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LEARNING OBJECTIVES

LEARNING OBJECTIVES

  1. List and describe the three major pathways of lipoprotein metabolism.

  2. Recognize clinically relevant hyperlipidemias and their laboratory correlates when presented with patient data.

  3. Discuss methods for measurement of routine lipid tests, noting limitations with each.

  4. Compare pediatric reference and target ranges for lipids with those in adults.

  5. Discuss current recommendations for laboratory lipid screening in children and adolescents.

INTRODUCTION

Laboratory investigation of lipids plays an important role in risk assessment, screening, and management of cardiovascular disease (CVD) and in the diagnosis of dyslipidemias. CVD is the leading cause of death in men and women in developed countries and it is well-established that elevated atherogenic lipids are an independent risk factor for CVD. This has led to routine testing of lipids as part of public health awareness and improvement initiatives, such as various 'Know Your Numbers' campaigns and incorporation of lipid values into cardiovascular risk prediction tools, such as the Framingham Risk Score1 and calculators published in the associated NCEP and ACC/AHA guidelines.2,3 According to these guidelines, lipid measurements are also recognized in therapeutic decision-making algorithms. Lipid testing is widely utilized in pediatrics, as evidence indicates that dyslipidemias often begin in childhood or adolescence and contribute to early atherosclerosis with extrapolation to premature CVD, if not treated. Current recommendations call for universal lipid screening in children of specified age ranges.4 Once identified, children with dyslipidemias may be effectively managed by diet and lifestyle changes and with pharmaceutical interventions, in specific cases. This chapter will review the basics of lipid biochemistry and metabolism with associated pathophysiology, describe methods for lipid measurement and summarize current recommendations for lipid screening in pediatrics.

BIOCHEMISTRY

Structure

Lipids are a structurally heterogeneous class of compounds that are relatively insoluble in water. The main types of lipids include fatty acids, phospholipids, triglycerides (TG), and cholesterol (cholesterol esters). Lipids are vital to normal metabolism and development as they are components of cell membranes, sources of energy, and precursor molecules for synthesis of other compounds, such as steroid hormones and bile acids. Because of their insolubility, lipids are transported in circulation as water-soluble lipoproteins. Lipoproteins are spherical structures comprised of two layers: an amphiphilic surface and a hydrophobic core. Cholesterol esters, free fatty acids, and TG form the inner core and the surface layer contains proteins (apolipoproteins), cholesterol, and a single layer of phospholipid. Lipoproteins are commonly classified, based on their hydrated density (in order of increasing density), as: chylomicrons (CM), very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Lipoprotein particle density is determined primarily by its protein and TG content. Figure 10-1 illustrates that particles with higher lipid content are less dense; therefore, they migrate closer to the top of the tube when centrifuged. These have also been categorized based on their electrophoretic mobility and apolipoprotein content, as both ...

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