16B09: Exam Report
Describe the immunology and drug treatment of anaphylaxis
32% of candidates passed this question.
It was expected candidates would detail the process of IgE mediated type I hypersensitivity reaction with some discussion of the mediators (Histamine / tryptase and others) and their consequences. Some detail describing time frame of response and the pre-exposure to Antigen (or a similar Antigen) was expected. Drug treatments would include oxygen and fluids as well as more specific agents such as adrenaline and steroids. Adrenaline is the mainstay of therapy and some comment on its haemodynamic role and prevention of ongoing mast cell degranulation was required.
Better answers noted steroids take time to work and some also discussed the role of histamine blocking agents.
S1i / 16B09: Describe the immunology and drug treatment of anaphylaxis
Definition
Anaphylaxis is a life threatening Type I mediated hypersensitivity reaction
NB Anaphylaxis (Gk. without protection) – refers to the original theory that the body had used up its protection mechanisms on first exposure and that it was without defence on subsequent exposure to the Ag
Immunology of Anaphylaxis
Trigger: drugs (NMBD), NSAIDs, contrast, latex
Primary Exposure
- Antigen (Ag) presented by Th cells to B cells
- B cells activated to become:
- Memory B cells → live in lymphoid tissue and release specific IgE if Ag represents
- Plasma Cells → Plasma cells secrete large amounts of IgE into circulation → interact with high-affinite IgE receptors on Mast Cells (MCs) and Basophils ‘priming’ them, this is known as Sensitization
- No symptoms
Secondary Exposure
- Ag binds IgE on MCs & Basophils → IgE crosslink → MASS MC degranulation → release of allergenic mediators
- Memory B cells activated → more IgE coating MCs & degranulation
- Mediator release is responsible for the anaphylaxis triad; Vasodilatory shock, Angioedema & Bronchoconstriction
- Mediators:
- Histamine: increases vascular permeability → angioedema, smooth muscle contraction → bronchoconstriction, relaxation of smooth muscle → vasodilation
- Bradykinin: production of prostacyclin & NO → mass vasodilation & hypotension. Bradykinin on its own causes itch and increased vascular permeability
- PGD2: chemotactic for neutrophils, activates eosinophiles
- Tryptase: activates complement, coagulation & kallikrein-kinin pathways
- Leukotrienes: trigger sm m contraction of bronchioles
- Platelet activating factor: platelet activation, aggregation
Drug Tx of Anaphylaxis
Immediate Management
- Stop exposure to potential triggers
- Call for help
- Airway maintenance w 100% FiO2
- Elevate legs
- Cardiac arrest? → ALS
- Adrenaline
- Fluid Bolus
Secondary Management
- Antihistamines
- Steroids
- Bronchodilators
- +/- Adrenaline infusion
Drug
Adrenaline
Mechanism of Action
α1 – vasoconstriction
β1 – positive inotropy
β2 – bronchodilation
β2 – mast cell and basophil stabilisation
Drug
Fluids
Mechanism of Action
Restore circulating volume. Increase preload and CO
Drug
Oxygen
Mechanism of Action
Support respiratory system in setting of severe bronchoconstriction and airway oedema
Drug
Antihistamines
Mechanism of Action
H1 & H2 antihistamines relieve cutaneous signs and symptoms but have minimal effect on systemic mast cell and basophil degranulation
Drug
Bronchodilators
Mechanism of Action
Improve airway resistance
Drug
Steroids
Mechanism of Action
Glucocorticoids as suppressants of inflammation are used to prevent the late phase of anaphylaxis