Porth's Essentials of Pathophysiology, 4e

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Disorders of Blood Flow and Blood Pressure

C h a p t e r 1 8

cholesterol and triglycerides from the intestine to the liver. The endogenous pathway involves the processing of triglycerides and cholesterol by the liver and their distribution throughout the body (Fig. 18-4). Exogenous Pathway. The exogenous pathway involves the chylomicron transport of dietary triglycerides and cholesterol from the intestines to the liver. The chylomi- crons, which are the largest of the lipoprotein molecules, are synthesized in the wall of the small intestine. These triglyceride-rich lipoproteins transfer their triglycerides to peripheral tissues, especially adipose tissue and skel- etal muscle, for energy and storage. The remnant chy- lomicron particles, which contain cholesterol, are then taken up by the liver and the cholesterol is used in the synthesis of VLDL or excreted in the bile. Endogenous Pathway. The liver is the central site for handling of lipids: it is able to store glycerols and fats in its cells; synthesize triglycerides; and use esterified cho- lesterol and triglycerides to form VLDL. Like chylomi- crons, VLDLs carry their triglycerides to fat and muscle cells, where the triglycerides are removed. The resulting IDL particles, which are reduced in triglyceride content and enriched in cholesterol, are then taken to the liver and recycled to form VLDL or converted to LDL. Low-Density Lipoproteins Sometimes called bad cholesterol , LDL is the main car- rier of cholesterol. Low-density lipoprotein particles are rich in cholesterol and cholesterol esters. Approximately 60% of the LDL is transported back to the liver, where its apoB-100 binds to specific LDL receptors on liver cells, allowing the particles to be internalized. 2,7,9 The remain- ing 40% of LDL particles are carried to extrahepatic tissues, such as those of the adrenal cortex and gonads, which also have apoB-100 receptors that allow them to internalize the LDL particles and use the cholesterol in the synthesis of their cell membranes and steroid hormones. There are different types of LDL, and some people with markedly elevated LDL do not develop atheroscle- rotic vascular disease, whereas other people with only modest elevations in LDL develop severe disease. This can be partially explained by the quality and size of the LDL particles. Small, dense LDL is more toxic or ath- erogenic to the endothelium than large, buoyant LDL. It is more likely to enter the vessel wall, become oxidized, and trigger the atherosclerotic process. High-Density Lipoproteins Often referred to as the good cholesterol, HDL is synthe- sized by several pathways, including direct secretion by the intestine and liver and transfer of lipid constituents released during lipolysis of lipoproteins that contain apo- B100. It participates in reverse cholesterol transport (see Fig. 18-4)—that is, carrying cholesterol from the periph- eral tissues back to the liver. Epidemiologic studies show an inverse relation between HDL levels and the develop- ment of atherosclerosis. 6 It is thought that HDL, which is low in cholesterol and rich in surface phospholipids,

Low density

Chylomicrons 80%–90% triglycerides, 2% protein

VLDL 55%–65% triglycerides,

10% cholesterol, 5%–10% protein

LDL 10% triglycerides, 50% cholesterol, 25% protein

HDL 5% triglycerides, 20% cholesterol, 50% protein

High density

apoB-100) remain attached to the same lipoprotein par- ticle from biosynthesis to breakdown. 8 There are two pathways involved in the generation and transport of lipoproteins: the exogenous intesti- nal and endogenous hepatic pathways. 1,2,7,9 The exog- enous pathway is involved in the transport of dietary FIGURE 18-2. Lipoproteins are named based on their protein content, which is measured in density. Because fats are less dense than proteins, as the proportion of triglycerides decreases, the density increases. HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very–low-density lipoprotein.

Apolipoproteins

Cholesterol esters

Nonesterified cholesterol

Phospholipids

Triglycerides

FIGURE 18-3. General structure of a lipoprotein.The cholesterol esters and triglycerides are located in the hydrophobic core of the macromolecule, surrounded by an outer hydrophilic shell of phospholipids, nonesterified lipoproteins, and apolipoproteins.