USMLE/COMLEX 3 - Hyperlipidemia Pathophysiology

Here are key facts for USMLE/COMLEX 3 from the Hyperlipidemia Pathophysiology tutorial, as well as points of interest at the end that are not directly addressed in this tutorial but should help you prepare for the boards.

• --

1. Cardiovascular risk assessment: Hyperlipidemia is often asymptomatic, but it significantly increases one's risk for cardiovascular diseases, especially atherosclerosis 2. Primary vs Secondary: Primary lipidemias can be exacerbated by secondary causes 3. Xanthoma recognition: These are created by lipid deposits in the skin associated with foam cells (macrophages that have ingested lipids) 1. Distribution patterns: Tuberous xanthomas form small to large bulges in the skin over the joints, particularly the elbows and knees 2. Eruptive type: Eruptive xanthomas are erythematous bumps that tend to appear on the buttocks, shoulders, and extensor surfaces 3. Ocular findings: Plane xanthomas are thin yellow plaques. Xanthelasma is characterized by plaques around the eyelids 4. Hand examination: Palmar xanthomas are characterized by yellow plaques that form along the creases of the palm of the hands 5. Achilles examination: Tendinous xanthomas are bumps that form over the tendons or ligaments. The Achilles tendon at the posterior ankle is a common site for these xanthomas 1. Lipid panel interpretation: Hypercholesterolemia is often defined as: Total cholesterol > 200 mg/dL, Low-Density Lipoproteins > 130 mg/dL, High-Density Lipoproteins < 40 mg/dL 2. Triglyceride evaluation: Hypertriglyceridemia = levels above 150 mg/dL

• --

1. Type I (Hyperchylomicronemia): Occurs when there is a deficiency in lipoprotein lipase or an alteration in apolipoprotein C-II, which activates lipoprotein lipase. These deficiencies cause elevated chylomicrons and triglyceride levels exceeding 500 mg/dL. This disorder is associated with acute pancreatitis, eruptive xanthomas, and, when triglyceride levels are exceedingly high, lipemia retinalis 2. Type IIa (Hypercholesterinemia): Occurs when LDL receptors are deficient. Results in elevated Low-Density Lipoproteins and cholesterol. There are heterozygous and homozygous forms. Patients are at increased risk of premature Atherosclerotic Cardiovascular Disease (ASCVD), tendinous xanthomas, and, corneal arcus, which is a whitish ring around the iris 3. Type IIb (Hyperlipidemia): Occurs when there is a reduction in LDL receptors or increased apolipoprotein B. Characterized by elevated Low Density Lipoproteins and Very Low Density Lipoproteins. Both triglycerides and cholesterol are also elevated. Patients are at increased risk of premature ASCVD and may have tendinous xanthomas. This is the most common inherited dyslipidemia 4. Type III (Dysbetalipoproteinemia): Occurs when apolipoprotein E-2 is defective. The disorder is characterized by elevated chylomicron remnants and Intermediate Density Lipoproteins (hence, this disorder is sometimes called Remnant Removal Disease). Both triglyceride and cholesterol levels are elevated. Patients are at increased risk of ASCVD, and may have palmar xanthoma and/or tuberoeruptive xanthomas of the elbows and knees 5. Type IV (Hypertriglyceridemia): Characterized by increased production and decreased secretion of Very Low Density Lipoproteins. Elevated levels of triglycerides. Patients are at increased risk for acute pancreatitis and ASCVD. Type IV is another relatively common inherited hyperlipidemia 6. Type V (Mixed hypertriglyceridemia): Associated with increased Very Low Density Lipoprotein production and decreased Low Density Lipoprotein production. Characterized by elevations in chylomicron remnants and VLDL. Increased triglyceride and cholesterol levels. Patients are at risk for acute pancreatitis, eruptive xanthomas, and ASCVD 1. Dietary counseling: The most significant contributors in the United States are diets high in saturated fats, cholesterol, and trans fats, coupled with sedentary lifestyles 2. Alcohol management: High levels of alcohol consumption also elevate lipid levels 3. Underlying condition treatment: Several other disorders may contribute to hyperlipidemia, including: diabetes mellitus, chronic kidney disease, nephrotic syndrome, hypothyroidism, cholestatic liver diseases, and Cushing syndrome 4. Medication review: Several drugs can cause hyperlipidemia, including oral contraceptives, diuretics, beta-blockers, and antiretroviral agents

• --

1. Pancreatitis assessment: Recognizing severe hypertriglyceridemia as a cause of acute pancreatitis 2. Emergency treatment: Appropriate management of lipid-induced pancreatitis 3. Cardiovascular risk stratification: Tools for comprehensive risk assessment 1. Evidence-based therapy selection: Tailoring treatment to specific lipid abnormalities 2. Statin intolerance management: Strategies for patients who cannot tolerate first-line therapy 3. Familial hypercholesterolemia treatment: Special considerations for genetic disorders 1. Primary prevention strategies: Early detection and management of asymptomatic hyperlipidemia 2. Secondary prevention protocols: Aggressive management post-cardiovascular events 3. Therapeutic monitoring: Clinical and laboratory parameters for treatment efficacy