Anaphylaxis: mediators of inflammation

Question 1

Histamine

Answer 1

Primary mast cells
Increases VP, vasodilation, bronchoconstriction and gastric acid

Question 2

Proteases

Answer 2

Primary mast cells
Increases kinin, activates complement, can progress into DIC-like syndrome

Question 3

Heparin

Answer 3

Primary mast cells, packaged with Trypase and Chylase. Tends to counter T.
Anticoagulant, urticaria, immune

Question 4

NCFTA

Answer 4

Primary mast cells
Neutrophil chemotaxis

Question 5

ECTFA

Answer 5

Primary mast cells
Eosinophil chemotaxis

Question 6

PGE2/PGD2

Answer 6

Secondary AA cascade
Increased VP, vasodilation and bronchoconstriction

Question 7

Prostacyclin

Answer 7

Secondary AA cascade
Increase vasodilation, causes plt aggregation

Question 8

Leukotrienes

Answer 8

Secondary AA cascade
Increase VP, vasodilation, bronchoconstriction, and WBCs

Question 9

Thromboxane A2

Answer 9

Secondary AA Cascade
Plt aggregation, SM contraction

Question 10

PAF

Answer 10

Secondary AA Cascade
Initiates and amplifies inflammation and thrombosis
Marked vasodilation and hypotension
Increased VP, massive fluid shifts
PAF/P13K pathway - increases eNOS and NO -> activates soluble guanylate cyclase (sGC) = marked vasodilation and hypotension
Amplifies anaphylaxis

Question 11

Epinephrine

Answer 11

a1 receptor: Increase vasoconstriction, increase vascular resistance, decrease mucosal edema
a2 receptor: decrease insulin release, decrease norepinephrine release
B1-adrenergic receptor: increase inotropy, increase chronotropy
B2-adrenergic receptor: increase bronchodilation, increase vasodilation, increase glycogenolysis, decrease mediator release

Question 12

Epinephrine effect specific to anaphylaxis?

Answer 12

Phosphorylation and inactivation of PAFr
Early administration reduces morbidity and mortality in human anaphylaxis
Delayed administration associated with increased mortality, and is progressively less effective with time