Sepsis, anaphylaxis, and distributive Shock

Question 1

What is meant by shock?

Answer 1

Inadequate cellular perfusion and oxygen uptake with conseuqent tissue hypoxia and organ failure

Question 2

Define sepsis

Answer 2

Suspected/proven infection plus a system inflammatory response syndrome

Question 3

Define severe sepsis

Answer 3

Sepsis plus organ dysfunction

Question 4

Define septic shock

Answer 4

Severe sepsis + hypotension despite adequate volume resucitation

Question 5

Why may patients be susceptible to severe sepsis?

Answer 5

Genetic polymorphisms related to immunity and inflammation

Acquired immune system deficiencies

Not being vaccinated

Question 6

Give examples of bacteria susceptible to in-hospital patients?

Answer 6

MRSA (methicillin resistant Staphylococcus aureus)

Extended spectrum beta lactamase producing gram -ve enteric organisms

Question 7

Give examples of bacteria susceptible to patients after splenectomy?

Answer 7

Streptococcus pneumoniae (pneumococcus)

Question 8

Give examples of bacteria susceptible to those in school, uni, or military?

Answer 8

Neiseirria meningitidis

Question 9

Give examples of bacteria susceptible to those with an intravascular catheter?

Answer 9

Staphlycocci

Question 10

Give examples of bacteria susceptible to those intubated/ventilated?

Answer 10

Gram -ve enteric organisms
Pseudomonas
MRSA
Candida

Question 11

Give examples of microbes susceptible to those who are pharmacologicallt immmunosuppressed?

Answer 11

Pneumocystis jirovecil
CMV
Candida spp
Arpergillus spp
Nocardia spp

Question 12

Give examples of bacteria susceptible to those on foreign travel?

Answer 12

Malaria

Legionella

Question 13

Give examples of bacteria susceptible to those very young or old?

Answer 13

Listeria monocytogenes

Question 14

List the four main stages of the pathophysiology of sepsis?

Answer 14

Localised infection/inflammation
SIRS
Sepsis with organ damage/failure
Immunosuppresion in late sepsis

Question 15

Why does acute inflammation occur?

Answer 15

A result of innate immunity in vascularised tissue

Question 16

How is the innate immunity process stimulated?

Answer 16

Toll-like receptors on the host cell recognise bacterial exo/endo-toxins and other microbial components (PAMPs)

Products of damage recognised by DAMPs (damage associated molecular patterns)

Receptor binding => transcription of cytokine-related genes

Cytokines and other mediators facilitate vascular changes and recruitment of inflammatory cells

Question 17

Cells involved in acute inflammation?

Answer 17

Mast cells
Macrophages
Neutrophils

Question 18

List some of the chemical mediators of acute inflammation

Answer 18

Complement system
Kinin system
Vasoactive amines - histamine, serotonin
Prostaglandins, leukotrines
Cytokines and chemokines
NO

Question 19

Which chemical mediators cause vasodilatation?

Answer 19

Prostoglandins
NO
Histamine

Question 20

Which chemical mediators cause increased vascular permeability?

Answer 20

Vasoactive amines
C3a, C5a
Bradykinin
Leukotrienes
PAF C4, D4, E4
Substance P

Question 21

Which chemical mediators can act as chemotaxis or for leucocyte recruitment and activation?

Answer 21

C5a
Leukotrienes B4
Chemokines
IL-1
TNF
Bacterial products

Question 22

Which chemical mediators can cause fever?

Answer 22

IL-1
TNF
Prostaglandins

Question 23

Which chemical mediators can cause pain?

Answer 23

Prostaglandins

Bradykinin

Question 24

Which chemical mediators can cause tissue damage?

Answer 24

Neutrophil and macrophage
Lysosomal enymes
Oxygen metabolites
NO

Question 25

Describe the sequence of events for inflammation

Answer 25

1) Injury - invasion of microorganisms, effects of toxins, tissue necrosis 2) Mast cell degranulation 3) Macrophage activation 4) Compliment and other mediators activation 5) Vascular dilatation and increased permeability 6) Recruitment of neutrophils, migration and activation 7) Phagocytosis + destruction/elimination of microbe etc.

Question 26

What are the characteristics of adaptive immunity?

Answer 26

Antigen-specific response Days or weeks to develop Mediated through T and B lymphocytes Has memory Chronic inflammation, allergy and hypersensitivity are all signs of adaptive response

Question 27

What is the role of adaptive immunity in sepsis?

Answer 27

Amplification of the inflammatory response Antigen-specific Ig facilitates opsonisation and phagocytosis T cell subsets are modified in sepsis - Th1 - secrete pro inflammatory cytokines - Th2 secrete anti inflammatory cytokines

Question 28

What are the features associated with SIRS?

Answer 28

``` Fever Tachycardia Tachypnoea Leukocytosis Acute phase protein secretion - procalcitonin - CRP ```

Question 29

What is anaphylactic shock?

Answer 29

A severe systemic type 1 hypersensitivity reaction mediated by mast cells

Question 30

List the classification of hypersensitivity reactions

Answer 30

Type 1 - immediate hypersensntivity Type 2 - antibody-mediated Type 3 - immune complex mediated Type 4 - cell-mediated

Question 31

What are the features of a type 1 hypersensitivity reaction?

Answer 31

Rapidly developing immunologic reaction Antigen-Antibody is bound to mast cells Requires prior sensitisation the antigen to allow binding of IgE to mast cells Often occurs in two phases: early and delayed Usually localised but sometimes systemic (i.e. anaphylaxis) Susceptibility is often genetically determined

Question 32

List the mediators released by the degranulation of mast cells

Answer 32

Histamine Proteases Chemotactic factors

Question 33

What is physiological effect of mediator release as a result of mast cell degranulation?

Answer 33

Smooth muscle spasm Blood vessel dilatation & incr. permeability =>oedema Chemotaxis and leukocyte infiltration => 2ndry effects Mucous secretion Tissue damage