USMLE/COMLEX 2 - Hyperlipidemia Pathophysiology

Here are key facts for USMLE/COMLEX 2 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.

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1. Often asymptomatic: Hyperlipidemia is often asymptomatic, but it significantly increases one's risk for cardiovascular diseases, especially atherosclerosis 2. Xanthomas: These are created by lipid deposits in the skin associated with foam cells (macrophages that have ingested lipids) 3. Cardiovascular risk: Hyperlipidemia is often asymptomatic, but it significantly increases one's risk for cardiovascular diseases, especially atherosclerosis 1. Tuberous xanthomas: Tuberous xanthomas form small to large bulges in the skin over the joints, particularly the elbows and knees 2. Eruptive xanthomas: Eruptive xanthomas are erythematous bumps that tend to appear on the buttocks, shoulders, and extensor surfaces 3. Plane xanthomas: Plane xanthomas are thin yellow plaques. Xanthelasma is characterized by plaques around the eyelids 4. Palmar xanthomas: Palmar xanthomas are characterized by yellow plaques that form along the creases of the palm of the hands 5. Tendinous xanthomas: 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. Hypercholesterolemia: Total cholesterol > 200 mg/dL, Low-Density Lipoproteins > 130 mg/dL, High-Density Lipoproteins < 40 mg/dL 2. Hypertriglyceridemia: Hypertriglyceridemia = levels above 150 mg/dL

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1. Hyperchylomicronemia (Type I): 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. Hypercholesterinemia (Type IIa): Occurs when LDL receptors are deficient. Results in elevated Low-Density Lipoproteins and cholesterol. 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. Hyperlipidemia (Type IIb): 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. Dysbetalipoproteinemia (Type III): Occurs when apolipoprotein E-2 is defective. The disorder is characterized by elevated chylomicron remnants and Intermediate Density Lipoproteins. 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. Hypertriglyceridemia (Type IV): 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. Mixed hypertriglyceridemia (Type V): 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 factors: The most significant contributors in the United States are diets high in saturated fats, cholesterol, and trans fats, coupled with sedentary lifestyles 2. Alcohol consumption: High levels of alcohol consumption also elevate lipid levels 3. Medical conditions: Several other disorders may contribute to hyperlipidemia, including: diabetes mellitus, chronic kidney disease, nephrotic syndrome, hypothyroidism, cholestatic liver diseases, and Cushing syndrome 4. Medications: Several drugs can cause hyperlipidemia, including oral contraceptives, diuretics, beta-blockers, and antiretroviral agents

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Below is additional information important for USMLE Step 2 CK & COMLEX Level 2: 1. Risk stratification: Assessment of cardiovascular risk guides treatment intensity 2. Lifestyle modifications: Diet modifications, exercise, and weight management are first-line interventions 3. Pharmacologic therapy: Selection based on lipid profile and cardiovascular risk 1. Statins: First-line agents for LDL reduction and cardiovascular risk reduction 2. Fibrates: For hypertriglyceridemia management 3. Bile acid sequestrants: Second-line agents for LDL reduction 4. PCSK9 inhibitors: For refractory hypercholesterolemia 5. Ezetimibe: Inhibits intestinal cholesterol absorption 1. Lipid panel monitoring: Frequency based on risk level and treatment 2. Liver function tests: For patients on statins 3. Muscle enzyme monitoring: For patients with statin-related myalgia 4. Medication adherence assessment: Critical for treatment success