141. Anaphylaxis Flashcards
What are the different types of hypersensitivity?
- Type I (Immediate hypersensitivity):
Mediated by IgE antibodies, causing rapid reactions like allergic rhinitis, hay fever, food allergies, anaphylaxis, and bee sting reactions. - Type II (Cytotoxic hypersensitivity):
Involves antibodies binding to cell surface antigens, leading to cell destruction; examples include autoimmune hemolytic anemia, blood transfusion reactions. - Type III (Immune complex-mediated):
Caused by deposition of antigen-antibody complexes in tissues, leading to inflammation; examples include serum sickness, systemic lupus erythematosus (SLE), and post-streptococcal glomerulonephritis.
Type IV (Delayed-type hypersensitivity):
Mediated by T cells, causing delayed reactions like contact dermatitis from poison ivy, tuberculin skin test, and graft-versus-host disease.
What signs predominate in dogs and cats with anaphylaxis?
In dogs, signs of gastrointestinal compromise, hepatic congestion, and portal hypertension predominate. In cats, acute respiratory distress, airway edema, and bronchial secretions may be more prominent.
Which Ig is involved in anaphylaxis?
E
What is the MOA of anaphylaxis?
IgE-mediated event that requires an initial, clinically silent sensitization to an antigen. The subsequent IgE antibodies produced bind to high-affinity Fc-epsilon-R1 receptors located on tissue mast cells and circulating basophils. Upon reexposure, the same antigen binds and cross-links two cell-bound IgE antibodies, resulting in a conformation change, calcium influx, second messenger system activation, and release of preformed as well as newly formed mediators.
What does mast cell degranulation release?
Mast cell degranulation releases numerous mediators including histamine, tryptase (powerful molecule activating complement), heparin, and cytokines.
What do prostaglandins cause?
constriction of coronary and bronchial smooth muscle
What are the effects of platelet activating factor?
bronchoconstriction, increased vascular permeability, vasodilation, and platelet aggregation.
Apart from the classic IgE-mediated immunological
pathway, a second pathway of systemic anaphylaxis was
recently identified in murine models of anaphylaxis. What is it?
The
alternative pathway is mediated by immunoglobulin G
(IgG) production and binding to the low-affinity IgG
receptor Fc-gamma-RIII on macrophages. Re-exposure
to an antigen induces anaphylaxis by formation of IgG
antigen complexes. Complexes bind to Fc-gamma-RIII
and cross-linkage of the receptor causes release of PAF
from macrophages. In the alternative pathway, PAF
rather than histamine is primarily responsible for devel
opment
of hemodynamic alterations. The signifi
cance
of an alternative pathway of anaphylaxis in dogs
and cats is yet to be determined.
What about the role of heparin?
Interestingly, heparin is also contained in mast cells, which can result in a hypocoagulable state in some patients with anaphylaxis.
List the diverse effects of histamine based on the receptor.
H1, H2, H3 and H4
The H1 receptor activates smooth muscle contraction and endothelial changes resulting in vasodilation and increased vascular permeability. The H2 receptor is best known for modulating gastric acid secretion and regulation of cardiac myocytes. The less well-known H3 and H4 receptors are involved in peripheral and central neurotransmitter release, respectively, as well as mediating the immune response.
Explain cardiovascular collapse during anaphylaxis
vasodilatory shock, cardiogenic shock, dysrhythmias, and evidence of cardiac ischemia. Both peripheral and central release of vasoactive substances such as dopamine and norepinephrine is compromised during anaphylaxis, further perpetuating signs of shock.
What is the MOA of epinephrine when treating anaphylaxis?
α1-receptor activity results in vasoconstriction, ameliorating the vasodilatory shock state and improving blood pressure and coronary flow.
Epinephrine induced vasoconstriction also stabilizes and relieves upper airway obstruction and mucosal edema.
Its β1-receptor-mediated activity results in positive inotropy, chronotropy, and improvement in cardiac output, while its β2-receptor activity results in bronchodilation and stabilization of mast cells, preventing further degranulation and release of mediators of anaphylaxis.
Based on these specific pharmacologic mechanisms of epinephrine as they pertain to the pathophysiology of anaphylaxis, it remains the central drug for its management
Discuss the use of glucocorticoid in anaphylaxis
Glucocorticoids’ onset of action is hours after administration, they should not be considered a first-line drug for the management of anaphylaxis; rather, they downregulate the late-phase eosinophilic response and block the arachidonic acid cascade, tempering delayed inflammatory cascades.
A 2012 Cochrane review could not find evidence to support the use of glucocorticoids in anaphylaxis, and they are not recommended as empiric therapy in the current human guidelines for treating the symptoms of severe anaphylaxis.
Can hypersensitivity or anaphylaxis happen upon first exposure and how?
Yes. Non-immunological triggers
for anaphylaxis have also been described when physical
factors such as heat, cold, or pharmaceuticals cause
degranulation of mast cells and basophils without participation
of immunoglobulins. This mechanism does
not require sensitization, so hypersensitivity or anaphylaxis
can occur upon the first exposure to an antigen.
