LO6; Lipids

Lipids

Cholesterol and Blood Cells

  • Cholesterol illustration extracted from Britannica ImageQuest.

  • Reference: Encyclopædia Britannica, 2 Nov 2020.

Heart Attack and Atherosclerosis

  • The video discusses heart attacks as a consequence of atherosclerosis.

Clinical Significance of Lipids

  • Source of energy for the body.

  • Essential for utilizing fat-soluble vitamins.

  • Contributes to maintaining healthy skin.

Functions of Lipids in the Body

  • Body cells extract fat and cholesterol from the blood:

    • Create cell membranes.

    • Synthesize steroid hormones.

    • Form the myelin sheath around neurons.

    • Cushion organs with fatty deposits.

  • Illustration of lipid bilayer from Britannica ImageQuest (25 May 2016).

Monitoring of Lipids and Cardiovascular Disease

  • Lipids are not primarily used for monitoring myocardial infarction (MI) but can assess cardiovascular disease risk.

  • Common tests for lipid measurement include:

    • Triglycerides

    • Total Cholesterol

    • Low-Density Lipoprotein Cholesterol (LDL)

    • High-Density Lipoprotein Cholesterol (HDL)

Endogenous Lipids

  • Most cholesterol is synthesized by the body:

    • Dietary sources: 150-300 mg per day.

    • Liver synthesis: approximately 1.5g per day.

  • Lipids synthesized in the liver are transported as lipoproteins throughout the body.

Exogenous Lipids

  • Approximately 40% of the American caloric intake comes from lipids.

  • During digestion, the gallbladder contributes bile to the small intestine through the bile duct, which breaks down lipids (emulsification).

Digestive Enzymes for Lipids

  • Key enzymes acting on lipids include:

    • Lipase

    • Cholesterolesterase

    • Phospholipase

  • Produced in the pancreas, these enzymes operate within the small intestine to release free fatty acids and cholesterol.

Absorption of Lipids

  • Digested lipid particles enter intestinal mucosal cells and subsequently the lymphatic and circulatory systems.

  • Short and medium-chain fatty acids are bound to albumin for transport.

  • Long-chain fatty acids are packaged into chylomicrons in the mucosal cells, released into the lymph, then bloodstream.

  • Traditionally, non-fasting specimens are not considered suitable for lipid testing (though this is changing).

Lipid Profile Testing

  • The lipid profile is a set of tests used to assess the risk of coronary heart disease that includes:

    • Triglyceride levels

    • Total Cholesterol

    • HDL Cholesterol

    • LDL Cholesterol

Triglycerides

  • Composition: 95% of stored fat is in the form of triglycerides, consisting of a glycerol backbone with three fatty acids linked by ester bonds.

  • When glucose is insufficient, stored fat is utilized as an alternative energy source, producing ATP.

  • Triglycerides from animal sources contain saturated fatty acids (solid at room temperature), while those from plant sources contain unsaturated fatty acids (liquid oil at room temperature).

  • Transported in chylomicrons, with regulation of storage and gluconeogenesis being influenced by insulin and hormone-sensitive lipase.

Triglycerides Concentration Post-Meal

  • Levels are notably affected when a patient is not fasting.

  • Chylomicrons peak concentration in circulation 1-2 hours post-meal.

  • Note: If triglycerides exceed 4.52 mmol/L, LDL cholesterol cannot be calculated using the Friedewald formula.

Cholesterol Overview

  • Cholesterol is a waxy, steroid alcohol present in animal products and synthesized from Acetyl-CoA in the liver.

  • Major uses of cholesterol include:

    • Structural component of cell membranes.

    • Component of bile acids aiding in fat digestion.

    • Precursor for steroid hormones (e.g., glucocorticoids, estrogen).

    • Involved in the production of Vitamin D.

Cholesterol and Heart Disease

  • Uncontrolled high levels of certain cholesterol fractions can contribute to coronary artery disease (CAD) and atherosclerosis.

  • Distinction:

    • HDL (good cholesterol) versus LDL (bad cholesterol).

Types of Lipoproteins

  • Various lipoproteins categorized based on density:

    • Chylomicrons—largest and least dense, transport triglycerides from the intestine to the liver and tissues, causing serum cloudiness.

    • Very-Low-Density Lipoproteins (VLDL)—transport triglycerides to tissues, largest quantity increases with high carb, saturated fat, and trans fat intake.

    • Low-Density Lipoproteins (LDL)—transports cholesterol to peripheral tissues, contributes to atherosclerosis and coronary heart disease.

    • High-Density Lipoprotein (HDL)—produces protective effects against CAD.

Apolipoproteins

  • Proteins associated with lipoproteins that serve various functions:

    • Provide structural support.

    • Control enzyme activity.

    • Facilitate lipoprotein clearance from plasma.

  • Major apolipoproteins:

    • Apolipoprotein A-1—primary protein of HDL.

    • Apolipoprotein B-100—primary protein of LDL.

Apolipoprotein Ratios and Clinical Significance

  • The ratio of Apolipoprotein B to Apolipoprotein A1 serves as an indicator of lipid metabolism disorders and atherosclerosis risk.

  • High Apolipoprotein A1 and low Apolipoprotein B correlate with lower risk percentages for coronary heart disease.

Dyslipidemia

  • Disorders causing abnormal lipid results can be:

    • Genetic

    • Environmental/lifestyle

    • Secondary to other conditions (e.g., diabetes).

Hypercholesterolemia

  • Familial genetic condition due to LDL receptor gene defects leading to high LDL-C levels:

    • Heterozygous: LDL-C levels range from 5-14 mmol/L, with early-onset atherosclerosis.

    • Homozygous: LDL-C levels exceed 13 mmol/L, heart disease possible in teens, skin, tendon, and cornea cholesterol deposits can occur.

Lifestyle Factors of Hypercholesterolemia

  • Includes:

    • Increased dietary cholesterol intake.

    • Smoking.

    • Sedentary lifestyle.

    • Alcohol misuse.

    • Obesity.

    • Medication-related causes.

Secondary Causes of Hypercholesterolemia

  • Related to hypothyroidism and diseases affecting the liver and kidneys.

Hypertriglyceridemia

  • Familial, mainly autosomal dominant, leads to moderate triglyceride increases due to overproduction of VLDLs.

  • Other disorders causing this condition may affect endocrine hormones or metabolism.

Arteriosclerosis

  • Defined in Taber’s Cyclopedic Medical Dictionary as thickening, hardening, and loss of elasticity of arterial walls, with three recognized forms:

    • Atherosclerosis

    • Sclerosis of arterioles

    • Calcific sclerosis.

Atherosclerosis

  • The predominant form of arteriosclerosis characterized by cholesterol, fat, and calcium-lipid deposits in arterial walls, diminishing blood flow, especially in vital organs such as the heart and brain.

  • Causes angina due to reduced oxygen-rich blood and may induce ischemia/blockages leading to cellular death.

  • Associated with diabetes and can lead to cardiovascular disease.

Pathophysiology of Atherosclerosis

  • Inflammation and oxidation of cholesterol attract macrophages that engulf cholesterol, forming foam cells, leading to plaque development.

  • Plaques narrow vessels, hinder blood flow, and can cause significant organ dysfunction or disease.

Diabetes and Heart Disease

  • Diabetics face heightened risks of heart diseases and myocardial infarction.

  • Correlation exists between elevated glucose levels, inflammation, triglycerides, and abnormal lipid profiles.

Enzymatic Breakdown of Stored Fat

  • Hormone sensitive lipase (HSL) releases stored fatty acids by converting triglycerides.

  • Insulin inhibits HSL, reducing fat breakdown.

  • Insulin resistance increases activity of HSL, leading to excessive free fatty acids production and VLDLs.

Lipoprotein Lipase (LPL)

  • Breaks down triglycerides in chylomicrons and VLDL; its effectiveness decreases with insulin resistance, causing lower triglyceride clearance in diabetics.

Diabetic Lipid Profiles

  • Diabetics often have small, dense LDL particles that linger longer in plasma, facilitating arterial wall penetration and oxidative susceptibility, resulting in increased atherosclerosis risk.

Laboratory Testing of Lipids

  • Total cholesterol measurement encompasses all cholesterol across lipoproteins utilizing a first-order enzymatic colorimetric reaction involving peroxidase.

Triglyceride Measurement Methods

  • Involves enzymatic assays to hydrolyze triglycerides into glycerol and fatty acids, monitored via colorimetric methods.

HDL-C Testing Methods

  • HDL determination employs methods to eliminate non-HDL fractions to quantify remaining HDL cholesterol, often using precipitation techniques.

LDL-C Calculation Methods

  • LDL levels estimated using the Friedewald formula, though new methods directly measure LDL for improved accuracy.

  • Friedewald formula: LDL=Tchol−HDL−VLDLLDL = Tchol - HDL - VLDL where VLDL=Trig2.22VLDL = \frac{Trig}{2.22}.

    • Not applicable if triglycerides exceed 4.52 mmol/L or if samples contain increased chylomicrons.

Reporting Guidelines for Lipid Testing

  • LDL calculation inaccuracies warrant reporting only triglycerides, HDL, and total cholesterol when triglycerides exceed 4.52 mmol/L.

  • Indicate in reports if LDL cannot be provided due to invalid calculations.

New Calculative Methods

  • Variations of the Friedewald formula like the Martin-Hopkins approach yield less estimation error, employing factors dependent on non-HDL-C and triglyceride values for VLDL.

Non-HDL Cholesterol

  • A metric reflecting cardiovascular disease risk, calculated as total cholesterol minus HDL-C; higher values indicate heightened risk.

Classification of Apolipoproteins

  • Apolipoproteins classified by their flotation density and analyzed through turbidimetric and nephelometric immunoassays, ELISA, and RIA methods.