocity is the distance a given volume of blood will move in a given time (mm/sec). Flow velocity is dependent on the total cross-sectional area of the blood vessel and the flow rate. If flow rate remains constant, blood flow will be faster through smal l vessels than large ones. Seeing that the total cross- sectional area of all the capillar ies is large, the flow velocity will be low in the capillaries. The flow velocity is the faste st in the arterial system and the lowest in capillaries and venules. Circulation and Vascular resistance Structure of the blood vessels Consists of 3 layers (exception being the capillary and venules): tunica interna , tunica media en tunica externa. Endothelium of the t. interna is in direct contact with the blood. The smooth muscle layer of the t. media contains elastin and collagen and is als

o innervated with sympathetic nerves. The tunica externa is a layer of connective tissue that keeps the blood vessel i n position. Types of blood vessels Arteries arterioles capillaries venules veins Arteries are distribution vessels: contain large diameter with low resistance Large arteries: Aorta en pulmonary arteries Elastic vessels: lots of elastin and collagen and little smooth muscle Functions: Temporary reservoir Pumps blood (elastic recoil) Monitor system for blood pressure (eg. Baroreceptors in carotid artery & aortic arch) Medium arteries: Cerebral arteries en brachial arteries Muscular arteries (little elastic and more smooth muscle) Functions: link between large and small arteries Arterioles (NB in the regulation of flow to the capillary bed) Distribution and resistance vessels Thick layer of smooth muscle richly supplied with sympathetic nerves; also sensi tive to some hormones and chemical changes in blood Is always partially constricted Functions: control vascular resistance and determines distribution of blood to d ifferent organs Helps regulate arterial blood pressure Veins Walls are thinner en diameter is larger than for arteries Veins are more compliant than arteries Have lots of smooth muscle and connective tissue Valves: prevent the back flow of blood (particularly in parts where vessels tend to be compressed, e.g. In skeletal muscle. Functions: i) transports blood from distal vascular bed to the heart ii) serves as a blood reservoir (66 % of blood) Capillaries Capillaries branch either directly out of arterioles, or from a metarteriole (is a conduit between arterioles en venules). Has largest cross-sectional area flow rate very slow Walls are very permeable Diameter: 3-8 m m; thickness: 1-2 m m 3 layers: endothelium basal lamina of proteoglycans thin collagen and reticular fibres NB: no smooth muscle and thus cannot alter diameter Functions: link between the blood and tissue for the exchange of: water, gasses, electrolytes, nutrients etc. Tissues that are metabolically active have a larger capillary bed. Pre-capillary sphincters Consists of a ring smooth muscle No nerve supply High myogenic tone and sensitive to local metabolic changes Functions: control blood flow through capillaries. Blood vessel compliance

Blood vessels are elastic and are stretched by blood, which is under pressure. T he degree to which a blood vessel is stretched is a function of its compliance and the pressure of the blood in the blood vessel. Compliance (C) = D V/ D P, where D V is the change in volume and D P, the change pressure applied to the vessel wall. The latter is the pressure inside the blood vessel minus the pressure outside the blood vessel. The more compliant the blood vessel , the greater the change in volume for a given transmural pressure. Blood pressure in the systemic circulation Blood pressure is the highest in the arteries and decreases gradually as it move s through the circulatory system. The decrease in blood pressure occurs as a resul t of the resistance to flow in the vessels this resistance to flow leads to a loss of energy. The rapid pressure increase that is generated with ventricular systole that forc es blood into the aorta, can be felt as a pulse. The pressure wave is transmitted b y the blood and moves about 10X faster than the blood itself. The intensity/strength o f the pulse decreases over a distance and is absent at the capillaries. Aorta and large arteries present little resistance against flow because they are elastic and serve as pressure reservoir/buffer that is used to propel blood while the he art is in diastole. Indeed, the arterial system temporarily absorbs some of the pressure t hat the ventricles generate. 95% of the energy is stored as potential energy in the aorta during systole. This energy is converted to kinetic energy during diastole to en sure the maintenance of flow of blood to the peripheral organs. Mean arterial blood pressure It is the mean pressure (blood pressure) in the arteries during the cardiac cycl e. When at rest, diastole lasts 2 as long as systole and therefore the mean arterial pre ssure (MAP) is therefore closer to the arterial diastolic pressure than the arterial s ystolic pressure. Mean arterial BP = diastolic pressure + (systolic pressure diastolic pressure) 3 The arterial pulse pressure curve Diagnostic value: pulse rate, pulse rhythm and blood volume Pulse pressure = syst BP diast BP = 120 80 mmHg = 40 mmHg In other words, the amount the pressure in the arteries rises by 40 mmHg during ventricular systole from 80 mmHg to 120 mmHg, and then drops again to 80 mmHg during ventricular diastole. Pulse pressure is therefore a function of stroke volume (volume of blood ejected during systole) and the compliance (elasticity) of the aorta. An increase in SV (at the same HR and total peripheral resistance) causes an inc rease in the stretch of the aorta, in other words, an increase in systolic BP and a highe

r pulse pressure, meaning a stronger pulse. The less the compliance (elasticity) of the aorta, the greater the rise in BP fo r a given change in volume, which thus results in a higher pulse pressure. Heart rate only has an effect on pulse pressure if it changes stroke volume. If HR increases so much that diastolic filling is reduced,then pulse pressure will fal l (weaker pulse) even if CO increased and MAP increased. Tachycardia is therefore usually associated with a decrease in pulse pressure (small SV), while bradycardia cause s an increase in pulse pressure (larger SV). Total peripheral resistance Arterioles contribute about 60% to the total peripheral resistance in the circul ation system. The total peripheral resistance is determined by the viscosity of the bl ood and the diameter of the vessels (mainly arterioles) that are being perfused. Remembe r R 1/r4 (where r = radius of the blood vessels) is controlled by reflexes (extrinsi c) and local (intrinsic) control mechanisms. Vasoconstriction and vasodilatation of arterioles is achieved by autonomic nervo us system control of the smooth muscle of arterioles. Circulating hormones (extrins ic control), neurotransmitters from autonomic nerves (extrinsic control) and other locally produced metabolites (intrinsic control) also play a role. Intrinsic control / myogenic autoregulation An increase in blood pressure will lead to an increase in blood flow. Smooth mus cle in the arteriole however has the ability to contract when the blood vessel wall is stretched by an increased pressure. This will in turn cause an increase in resis tance and a decrease in blood flow. This allows arterioles to regulate flow directly so th at blood flow to a specific capillary bed in an organ can be regulated independent of MAP . The mechanism by which the arteriole contracts is unknown. There is however a sugges tion that stretch opens the Ca2+ channels and that the smooth muscle then contracts. Some tissues have a high tone (the skin and resting skeletal muscle), while others ha ve a low tone under resting conditions (e.g. cerebral and coronary vessels). In numerous tissues this characteristic is used to regulate blood flow to satisfy metabolic requirem ents of the tissue. When blood pressure suddenly increases (and the blood flow to the ti ssue increases), the vessel reacts by vasoconstricting. The tissue can therefore norm alise blood flow to original levels through auto-regulation. Mechanisms responsible for auto-regulation: Increased tissue pressure (edema increases extra-vascular pressure and compressi on). Myogenic effect: stretch of smooth muscle causes contraction of the muscle. Vasodilators that are released (local effects), e.g. NO, CO2, lactate, K+ , pros

taglandins and adenosine, and histamine. Active hyperemia is an increase in blood flow to tissues as a result of an incre ase in the metabolic rate of the tissue. Reactive hyperemia is the increase in blood flow to tissue after a period of red uced/mal perfusion of the tissue. Extrinsic control Hormones Vasodilators such as bradykinin and histamine can be produced at one site and re leased via the circulation at another where it can have its effects. Noradrenaline (from the adrenal medulla), angiotensin II (from the kidney) and A DH (from the pituitary gland) cause vasoconstriction when present in adequate amoun ts. Neural control Sympathetic vasoconstrictor fibres to arteries, arterioles and veins. Transmitter: nor-adrenaline. Stimulation causes vasoconstriction and increased arteriolar resistance. Sympathetic vasodilator fibres (restricted distribution, NB. in skeletal muscle) . The venous system The walls of veins are relatively thin and contain little elastin which means th at blood returning to the heart can accumulate in the veins. The extent to which blood accumulates in the veins is determined by the tone of the smooth muscle (known a s the veno-motor tone). The venous smooth muscle tone is controlled by the activity of the sympathetic nerves that innervate these vessels. When the cardiac output is elevated as is the case with exercise, the veno-motor tone increases and the veins vasoconstrict. The result is that blood that accumulates in the veins is mobilized and is spread to the active muscles and tissues. Blood will a lso return to the heart faster under these conditions. Venous function and compliance The venous system is far more (20-25 times) compliant than the arterial system. In this system a large change in blood volume therefore causes a small change in pressur e. The smooth muscle in the wall of the veins is under the influence of the sympath etic constrictor fibres and increased sympathetic stimulation of the smooth muscle wi ll cause an increased pressure in the veins. This will promote venous return to the heart. Venous return The return of blood from the peripheral tissue to the heart (venous return) is a function of the venous pressure gradient ( 15 mmHg peripheral venous pressure mmHg right atrial pressure). Any factors that increase this gradient, promotes v enous return, while factors that decrease the gradient, decrease venous return. Change s in venous return are reflected in changes in cardiac output. A decrease in arteriolar resistance causes an increase in the peripheral venous pressure. This increases the pressure gradient (provided the pressure in the rig

ht atrium remains constant) and consequently the cardiac output. If the pressure in the right atrium rises by the same degree, the pressure gradient will not increase. The increased blood volume will then remain in the veins. Venous return is influenced by: Pressure in the RA Total blood volume Sympathetic influence on veins Skeletal muscle pump Respiratory pump The skeletal muscle pump When skeletal muscle contracts, veins that run through the muscle is compressed. The presence of valves in the veins ensures that blood that has been squeezed out of the veins does not flow back. Blood is therefore forced in the direction of the hear t. When the muscle pump is inactive, blood accumulates in the veins. This causes an incr ease in peripheral venous pressure and central venous pressure. The drop in venous retur n causes a drop in stroke volume and cardiac output. Soldiers/guards that have to stand on the spot for a long time often faint. This can be prevented by contracting an d relaxing the skeletal muscles in the lower extremities. The skeletal muscle pump can improve venous return and cardiac output. The respiratory pump Venous return is also influenced by breathing. During inspiration, the thoracic cavity enlarges and the intrathoracic pressure decreases below that of atmospheric pres sure. This low pressure causes a decrease in pressure in the inferior vena cava and ce ntral venous pressure decreases. This causes more blood to flow from the abdominal vei ns to the vena cava. The expansion of the thoracic cavity also applies pressure on the abdominal veins, pressing blood out of them. These factors promote the movement of blood from the abdomen to the thorax. During expiration, the situation is revers ed. Systemic blood pressure measurement Arterial blood pressure (blood pressure) is the pressure that is generated by th e pump action of the heart and is the main pressure that drives blood forward through t he vasculature. Although arterial pressure is not stable (varies between the SP and DP), it is useful to have a single pressure value to quantify the driving force which mo ves the blood through the blood vessels. Mean arterial BP (MAP) = Diast BP + (syst. BP - diast. BP) 3 Normal BP = 120/80 mmHg Indirect measurements: sphygmomanometer Direct measurement: Swan Ganz catheter BP is lower in:

Small children Women up to menopause In the lying position BP is higher in: Older people Persons that are obese During psychological stress During exercise Indirect determination of blood pressure. Systolic pressure is the highest pressure in the arteries during systole and is due to the ejection of blood from the ventricles. Diastolic pressure is the lowest pressure in the arteries during ventricular dia stole. Physiological factor that determine BP BP = CO x peripheral resistance CO = SV x HR but the two factors will only play a role if cardiac output changes . If cardiac output decreases then BP will be maintained by peripheral vasoconstricti on. If CO increases as is the case during exercise, mean arterial blood pressure will r emain constant if there is peripheral vasodilatation (total peripheral resistance decr eases). Peripheral resistance: resistance the blood experiences in the circulatory syste m. Elastic vessels: mechanical pump Volume of blood: is normally maintained constant. Compensation for a decrease in blood volume is more complex and normally require s an integrated response by both the kidneys and the CVS. The kidneys do not replace the lost blood but maintain the blood volume and prevent a further loss in blood pre ssure. The solution is to take in fluids by mouth or via intravenous drip administratio n. The cardiovascular adaptations are restricted to vasoconstriction and increased sympathetic activity to the heart. Viscosity of blood: Number of RBC and plasma proteins determine viscosity It remains more or less constant Plays a role in peripheral resistance Control of blood pressure Blood pressure is the driving force that propels blood through the body and the maintenance of blood pressure is therefore essential for the proper perfusion of organ such as the brain, heart and central nervous system. Blood pressure is maintaine d by the cardiovascular control centre in the medulla oblongata, and monitored by pre ssure sensors in the CVS. The information is then integrated by the control center and various effectors will, through various mechanisms, modulate BP if necessary. Short term process that influence BP within seconds to hours Neural control (ANS) and baroreceptors CO and arteriolar diameter Long term processes that influence BP lasts days to weeks Hormonal and renal Peripheral resistance and blood volume Short term control of blood pressure Neural control

Sensors: baroreceptors (stretch receptors) Aortic arch and carotid sinus Muscle of the RA, LA, LV and pulmonary arteries With stretch, the frequency of the action potentials increases in the nerve fibr es, while shrinking of the chamber walls has the opposite effect. The stretch receptors monitor both the absolute pressure and the rate at which t he pressure changes. These receptors adapt to pressure changes quickly. Integrator: medulla Consists of 2 areas of importance: The sensory area where sensory information is received The vasomotor centre from where impulses are sent out The sensory area Various receptors in CVS project to this area: baroreceptors, volume receptors, chemoreceptors and other visceral receptors There are also projections from the brain cortex and hypothalamus The vasomotor centre Pressor area Efferent impulses by sympathetic nervous system to: Smooth muscle of blood vessels: increase muscle tone SA and AV-node, conduction tissue: (+) chronotropic and (+) dromotropic Atrial and ventricular muscle: (+) inotropic Depressor area Impulses to the SA and AV node: (-) chronotropic Effectors All blood vessels, except capillaries and venules, contain smooth muscle and are innervated with sympathetic neurons. The heart receives both sympathetic and parasympathetic nerve fibres. The baroreceptor reflex The reflex is the primary homeostatic control mechanism for day to day and minut e to minute control of BP. Baroreceptors that are sensitive to stretch are located in the carotid sinus and aortic arch. The receptors monitor the pressure of the blood t o the body (aorta) and brain (carotid). The two receptors are tonically active and gen erate APs at normal BPs. With increased pressure, more action potentials are generated and at lower BPs, fewer action potentials are generated by the receptors. When arterial blood pressure is elevated for more than 15 minutes the threshold for baroreceptor activity changes to a higher threshold. This property restricts baroreceptors to being effective only in maintaining BP for the short term perio ds. A good example of this change in the threshold of the baroreceptor is during pro longed exercise where the systolic blood pressure can be elevated for prolonged periods of time. BARORECEPTOR REFLEX Body position/posture and blood pressure When one lies down, blood is evenly spread through the body. Once one stands up, blood pools in the veins of the lower extremities and venous return decreases. The res ult is a decrease in CO and blood pressure. This drop in blood pressure is termed orthost atic hypotension. The carotid and aortic baroreceptors register this decrease in BP a

nd rectify this BP drop by the baroreceptor reflex. Virtually the opposite of what was seen in the diagram on the previous page where increased blood pressure was the cause of baroreceptor activation. Long term control of BP Humoral control Angiotensin II: powerful vasoconstrictor Noradrenaline: via a 1-adrenergic receptor of arterioles vasoconstriction (there fore peripheral resistance) Adrenaline: At physiological concentrations: via b 2adrenergic receptors in blood vessels of skeletal muscle, liver and heart vasodilatation (therefore in peripheral resistance) High concentrations: via a 1-adrenergic receptors vasoconstriction ADH: under the control of the hypothalamus released from the pituitary the permeability of the distal collecting duct in the kidney to water causes uri ne concentration to increase. Stimuli for ADH release: plasma osmolarity atrial stretch ( activation of stretch receptors) stress situations (surgery, physical injury) effects: water retention peripheral vasoconstriction ( vascular resistance). Only in high concentrations, as is the case during severe volume loss. Chemical control of BP Chemoreceptor stimulation of the vasomotor centre: primary function is to contro l breathing Peripheral chemoreceptors; carotid- and aorta bodies Increased impulse frequency with: decrease in PaO2 (hypoxia) increased PaCO2 lowered pH (acidosis) Central chemoreceptors: medulla increased PaCO2 decreased pH Moderate changes in blood gas levels influence breathing, external changes can however also influence BP. Response: reflex vasoconstriction of arterioles and large veins of the splancnic circulati on. vasodilatation of the myocardial and cerebral vessels. increased HR and increased CO \ BP