Atlas of pathophysiology, 2 Edition

Part II - Disorders

Immunologic Disorders

Anaphylaxis

Anaphylaxis is an acute, potentially life-threatening type I (immediate) hypersensitivity reaction marked by sudden onset of rapidly progressive urticaria (vascular swelling in skin, accompanied by itching) and respiratory distress. With prompt recognition and treatment, prognosis is good. A severe reaction may precipitate vascular collapse, leading to systemic shock and, sometimes, death. Typically occurring within minutes, the reaction can occur up to 1 hour after reexposure to an antigen.

Causes

Ingestion of or other systemic exposure to sensitizing drugs or other substances, such as:

·   serums (usually horse serum), vaccines, allergen extracts

·   diagnostic chemicals, such as sulfobromophthalein, sodium dehydrocholate, radiographic contrast media

·   enzymes such as L-asparaginase in chemotherapeutic regimens

·   hormones such as insulin

·   penicillin or other antibiotics, sulfonamides

·   salicylates

·   food proteins, as in legumes, nuts, berries, seafood, egg albumin

·   sulfite food additives, common in dried fruits and vegetables, salad bars

·   insect venom.

Clinical Tip

Latex allergy is a hypersensitivity reaction to products that contain natural latex derived from the sap of a rubber tree, not synthetic latex. Natural latex is increasingly present in products in the home and workplace. Hypersensitivity reactions can range from local dermatitis to life-threatening anaphylactic reaction.

Pathophysiology

Anaphylaxis requires previous sensitization or exposure to the specific antigen, resulting in immunoglobulin (Ig) E production by plasma cells in the lymph nodes and enhancement by helper T cells. IgE antibodies then bind to membrane receptors on mast cells in connective tissue and basophils in the blood.

On reexposure, IgM and IgG recognize the antigen as foreign and bind to it. Destruction of the antigen by the complement cascade begins. Continued antigen presence activates IgE on basophils, which promotes the release of mediators, including histamine, serotonin, and eosinophil chemotactic factor of anaphylaxis (ECF-A) and platelet–activating factor. The sudden release of histamine causes vasodilation and increases capillary permeability.

Activated IgE also stimulates mast cells in connective tissue along the venule walls to release more histamine and ECF-A. These substances produce disruptive lesions that weaken the venules.

In the lungs, histamine causes endothelial cells to burst and endothelial tissue to tear away from surrounding tissue. Fluids leak into the alveoli, and leukotrienes prevent the alveoli from expanding, thus reducing pulmonary compliance.

At the same time, basophils and mast cells begin to release prostaglandins and bradykinin along with histamine and serotonin. These chemical mediators spread through the body in the circulation, triggering systemic responses: vasodilation, smooth muscle contraction, and increased mucus production. The mediators also induce vascular collapse by increasing vascular permeability, which leads to decreased peripheral resistance and plasma leakage from the vessels to the extravascular tissues. Consequent reduction of blood volume causes hypotension, hypovolemic shock, and cardiac dysfunction.

Signs and symptoms

·   Sudden physical distress within seconds or minutes after exposure to an allergen

·   Delayed or persistent reaction may occur up to 24 hours later (severity of the reaction relates inversely to the interval between exposure to the allergen and the onset of symptoms)

Usual initial symptoms

·   Feeling of impending doom or fright

·   Sweating

·   Sneezing, shortness of breath, nasal pruritus, urticaria, angioedema

Systemic manifestations

·   Hypotension, shock, cardiac arrhythmias

·   Edema of the upper respiratory tract, resulting in hypopharyngeal and laryngeal obstruction

·   Hoarseness, stridor, wheezing, and accessory muscle use

·   Severe stomach cramps, nausea, diarrhea, and urinary urgency and incontinence

Diagnostic test results

No single diagnostic test can identify anaphylaxis. The following tests provide clues to the patient's risk of anaphylaxis:

·   Skin tests show hypersensitivity to a certain allergen.

·   Laboratory studies reveal elevated serum IgE levels.

Treatment

·   Immediate administration of epinephrine to reverse bronchoconstriction and cause vasoconstriction

·   Tracheostomy or endotracheal intubation and mechanical ventilation

·   Oxygen therapy

·   I.V. vasopressors, such as norepinephrine and dopamine

·   Longer-acting epinephrine, corticosteroids, antihistamines, histamine-2 blocker

·   Albuterol mini-nebulizer treatment

·   Volume expanders

·   Cardiopulmonary resuscitation

P.265

DEVELOPMENT OF ANAPHYLAXIS

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1. Response to antigen
Immunoglobulins (Ig) M and G recognize and bind the antigen. The patient has no signs or symptoms.

2. Release of chemical mediators
Activated IgE on basophils promotes the release of mediators: histamine, serotonin, and leukotrienes. The patient develops nasal congestion, itchy and watery eyes, flushing, weakness, and anxiety.

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3. Intensified response
Mast cells release more histamine and eosinophil chemotactic factor of anaphylaxis (ECF-A), which create venule-weakening lesions. Signs and symptoms worsen; swelling and wheals appear.

4. Respiratory distress
In the lungs, histamine causes endothelial cell destruction and fluid leak into alveoli. The patient develops changes in level of consciousness, respiratory distress and, possibly, seizures.

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5. Deterioration
Meanwhile, mediators increase vascular permeability, causing fluid to leak from the vessels. Shock, confusion, tachycardia, and hypotension, signal vascular collapse.

6. Failure of compensatory mechanisms
Endothelial cell damage causes basophils and mast cells to release heparin and mediator-neutralizing substances. However, anaphylaxis is now irreversible. Hemorrhage, disseminated intravascular coagulation, and cardiac arrest can occur.

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