USMLE/COMLEX 1 - Hyperlipidemia Pathophysiology

Here are key facts for USMLE/COMLEX 1 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. Two classification systems: Fredrickson (focuses on inherited disorders) and Primary vs Secondary 2. Primary hyperlipidemias: Genetic causes 3. Secondary hyperlipidemias: Acquired causes that can exacerbate primary disorders 1. Chylomicrons: Deliver dietary triglycerides and cholesterol to liver and peripheral tissues 2. VLDL: Liver-produced, triglyceride-rich 3. IDL (VLDL remnants): Produced when triglycerides are removed from VLDL, cholesterol-rich 4. LDL ("bad" cholesterol): Cholesterol-rich, distributes cholesterol throughout body, contributes to atherosclerosis 5. HDL ("good" cholesterol): Part of reverse cholesterol transport pathway, carries cholesterol from peripheral tissues to liver 1. Hypercholesterolemia: Total cholesterol >200 mg/dL, LDL >130 mg/dL, HDL <40 mg/dL 2. Hypertriglyceridemia: Levels above 150 mg/dL 1. Definition: Lipid deposits in skin associated with foam cells (lipid-laden macrophages) 2. Types: Tuberous (joints), Eruptive (buttocks/shoulders), Plane (thin plaques), Xanthelasma (eyelids), Palmar (hand creases), Tendinous (tendons/ligaments)

• --

1. Hyperchylomicronemia (Type I): Lipoprotein lipase deficiency or apoC-II alteration; elevated chylomicrons and triglycerides >500 mg/dL; associated with acute pancreatitis and eruptive xanthomas 2. Hypercholesterinemia (Type IIa): LDL receptor deficiency; elevated LDL and cholesterol; increased ASCVD risk, tendinous xanthomas, corneal arcus 3. Hyperlipidemia (Type IIb): LDL receptor reduction or increased apoB; elevated LDL and VLDL; increased cholesterol and triglycerides; most common inherited dyslipidemia 4. Dysbetalipoproteinemia (Type III): Defective apoE-2; elevated chylomicron remnants and IDL; increased triglycerides and cholesterol; palmar and tuberoeruptive xanthomas 5. Hypertriglyceridemia (Type IV): Increased VLDL production and decreased secretion; elevated triglycerides; risk for pancreatitis and ASCVD; another common inherited hyperlipidemia 6. Mixed hypertriglyceridemia (Type V): Increased VLDL production and decreased LDL production; elevated chylomicron remnants and VLDL; increased triglycerides and cholesterol; risk for pancreatitis, eruptive xanthomas, and ASCVD 1. Diet: High saturated fats, cholesterol, and trans fats with sedentary lifestyle (major US contributor) 2. Alcohol: High consumption elevates lipid levels 3. Medical conditions: Diabetes mellitus, chronic kidney disease, nephrotic syndrome, hypothyroidism, cholestatic liver diseases, Cushing syndrome 4. Medications: Oral contraceptives, diuretics, beta-blockers, antiretroviral agents

• --

Below is additional information important for USMLE & COMLEX 1: 1. Atherosclerotic Cardiovascular Disease (ASCVD): Major complication of hyperlipidemia requiring risk assessment and management 2. Lipemia retinalis: Ocular manifestation with extremely high triglyceride levels 3. Pancreatitis risk: Significantly increased with triglycerides >500 mg/dL 1. Fasting lipid panel: Standard initial test for hyperlipidemia evaluation 2. Non-HDL cholesterol: Important risk marker (Total cholesterol minus HDL) 3. Lipoprotein(a): Emerging risk factor for cardiovascular disease 1. Lifestyle modifications: First-line therapy for most hyperlipidemias 2. Statins: First-line pharmacologic therapy for elevated LDL 3. Fibrates: Primarily for hypertriglyceridemia 4. PCSK9 inhibitors: For refractory hypercholesterolemia or statin intolerance 5. Special considerations: Pregnancy, pediatric patients, elderly patients