Porth's Essentials of Pathophysiology, 4e

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Circulatory Function

U N I T 5

Vascular smooth muscle cells also synthesize colla- gen, elastin, and other components of the extracellular matrix; elaborate growth factors and cytokines; and after vascular injury migrate into the intima and pro- liferate. 1 Thus, smooth muscle cells are important in both normal vascular repair and pathologic processes such as atherosclerosis. The migratory and proliferative activities of vascular smooth muscle cells are stimulated by growth promoters and inhibitors, such as platelet- derived growth factor, thrombin, fibroblast growth fac- tor, cytokines, and nitric oxide.

arteries tends to be affected by different disease pro- cesses. The discussion in this section focuses on hyper- lipidemia and atherosclerosis, the vasculitides, arterial disease of the extremities, and arterial aneurysms. Hyperlipidemia Hyperlipidemia is a medical condition characterized by an elevation of any or all lipid profiles and/or lipopro- teins in the blood. Hyperlipidemias can be classified as either primary or secondary. 5 Primary hyperlipidemias are probably genetically based, but the genetic defects are known for only a minority of patients. Secondary hyperlipidemia may result from diseases such as diabe- tes, thyroid disease, renal disorders, liver disorders, and Cushing syndrome, as well as obesity, alcohol consump- tion, estrogen administration, and other drug-associated changes in lipid metabolism. Besides the primary and sec- ondary hyperlipidemia subtypes, hyperlipidemia is also classified according to the type of lipid that is elevated— hypercholesterolemia, hypertriglyceridemia, or both in combined hyperlipidemia. The condition, specifically hypercholesteremia, is strongly associated with the development of atherosclerosis, which causes more morbidity and mortality in the Western world than any other disorder. By the year 2025, it is predicted that car- diovascular mortality will likely exceed that of every other major disease group including infections, cancer, and trauma. 6 Lipoprotein Metabolism andTransport Because lipids, namely cholesterol and triglycerides, are insoluble in plasma, they are encapsulated by special fat- carrying proteins called lipoproteins for transport in the blood. There are five main types of lipoproteins, classi- fied by their protein content or densities: chylomicrons, very–low-density lipoprotein (VLDL), intermediate- density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Thus, VLDLs carry large amounts of triglycerides and much less cholesterol and protein. Low-density lipoprotein is the main carrier of cholesterol, whereas HDL is about 50% protein and carries less cholesterol and little triglyceride (Fig. 18-2). Lipoproteins are macromolecules made up of a hydro- phobic core of insoluble cholesterol esters and triglycer- ides, surrounded by a hydrophilic outer shell of soluble phospholipids, and nonesterified cholesterol 7 (Fig. 18-3). In addition, the shell contains a variety of apolipopro- teins, proteins that bind lipids, thereby increasing the stability and water solubility of the resulting lipopro- tein. The apolipoproteins also activate certain enzymes required for normal lipoprotein metabolism, and they serve as reactive sites that specific receptors on periph- eral tissues can recognize and use in the endocytosis and metabolism of the lipoproteins. Apolipoproteins can be grouped into two classes: exchangeable and nonex- changeable. Exchangeable apolipoproteins (e.g., apoA- I, apoC-II, and apoE) are able to dissociate from one lipoprotein and associate with another, whereas the nonexchangeable apolipoproteins (e.g., apoB-48 and

SUMMARY CONCEPTS

■■ The walls of blood vessels are composed of an inner layer of endothelial cells, a middle layer of vascular smooth muscle, and an outer layer of loosely woven collagen tissue. ■■ The endothelium, which forms a continuous lining for the entire vascular system, controls the transfer of molecules across the vascular wall and plays a role in the control of platelet adhesion and blood clotting, modulation of blood flow and vascular resistance, metabolism of hormones, regulation of immune and inflammatory reactions, and elaboration of factors that influence the growth of other cell types, particularly the smooth muscle cells. ■■ The term endothelial dysfunction describes changes in endothelial function that occur in response to stimuli derived from cardiovascular risk factors such as smoking, hyperlipidemia, hypertension, insulin resistance and diabetes, and obesity. ■■ Vascular smooth muscle cells, which form the middle layer of blood vessels, control the dilation and constriction of blood vessels, elaborate growth factors, and synthesize collagen, elastin, and other components of the extracellular matrix that are important in both normal vascular repair and pathologic processes such as atherosclerosis.

Disorders of the Arterial Circulation

The arterial system distributes blood to all the tissues in the body. There are three types of arteries: large elas- tic arteries, including the aorta and its distal branches; medium-sized arteries, such as the coronary and renal arteries; and small arteries and arterioles that pass through the tissues. Each of these different types of