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The pathophysiology of anaphylaxis, the difference between anaphylactic and anaphylactoid reactions, and their management.

The practice of anesthesiology has its background in the fields of physiology and pharmacology. Anesthesiologists administer medications for sedation, analgesia, induction of anesthesia, muscle relaxation, and for control of blood pressure. All of the medications that we use have adverse effects that are usually dose related. Many medications may lead to a severe systemic allergic reaction. This week we will discuss the pathophysiology of anaphylaxis, the difference between anaphylactic and anaphylactoid reactions, and their management.

1.  What is the definition of anaphylaxis?
2.  What is the difference between anaphylactic and anaphylactoid reactions?
3.  Can you describe the pathway leading to a release of mediators during an anaphylactic reaction?

麻醉学需要生理学和药理学的背景知识。麻醉科医生通过麻醉药物产生镇静、镇痛、麻醉诱导、肌肉松弛并控制血压等。我们使用的所有药物均有剂量相关的副作用，很多药物可导致严重的全身过敏反应。本周我们讨论过敏反应的病理生理，过敏反应与类过敏反应的区别及其治疗。

1.  过敏反应的定义？
2.  过敏反应与类过敏反应的区别？
3.  请叙述发生过敏反应时介质释放的途径。

参考答案：

1.  过敏反应的定义？

过敏反应一词的使用要回溯到上世纪初，Richet和Portier发现在对犬首次注射一种外界物质时并无异常，但再次注射注射相同物质时却出现了支气管痉挛、休克，甚至死亡[1-3]。希腊语中预防的意思是“保护”，过敏反应的意思是“抗保护”。2年后，von Pirquet首先使用了变态反应一词，其认为是抗原导致超敏反应期间的反应性的变化，并出现不可预测的生物学反应[4]。

药物有害效应与剂量相关，常可预测，而过敏反应则与剂量无关。过敏反应定义为：是一种有可能威胁生命的全身变态性反应，常伴随一系列症状，如面色潮红到心血管性虚脱等。过敏伴随的症状还有可导致严重的支气管痉挛的支气管收缩、皮肤表现如荨麻疹、血管性水肿。过敏可在无任何先兆情况下发生，常可导致心血管虚脱。过敏反应由肥大细胞作用于外界物之后产生的抗体介导。

2.  过敏反应与类过敏反应的区别？

过敏反应由对抗异物的抗体所介导，而类过敏性反应并非免疫介导[2]。IgE抗体为免疫反应的标志，与导致过敏反应的介质的释放有关。介质的释放有非免疫学机制，与类过敏性反应有关。过敏反应与类过敏反应两者最初的表现相似，通过临床表现很难区分。

区分两种反应的唯一途径是通过检测血清生化指标。过敏反应后IgE抗体和纤维蛋白溶酶（肥大细胞脱颗粒作用释放的一种酶）增加[2]。

3.  请叙述发生过敏反应时介质释放的途径。

异物首次入侵时机体的浆细胞产生IgE抗体，并与肥大细胞的表面受体结合。当异物再次入侵时，IgE抗体与外界抗原结合，导致肥大细胞释放组织胺和花生四烯酸的代谢产物，导致血管通透性增加、血管舒张、支气管收缩。

What is the definition of anaphylaxis?

The use of the word anaphylaxis dates back to the beginning of the last century, when Richet and Portier observed dogs that tolerated the first injection of a foreign substance, but developed bronchial spasm, shock, and occasionally died when the same substance was administered for a second time (1-3). Prophylaxis means "protection" in Greek, and anaphylaxis means "against protection". Two years later, the term allergy was coined by von Pirquet, who noted that antigens induced changes in reactivity during hypersensitivity reactions, and this led to an unpredictable biologic response (4).
Adverse drug effects are dose related and often predictable. Anaphylaxis is not usually dose related. Anaphylaxis has been defined as a potentially life threatening systemic allergic reaction, often associated with a variety of symptoms that range from flushing to cardiovascular collapse. Other symptoms associated with anaphylaxis include bronchoconstriction that may lead to severe bronchospasm, and cutaneous signs such as urticaria and angioedema. Anaphylaxis may occur without any warning, often leading to cardiovascular collapse. Anaphylactic reactions are mediated by antibodies that bind to mast cells upon exposure to a foreign antigen.

What is the difference between anaphylactic and anaphylactoid reactions?

Anaphylactic reactions are mediated by antibodies that react against a foreign antigen, while anaphylactoid reactions are not immune mediated (2). The IgE antibody is the hallmark of the immunologic response and is involved in the release of mediators that lead to anaphylaxis. There are other nonimmunologic mechanisms that lead to a release of mediators, and that are involved in an anaphylactoid reaction. The initial presentation of anaphylactic and anaphylactoid reactions is similar, and it is impossible to differentiate between these two reactions based on their clinical presentation.
The only way to differentiate between these two reactions is via the measurement of serum biochemical assays. IgE antibodies and serum tryptase, an enzyme released on mast cell degranulation, are increased following an anaphylactic reaction (2).

Can you describe the pathway leading to a release of mediators during an anaphylactic reaction?

Plasma cells produce IgE antibodies on first exposure to a foreign antigen. The IgE then binds to the surface receptors on mast cells. On a new exposure, the IgE antibodies are crosslinked by the foreign antigen, causing the mast cells to release histamine and arachidonic acid metabolites leading to increased vascular permeability, vasodilation, and bronchoconstriction.

References:

1.  Ferrigno M. M. Etymology Corner. Bulletin of Anesthesia History 1997;15:2.
2.  Levy JH. Allergy and adverse drug reactions. American Society of Anesthesiologists Annual Meeting Refresher Course Lectures 2000;162:1-7.
3.  Portier MM, Richet C. De l'action anaphylactique de certains venims. C R Soc Biol 1902;54:170-2.
4.  Kay AB. Allergy and allergic diseases. N Engl J Med 2001;344:30-7.


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