Physiology, Vascular

Organ Systems Involved

The perfusion of tissues through vessels is dependent on the adequate pumping function of the heart. Arteries carry blood away from the heart, with veins transporting blood back to it. The microcirculation becomes progressively thinner in terms of wall thickness at the level of the capillaries to promote the necessary exchange of gases and metabolites, and removal of waste. Except for the capillaries (endothelial cells only), the wall of these vessel conduits consists of three layers, an inner intima, a middle media, and an outer adventitia. Of the intrinsic vessel wall components, endothelial cells form a thin non-fenestrated layer connected by tight junctions in most arteries, veins, and capillaries of the circulatory system to regulate homeostasis. Fenestrated endothelial cells are present in the circulatory beds of the gastrointestinal tract, kidneys, and endocrine/exocrine glands, where increased transport and filtration exists. Vascular SMCs (vSMCs) are a second component that is absent in capillaries but exists elsewhere to provide tension via its contractile properties.[2] However, the elastic tension of the vascular wall is mostly mediated by collagen and elastic fiber components, the former, composed of type I and III collagen, is less extensible, while the latter, composed of elastin and myofibrils, accommodates most of vessel distension ability with pressure.[3][4] While neither fiber component exists in the capillaries, a more substantial elastic fiber component is present in the large elastic arteries (e.g., the aorta) compared to the large veins (e.g., vena cava), which relates to the ability for arteries to withstand transmural (full-thickness) pressure differences better. At the level of the muscular arteries, and the arteriolar component of the microcirculation, more SMC components are seen to facilitate necessary contraction for blood flow regulation.

Function

Quite broadly, the vascular system distributes, exchanges, and collects gas and metabolites to and from the heart in coordination with ventilation by the lungs. Of the conduits away from the heart, the elastic arteries maintain a potential energy gradient necessary to maintain flow with high pressure during the diastolic period of the heart. The muscular arteries and arterioles are where the regulation of blood flow most occurs, with arterioles having the capacity to convert pulsatile flow to steady flow creating the greatest drop in pressure.[5] Conversely, the arterioles occupy the greatest vascular resistance. At the thinnest part of the microcirculation, the capillaries are responsible for the actual exchange of nutrients and oxygen to the tissue bed, and in return removing metabolic byproducts and waste. To this aim, the mechanisms utilized by the capillaries include diffusion, bulk flow, and carrier-mediated transport.[6] Regarding conduits transmitting flow to the heart, veins serve as low-pressure reservoirs of fluids in addition to being conduits and do have some smooth muscle cells that permit venoconstriction to maintain blood pressure. Thus, the circulatory system can be split into a high-pressure system, extending from the contracted left ventricle to the systemic arterioles, and a low-pressure system, extending from the capillaries, through the veins and right heart, and into the lung and back to the relaxed left heart. Likewise, the pulmonary circuit (10% of the circulation) is a low-pressure system with low intravascular pressure, compared to the systemic circuit (85% of the circulation, remaining 5% is in the heart) with a higher intravascular pressure.[7]

Mechanism

Relationship of pressure, flow, and resistance in fluid movement

Fundamental to understanding hemodynamics, the functional basis of the vascular system is to appreciate the relationship between intravascular pressure (P), vascular resistance (R), and flow (F). Thinking broadly, resistance refers to the opposition to flow and is mediated directly by vSMCs, whereas pressure is a measurement of force. The gradient in pressure creates a conversion of potential to kinetic energy, which is flow. The change in P between two points in the circulation is determined by the R between them and the F, delta P = FxR. However, R depends for one on the average radius of the vessel, as described by the inverse of Poiseuille’s flow equation, R = 8nL/pi(delta P)r, where ‘r’ is the radius of the vessel, ‘n’ is the viscosity of the fluid, and ‘L’ is the length of the vessel. Second, R also depends on the number of vessels in parallel, where parallel circuits confer lower R (relative to circuits in series). Therefore, this explains why the aggregated R is highest in the arterioles, as while a capillary has higher individual R than an individual arteriole, capillaries exist far more than arterioles.[8] Within the microcirculation, the precapillary R and postcapillary R determine capillary P, which influences the movement of fluid between the capillaries and the interstitial fluid. Normally, the postcapillary R is lower than the precapillary R, but in cases of arteriolar constriction or venular dilation, an increase in the magnitude of this difference occurs dropping capillary hydrostatic pressure and decreasing the driving force for movement of fluid out of the capillaries. Conversely, with arteriolar dilation or venular constriction, the precapillary R can become lower than the postcapillary R, which raises the capillary hydrostatic pressure and can promote transudation of fluid from the capillaries into the interstitial fluid.

Pressure and blood flow of elastic vascular vessels

It is pertinent to realize that the Poiseuille flow equation is modeled after flow in a rigid tube, corresponding to a linear pressure-flow relationship. However, as described, arteries and veins contain elastic properties that alter the relationship between pressure and flow. Due to the capacity of elastic vessels to distend, thus increasing the vessel radius, resistance is able to decrease to facilitate an increase in flow as a nonlinear relationship. Likewise, the concept of distensibility, or ability to withstand transmural pressure, is mediated by the content of elastic and collagen fibers. An appropriate index of distensibility is compliance (C), where C = delta volume/delta pressure and is a localized measurement.  It is the difference in compliance between arteries (low compliance) and veins (high compliance) that stratify their function as resistance vessels and capacitance vessels, respectively. However, while the compliance of these conduits of the vascular system is to accommodate the flow of fluid, the outward transmural pressure that creates distension must be balanced by the ability of the vascular wall to apply and adapt to tension. Hooke’s law (Force = k x (delta L), where k = the spring constant, and delta L is the change in length) models the force necessary for deformation by an elastic solid such as a spring. This deformation force over a specified cross-sectional area refers to the stress (deformation force/cross-sectional area = stress). To avoid a breaking point, such stress must be countered by an appropriate fractional change in length, or strain, which is modulated by a proportionality factor, Young’s elastic modulus, that is specific to material undergoing deformation. Applying these principles of stress and strain allow one to understand the opposing tension force against transmural pressure. Tension (T) is a circumferential force and is modeled by Laplace’s equation, T = transmural pressure x r, where r is the vessel radius, and is expressed in units of ‘dynes/cm’, and is closely related to stress. Likewise, by this relationship, the wall tension is highest in the stiffer aorta and small arteries, followed by the vena cava, corresponding to not simply higher transmural pressures but also elastic tissue components as well. To note, the vSMC can reduce the radius of a vessel to provide a component of active tension that decreases the tension required by muscle exertion. In fact, such local vSMC control is modulated by extrinsic factors such as hormones, cytokines, oxygen free radicals, or shearing forces.

Pathophysiology

The pathophysiology related to vascular physiology is rooted in the hemodynamic parameters described. Among several associated conditions, the following are common sequelae to consider:

• Aging/Hypertension: Most notably with the aorta, there is a decrease in compliance with age due to a loss in elasticity.[9] The stiffer vessel is also due to an increase in fibrotic changes with an increase in collagen fibers and their cross-linking. Thus with older age, higher blood pressures become prevalent. Likewise, the pathophysiology of hypertension is similar to risk factors such as diabetes, hypercholesterolemia, and cigarette smoking contributing to the same arteriosclerotic changes.
• Vessel Aneurysm: With a loss or defective elastic components of a vessel, as noted with connective tissue diseases, the outward transmural pressure (distension) can be unbalanced with an inadequate tension force (as applied by Laplace), which allows for an aneurysm to form which is susceptible to rupture.[10] The aneurysmal rupture in the brain results in life-threatening subarachnoid hemorrhage. 
• Atherosclerosis: In cases where the stress to move fluid forward (same stress that causes deformation of the vessel) is too large, due to changes in blood components, for example, smooth laminar flow is broken. Such flow can disrupt the endothelial layer of the vessel causing a proinflammatory response with the release of several pro-atherogenic factors (i.e., interleukin-1, tumor necrosis factor, and plasminogen activator inhibitor-1) that lead to the formation and progression of atherosclerotic plaque.[11]
• Dissection: When there is severe stress on the vessel wall that can lead to dissection of the blood vessel. Cervicocerebral dissection occurs commonly in young people. It can be due to various reasons, including trauma, fibromuscular dysplasia, Marfan syndrome, and several other causes. Up to one-half of the patients have a headache. Usually, the extracranial dissection is associated with good prognosis. 
• Reversible Cerebral Vasoconstriction Syndrome: This is associated with vasoconstrictive medications, pregnancy, illicit drugs, etc. Most patients have severe thunderclap headache. It presents as subarachnoid hemorrhages, ischemic stroke, and lobar hemorrhages. Calcium channel blockers are the initial therapy. The recurrence is rare. 

Clinical Significance

The following items are pertinent to the clinical assessment of the status of the vascular system:

• Blood pressure (BP): normal BP -  less than 120 (systolic [S]) and  under 80 (diastolic [D]); elevated BP - 120 to 129 S and less than 80 D; hypertension stage 1: 130 to 139 S or 80 to 89 D; hypertension stage 2: over 140 S or greater than 90 D; hypertensive crisis: over 180 S and/or greater than 120 D.[12]
• Pulses - Palpation in the arterial regions of the carotid, femoral, popliteal, dorsalis pedis, posterior tibial, etc. for the distribution of blood flow.
• Bruit – Auscultation for vibration sound localized to an arterial wall that is caused by turbulence and suggests a lesion.
• Skin findings – Cyanosis, pallor, edema, and ulceration can indicate a vascular etiology. With ulceration, distal ulceration of the foot is more associated with an arterial etiology compared to ulceration of the malleolar region, which better suggests a venous cause.
• Capillary refill – Refers to the amount of time required for refill after compression of a nailbed, and indicates perfusion status.