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Encyclopedia > Anaphylaxis
Anaphylaxis
Classification and external resources
ICD-10 T78.2
DiseasesDB 29153
eMedicine med/128 
MeSH D000707

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).[1] 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.[2] The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // S00-T98 - Injury, poisoning and certain other consequences of external causes (S00-S09) Injuries to the head (S00) Superficial injury of head (S01) Open wound of head (S02) Fracture of skull and facial bones (S03) Dislocation, sprain and strain of joints and ligaments of head (S04) Injury of cranial nerves... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... In medicine, an acute disease is a disease with either or both of: a rapid onset; a short course (as opposed to a chronic course). ... For transport in plants, see Vascular tissue. ... This article needs cleanup. ... Allergy is an abnormal reaction to a substance foreign to the body that is acquired, predictable and rapid. ... Subclasses & Infraclasses Subclass †Allotheria* Subclass Prototheria Subclass Theria Infraclass †Trituberculata Infraclass Metatheria Infraclass Eutheria For the folk-rock band see The Mammals. ...


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. Mast cells A mast cell (or mastocyte) is a resident cell of areolar connective tissue (loose connective tissue) that contains many granules rich in histamine and heparin. ... Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. ... This article or section does not cite any references or sources. ... E1 - Alprostadil I2 - Prostacyclin A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. ... Leukotrienes are autocrine and paracrine eicosanoid lipid mediators derived from arachidonic acid by 5-lipoxygenase. ... The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... This page is about the condition called edema. ... The bronchioles are the first airway branches that no longer contain cartilage. ... The mucous membranes (or mucosa) are linings of ectodermic origin, covered in epithelium, that line various body cavities and internal organs. ... Bronchoconstriction is the constriction of the airways in the lungs due to the tighting of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. ...


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 are 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.[3] Anaphylaxis results in approximately 18 deaths per year in the U.S. (compared to 2.4 million deaths from all causes each year in the U.S.[4]). The most common presentation includes sudden cardiovascular collapse (88% of reported cases of severe anaphylaxis). Penicillin core structure Penicillin (abbreviated PCN) is a group of β-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. ...


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 is mediated by immunoglobulin E (IgE), and pseudo-anaphylaxis occurs due to all other causes.[5] The distinction is primarily made by those studying mechanisms of allergic reactions. The degranulation process in a Mast cell. ... Mast cells A mast cell (or mastocyte) is a resident cell of areolar connective tissue (loose connective tissue) that contains many granules rich in histamine and heparin. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...

Contents

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). Immunoglobulin E (IgE) is an antibody subclass (known as isotypes), found only in mammals. ... IGE (Internet Gaming Entertainment) is the largest MMORPG services company world-wide, with offices in Los Angeles, Hong Kong, and Miami. ... Anaphylatoxins, or anaphylotoxins, are fragments (C3a, C4a or C5a) that are produced during the pathways of the complement system. ... This article or section does not cite any references or sources. ... Mast cells A mast cell (or mastocyte) is a resident cell of areolar connective tissue (loose connective tissue) that contains many granules rich in histamine and heparin. ... The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... An arteriole is a blood vessel that extends and branchs out from an artery and leads to capillaries. ... The bronchioles are the first airway branches that no longer contain cartilage. ... Bronchospasm is a difficulty in breathing caused by a sudden constriction of the muscles in the walls of the bronchioles. ...


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 diarrhoea. 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. This article or section does not cite any references or sources. ... Wheezes are continuous, coarse, whistling sounds produced in the respiratory airways during breathing. ... Dyspnea (Latin dyspnoea, Greek dyspnoia from dyspnoos, short of breath) or shortness of breath (SOB) is perceived difficulty breathing or pain on breathing. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and... Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. ... A cramp is an unpleasant sensation caused by contraction, usually of a muscle. ... Heaving redirects here. ... Diarrhoea is the correct way to spell the word Diarrhoea. ... A vasodilator is a drug or chemical that relaxes the smooth muscle in blood vessels, which causes them to dilate. ... The alveoli (singular:alveolus), tiny hollow sacs which are continuous with the airways, are the sites of gas exchange with the blood. ... Pulmonary edema is swelling and/or fluid accumulation in the lungs. ...


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.[6] However, symptoms of anaphylaxis usually appear very quickly once they do begin. Polyuria is the passage of a large volume of urine in a given period. ... There are two forms of respiratory distress syndrome: ARDS, which is acute (or adult) respiratory distress syndrome or infant respiratory distress syndrome which is a complication of premature birth. ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... Encephalitis is an acute inflammation of the brain, commonly caused by a viral infection. ... It has been suggested that Central Ischaemic Response be merged into this article or section. ... Unconsciousness is the absence of consciousness. ... For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. ... Angioedema (BE: angiooedema), also known by its eponym Quinckes edema, is the rapid swelling (edema) of the skin, mucosa and submucosal tissues. ... The tear system. ... Angioedema (BE: angiooedema), also known by its eponym Quinckes edema, is the rapid swelling (edema) of the skin, mucosa and submucosal tissues. ... Heaving redirects here. ... For other uses, see Itch (disambiguation). ... Diarrhoea is the correct way to spell the word Diarrhoea. ... Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. ... Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components[1]. These components combine to create the feelings that we typically recognize as anger and known as fear, apprehension, or worry. ...


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. Urticaria or Hives is a relatively common form of allergic reaction that causes. ... Angioedema (BE: angiooedema), also known by its eponym Quinckes edema, is the rapid swelling (edema) of the skin, mucosa and submucosal tissues. ...


Some drugs (polymyxin, morphine, x-ray dye, and others) may cause an "anaphylactoid" reaction (anaphylactic-like reaction) on the first exposure.[7] 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. Polymyxins are cationic detergent antibiotics, with a general structure of a cyclic peptide with a long hydrophobic tail. ... This article is about the drug. ... Toxic redirects here, but this is also the name of a song by Britney Spears; see Toxic (song) Look up toxic and toxicity in Wiktionary, the free dictionary. ...


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. Insect bites and stings can cause an immediate skin reaction often resulting in redness and swelling in the injured area. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ... In medicine, food allergy is hypersensitivity to dietary substances, leading to various types of gastrointestinal complaints. ... SEM image of pollen grains from a variety of common plants: sunflower (Helianthus annuus), morning glory (Ipomoea purpurea), prairie hollyhock (Sidalcea malviflora), oriental lily (Lilium auratum), evening primrose (Oenothera fruticosa), and castor bean (Ricinus communis). ... This does not cite its references or sources. ... Fluorescein is a fluorophore commonly used in microscopy, in a type of dye laser as the gain medium, in forensics and serology to detect latent blood stains, and in dye tracing. ... For other uses, see Eye (disambiguation). ...


Anaphylaxis occurs infrequently. However, it is life-threatening and can occur at any time. Risks include prior history of any type of allergic reaction.


Treatment

Emergency treatment

A woman being treated in emerge after going into anaphylactic shock
A woman being treated in emerge after going into anaphylactic shock

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 cannot 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 is the only way to get oxygen to him or her until professional help is available. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... The emergency department (ED), sometimes termed the emergency room (ER), emergency ward (EW), accident & emergency (A&E) department or casualty department is a hospital or primary care department that provides initial treatment to patients with a broad spectrum of illnesses and injuries, some of which may be life-threatening and... {{Otheruses4|the medical term|the Australian television series|Medical Emergenc an immediate threat to a persons life or long term health. ... The airways are those parts of the respiratory system through which air flows, to get from the external environment to the alveoli. ... Respiratory failure is a medical term for inadequate gas exchange by the respiratory system. ... Respiratory arrest is the cessation of the normal tidal flow of the lungs due to paralysis of the diaphragm, collapse of the lung or any number of respiratory failures. ... It has been suggested that this article or section be merged with Distress call. ... First aid is a series of simple, life-saving medical techniques that a non-doctor or layman can be trained to perform. ... CPR redirects here. ...


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 (i.e. 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. Adrenaline redirects here. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is an beta-adrenergic receptor, and also denotes the human gene encoding it. ... A bronchodilator is a medication intended to improve bronchial airflow. ... This article or section does not cite any references or sources. ... For other uses, see Asthma (disambiguation). ... A 0. ... Twinject is the registered trademark of the first epinephrine autoinjector that contains two doses. ...


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.[8] 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. This article or section does not cite any references or sources. ... Ventricular tachycardia (V-tach or VT) is a fast rhythm that originates in one of the ventricles of the heart. ...


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. Diphenhydramine hydrochloride (trade name Benadryl as produced by Johnson & Johnson, or Dimedrol outside the U.S. & Canada. ... Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. ...


Clinical care

Paramedic treatment in the field includes administration of epinephrine IM, antihistamines IM (e.g. 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. The Star of Life, a globally recognized symbol for Emergency medical services. ... Adrenaline redirects here. ... Intramuscular injection is an injection of a substance directly into a muscle. ... Chlorphenamine (INN) or chlorpheniramine (USAN, former BAN), commonly marketed as its salt chlorphenamine maleate (CPM), is first-generation antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. ... Diphenhydramine hydrochloride (trade name Benadryl as produced by Johnson & Johnson, or Dimedrol outside the U.S. & Canada. ... Hydrocortisone is a synthetic corticosteroid drug which may be given by injection or by topical application. ... This article is about the chemical element and its most stable form, or dioxygen. ... This article or section needs copy editing for grammar, style, cohesion, tone and/or spelling. ...


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. In cricothyrotomy, the incision or puncture is made through the cricothyroid membrane inbetween the thyroid cartilage and the cricoid cartilage. ... Completed tracheotomy: 1 - Vocal cords 2 - Thyroid cartilage 3 - Cricoid cartilage 4 - Tracheal cartilages 5 - Balloon cuff A tracheotomy is a procedure performed by paramedics, emergency physicians and surgeons in order to secure an airway. ...


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 (e.g. 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. For the town in the Republic of Ireland, see Hospital, County Limerick. ... Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. ... An H1 antihistamine is a histamine antagonist which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the H1 receptor. ... Diphenhydramine hydrochloride (trade name Benadryl as produced by Johnson & Johnson, or Dimedrol outside the U.S. & Canada. ... Chlorphenamine (INN) or chlorpheniramine (USAN, former BAN), commonly marketed as its salt chlorphenamine maleate (CPM), is first-generation antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. ... Hydrocortisone is a synthetic corticosteroid drug which may be given by injection or by topical application. ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... A bronchodilator is a medication intended to improve bronchial airflow. ... Salbutamol (INN) or albuterol (USAN) is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and COPD. Salbutamol sulphate is usually given by the inhaled route for direct effect on bronchial smooth muscle. ... mechanical or forced ventilation is the use of powered equipment, e. ...


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.[8]


Many anaphylactic patients will be sent home or released after the initial reaction is declared over. Yet, the possibility of a rebound reactions are almost always bound to happen. Most people with anaphylaxis have a rebound a few hours after the initial reaction, yet there are cases where a rebound would occur after as much time as a week


Planning for emergency treatment

The Asthma and Allergy Foundation of America advises patients prone to anaphylaxis to have an "allergy action plan" on file at school, home, or in their office to aid others in case of an anaphylactic emergency, and provides a free "plan" form.[9] Action plans are considered essential to quality emergency care. Many authorities advocate immunotherapy to prevent future episodes of anaphylaxis.[10] The Asthma and Allergy Foundation of America (AAFA) is a non-profit organization dedicated to finding a cure for and controlling asthma, food allergies, nasal allergies and other allergic diseases. ...


Beta-blockers may aggravate anaphylactic reactions and interfere with treatment. Skeletal formula of propranolol, the first clinically successful beta blocker Beta blockers (sometimes written as β-blockers) are a class of drugs used for various indications, but particularly for the management of cardiac arrhythmias and cardioprotection after myocardial infarction. ...


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.[11]


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.[12] 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.[13]


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.[12] They contain large granules that store a variety of mediator molecules including the vasoactive amine, histamine. Histamine causes dilation of local blood vessels and smooth-muscle contraction. Other molecules in the mast cell granules include lipid inflammatory mediators such as prostaglandin D2¬ and leukotriene C4 as well as tumor necrosis factor-α (TNF-α), a cytokine.[12] The importance of TNF-α is most noted in the activation of the endothelium. TNF-α, the prototype of the TNF family cytokines, can induce endothelial cells to present E-selectin and ICAM-1, both of which are cell adhesion molecules (CAM) that mediate the “roll and stick” mechanism of leukocyte extravasation, termed diapedesis. While this process is essential for the recruit of leukocytes to a localized area during an inflammatory response, it can be catastrophic in cases of systemic infection. Point in case, the presence of said infection in the bloodstream, or sepsis, is accompanied by the release of TNF-α by macrophages in liver, spleen, and other systemic sites. The systemic release of TNF-α causes vasodilatation, which leads to a loss of blood pressure and increased vascular permeability, leading to a loss of plasma volume and eventually to shock.[12]


TNF-α, along with the other aforementioned mast cell granule contents become exocytosed upon activation of the mast cell. Activation is achieved only when IgE, bound to the high-affinity Fcε receptors (FcεR1), are cross-linked by multivalent antigen. The FcεR1 is a tetrameric receptor composed of a single α chain, responsible for binding the IgE, associated with a single β chain and a disulfide linked homodimer of γ chains that initiate the cell signal pathway.[14] 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.[12] Their phosphorylation in the β and γ chains provide high-affinity docking sites for the SH2 domains of additional LYN and the SYK (spleen tyrosine kinasse), respectively.[15] These SH2 domains (Src homology 2 domian) are found in a numerous cell-signaling proteins and bind to phosphotyrosine through a very specific sequence.[12] As the signal continues to propagate through the pathway, the membrane bound molecule, named linker for activation of T cells (LAT), is phosphoyraleted by the LYN and SYK and acts as a scaffold protein, organizing other molecules that complete the degranulation of mast cells, as well as promote further cytokine production.[16] 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 is 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.[15]


While this cell single pathway is sufficient to induce degraluation, it is not the only effective mechanism. Studies with LYK deficient mice have shown that degranulation is still inducible.[16] Consequently, several alternative pathways leading to mast cell degranulation have been mapped. The first of which, dubbed the “complementary” pathway, determined that the crosstalk between LYK and another Src family PTK, called FYN, is an essential interaction to degranulation, along with the preferential activity of Phosphoatidylinositol 3-kinase (PI-3K) over PLC. Studies have also elucidated subsequent pathways that utilize the integration of G-protein-coupled receptors to mediate the degranulation and cytokine production mechanism of activated mast cells.9


IgE binding to FcεR1 in the absence of a specific antigen still induces the up-regulation of FcεR1 surface expression in mast cells through autocrine signaling of cytokines.[17] 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.[14] 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.[17] 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.[14]


References

  1. ^ "Anaphylaxis." Etymology. Oxford English Dictionary. http://dictionary.oed.com.
  2. ^ Anaphylaxis. Health. AllRefer.com (2002-01-17). Retrieved on 2007-01-29.
  3. ^ Neugut AI, Ghatak AT, Miller RL (January 2001). "Anaphylaxis in the United States: an investigation into its epidemiology". Arch. Intern. Med. 161 (1): 15–21. doi:10.1001/archinte.161.1.15. PMID 11146694. 
  4. ^ Deaths/Mortality. National Center for Health Statistics. Retrieved on 2008-04-22.
  5. ^ Limmer D, Mistovich JJ, Krost WS (November 17th, 2005). Anaphylactic and Anaphylactoid Reactions -- Prehospital Pathophysiology. EMSResponder.com. Retrieved on 2007-11-27.
  6. ^ Food Allergies. Asthma and Allergy Foundation of America (March 28, 2007).
  7. ^ Mastocytosis: Allergic Reactions: Merck Manual Home Edition. Retrieved on 2007-11-27.
  8. ^ a b Emergency treatment of anaphylactic reactions -- Guidelines for healthcare providers (PDF). Resuscitation Council (UK) (January 2008). Retrieved on 2008-04-22.
  9. ^ Asthma and Allergy Foundation of America - Information About Asthma, Allergies, Food Allergies and More!. Retrieved on 2007-11-27.
  10. ^ Fact Sheet - ACAAI. Retrieved on 2007-11-27.
  11. ^ Bousquet J, Müller UR, Dreborg S, et al (1987). "Immunotherapy with Hymenoptera venoms. Position paper of the Working Group on Immunotherapy of the European Academy of Allergy and Clinical Immunology". Allergy 42 (6): 401–13. PMID 3310714. 
  12. ^ a b c d e f Murphy, Kenneth (November 27, 2007). Janeway's Immunobiology, 7th edition, New York: Garland Science. ISBN 0-8153-4123-7. 
  13. ^ Kitaura J, Kinoshita T, Matsumoto M, et al (April 2005). "IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion". Blood 105 (8): 3222–9. doi:10.1182/blood-2004-11-4205. PMID 15637135. 
  14. ^ a b c Paolini R, Jouvin MH, Kinet JP (October 1991). "Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement". Nature 353 (6347): 855–8. doi:10.1038/353855a0. PMID 1834946. 
  15. ^ a b Gilfillan AM, Tkaczyk C (March 2006). "Integrated signalling pathways for mast-cell activation". Nat. Rev. Immunol. 6 (3): 218–30. doi:10.1038/nri1782. PMID 16470226. 
  16. ^ a b Parravicini V, Gadina M, Kovarova M, et al (August 2002). "Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation". Nat. Immunol. 3 (8): 741–8. doi:10.1038/ni817. PMID 12089510. 
  17. ^ a b Kitaura J, Song J, Tsai M, et al (October 2003). "Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI". Proc. Natl. Acad. Sci. U.S.A. 100 (22): 12911–6. doi:10.1073/pnas.1735525100. PMID 14569021. 

Also see: 2002 (number). ... is the 17th day of the year in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 29th day of the year in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini (or common era), in accordance with the Gregorian calendar. ... is the 112th day of the year (113th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 331st day of the year (332nd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 331st day of the year (332nd in leap years) in the Gregorian calendar. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini (or common era), in accordance with the Gregorian calendar. ... is the 112th day of the year (113th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 331st day of the year (332nd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 331st day of the year (332nd in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

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In medicine, a trauma patient has suffered serious and life-threatening physical injury resulting in secondary complications such as shock, respiratory failure and death. ... An embolism occurs when an object (the embolus, plural emboli) migrates from one part of the body (through circulation) and cause(s) a blockage (occlusion) of a blood vessel in another part of the body. ... An air embolism, or more WITCH generally gas embolism, is a medical condition caused by gas bubbles in the bloodstream (embolism in a medical context refers to any large moving mass or defect in the blood stream). ... A fat embolism is a type of embolism that is often (but not always) caused by physical trauma. ... Crush syndrome: is a reperfusion injury as a result of traumatic rhabdomyolysis causing a severe systemic manifestation of trauma and dead tissues ( ischemia –from lack of O2 getting to the tissues there by destroying the tissue) involving soft tissues, principally skeletal muscle, due to prolonged severe crushing. ... Rhabdomyolysis is the rapid breakdown of skeletal muscle tissue due to traumatic injury, either mechanical, physical or chemical. ... Compartment syndrome is characterized by increased pressure within one or more fascial compartments so that vascular perfusion is compromised. ... Volkmanns contrature, also known as Volkmanns ischaemic contracture, is a permanent flexion contracture of the hand at the wrist, resulting in a claw-like deformity of the hand and fingers. ... Surgery Surgery is the medical specialty that treats diseases or injuries by operative manual and instrumental treatment. ... See also Healing, North East Lincolnshire Healing is the process where the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area. ... Serum sickness is a reaction to an antiserum derived from an animal source. ... Malignant hyperthermia (MH or MHS for malignant hyperthermia syndrome, or malignant hyperpyrexia due to anaesthesia) is a rare life-threatening condition that is triggered by exposure to certain drugs used for general anaesthesia (specifically all volatile anaesthetics), nearly all gas anaesthetics, and the neuromuscular blocking agent succinylcholine. ...

  Results from FactBites:
 
eMedicine - Anaphylaxis : Article by Richard S Krause (6288 words)
The true incidence of anaphylaxis is unknown, partly because of the lack of a precise definition of the syndrome.
Anaphylaxis due to foods may be an underrecognized cause of sudden death and an unappreciated cause of diagnosed anaphylaxis.
Corticosteroids are used in anaphylaxis primarily to decrease the incidence and severity of delayed or biphasic reactions.
A Practical Guide to Anaphylaxis - October 1, 2003 - American Family Physician (3335 words)
Anaphylaxis is a life-threatening reaction with respiratory, cardiovascular, cutaneous, or gastrointestinal manifestations resulting from exposure to an offending agent, usually a food, insect sting, medication, or physical factor.
Prompt treatment of anaphylaxis is critical, with subcutaneous or intramuscular epinephrine and intravenous fluids remaining the mainstay of management.
If the diagnosis of anaphylaxis is not clear, laboratory evaluation can include plasma histamine levels, which rise as soon as five to 10 minutes after onset but remain elevated for only 30 to 60 minutes.
  More results at FactBites »

 
 

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