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Flashcards in Sepsis - Immunopathogenesis Deck (33)
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1

What type of disease is sepsis

An inflammatory disease

2

What cells express pattern-recognition receptors

Macrophages
Neutrophils
Epithelial cells

3

What are DAMPs

Endogenous factors released during cell damage

4

What are PAMPs

Exogenous molecules expressed by microbes

5

What system most significantly contributes to the amplification of systemic inflammation in sepsis

Complement

6

Which 2 systems are activated by leaky vessels and blood clotting

Vascular endothelium
Coagulation

7

What significant phenomenon occurs to both T and B cells and characterises late immunosuppression in sepsis

Apoptosis

8

Immunopathogenesis of sepsis is associated with the activation of what systems

Innate immunity
Complement system
Vascular endothelium
Coagulation system
Adaptive immunity

9

What happens when PRRs are activated

Activation of inflammatory signalling pathways

10

What are PRRs

Pattern recognition receptors

11

What happens after inflammatory signalling pathways are activated

The pathways will converge and activate several important transcription factors which will each regulate transcription of genes encoding cytokines and chemokines

12

What is TNFa

A master regulatory cytokine that has a diverse array of functions on multiple different immune cell types including innate and adaptive

13

Describe the local effects of TNFa

TNFa stimulates expression of adhesion molecules on endothelial cells and proteins that trigger blood clotting
This recruits immune cells to the site of infection and prevents pathogens from spreading via the blood

14

What happens if TNFa is unsuccessful in containing microbes

Macrophages in the liver and spleen will be activated which will release TMFa systemically which ultimately leads to intravascular coagulation, preventing blood flow to organs leading to organ failure and death

15

What does the systemic release of TNFa lead to

Systemic vasodilation
Increased vascular permeability
Loss of blood pressure
Systemic blood clotting of microvasculature
Contributes to onset of sepsis and septic shock

16

When is the complement system activated

Immediately upon recognition of PAMPs and DAMPs

17

What occurs after the complement system is activated

The peptides C3a and C5a are generated

18

What is C5a

A potent chemoattractant which significantly amplifies inflammation

19

What is the effect on sepsis of the activation of complement

Contributes to vasodilation, tissue damage and organ failure

20

What is the endothelial barrier

Continuous barrier that coats the vascular system and separates the fluid phase of the blood from the tissues
Normally serves as an anticoagulant surface

21

Describe endothelial barrier dysfunction

Sepsis produces changes which converts the endothelium into a pro-coagulant state
This endothelium mediates loss of fluid through tight junctions and facilitates the recruitment and attachment of inflammatory cells

22

How can endothelial barrier dysfunction lead to septic shock

Leaky capillary membranes create a loss of plasma proteins and fluid into the extravascular space
Vasodilation alters capillary blood flow which contributes to septic shock

23

What should be used if a patient is in septic shock

A vasoconstrictive agent such as noradrenaline or vasopressin in order to maintain blood pressure and try to keep the patient alive

24

What characterises hypercoagulation caused by sepsis

Microvascular thrombi
Fibrin deposition
Neutrophil extraction trap formation
Endothelial injury

25

What can activate the coagulation cascade in sepsis

Microorganisms and DAMPs
Complement activation and the release of inflammatory cytokines

26

What are the consequences of widespread coagulation

Uncontrolled bleeding - occurs as a result of the consumption of clotting factors leading to a situation where patients can suffer from the clotting and uncontrolled bleeding

27

What are common signs and symptoms signalling that sepsis has affected a particular organ

Neurological - altered mental state
Pulmonary - hypoxaemia or ARDs
Cardiovascular - shock
Renal - oligouria

28

What is ARDs

Acute Respiratory Distress Syndrome
When the lungs fill with inflammatory infiltrate and fluid - patients can’t get enough oxygen into the blood

29

What is oligouria

A significantly reduced urine output

30

What do sepsis patients experience besides inflammation

Immunosuppression

31

What is caused by excessive inflammation

Sustained inflammation causes tissue injury
Strong activation of innate immunity via PAMPs and DAMPs
Sustained hyperinflammation
Activation of complement system, coagulation system and vascular endothelium

32

What does immunosuppression cause in patients with sepsis

Apoptosis of T cells and B cells
Dysfunctional dendritic cells
Delayed apoptosis of immature dysfunctional neutrophils

33

What is the best treatment for patients with sepsis

Intravenous early antibiotics within the 1st hour of diagnosis