USMLE – Immunology – Anaphylaxis
Systemic anaphylaxis is the occurrence of IgE mediated, allergic reactions simultaneously in multiple organ systems, usually the cardiovascular, cutaneous, gastrointestinal, and respiratory. It is a secondary response; i.e., it requires previous exposure to the allergen to induce production of sufficient allergen specific IgE to cause the generalized reaction. It is distributed equally among geographic, racial, and sexual populations. Its incidence in the general population is ~4/107, but may be 1000 times higher in hospital populations.
Anaphylactoid reactions are those which produce the symptoms of anaphylaxis in the absence of an IgE mediated allergic reaction. They may be induced by exercise, cold air, emotional stress, or highly charged compounds such as iodinated contrast media used in obtaining radiographs.
Symptoms appear within minutes of exposure to the inducing allergen. The particular complex of symptoms depends on the systems affected. Hypotension and shock are signs of systemic vasodilation and fluid loss into the tissues. These may lead to cardiac ischemia that is commonly found in anaphylactic reactions. They are the most immediately life threatening since they can lead to death within minutes of exposure to the allergen.
Generalized puritis (itching), erythema (redness), uriticaria, and angioedema reflect cutaneous involvement; vomiting, abdominal cramps, and diarrhea are signs of gastrointestinal responses; shortness of breath, hypersecretion of mucous and nasal fluids, wheezing, bronchospasm show respiratory involvement. Respiratory distress must also be dealt with quickly since it can also be rapidly lethal.
A generalized release of the vasoactive mediators from basophils and mast cells initiates the response. Respiratory responses are essentially identical to those seen in an acute asthma attack. Histamine binding to the H1 receptors in the lungs cause brochospasm, whereas H2 receptor activation in the upper respiratory tract produces vasodilation and inflammation. Leukotrienes induce the copious mucus secretion in the lungs that may plug constricted broncioles and cause asphyxiation.
Hypovolemic shock results from systemic release of histamine. Vascular H2 receptors cause smooth muscle relaxation producing generalized vasodilation of the arterioles and increased vascular permeability. The increased vascular volume is exacerbated by rapid transudation of fluid through the postcapillary venules thereby reducing blood volume. The generalized vasodilation also produces gross congestion and edema in the liver, spleen and kidney which may lead to irreversible damage in prolonged reactions.
Conversely, the smooth muscle along the intestinal tract has mostly H1 receptors whose activation causes contraction. This leads to the GI spasm and abdominal cramping. This is exacerbated by serotonin which is also released by mast/basophil degranulation.