Physiology of the Peripheral Vascular System Ricardo T. Quintos, MD Associate Professor University of the Philippines College of Medicine inhis treatise Exercitatio Anatomica de ‘Mow Cordis et Sanguiniy, published in 1628, William Harvey (1578-1657) first described the closed circulation of blood. This book is considered to be the most important and most valuable book in the history of medicine. Systemic blood pressure was first measured in a horse in 1733 by Stephen Hales (1677-1761). In 1828 the mercury manometer was invented by Jean Leonard Marie Poiseuille (1799- 1869), who first described the factors controiling the flow of fluids through cylindrical tubes. Notable contributions by Emest Henry Starling (1866-1927) and others gave vascular physiology a firm foundation in anatomy, physics, biochemistry, and now molecular biology. General Structure and Function ‘The systemic circulation is made up of all the blood vessels between the aortic root and the right atrium. Each segment of the circulation has an ideal and distinctive combination of size, wall thickness, wall composition, cross-sectional area, and blood flow velocity that best fulfills its function (Table 1). The aorta and large arteries have thick walls with high collagen and elastin contents and function primarily to deliver and distribute blood under high pressure to the various tissue beds. Smaller arteries and arterioles, with larger proportions of smooth muscle, act as variable resistors, dynamically directing blood flow to individual organs and tissue beds according to changing local needs. The microcirculation, consisting of capillaries and venuies with walls that are’one cell layer thick, delivers oxygen, nutrients, and biologically active substances to individual cells and collects carbon dioxide, metabolic byproducts, and locally synthesized agents for transport to other locations. The venous system is a collection network that also has a capacitance function that moderates the volume of blood returned to the right heart as part of the control of cardiac output. The lymphatic system primarily collects surplus interstitial fluid and proteia from the interstitial spaces and retums it to the venous system. Table 1. Relationship between arterial size, cross-sectional area, blood flow velocity and fraction of blood volume. . Diameter Gross Mlow Fraction’ (cm) sectional ‘Velocity of blood Vesa 3 area (cm/sec) volume (ema) (%) ‘Aare, 2 3 30 10 Asteriole 3x10 800 On 1 Capillaries 810-4 3500 0.026 3s Vena 3 7 4 5 Cava {ibe bean coniaing 10% of blood volume A HF ‘The circulation is a continuous closed system, and although brief pooling may occur, cardiac output must equal the sum of the regional flows. Further, the pulmonary and systemic flows must remain equal over time. ‘The proportion of the blood volume contained in each segment of the systemic circulation is also shown in Table 1. At any time the major portion of the blood volume is in the venous circulation, which acts as a féservoir. Although only 5 percent of the blood volume is in the capillary bed, the totalsurface area of the capillary bed is enormous. The capillary beds and sinusoids of the spleen, liver, splanchnic veins, and subcutaneous plexi may also aet as specific blood reservoirs. Arterial structure and function All arteries are formed by an intima, a media and an adventitia. ‘The intima consists of a thin monolayer of endothelial cells, covered by a layer of glycoprotein (glycocalyx) on the luminal surface. ‘The internal elastic lamina separates the intima from the media. The media comprises smooth muscle cells in an elastin and collagen matrix. The elastin permits distension of the artery while the collagen bundles provide tensile strength, limit distension, and prevent disruption. The thickness of the media is closely related to the radius of the artery. The adventitia is separated from the media, in some arteries, by an external elastic lamina. The adventitia consists of sparse fibroblasts with layers of elastin and collagen fibers, adding further strength to the wall. It merges with the loose connective tissue that surrounds all vessels. ‘There is a gradual diminution in the size of the arteries as they progress from the aorta to the precapillary arterioles. This is accompanied by a progressive ‘increase in cross-sectional area and a proportional reduction in blood flow velocity. The elastic or conducting arteries (aorta, innominate, subclavian, common carotid, and common iliac arteries) have a large elastin component in the media that allows distension, blood pooling, and storing of potential energy during cardiac systole and then recoil during diastole afier aortic valve closure (Windkessel effect). ‘This capacitance function serves to modulate a more uniform flow and pressure into the distributive and muscular arteries, also known as resistance arteries. The muscular arteries tat comprise most of the arterial tree are characterized b dense smooth muscle in the ‘media that is capable of changing luminal size. Blood flow can be directed into individual regional beds according to varying needs. The smooth muscle in the media not only has the ability to contract and maintain arterial tone but also can synthesize connective tissue proteins. The thickness of the media in arteries varies depending on the internal pressure and external forces to which they are ‘ezposed, ¢.g., the media is thicker in arteries of the lower extremity than the upper extremity. Microcirculation structure and function ‘The microcirculation comprises arterioles, metarterioles (or terminal arterioles), precapillary sphincters, capillaries, venules, and arteriolovenular anastomoses (or thoroughfare channels). Each arteriole feeds a microcirculatory unit consisting of 10 to 100 capillaries, which results in a dramatic increase in cross-sectional area and reduction in blood flow velocity, thereby allowing prolonged contact times for metabolic exchanges to take place. These exchanges between the circulation and the extravascular compartment occur mainly across capillaries and venules, with the venous end being more permeable to water and solutes than the arteriolar end. Precapillary sphincters function to control flow into regional beds by varying resistance according to the specific metabolic needs. Direct arteriolovenular anastomoses, usually side branches from terminal arterioles, may shunt blood directly into the venous bed, bypassing the capillary bed. In the skin, these shunts play an important role in regulating heat loss and controlling body temperature. ‘Transport across the capillary from the Juminal to the abluminal surface is the subject of intense research and is certainly one of the most fundamental events in biology. Simple diffusion is controlled by osmotic gradients and moves water and small water-or fat- soluble molecules across the endothelial lining. This is the primary mechanism for exchange of gases, nutrients, and wast products between tissue cells and the blood. Because the diffusion is so unrestricted and 2rapid, the concentration gradient across the capillary wall is a function of the delivery rate of blood flow. Starling’s Law. The movement of water between the capillary lumen and interstitial space is controlled by the net effect of the intraluminal hydrostatic pressure and the relative osmotic pressure, a phenomenon described by Starling in 1896. The entering pressure into the capillary bed is approximately 30mmHg and the exiting pressure approximately 10-15mmHg. The interstitial fluid pressure may actually be slightly negative, increasing the total pressure gradient across the capillary. The osmotic pressure of blood, which draws water intravascularly, is produced largely by the plasma proteins, especially albumin. Net movement of water across a particular point in the microcirculation is therefore determined by the sum of the net hydrostatic pressure and net ‘osmotic pressure of the intravascular space and the interstitial space. teq. 1) Net filtration rate = (Pe — Pi) - (uc ~ al) where Pe = hydrostatic pressure of intracapillary fluid xe = oncotic pressure of intracapillary fluid Pi and ai = same quantities for interstitial fluid In addition to these pressure effects, the movement of fluid across the capillary is further determined by capillary area, viscosity of the filtrate, and wall thickness, with viscosity and wall thickness exerting a hindering effect. These factors define the capillary filtration coefficient, which is a ‘measure of capillary permeability and surface area ‘Venons structure and function ‘The venous system is a large reservoir that contains up to three quarters of the blood volume. Several capillaries join to form a venule, which join to form veins. Running along with the arteries, although more numerous, the veins gradually increase in size and decrease in number as they channel blood back to the heart. Alll veins large enough to be visible contain smooth muscle elements. Larger veins have an intima, media and adventitia, but the layers are less distinct than in arteries. The muscular and elastic tissue is not as well developed, but the connective tissue is more prominent. The thickness of the muscular layer is related to the hydrostatic pressure, therefore, more dependent veins have thicker walls. Veins of medium caliber, particularly of the extremities, have bicuspid valves that ensure a unidirectional flow to the heart, Large internal veins such as the vena cava, common iliac, hepatic, renal, mesenteric, splenic and portal veins, are valveless. ‘Venous pressure dynamics are important to the understanding of the pathophysiology of some venous discases and the tests used to diagnose them. Normally, venous pressure is Jow in the recumbent position (10-12mmHg) but rises upon standing (90-100mmHg at the foot). In normal individuals, as much as 15-20 percent of the blood volume may be lost by standing still due to fluid extravasation from the increased hydrostatic pressure, resulting in a drop in cardiac output, The contraction and relaxation of muscles within the confined fascial compartments of the lower extremities compress the veins and help pump venous blood back to the heart, This muscle pump functions as a peripheral heart and provides up to one third of the energy required for the circulation of the blood. Lymphatic structure and function ‘The lymph capillaries parallel the blood capillaries in most tissues, the major exceptions being the central nervous system, 3cartilage, bone, and bone marrow. The lymphatic system is an open draipage system, with the lymph capillaries originating blindly in the interstitial spaces. The lymph capillaries feed into the larger lymphatic vessels that coalesce to form the thoracic and right lymphatic ducts. These then enter the subclavian veins on each side near their junctions with the internal jugular veins. On their way to join the venous circulation, lymphatic channels course through numerous iymph nodes (about 1000 in humans) that act as filters, tapping bacteria and other particulate matter. Like veins, lymphatics contain valves that promote unidirectional Hlow toward the larger ducts in the neck. This largely passive lymphatic circulation is maintained by such processes as tissue pressure, muscle contractions, respiratory movemeats, and arterial pulsations. Lymph, made up of water, electrolytes, and. protein, serves mainly to conserve plasma proteins lost through the biood capillary walls and as a filtration system through the lymph nodes to scavenge foreign material, bacteria, and antigenic substances. In the gastrointestinal tract, lymph flow contributes {© the transport of absorbed nutrients, especially Fat, into the circulation.