FRCA Notes

Pathophysiology of Trauma

The curriculum explicitly asks for knowledge of 'the complex pathophysiological changes that occur in all patients with multiple injuries'.

Resources

  • Trauma causes complex pathophysiological changes which disturb organ homeostasis
  • The degree of organ dysfunction is determined by the injury load
  • There is therefore greater homeostatic dysfunction in those who experience polytrauma, which may be defined as severe injury in ≥2 body regions

Primary Injury

  • The initial trauma load causes injury to the brain and other organs, bony skeleton and vascular architecture (i.e. major haemorrhage)
  • There may be death from raised ICP or exsanguination

  • This initial injury leads to:
    • Shock, and hyperlactataemia
    • Microvascular flow abnormalities
    • Primary coagulopathy

Secondary Injury

  • Secondary injury, at the cellular level, is mediated by:
    • Complement activation
    • Damage-associated molecular patterns
  • The primary mediators are neutrophils, who undergo adhesion, transmigration and degranulation with release of reactive oxygen species

  • There is consequent:
    • Ischaemia-reperfusion injury
    • Cellular apoptosis
    • Tissue necrosis

Injury Severity Score

  • The most reliable indicator of injury load is the Injury Severity Score (ISS)
  • An ISS >15 indicates major/severe traumatic injury
  • It was initially derived from blunt, traumatic injury from motor vehicle collisions

  • It measures the most severe injury in each of six organ systems
  • Each organ system is given an abbreviated injury scale from 0 - 6, where 0 is no injury and 6 is unsurvivable
  • The organ systems with the three highest scores (A, B and C) are used, and ISS = A2 + B2 + C2

  • The degree of primary injury is related to:
    • The energy (mechanical, thermal) applied to the body
    • The degree of disruption to organs, tissues and bone
    • The distribution of injuries
  • Early deaths from trauma occur within 24hrs of primary injury, usually due to brain injury or major haemorrhage

Brain injury

  • Present in 60% of patients with an ISS >15
  • Acute haemorrhage (ICH, SDH, EDH, SAH) or cerebral oedema lead to raised ICP
  • There is subsequent reduction in CPP and a lethal intracranial compartment syndrome

Major haemorrhage

  • Accounts for a high proportion of deaths within 24hrs, usually due to large vessel disruption
  • Pelvic or visceral haemorrhage following blunt trauma is most common in the UK
  • Haemorrhagic shock may contribute to further brain injury:
Class Volume lost HR BP Pulse pressure RR CNS UO (ml/hr)
1 <750ml (<15%) <100 Normal Normal/increased 14-20 Anxious >30
2 750-1500ml (15-30%) 100-120 Normal Decreased 20-30 Anxious 20-30
3 1500-2000ml (30-40%) 120-140 Decreased Decreased 30-40 Confused 5-15
4 >2000ml (>40%) >140 Decreased Decreased >40 Lethargic Negligible

Coagulation

  • Severe injury results in the development of the acute coagulopathy of trauma shock
  • Evidence suggests it is related to the traumatic insult, rather than dilutional in nature
  • Elevated prothrombin time is most commonly seen (aim for a PT<15s, or INR <1.5)

  • Following injury or trauma there is a host immune response
  • Inflammatory mediators are release locally at the site(s) of injury, but there may be systemic amplification
  • The balance between pro- and anti-inflammatory mediators results in a 'SIRS' response

Mediators

  • Cytokines involved in the process include:
    • Hyper-acute inflammatory cytokines: TNF-ɑ, IL-1β
    • IL-6, a subacute cytokine whose levels correlated with ISS, degree of organ failure, ARDS and death
    • IL-8, whose levels also correlated with outcome
    • Anti-inflammatory cytokines e.g. IL-10 are later produced by white cells to help modulate production of pro-inflammatory cytokines

  • Activation of the complement pathway occurs
  • The degree of pro-inflammatory peptide release corresponds to severity of the insult
  • C3a, C4a and C5a promote a pro-inflammatory microenvironment:
    • Chemotaxis of leukocytes
    • Phagocytic cell degranulation
    • Increased vascular permeability
    • Smooth muscle contraction
    • Production of oxygen free radicals

Effectors

  • Neutrophils are important effectors following trauma, primed by pro-inflammatory mediators and attracted to sites of injury by Il-8 and other chemokines
  • PMNs migrate into tissue via damaged endothelium and degranulate, releasing toxic substances including proteases and reactive oxygen species
  • Surgery and infection contribute to 'second-hit' priming of leukocytes and persistently raised Il-6 levels

Immune suppression

  • A relative state of immunosuppression can supervene, the counter-inflammatory response syndrome
  • IL-10 inhibits transcription factors such as NK-𝜅β, reducing production of pro-niflammatory cytokines
  • The balance between pro- and anti-inflammatory reactions may be influenced by interventions such as surgery, blood transfusion and infection

  • Improving trauma care, including understanding the influence of anaesthetic and intensive care interventions, can help reduce post-traumatic hyperinflammation and subsequent morbidity/mortality