Metabolic Effects of Critical Illness

Metabolic Effects of Critical Illness

David Ray Velez, MD

Catabolism

  • Catabolism Predominates in Critical Illness Causing Breakdown of Glycogen, Protein, and Fat
  • Glucose is the Preferential Substrate in Critical Illness
  • Liver Produces Large Amounts of Glucose Causing a Stress Hyperglycemia

Glucose Production

  • Glycogenolysis: Glycogen Store Breakdown to Glucose
    • Stores are Rapidly Used/Depleted Early in the Stress Response
    • Muscle (2/3 of Stores) – Only Available Locally
    • Liver (1/3 of Stores) – Available Systemically
  • Gluconeogenesis: Glucose Creation from Non-Glycogen Precursors
    • Produced from Alanine, Glycerol, and Lactate (Cori Cycle) in the Liver (Primarily) and Kidney
    • Proteolysis: Muscle Proteins Breakdown to Amino Acids (Alanine and Glutamine) for Gluconeogenesis
      • Causes Muscle Wasting – Lose 1-5% of Lean Body Mass Per Day (ICU-Acquired Weakness)
      • Significantly Negative Nitrogen Balance
    • Lipolysis: Fat/Lipid Breakdown to Fatty Acids for Energy Production
      • Lipids are Used Less than Carbohydrates – Lipid Conversion to ATP Requires Significant Oxygen in Mitochondria (Often Unavailable in Critical Illness)

Insulin Resistance

  • Can Develop During Critical Illness Even without Preexisting Diabetes
  • Causes:
    • Stress Response Stimulating Cortisol and Catecholamine Release
    • Systemic Inflammation Impairing Insulin Effects
    • Tissue Injury
    • Malnutrition
  • Hepatic Glycogenolysis and Gluconeogenesis are Overactivated
  • Insulin-Driven Carbohydrate/Glucose Delivery to Peripheral Tissues is Not a Priority
  • Can Exacerbate Hyperglycemia and Increase Morbidity and Mortality

Phases

  • Ebb Phase (8-24 Hours): Dominated by Circulatory Changes Requiring Resuscitation
  • Catabolic Phase (3-10 Days): Dominated by Catabolism Due to Cytokine Mediators (IL-6)
  • Anabolic Phase (Recovery): Dominated by Anabolism with Repair and Synthetic Activity

ICU-Acquired Weakness

  • Muscle Loss Starts within 4 Hours of Being Immobilized in the ICU
  • 1% of Muscle Mass is Lost Every Day of Immobilization
  • Risk Factors:
    • Prolonged Bedrest or Immobilization
    • Severity of Illness (Sepsis, SIRS, Multiple Organ Failure, etc)
    • Hyperglycemia
    • TPN
    • Elderly
    • Female Sex
    • Premorbid Obesity
    • Steroids
    • Sedatives or Paralysis
  • Pathogenesis is Multifactorial
  • Increases Risk of Infections, Dysphagia, Prolonged Mechanical Ventilation, LOS, and Mortality