Vessel Wall Biology

Large Arteries

The arterial system commences with the aorta and its branches, whose primary function is to provide a conduit for blood flow to the peripheral tissues and to smooth out the pulsations of intermittent ventricular ejection. In general, larger arteries are elastic arteries while smaller arteries are muscular arteries. The larger arteries are predominantly under control of downstream resistance vessels, and there is little evidence that vasomotor changes in large arteries occur independently of those in small resistive arteries. Changes in caliber of large arteries occur passively through changes in transmural pressure and actively through changes in vascular smooth muscle cell (SMC) contraction. Arteriolar vasomotion may induce systemic or local blood pressure changes that alter the diameter of the artery and its viscoelastic properties. Arteriolar constriction or dilation may also modify arterial SMC tone through the endothelium-dependent mechanism of high-flow dilation.

The large arteries cushion the pulsations that are characterized by the relationships between oscillatory pressure, flow, and frequency, which in turn depend on arterial diameter and elasticity. Because of their significant size, the aorta and the large arteries offer little resistance to blood flow. Large arteries store a large portion of the blood volume during systole and drain it during diastole. They are able to accommodate the stroke volume ejected with each contraction of the heart. This ability allows for propagation of the pulse and also offers dynamic resistance to the oscillatory components of pulsatile flow.

Blood pressure is highest at the origin of systemic circulation, although decreases in blood pressure are not linear with vessel diameter or distance down the vascular tree. Blood pressure decreases to 30% to 40% of aortic pressure in vessels 250 to 50 μm in diameter. Significant pressure drop occurs in the terminal arterioles, which branch into small capillaries with diameters less than 100 μm ( Fig. 3.1 ). In vessels smaller than 60 μm, no correlation has been found between central arterial pressure and microvascular pressure, suggesting that perfusion pressure is controlled directly in these blood vessels and those with smaller diameters.

Small Arteries

Small arteries are considered muscular arteries and are involved in vascular resistance. Initially, it was believed that resistance arteries consisted solely of arterioles with only one layer of SMC and diameters of less than 30 to 50 μm. However, approximately 50% of precapillary resistance lies proximal to the arterioles and to vessels with diameters of <100 μm. The resistance provided by a small artery is a function of the diameter–pressure relation. This compliance depends on the amount, arrangement, and characteristics of the connective tissues and SMC and on the activation level of SMC. There are approximately six layers of SMC in 300-μm vessels that decrease to a monolayer in 30- to 50-μm arterioles. The volume fraction of SMC in the media of small arteries as seen by electron micrographs is from 70% to 85%, a fraction that is greater than in larger vessels.

Arterioles

Arterioles are the chief source of vascular resistance and control the distribution of flow. Smooth muscle contraction and dilation is the primary source of vascular resistance. Abnormal constriction and dilation cause systemic hypertension and hypotension, respectively. The regulation of constriction and dilation is controlled by both sympathetic and parasympathetic innervation. Vasomotor responses depend on arteriolar territory, as in the case of emotional stress; emotional stress dilates arterioles of skeletal muscles through activation of cholinergic vasodilator fibers and release of epinephrine, while it constricts the splanchnic and renal arterioles.

Capillaries

Capillaries are responsible for the transfer of nutrient materials and waste products between blood and tissues. The blood volume of all capillaries is significantly larger than that of the aorta, causing a decrease in blood pressure and flow rate. The low rate of blood flow and large surface area facilitate the provision of nutrients and oxygen to surrounding tissue; the absorption of nutrients, waste products, and carbon dioxide; and the excretion of waste products from the body. Capillaries have a wide variety of configurations dependent on the structure of the endothelium, which is in turn related to the function of their specific vascular bed. They may be nonfenestrated continuous, fenestrated continuous, or discontinuous ( Fig. 3.2 ).

Nonfenestrated continuous endothelium functions as a selective filter and exists in capillaries all throughout the body. Fenestrated endothelium occurs in locations of increased filtration or transendothelial transport, including the capillaries of exocrine and endocrine glands, gastric and intestinal mucosa, choroid plexus, glomeruli, and renal tubules. The majority of fenestrae have a 5- to 6-nm nonmembranous diaphragm across their openings, although fenestral density varies in differing vascular beds and increases with greater need to absorb or secrete. Discontinuous endothelium possesses larger fenestrations, ranging from 100 to 200 nm in diameter. These fenestrations lack a diaphragm and contain gaps or pores within individual cells. Such capillaries form large irregularly shaped vessels, such as in hepatic sinusoids.

Venules

Postcapillary venules are the smallest of venous vessels and form from the confluence of several capillaries. Their dimensions have ranges of 50 to 650 μm in length and 10 to 50 μm in diameter. Similar in structure to large capillaries, they have an endothelium and pericytes but no SMC layer. The attenuated endothelium is 0.2 to 0.4 μm wide. The endothelium is loosely organized and leaky with only a few intercellular junctions linking cells. A thin basal lamina is present. Given these characteristics and their slow flow, they are the main sites for white blood cell diapedesis and tissue exudate from circulation to interstitial tissue during inflammation. ^, Postcapillary venules drain into collecting venules, which are larger but structurally similar with more pericytes. These continue to drain into muscular venules, which have one or two layers of SMC.

Veins

Veins form from the confluence of multiple venules. Typical small and medium-sized veins are 1 to 9 mm in diameter and contain valves. Compliance is extremely high for veins in comparison with arteries. A relaxed vein can increase in volume by up to 200% for a small increase in transmural pressure from 0 to 10 mm Hg. This increase reflects a change in geometry, with a low-pressure vein having an ellipsoidal cross-section that becomes circular with a small pressure increase, greatly enlarging the cross-sectional area. The adventitia, usually the thickest layer, consists primarily of longitudinally oriented collagen fibers. It may be continuous with the surrounding collagen of the supporting tissue.

Venae Cavae

The superior and inferior venae cavae are the largest veins and deliver deoxygenated blood into the right atrium of the heart. At the entrance to the heart, venae cavae and pulmonary veins have extensive vasa vasorum and can have a small amount of cardiac tissue in the adventitia. Other large systemic veins, such as the portal, pulmonary, azygos, splenic, and mesenteric veins, have similar features. The innermost layers have a distinct layer of fibroelastic tissue and a thin layer of circumferentially oriented SMC. A thick adventitia is most notable for the numerous bundles of longitudinally oriented collagen and smooth muscle fibers. Elastic fibers may be scattered throughout all the layers.

Lymphatics

The lymphatic system is a unidirectional flow network originating in the interstitial space throughout the body, draining fluid from the ECM into initial lymphatics, which in turn contribute to gradually larger precollecting lymphatics, collecting lymphatics, trunks, and ducts.

Initial Lymphatics

The lymphatic system starts in connective tissue spaces at blind-ended vessels called initial lymphatics. These are most abundant in the connective tissue of the skin; beneath the mucous membranes of the respiratory, gastrointestinal, and genitourinary tracts; and in the connective tissue of the liver. Skin on the lower extremities has a denser network of lymphatics than other areas. The capacity for transport is also higher in the lower extremities to compensate for increased interstitial fluid filtration due to gravity.

The influx of lymph is enabled by endothelial microvalves. When the vessels are collapsed, the endothelial cells (EC) have overlapping extensions of cell membrane interconnected by discontinuous buttonlike junctions. Gaps are made possible by anchoring filaments, 6 to 10 nm in diameter, that anchor the EC externally to the surrounding connective tissue. ^, When the interstitial fluid pressure increases and the surrounding matrix expands, the EC anchored to this matrix are prevented from collapsing and allow fluid to flow through the resultant gaps between them. As the interstitial fluid decreases and internal pressure rises, the EC come together, overlap, and the gaps close ( Fig. 3.3 ). In this way, the unidirectional flow of lymph into the lymphatics is ensured.