Systemic response to trauma Flashcards
How does SIRS differ from sepsis, severe sepsis and septic shock.
SIRS is suspected if a patient has 2 or more of the following; Temperature >38, <36 HR >90/min RR>20/min WCC >12.
It basically describes an excessive innate immune response
Sepsis is when someone is SIRS + presumed/confirmed infection
Severe sepsis- as above with quantitative evidence of organ dysfunction
Septic shock- severe sepsis with refractory hypotension
What are DAMPS? What do they promote?
Damage associated molecular patterns. Intracellular molecules that are ‘hidden’ in normal physiological conditions but in physiological stressful conditions are pro inflammatory and profibrotic
How are DAMPS expressed?
Actively secreted by stressed immune cells;
Exposed on stressed cells,
Passively released into the extracellular environment from dying cells or the damaged extracellular matrix
Why is inflammation beneficial in a traumatic injury?
Clear and rebuild!
Immune cells:
Remove cellular debris
Phagocytose invading pathogen that could cause infection e.g. in an open wound
Promote tissue regeneration - CYTOKINES that promote collagen production, cellular migration, wound epithelialisation and angiogenesis
Give an example of a DAMP
HMGB1
What can very high levels of DAMPS lead to?
Prolonged elevated pro inflammatory response which increases a patients susceptibility to other infections. If the patient becomes septic, this can lead to multiple organ failure
What secretes DAMPS?
Activated immune cells and necrotic cells
What cells do DAMPS directly activate? What system is also activated by DAMPS?
Neutrophils and monocytes. The complement system is also activated by DAMPS.
What is complement?
Plasma proteins that perform extracellular killing of pathogens without prior phagocytosis.
Complement triggers the release of interleukins. What are interleukins?
Pro inflammatory cytokines e.g. IL 1, IL 2 , IL 6
Give some examples of some anti-inflammatory cytokines
IL 10, Transforming growth factor beta
Also have cytokine antagonists such as IL 1Ra
Why do some patients die from multiple organ failure following trauma?
Trauma can result in a vicious cycle of inflammation, immunoparesis (reduced immunoglobulin) and infection. This can lead to sepsis and multiple organ failure. Reduced supply of complement is integral to patients’ state of immunosuppression
In trauma patients, what syndrome can persistent inflammation lead to?
PICS
persistent inflammation, immunosuppression and catabolism syndrome
Following trauma, does the activation of the coagulation cascade lead to a pro or anti inflammatory response? Why?
Pro inflammatory response.
Clotting stage
Platelets release leucocyte-platelet aggregates which cause endothelial damage.
Fibrin is a chemoattractant, attracting neutrophils.
Fibrinolytic stage
Plasmin- stimulates complement cascade
What immune cells release reactive oxygen species and proteases that can cause localised tissue damage?
Neutrophils
What hormone has a major anti-inflammatory effect?
Cortisol
What is the significance of the cortisol:DHEA ratio?
DHEA= dehydroepiandrosterone.
Increased activation of the hyperthalamo-pituitary adrenal axis following trauma which leads to increased cortisol levels. This increases the cortisol:DHEA ratio which is associated with an increased risk of infection.
Animal studies have shown benefit in administering DHEA in sepsis
Does evidence suggest lipids are beneficial or harmful in the acute inflammatory response? Give an example
Beneficial at reducing the acute inflammatory response. Statins and dietary modifications are being tested.
How is the brain affected in the systemic inflammatory response?
Pro inflammatory cytokines disrupt the blood brain barrier
Complement increase can lead to inflammation and secondary injury.
What is inflammaging?
Inflammaging is when elderly patients have a low grade inflammatory state at baseline. When an injury occurs, SIRs responses in elderly patients is exaggerated because the body has been promoted with its elevated baseline levels of pro inflammatory cytokines. The response may also be exaggerated because elderly patients are less able to produce anti-inflammatory cytokines.
What is immunosenescence?
Elderly patients are less able to respond to pathogens due to a declining innate and adaptive immune response.
Describe the role of platelets in the immune response to trauma
- Platelets release pro inflammatory mediators which promote SIRS response. Activation of the immune response increased the number of platelets (self-perpetuating cycle)
- Platelets release leucocyte-platelet aggregates which activate immune cells and cause endothelial damage.
What role does fibrin play in the immune response to trauma?
Acts as a chemoattractant, attracting neutrophils
What role does plasmin play in the immune response to trauma?
Stimulates the complement cascade
How does hydrocortisone improve outcomes in SIRS?
Halve hospital-acquired pneumonia and mechanical ventilations free days
How does tranexamic acid work? Why is tranexamic acid used in trauma patients?
Stops plasminogen converting to plasmin stabilising clots formed post haemorrhage. It also reduces plasmin formation which reduces complement activation caused by the fibrin degradation produces.
Why is starch a harmful resuscitation fluid?
Leaks across endothelium
What is permissive hypotension? What is its purpose?
Deliberately maintaining a systolic blood pressure of 80-90mmHg to stabilise clots before surgery.
What are the dangers of permissive hypotension in relation to the immune system?
Can aggravate the systemic inflammatory response therefore restoration of blood pressure once haemostats is secured.
What two interventions stimulate natural immunity?
Biological agents and nutritional therapies
What do biological agents do? Give an example
Target a specific part of the immune system e.g. immunoglobulin reduces pneumonia
Why are nutritional agents given post trauma? Give an example
Nutritional agents reduce the risk of infection and hence mortality. For example gluten is associated with reduced mortality. Probiotics also reduce hospital related infection and ventilation-assisted pneumonia
What can be given to prevent microbial proliferation in trauma patients?
Prophylactic antibiotics
Give the most common cause of death for patients dying 8 hours-3days post trauma
TBI
Give some common causes of death for patients dying 3 days+ post trauma
Trauma induced MOF Sepsis ARDS VTE AKI
What are PAMPS?
Non self molecules- stands for pathogen associated molecular patterns
List three immune cells that are unregulated during the hyper acute phase of trauma and three immune cells that are down regulated
Unregulated: Neutrophils, Monocytes, NK cells (Innate immune response)
Down regulated:
T cells, B cells, dendritic cells
What four treatments are given during a RSI?
Ketamine- induction agent
Rocuronium- paralytic agent
Fentanyl- induction agent
+/- Midazolam
What do blood transfusions put patients at risk of?
Nosocomial infections and cancer
