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  <head>
    <title>089-03 Fasting adaptation, ketone-body metabolism, ketoacidosis, and lipid disorders</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Fasting, ketones, and lipid disorders">
      <outline text="Hormonal direction of fuel">
        <outline text="Insulin promotes storage, suppresses release">
          <outline text="Blocks lipolysis, ketogenesis, proteolysis"/>
        </outline>
        <outline text="Glucagon supports hepatic glucose output"/>
        <outline text="Insulin-to-glucagon ratio sets direction"/>
      </outline>
      <outline text="Stages of fasting">
        <outline text="Overnight: liver glycogen maintains glucose"/>
        <outline text="Lipolysis releases fatty acids and glycerol">
          <outline text="Muscle and liver oxidise fat, sparing glucose"/>
        </outline>
        <outline text="Glycerol, lactate, alanine feed gluconeogenesis"/>
        <outline text="After about a day gluconeogenesis dominates">
          <outline text="Powered by fatty-acid oxidation"/>
        </outline>
        <outline text="Ketones reduce brain glucose use">
          <outline text="Spares muscle protein"/>
        </outline>
      </outline>
      <outline text="Ketogenesis">
        <outline text="Hepatic mitochondrial matrix"/>
        <outline text="Acetyl-CoA exceeds cycle capacity">
          <outline text="Oxaloacetate diverted to gluconeogenesis"/>
          <outline text="High NADH slows the cycle"/>
        </outline>
        <outline text="HMG-CoA synthase then lyase"/>
        <outline text="Acetoacetate reduced to beta-hydroxybutyrate">
          <outline text="Set by NADH-to-NAD ratio"/>
        </outline>
        <outline text="Acetone forms spontaneously, exhaled"/>
      </outline>
      <outline text="Ketone use">
        <outline text="Liver lacks thiophorase"/>
        <outline text="Extrahepatic tissues activate acetoacetate">
          <outline text="Split to two acetyl units and oxidised"/>
        </outline>
        <outline text="Heart, muscle, renal cortex, adapted brain"/>
        <outline text="Red cells cannot use ketones"/>
        <outline text="Brain still needs some glucose">
          <outline text="Glycerol and glucogenic amino acids supply it"/>
        </outline>
      </outline>
      <outline text="Ketosis versus ketoacidosis">
        <outline text="Nutritional ketosis keeps restraining insulin">
          <outline text="pH regulated, kidneys excrete acid"/>
        </outline>
        <outline text="Concentration alone does not define acidosis"/>
        <outline text="Diabetic ketoacidosis: severe insulin deficiency">
          <outline text="Malonyl-CoA falls, entry accelerates"/>
          <outline text="Osmotic diuresis amplifies disorder"/>
        </outline>
        <outline text="High-anion-gap metabolic acidosis">
          <outline text="Kussmaul breathing compensates"/>
        </outline>
        <outline text="Potassium depleted despite normal serum level"/>
      </outline>
      <outline text="Treating ketoacidosis">
        <outline text="Fluids, insulin, measured potassium, precipitant"/>
        <outline text="Add glucose so insulin can continue"/>
        <outline text="Bicarbonate rarely needed"/>
        <outline text="SGLT2 inhibitors: only modest hyperglycaemia"/>
        <outline text="Alcoholic ketoacidosis">
          <outline text="High NADH favours beta-hydroxybutyrate"/>
          <outline text="Thiamine, dextrose, electrolytes"/>
        </outline>
        <outline text="Nitroprusside mainly detects acetoacetate">
          <outline text="Underestimates severity, high in recovery"/>
        </outline>
      </outline>
      <outline text="Ketone signalling and starvation">
        <outline text="Beta-hydroxybutyrate is also a signal">
          <outline text="Universal benefit claims exceed evidence"/>
        </outline>
        <outline text="Ketogenic diet reduces some seizures"/>
        <outline text="Prolonged fasting lowers energy expenditure"/>
        <outline text="Refeeding shifts phosphate, potassium, magnesium">
          <outline text="Thiamine, cautious start, monitoring"/>
        </outline>
      </outline>
      <outline text="Lipid disorders">
        <outline text="Steatosis: supply exceeds oxidation and export">
          <outline text="Hepatic lipogenesis stays insulin responsive"/>
        </outline>
        <outline text="Very high triglycerides cause pancreatitis"/>
        <outline text="Familial hypercholesterolaemia">
          <outline text="Tendon xanthomas, premature vascular disease"/>
        </outline>
        <outline text="Acid lipase deficiency and Niemann-Pick C"/>
        <outline text="Sphingolipids accumulate in macrophages or neurons">
          <outline text="Enzyme replacement rarely reaches the brain"/>
        </outline>
        <outline text="Adrenoleukodystrophy: very-long-chain transport"/>
        <outline text="Zellweger spectrum: peroxisome assembly"/>
      </outline>
      <outline text="Adipose tissue and integration">
        <outline text="Obesity: adipose expansion and dysfunction">
          <outline text="Ectopic lipid drives insulin resistance"/>
        </outline>
        <outline text="Brown fat makes heat via uncoupling protein 1">
          <outline text="Appetite offsets pharmacological activation"/>
        </outline>
        <outline text="Fasting is an interorgan negotiation">
          <outline text="Lost insulin and renal restraint: danger"/>
        </outline>
      </outline>
    </outline>
  </body>
</opml>
