Updated: 9/7/2017

Cholesterol

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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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