Metabolic Response to Injury - Bailey and Love's Short Practice of Surgery (28th Ed.)

Overview

1. Phases of the Metabolic Response

• Hypovolaemia, decreased basal metabolic rate, reduced cardiac output, hypothermia and lactic acidosis
• Main role: conserve circulating volume and energy stores to maximise survival
• Triggers a Systemic Inflammatory Response Syndrome (SIRS)
• Effects include muscle breakdown, weight loss and hyperglycaemia

• Rebuilding phase - may last weeks after serious injury
• Body starts to restore lean tissue and fat stores

2. Magnitude of the Injury Response

3. Mediators of the Metabolic Response

Tissue Damage and Inflammation

• Tissue injury releases DAMPs (damage-associated molecular patterns) or "alarmins" (e.g. heat shock proteins, HMGB1, S100 proteins, nucleic acid fragments)
• DAMPs are sensed by Pattern Recognition Receptors (PRRs) - Toll-like receptors and NOD-like receptors on macrophages, neutrophils, and dendritic cells
• PRR activation triggers inflammasome formation, activating caspases and releasing key cytokines: IL-1, IL-6, TNF-alpha, interferons and chemokines
• This initiates a sterile systemic inflammatory cascade
• Uncontrolled SIRS risks acute kidney injury, acute lung injury, coagulopathy and MODS

Neuroendocrine Response

• Cortisol: rises from adrenal cortex, promotes gluconeogenesis and protein catabolism, immunosuppressive at high levels but synergistic with IL-6 for hepatic acute-phase response
• Adrenaline/Noradrenaline: elevated, promoting glycogenolysis and lipolysis
• Glucagon: raised, driving gluconeogenesis
• Growth Hormone: rises, paradoxically creating resistance to its own anabolic effects
• ADH & Aldosterone: both elevated - cause oliguria and sodium/water retention in extracellular space

Cytokine Network

• Pro-inflammatory: IL-1, IL-6, IL-8, TNF-alpha - produced within first 24 hours; act on hypothalamus causing pyrexia; induce proteolysis in skeletal muscle; drive acute-phase protein production in liver
• Counter-inflammatory response (within hours): IL-1 receptor antagonist, TNF soluble receptors, IL-4, IL-5, IL-9, IL-10 - attempt to limit systemic organ damage
• Nitric oxide (via iNOS) and prostanoids (via COX-2) also act as key inflammatory mediators

4. Key Metabolic Changes

Hypermetabolism

• Energy expenditure is 15-25% above predicted resting values in most trauma patients (burns patients may be even higher)
• Caused by: central thermodysregulation from cytokines, increased sympathetic activity, wound hyperaemia and ischaemia, increased protein turnover, and nutritional support
• Skeletal muscle wasting ultimately limits the volume of metabolically active tissue

Skeletal Muscle Protein Catabolism

• Net protein loss occurs in response to injury; up to 75 g of muscle protein/day may be lost
• Muscle protein breakdown releases amino acids (especially glutamine and alanine) as substrates for hepatic gluconeogenesis
• Mediated at the molecular level by the ubiquitin-proteasome pathway
• Results: negative nitrogen balance, immobility, poor wound healing, hypostatic pneumonia, and potentially death if prolonged

Hepatic Acute-Phase Protein Response

• Liver reprioritises protein synthesis from structural proteins to positive acute-phase reactants (CRP, fibrinogen) - driven by IL-6
• Negative acute-phase reactants (albumin, transferrin) fall - not due to reduced synthesis but increased transcapillary escape from increased microvascular permeability
• Albumin TER may be increased threefold after major injury/sepsis
• This represents a "double-edged sword" - provides repair proteins but at the expense of lean tissue

Insulin Resistance and Hyperglycaemia

• Postoperative hyperglycaemia occurs from increased glucose production + decreased peripheral uptake
• Insulin may not rise appropriately after severe injury; within days, insulin production increases but peripheral resistance persists
• Mechanism: cytokine action + reduced responsiveness of glucose transporter GLUT4 in muscle cells
• Degree of resistance is proportional to injury magnitude (e.g. 2 weeks after upper abdominal surgery; prolonged with sepsis)
• Prolonged catabolism + insulin resistance = increased risk of septic complications (a "vicious catabolic cycle")
• Management in ICU: IV insulin infusion to maintain reasonable glycaemic control, though overly tight control risks hypoglycaemia

Lipolysis and Fat Metabolism

• Fat stores are mobilised to provide glycerol (for gluconeogenesis) and fatty acids (for energy)
• Adipose tissue lipolysis is driven by catecholamines and reduced insulin
• Ketone body production and utilisation may be impaired after trauma, unlike in simple starvation, worsening catabolism

5. Avoidable Factors Compounding the Response

6. Summary Boxes from Bailey and Love

• Increased counter-regulatory hormones: adrenaline, noradrenaline, cortisol, glucagon, growth hormone
• Increased energy requirements (up to 40 kcal/kg per day)
• Increased nitrogen requirements
• Insulin resistance and glucose intolerance
• Preferential oxidation of lipids
• Increased gluconeogenesis and protein catabolism
• Loss of adaptive ketogenesis
• Fluid retention with associated hypoalbuminaemia

7. Clinical Implications

• Successful management of the metabolic response improves outcomes and forms the basis of modern perioperative/Enhanced Recovery After Surgery (ERAS) care
• Key interventions include:
  • Pre-operative carbohydrate drinks (reduces perioperative insulin resistance and anxiety)
  • Minimally invasive surgery (less invasive surgery triggers less insulin resistance)
  • Maintaining normothermia intraoperatively (reduces wound infections, cardiac complications, and bleeding)
  • Early oral/enteral nutrition (protein-sparing, prevents starvation-induced gluconeogenesis)
  • Early mobilisation (counters immobility-driven muscle wasting)
  • Careful fluid balance (avoiding unnecessary saline loading)