Anaphylaxis Flashcards
What is anaphylaxis?
A serious allergic reaction with invariably rapid onset which untreated can be fatal. Most often occurs in young people and females.
What are the 4 signs of acute inflammation?
Rubor - Redness caused by skin vasodilation
Calor - Heat caused by vasodilation
Tumor - Swelling caused by plasma exudation
Dolor - Pain, unpleasant sensation caused by sensory nerve activation
5th - Loss of function
What are the features of anaphylaxis?
Rapid onset - full reaction after about 10-30mins
Generalised skin itching - pruritis
Tingling in extremities
Reddening of skin - erythema
Swelling - urticaria and angio-oedema
Rhinitis - itchy, runny nose
Conjunctivitis - itchy, runny eyes
Nausea, abdominal pain, vomiting
Breathing difficulty, laryngeal oedema or airway constriction
Hypotension - dizziness, fainting, collapse, can use consciousness
What are some inducers of anaphylaxis?
AKA Allergens (antigens). Foods: peanuts, tree nuts, egg, milk. Insect stings. Drugs. Latex. Hair dye. Most cases of anaphylaxis are idiopathic.
What are the different types of hypersensitivity reaction?
Type 1 - Immediate type, anaphylactic reaction (IgE antibodies)
Type 2 - Cytolytic reactions, autoimmune, IgG and IgM, targets vascular cells
Type 3 - Complement fixation, induces inflammation, IgG
Type 4 - Delayed type, sensitised T-lymphocytes - inflammation
Describe type 1 hypersensitivity mechanism of action
The IgE response is thought to be important in defense against certain parasites eg. nematode worms. The normal pathway is that the antigen binds to IgM molecules on the surface of the lymphocyte and stimulates proliferation and antibody secretion. The antibody is IgM which -> IgG as the immune response progresses. In type 1 hypersensitivity CD4+ T helper cells are activated which -> IgE production which is long term, causing sensitivity to that antigen.
How are mast cells and basophils involved in the anaphylactic response?
IgE binds to specific receptors on these cells. Mast cells are widely distributed in connective tissue and in association with epithelial mucosae. Mast cells and basophils have similar function. They have numerous prominent granules that contain inflammatory mediators eg histamine and arachidonic acid products which are secreted after antigens bind to cell surface IgE.
How is the anaphylactic response initiated by mast cells?
Each exposure to the allergen antigen results in the release of IgE which binds to the cell and the antigen. However, 2 cell surface IgEs must be crosslinked by an antigen in order to elicit the anaphylactic response. This leads to degranulation (histamine) and rapid synthesis of other granules such as prostaglandings, platelet activating factor, cytokines, cysteinyl leukotrienes etc.
What is the effect of the mediators released by mast cells?
The mediators released by mast cells act primarily on blood vessels and non vascular smooth muscles. In connective tissue, histamine leads to vessel dilation with increased blood flow to surface and increased fluid extrusion (oedema). Also, vasodilation in nondermal vascular beds. This leads to lowering of the BP. In mucosae, opposite effect occurs, constricting airways and intestinal walls
What is the main way to treat anaphylaxis?
ABC (Airway, breathing, circulation). Initial drug therapy aims to reverse bronchoconstriction and elevate BP to reestablish tissue perfusion. Treatment has to restore normal BP and breathing which adrenaline does.
Which histamine receptors are activated in the anaphylactic response?
H1 and H2 receptors. H1 is responsible for itching (sensory nerve activation), systemic vasodilation, bronchoconstriction, plasma exudation, abit of mucus, ileal contraction, and H2 is responsible for vasodilation, gastric acid secretion, increased sinus rhythm.
Match the mediator with the effect
Rubor/calor (vasodilation and hypotension) - Histamine, cys-LTs, prostaglandin, PAF
Tumor (plasma exudation) - Histamine, cys-LTs, PAF
Dolor (sensory nerve activation) - Histamine, prostaglandins
Smooth muscle contraction (airway and gut) - Histamine, cys-LTs, prostaglandins, PAF
Mucus secretion (obstructs airways) - Histamine, cys-LTs, maybe prostaglandin, PAF
Inflammation (possible later development) - cytokines eg TNF-a
Describe the mechanism of action of plasma exudation
Histamine, PGD2, cys-LTs, PAF interact with their receptors on endothelial cells which cause them to contract, causing a gap between the endothelial cells and so plasma can leak out
Describe the mechanism of action of dolor
Dolor is pain/tingling caused by sensory nerve activation. Histamine and PGD2 cause release of vasodilators from sensory nerves, and then they go to endothelial cells and also cause constriction.
How can we quantify plasma exudation?
Evans blue dye binds to albumin, which leaks out during exudation (after animal given histamine etc.), which turns the tissue blue or fluoresces orange.
