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Updated: Aug 4 2019

Cholesterol

  • Overview
    • Function
      • component of cell membrane
      • precursor for hormone synthesis
        • steroids
        • vitamin D
      • precursor for bile acid synthesis
        • means of excretion
          • >95% of bile acids are reabsorbed
        • ↑ in bile acid production used as a means to treat hypercholesterolemia
          • cholestyramine
            • resin that binds bile acids in the GI tract and prevents reabsorption
            • increases serum cholesterol usage in bile acid production
            • ↑ regulates LDL receptor
    • Sources
      • dietary intake
        • circulating serum LDL
          • uptake via endocytosis of LDL:LDL receptor complex
        • circulating serum HDL
          • transfer of cholesterol from HDL to hepatocyte via scavenger receptor (SR-B1)
            • high levels of this receptor in
              • hepatocytes
              • steroid producing tissues
      • de novo synthesis
        • occurs in hepatocytes
        • HMG-CoA reductase is rate limiting enzyme
          • inhibited by statins, glucagon, cholesterol
          • activated by insulin
    • Regulation
      • ↑ in intrahepatic [cholesterol]
        • ↓ expression of
          • HMG-CoA reductase
            • ↓ de novo cholesterol synthesis
          • LDL-receptor
            • ↓ in cholesterol-containing LDL uptake from serum
          • scavenger receptor (SR-B1)
            • ↓ cholesterol uptake from HDL
    • Transport
      • cholesterol is fat-soluble
        • ↑ transport by synthesis of a cholesteryl ester
          • dissolves into center of HDL
          • catalyzed by lecithin-cholesterol acyltransferase (LCAT)
            • enzyme in serum
            • activated by apoA-1 of HDL
      • see Apolipoproteins topic
    • Pathology
      • familial hypercholesterolemia
        • defective LDL receptor
        • AD
        • presentation
          • cholesterol deposition in skin
            • xanthelasma
              • in eyelid
            • tendon xanthomas
              • in skin above tendons
          • ↑ risk for coronary heart disease
      • atherosclerosis
        • risk factors (causes of endothelial cell damage)
          • smoking
          • ↑ LDL in serum
          • homocystinemia
          • diabetes
        • protective factors
          • antioxidants
            • vitamin E
              • protects LDL from oxidation
        • process
          • injury to endothelial cells of blood vessels
          • an inflammatory state is induced
            • T-cell activation
            • similar to a granuloma
          • cholesterol in the blood deposits in blood vessels
          • LDL oxidized and phagocytosed by macrophages
            • can become full of cholesterol
              • foam cells
          • fatty streak formed
          • fatty streak enlarges
          • fibrous cap formed
            • smooth muscle and endothelial cells migrate over the fatty streak
            • underlying tissue forms necrotic core
          • cap at risk of rupturing
            • exposes underlying endothelium and causes thrombosis
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