Chapter 3 delete this one

OBJECTIVES

  • To understand the current National Cholesterol Education Program guidelines
  • To understand risk related target goals
  • To be able to describe the various sources of lipids
  • To understand how the laboratory is used to monitor drug therapy

KEY TERMS

Chylomicron - class of lipoprotein that transports exogenous (dietary) triglycerides and cholesterol for metabolism

Dyslipidemia - disorder of lipoprotein metabolism

HDL - high density lipoprotein

IDL - intermediate density lipoprotein

LDL - low density lipoprotein

Lipid - heterogeneous group of fat and fat like substances, poorly soluble in aqueous solutions

Lipoprotein - lipid protein complex for transporting lipids in the blood

NCEP - National Cholesterol Education Program

Triglycerides - three fatty acids esterified to a glycerol backbone

VLDL - very low density lipoprotein

BACKGROUND SIGNIFICANCE

Lipids and lipoproteins are essential for a variety of biochemical processes and serve as hormones and energy reserves in addition to forming key elements of cell membranes. In disease states, lipids are most frequently monitored in association with atherosclerosis. Laboratory testing is essential for determining when to institute drug therapy and for monitoring disease progression. Understanding the role of the laboratory in management of dyslipidemia is essential for pharmacists as atherosclerosis and cardiac disease are the leading cause of death in developed countries.

C3PCF1.JPG

[[=Figure 1:Exogenous Lipoprotein Metabolism (TG, triglyceride; CE, cholesterol ester; FC, free cholesterol; PL, phospholipids; FA, fatty acids; LPL, lipoprotein lipase; B, apolipoprotein B-48; A, apoliprotein A-I; C, apoliprotein C-II; E, apoliprotein E; from Arch. Pathol. Lab. Med. 110:694-701, 1986)]]

Cholesterol and fatty acids are absorbed from the GI tract as chylomicrons (Figure 1). Chylomicrons are primarily triglycerides (90%) combined with cholesterol and apolipoproteins B-48 and A. In combination with HDL, apolipoprotein C, apolipoprotein E and lipoprotein lipase, a small percentage of the free fatty acids are released from the chylomicron triglyceride component. The free fatty acids are then taken up by either muscle or adipose cells. The remaining chylomicron remnant which contains 80-90% of the initial triglyceride component can then be internalized by hepatic cells. Hepatic cells synthesize triglyceride rich VLDL which is then released into circulation (Figure 2). Apolipoprotein CII activates lipoprotein lipase which releases free fatty acids to endothelial cells. The remaining VLDL remnant can either be taken back up by hepatocytes or be converted into IDL. Further metabolism results in LDL, where most of the triglyceride component of VLDL has been replaced with cholesterol. The major components of the various lipoprotein classes are shown in Table 1.

[[=Table 1 Major Lipids and Protein Components of Lipoprotein Classes]]

Variable Chylomicron VLDL IDL LDL HDL
Lipids TG TG TG, CE CE Phospholipids
Proteins AI, B-48, CI-CIII B-100, CI-CIII, E B-100, E B-100 AI, AII

From a clinical perspective, monitoring and reducing LDL is a primary goal of therapy.

C3PCF1.JPG

[[=Figure 2: Endogenous Lipoprotein Metabolism Pathway (IDL, intermediate-density lipoprotein; LCAT, lecithin choles- terol acyltransferase; B, apoliprotein B-100; E, apoliprotein E; from Arch. Pathol. Lab. Med. 110:694-701, 1986)]]

[[=Table 2: Adult Classifications of LDL, Total and HDL Cholesterol (mg/dL)]]

LDL Cholesterol Total Cholestrol HDL Cholestoerl
<100 Optimal <200 Desirable <40 Low
100-129 Near Optimal 200-239 Borderline high >60 High
130-159 Borderline > 240 High cell-content cell-content
160-189 High cell-content cell-content cell-content cell-content
> 190 cell-content cell-content cell-content cell-content cell-content
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