Porth's Essentials of Pathophysiology, 4e

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Disorders of Blood Flow and Blood Pressure

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tially reversible changes in endothelial function that occur in response to environmental stimuli. Endothelial cell dysfunction has been implicated in a number of pathologies including thrombosis, atherosclerosis, and hypertensive vascular lesions. 3,4 There is also evidence that the dysfunction contributes to conditions such as erectile dysfunction, disorders of the retina, kidney dis- ease, pulmonary hypertension, and septic shock. Inducers of endothelial dysfunction include cardio- vascular risk factors such as smoking, hyperlipidemia, hypertension, insulin resistance and diabetes, and aging that contribute to the development of atherosclerosis. Dysfunctional endothelial cells, in turn, produce pro- inflammatory cytokines, growth factors (e.g., vascular endothelial growth factor), reactive oxygen species, pro- coagulant or anticoagulant substances, and a variety of other disease-producing products. They also influence the reactivity of underlying smooth muscle cells through production of both relaxing factors (e.g., nitric oxide) and contracting factors (e.g., endothelins; see Chapter 17). Vascular Smooth Muscle Cells Vascular smooth muscle cells, which form the predomi- nant cellular layer in the tunica media, produce vasocon- striction or vasodilation. A network of vasomotor nerves of the sympathetic component of the autonomic nervous system supplies the smooth muscle in the blood vessels. These nerves are responsible for constriction of the vessel walls. Because they do not enter the tunica media of the blood vessel, the nerves do not synapse directly on the smooth muscle cells. Instead, they release the neurotrans- mitter norepinephrine, which diffuses into the media and acts on the nearby smooth muscle cells. The resulting impulses are propagated along the smooth muscle cells, causing contraction of the entire smooth muscle cell layer and thus reducing the radius of the vessel lumen.

Collagen and elastic fibers

Internal elastic membrane

Smooth muscle cell

Connective tissue

Endothelial cells

Lumen

Tunica externa (outer coat)

Tunica media (middle coat)

Tunica intima (inner coat)

FIGURE 18-1. Diagram of a typical artery showing the tunica externa, tunica media, and tunica intima.

Endothelial Cells Endothelial cells form a continuous lining for the entire vascular system called the endothelium. Once thought to be nothing more than a lining for blood vessels, it is now known that the endothelium is a versatile, multi- functional tissue that plays an active role in controlling vascular function 1–4 (Table 18-1). As a selectively perme- able monolayer, the endothelium controls the transfer of molecules across the vessel wall. The endothelium also plays a role in the modulation of blood flow and vascular resistance; control of platelet adhesion and blood clotting; metabolism of hormones; regulation of immune and inflammatory reactions; and elaboration of factors that influence the growth of other cell types, especially vascular smooth muscle cells. Structurally intact endothelial cells respond to vari- ous abnormal stimuli by adjusting their usual functions and by expressing newly acquired functions. 1 The term endothelial dysfunction describes several types of poten-

TABLE 18-1 Endothelial Cell Properties and Functions Major Properties

Associated Functions/Factors

Maintenance of a selectively permeable barrier

Controls the transfer of small and large molecules across the vessel wall

Regulation of thrombosis Elaboration of pro- and antithrombotic molecules (vonWillebrand factor, plasminogen activator) and antithrombotic molecules (prostacyclin, heparin-like molecules, plasminogen activator) Modulation of blood flow and vascular reactivity Elaboration of vasodilators (nitric oxide, prostacyclin) and vasoconstrictors (endothelins, angiotensin-converting enzyme) Regulation of cell growth, particularly smooth muscle cells Production of growth-stimulating factors (platelet-derived growth factor, hematopoietic colony-stimulating factor) and growth-inhibiting factors (heparin, transforming growth factor- β ) Regulation of inflammatory/immune responses Expression of adhesion molecules that regulate leukocyte migration and release of inflammatory and immune system mediators (e.g., interleukins, interferons) Maintenance of the extracellular matrix Synthesis of collagen, laminin, proteoglycans Involvement in lipoprotein metabolism Oxidation of very low density lipoproteins, low density lipoproteins, and cholesterol

Data from Schoen FJ. Blood vessels. In: Kumar V, Abbas AK, Fausto N, et al; eds. Robbins and Cotran Pathologic Basis of Disease, 8th ed. Philadelphia, PA: Saunders Elsevier; 2010:490–491; Ross MH, PawlinaW. Histology: AText and Atlas, 6th ed. Philadelphia, PA: Wolters Kluwer | Lippincott Williams &Wilkins; 2011:412–414.