Everything about Anaphylactic Shock totally explained
Anaphylaxis is an
acute systemic (multi-system) and severe Type I Hypersensitivity
allergic reaction in humans and other
mammals. The term comes from the Greek words ανα
ana (against) and φύλαξις
phylaxis (protection). Minute amounts of allergens may cause a life-threatening anaphylactic reaction. Anaphylaxis may occur after ingestion, skin contact, injection of an allergen or, in rare cases, inhalation.
Anaphylactic shock, the most severe type of anaphylaxis, occurs when an allergic response triggers a quick release from
mast cells of large quantities of
immunological mediators (
histamines,
prostaglandins,
leukotrienes) leading to systemic
vasodilation (associated with a sudden drop in blood pressure) and
edema of
bronchial mucosa (resulting in
bronchoconstriction and difficulty breathing). Anaphylactic shock can lead to death in a matter of minutes if left untreated.
An estimated 1.24% to 16.8% of the population of the
United States is considered "at risk" for having an anaphylactic reaction if they're exposed to one or more allergens, especially
penicillin and insect stings. Most of these people successfully avoid their allergens and will never experience anaphylaxis. Of those people who actually experience anaphylaxis, up to 1% may die as a result. Anaphylaxis results in fewer than 1,000 deaths per year in the U.S. (compared to 2.4 million deaths from all causes each year in the U.S.). The most common presentation includes sudden cardiovascular collapse (88% of reported cases of severe anaphylaxis).
Researchers typically distinguish between "
true anaphylaxis" and "
pseudo-anaphylaxis or an
anaphylactoid reaction." The symptoms, treatment, and risk of death are identical, but "true" anaphylaxis is always caused directly by
degranulation of
mast cells or basophils that's mediated by
immunoglobulin E (IgE), and pseudo-anaphylaxis occurs due to all other causes. The distinction is primarily made by those studying mechanisms of allergic reactions.
Symptoms
Symptoms of anaphylaxis are related to the action of
Immunoglobulin E (
IgE) and other
anaphylatoxins, which act to release
histamine and other mediator substances from
mast cells (degranulation). In addition to other effects, histamine induces
vasodilation of
arterioles and constriction of
bronchioles in the lungs, also known as
bronchospasm (constriction of the airways).
Tissues in different parts of the body release
histamine and other substances. This causes constriction of the airways, resulting in
wheezing,
difficulty breathing, and
gastrointestinal symptoms such as
abdominal pain,
cramps,
vomiting, and
diarrhea. Histamine causes the blood vessels to
dilate (which lowers blood pressure) and fluid to leak from the bloodstream into the tissues (which lowers the blood volume). These effects result in shock. Fluid can leak into the
alveoli (air sacs) of the lungs, causing
pulmonary edema.
Symptoms can include the following:
The time between ingestion of the allergen and anaphylaxis symptoms can vary for some patients depending on the amount of allergen consumed and their reaction time. Symptoms can appear immediately, or can be delayed by half an hour to several hours after ingestion. However, symptoms of anaphylaxis usually appear very quickly once they do begin.
Causes
Anaphylaxis is a severe, whole-body allergic reaction. After an initial exposure to a substance like bee sting toxin, the person's immune system becomes sensitized to that allergen- Shocking dose. On a subsequent exposure, an allergic reaction occurs. This reaction is sudden, severe, and involves the whole body.
Hives and
angioedema (hives on the lips, eyelids, throat, and/or tongue) often occur. Angioedema may be severe enough to block the airway. Prolonged anaphylaxis can cause heart arrhythmias.
Some drugs (
polymyxin,
morphine,
x-ray dye, and others) may cause an "anaphylactoid" reaction (anaphylactic-like reaction) on the
first exposure. This is usually due to a
toxic reaction, rather than the immune system mechanism that occurs with "true" anaphylaxis. The symptoms, risk for complications without treatment, and treatment are the same, however, for both types of reactions.
Anaphylaxis can occur in response to any allergen. Common causes include
insect bites/stings,
horse serum (used in some
vaccines),
food allergies, and
drug allergies.
Pollens and other inhaled allergens rarely cause anaphylaxis. In
opthamology, the dye
fluorescein used in some
eye exams is a well known trigger. Some people have an anaphylactic reaction with no identifiable cause.
Anaphylaxis occurs infrequently. However, it's life-threatening and can occur at any time. Risks include prior history of any type of allergic reaction.
Treatment
Emergency treatment
Anaphylaxis is a life-threatening
medical emergency because of rapid constriction of the
airway, often within minutes of onset, which can lead to
respiratory failure and
respiratory arrest. Brain and organ damage rapidly occurs if the patient can't breathe. Due to the severe nature of the emergency, patients experiencing or about to experience anaphylaxis require the
help of advanced medical personnel.
First aid measures for anaphylaxis include rescue breathing (part of
CPR). Rescue breathing may be hindered by the constricted airways, but if the victim stops breathing on his or her own, it's the only way to get oxygen to him or her until professional help is available.
Another treatment for anaphylaxis is administration of
epinephrine (adrenaline). Epinephrine prevents worsening of the airway constriction, stimulates the heart to continue beating, and may be life-saving. Epinephrine acts on
Beta-2 adrenergic receptors in the lung as a powerful
bronchodilator (for example it opens the airways), relieving allergic or
histamine-induced acute
asthmatic attack or anaphylaxis. If the patient has previously been diagnosed with anaphylaxis, he or she may be carrying an
EpiPen or
Twinject for immediate administration of epinephrine. However, use of an EpiPen or similar device only provides temporary and limited relief of symptoms.
Tachycardia (rapid heartbeat) results from stimulation of Beta-1 adrenergic receptors of the heart increasing contractility (positive inotropic effect) and frequency (chronotropic effect) and thus cardiac output. Repetitive administration of epinephrine can cause tachycardia and occasionally
ventricular tachycardia with heart rates potentially reaching 240 beats per minute, which itself can be fatal. Extra doses of epinephrine can sometimes cause
cardiac arrest. This is why some protocols advise
intramuscular injection of only 0.3–0.5mL of a 1:1,000 dilution.
Some patients with severe allergies routinely carry preloaded syringes containing epinephrine,
diphenhydramine (Benadryl), and
dexamethasone (Decadron) whenever they go to an unknown or uncontrolled environment.
Clinical care
Paramedic treatment in the field includes administration of
epinephrine IM, antihistamines IM (for example
chlorphenamine,
diphenhydramine), steroids such as
hydrocortisone, IV Fluid administration and in severe cases, pressor agents (which cause the heart to increase its contraction strength) such as dopamine for hypotension, administration of
oxygen, and
intubation during transport to advanced medical care.
In severe situations with profuse laryngeal edema (swelling of the airway),
cricothyrotomy or
tracheotomy may be required to maintain oxygenation. In these procedures, an incision is made through the anterior portion of the neck, over the cricoid membrane, and an endotracheal tube is inserted to allow mechanical ventilation of the victim.
The clinical treatment of anaphylaxis by a
doctor and in the
hospital setting aims to treat the cellular
hypersensitivity reaction as well as the symptoms.
Antihistamine drugs such as
diphenhydramine or
chlorphenamine (which inhibit the effects of histamine at histamine receptors) are continued but are usually not sufficient in anaphylaxis, and high doses of intravenous
corticosteroids such as
dexamethasone or
hydrocortisone are often required.
Hypotension is treated with
intravenous fluids and sometimes vasopressor drugs. For bronchospasm,
bronchodilator drugs (for example
salbutamol, known as Albuterol in the United States) are used. In severe cases, immediate treatment with epinephrine can be lifesaving. Supportive care with
mechanical ventilation may be required.
It is also possible to undergo a second reaction prior to medical attention or using an Epipen. It is suggested to seek one to two days of medical care.
The possibility of biphasic reactions (recurrence of anaphylaxis) requires that patients be monitored for four hours after being transported to medical care for anaphylaxis. Action plans are considered essential to quality emergency care. Many authorities advocate immunotherapy to prevent future episodes of anaphylaxis.
Beta-blockers may aggravate anaphylactic reactions and interfere with treatment.
Prevention
Immunotherapy with Hymenoptera venoms is especially effective and widely used throughout the world and is accepted as an effective treatment for most patients with allergy to bees, wasps, hornets, yellow jackets, white faced hornets, and fire ants.
The greatest success with prevention of anaphylaxis has been the use of allergy injections to prevent recurrence of sting allergy. The risk to an individual from a particular species of insect depends on complex interactions between likelihood of human contact, insect aggression, efficiency of the venom delivery apparatus, and venom allergenicity. According to most authorities, venom immunotherapy has been demonstrated to reduce the risk of systemic reactions below 1% to 3%. One simple method of venom extraction has been electrical stimulation to obtain venom, instead of dissecting the venom sac. An allergist will then provide venom immunotherapy which is highly efficacious in preventing future episodes of anaphylaxis.
Pathophysiology
Anaphylactic shock or systemic anaphylaxis is an allergic reaction to systematically administered antigen that causes circulatory collapse and suffocation due to tracheal swelling. Classified as a Type I hypersensitivity, anaphylaxis is mediated through the binding of antigen to the IgE antibody on connective tissue mast cells throughout the body, which ultimately leads to the disseminated release of inflammatory mediators. IgE antibodies can become responsive to innocuous antigens or allergens. Once IgE have become sensitized to allergens, their local production may persist for long periods of time even in the absence of allergen. After which, mast cells become the major effector cells for immediate hypersensitivity and chronic allergic reactions.
Mast cells are large cells found in particularly high concentrations in vascularized connective tissues just beneath epithelial surfaces, including the submucosal tissues of the gastrointestinal and respiratory tracts, and the dermis that lies just below the surface of the skin. Once the FcεR1 are aggregated by the cross-linking process, the immunoreceptor tryrosine-based activation motifs (ITAMs) in both the β and γ chains are phosphorylated by LYN, a protein tryrosine kinase (PTK) belonging to the Src family. The ITAM domain is simply conserved sequence motif generally composed of two YXXL/I sequences separated by about six to nine amino acids, where Y is tyrosine, L is leucine, I isoleucine and X any amino acid. These SH2 domains (Src homology 2 domian) are found in a numerous cell-signaling proteins and bind to phosphotyrosine through a very specific sequence. The most notable of these LAT affected molecules is Phospholipase C (PLC). As in many cell signaling pathways PLC hydrolyzes the phosphodiester bond in phosphoatidylinositol-4,5-bisphosphate [PI(4,5)P¬¬2] to yield diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP¬¬3)¬. A well-characterized second messenger, IP¬3¬, signals the release of calcium from the endoplasmic reticulum. The influx of cytosolic Ca2+ and phosphoatidylserine further active Phosphokinase C (PKC) bound to DAG. Together, it's the cytosolic Ca2+ and PKC signal the degranulation of the mast cell.4
Although less well mapped, similarly prevailing cell signaling molecules, such as Ras, a monomeric G protein, SOS (son of sevenless homologue) and MAPK (mitogen-activated protein kinase) lead to the upregulation of cytokines and the previously mentioned eicosanoids, prostaglandin D2¬ and leukotriene C4. However, not all IgE are equally capable of inducing such as secretion. Therefore, researchers have divided all invariant IgEs into two major categories: highly cytokinergic(HC), where the production and secretion of various cytokines and other activation events including degranulation is inducible, and poorly cytokinergic (PC) in which no autocrine signaling is observed. The former, HC IgE, brings forward a reaction in which cytokines are exocytosed and act as autocrine and paracrine signaling molecules. As such, mast cells with bound HC IgE attract other mast cells even in the absence of antigen crosslinking.
While the exact structural features that account for the function differences between HC and PC IgE has yet to be determined their effects are thought to be the result of intracellular cell signaling.
IgE binding to FcεR1 leads to a greater stability of the mast cell and increased production of surface receptors. The newly expressed FcεR1 then aggregate on the surface, independent of antigen binding. The cell signaling pathway then initiates and appears to involve components used in the alternative mechanisms. Mast cell migration is dependent on soluble factors such as adenosine, leukotriene B¬4 and other chemokines, whose secretion is dependent upon the activity of LYN and SYK. The degranulation of mast cells in the absence of antigen, can then be initiated by G-protein-couple receptors (GPCR) stimulated by soluble factors agonists and completed by downstream activity of PI3K.
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