Systemic response to trauma

Question 1

How does SIRS differ from sepsis, severe sepsis and septic shock.

Answer 1

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

Question 2

What are DAMPS? What do they promote?

Answer 2

Damage associated molecular patterns. Intracellular molecules that are ‘hidden’ in normal physiological conditions but in physiological stressful conditions are pro inflammatory and profibrotic

Question 3

How are DAMPS expressed?

Answer 3

Actively secreted by stressed immune cells;
Exposed on stressed cells,
Passively released into the extracellular environment from dying cells or the damaged extracellular matrix

Question 4

Why is inflammation beneficial in a traumatic injury?

Answer 4

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

Question 5

Give an example of a DAMP

Answer 5

HMGB1

Question 6

What can very high levels of DAMPS lead to?

Answer 6

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

Question 7

What secretes DAMPS?

Answer 7

Activated immune cells and necrotic cells

Question 8

What cells do DAMPS directly activate? What system is also activated by DAMPS?

Answer 8

Neutrophils and monocytes. The complement system is also activated by DAMPS.

Question 9

What is complement?

Answer 9

Plasma proteins that perform extracellular killing of pathogens without prior phagocytosis.

Question 10

Complement triggers the release of interleukins. What are interleukins?

Answer 10

Pro inflammatory cytokines e.g. IL 1, IL 2 , IL 6

Question 11

Give some examples of some anti-inflammatory cytokines

Answer 11

IL 10, Transforming growth factor beta

Also have cytokine antagonists such as IL 1Ra

Question 12

Why do some patients die from multiple organ failure following trauma?

Answer 12

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

Question 13

In trauma patients, what syndrome can persistent inflammation lead to?

Answer 13

PICS

persistent inflammation, immunosuppression and catabolism syndrome

Question 14

Following trauma, does the activation of the coagulation cascade lead to a pro or anti inflammatory response? Why?

Answer 14

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

Question 15

What immune cells release reactive oxygen species and proteases that can cause localised tissue damage?

Answer 15

Neutrophils

Question 16

What hormone has a major anti-inflammatory effect?

Answer 16

Cortisol

Question 17

What is the significance of the cortisol:DHEA ratio?

Answer 17

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

Question 18

Does evidence suggest lipids are beneficial or harmful in the acute inflammatory response? Give an example

Answer 18

Beneficial at reducing the acute inflammatory response. Statins and dietary modifications are being tested.

Question 19

How is the brain affected in the systemic inflammatory response?

Answer 19

Pro inflammatory cytokines disrupt the blood brain barrier

Complement increase can lead to inflammation and secondary injury.

Question 20

What is inflammaging?

Answer 20

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.

Question 21

What is immunosenescence?

Answer 21

Elderly patients are less able to respond to pathogens due to a declining innate and adaptive immune response.

Question 22

Describe the role of platelets in the immune response to trauma

Answer 22

• 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.

Question 23

What role does fibrin play in the immune response to trauma?

Answer 23

Acts as a chemoattractant, attracting neutrophils

Question 24

What role does plasmin play in the immune response to trauma?

Answer 24

Stimulates the complement cascade

Question 25

How does hydrocortisone improve outcomes in SIRS?

Answer 25

Halve hospital-acquired pneumonia and mechanical ventilations free days

Question 26

How does tranexamic acid work? Why is tranexamic acid used in trauma patients?

Answer 26

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.

Question 27

Why is starch a harmful resuscitation fluid?

Answer 27

Leaks across endothelium

Question 28

What is permissive hypotension? What is its purpose?

Answer 28

Deliberately maintaining a systolic blood pressure of 80-90mmHg to stabilise clots before surgery.

Question 29

What are the dangers of permissive hypotension in relation to the immune system?

Answer 29

Can aggravate the systemic inflammatory response therefore restoration of blood pressure once haemostats is secured.

Question 30

What two interventions stimulate natural immunity?

Answer 30

Biological agents and nutritional therapies

Question 31

What do biological agents do? Give an example

Answer 31

Target a specific part of the immune system e.g. immunoglobulin reduces pneumonia

Question 32

Why are nutritional agents given post trauma? Give an example

Answer 32

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

Question 33

What can be given to prevent microbial proliferation in trauma patients?

Answer 33

Prophylactic antibiotics

Question 34

Give the most common cause of death for patients dying 8 hours-3days post trauma

Answer 34

TBI

Question 35

Give some common causes of death for patients dying 3 days+ post trauma

Answer 35

Trauma induced MOF
Sepsis
ARDS
VTE
AKI

Question 36

What are PAMPS?

Answer 36

Non self molecules- stands for pathogen associated molecular patterns

Question 37

List three immune cells that are unregulated during the hyper acute phase of trauma and three immune cells that are down regulated

Answer 37

Unregulated: Neutrophils, Monocytes, NK cells (Innate immune response)

Down regulated:
T cells, B cells, dendritic cells

Question 38

What four treatments are given during a RSI?

Answer 38

Ketamine- induction agent
Rocuronium- paralytic agent
Fentanyl- induction agent
+/- Midazolam

Question 39

What do blood transfusions put patients at risk of?

Answer 39

Nosocomial infections and cancer