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Metabolic Response to Injury

Bailey & Love's Short Practice of Surgery, 28th Edition - Chapter 1

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1. INTRODUCTION & DEFINITION

• Hormonal (neuroendocrine)
• Inflammatory (cytokines)
• Neural circuits

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2. PHASES OF THE METABOLIC RESPONSE

A. Catabolic (Ebb) Phase

• Begins at the time of injury, lasts ~24-48 hours
• Dominated by: catecholamines, cortisol, aldosterone
• Features:
  • Hypovolaemia
  • Decreased basal metabolic rate (BMR)
  • Reduced cardiac output
  • Hypothermia
  • Lactic acidosis
• Purpose: Conserve circulating volume and energy stores for survival

B. Flow (Anabolic/Hypermetabolic) Phase

• Follows resuscitation; corresponds to SIRS
• Features:
  • Tissue oedema (vasodilation + increased capillary leakage)
  • Increased BMR (hypermetabolism)
  • Increased cardiac output
  • Raised body temperature
  • Leukocytosis
  • Increased O2 consumption
  • Increased gluconeogenesis
• Purpose: Mobilise energy stores for recovery and tissue repair

The more severe the injury, the greater the response - this is a graded relationship (Figure 1.1 in B&L).

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3. MEDIATORS OF THE METABOLIC RESPONSE

A. Tissue Damage & Inflammation (DAMPs Pathway)

• Tissue injury releases DAMPs (Damage-Associated Molecular Patterns) / alarmins
  • Key DAMPs: heat shock proteins, HMGB1, S100 proteins, nucleic acid fragments
• DAMPs are sensed by PRRs (Pattern Recognition Receptors):
  • Toll-like receptors (TLRs)
  • NOD-like receptors (NLRs)
• PRR activation → formation of inflammasomes → activate caspases → release:
  • IL-1, IL-6, TNF-α, interferons, chemokines
• Result: Sterile systemic inflammatory cascade → local inflammation → SIRS (if severe)
• DAMPs also activate endothelial cells and platelets → leaky capillaries + coagulopathy
• Uncontrolled SIRS → risk of acute kidney injury (AKI), acute lung injury (ALI), coagulopathy → MODS

Secondary Triggers of the Metabolic Response (Table 1.1):

These can amplify or prolong the catabolic phase, leading to organ failure or immune dysfunction.

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B. Neuroendocrine Response

• Pathway: Nociceptive neurones → spinal cord → thalamus → hypothalamus → pituitary
• Local inflammation + direct injury excites nociceptive neurones

• Provide essential substrates for survival from tissue breakdown
• Postpone anabolism
• Optimise host defence

These changes may be helpful short-term but harmful long-term, especially in the severely injured.

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4. METABOLIC CHANGES AFTER SURGERY AND TRAUMA

Carbohydrate Metabolism

• Hyperglycaemia ("stress diabetes") occurs due to:
  • Counter-regulatory hormones (cortisol, catecholamines, glucagon) → ↑gluconeogenesis
  • Insulin resistance (temporary, proportional to magnitude of injury)
• During shock: insulin levels may fall despite hyperglycaemia
• Within a few days: insulin production increases but resistance persists
• Risk: prolonged catabolism + insulin resistance → increased risk of septic complications
• Management: IV insulin infusion in ICU (avoid tight control due to hypoglycaemia risk)

Protein Metabolism

• Significant protein catabolism and muscle breakdown
• Increased urinary nitrogen excretion (negative nitrogen balance)
• Liver + skeletal muscle account for >50% of daily protein turnover
• Skeletal muscle: large mass, low turnover (1-2%/day)
• Liver: small mass (1.5 kg), high turnover (10-20%/day)

Acute-Phase Protein Response

• Proinflammatory cytokines (especially IL-6) → hepatic synthesis of positive acute-phase proteins
• Positive acute-phase reactants (↑): CRP, fibrinogen, ferritin, alpha-1 antitrypsin
• Negative acute-phase reactants (↓): Albumin, transferrin, prealbumin
• The fall in albumin = mainly due to increased transcapillary escape (not reduced synthesis)
• Albumin TER (transcapillary escape rate) may increase 3-fold after major injury/sepsis
• This acute-phase response is a "double-edged sword" - provides recovery proteins but at the cost of lean tissue

Fat Metabolism

• Fat mobilisation: triglycerides broken down → free fatty acids (FFAs) + glycerol
• FFAs used as energy by most tissues
• Increased lipolysis driven by catecholamines and cortisol

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5. CHANGES IN BODY COMPOSITION FOLLOWING INJURY

• Fat: 13 kg; Fat-free mass: 57 kg (protein 12 kg, water 42 L, minerals 3 kg)
• Protein mass: skeletal muscle (4 kg) + non-skeletal muscle/visceral (8 kg)
• Water: intracellular (28 L) + extracellular (14 L)

• Lean tissue wasting (especially skeletal muscle)
• Weight loss (fluid shifts + catabolism)
• Increased extracellular fluid (oedema due to capillary leak)

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6. MANAGING THE CATABOLIC STRESS RESPONSE

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7. AVOIDABLE FACTORS THAT COMPOUND THE RESPONSE

• Pain (amplifies neuroendocrine response)
• Hypothermia
• Starvation / poor nutrition
• Secondary sepsis
• Ongoing bleeding / ischaemia
• Unnecessary surgery

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8. KEY SUMMARY POINTS FOR EXAM

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