DB 2 – Advanced Pathophysiology

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University of Hawaii *

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N461

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Electrical Engineering

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Dec 6, 2023

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docx

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DB 2 – Advanced Pathophysiology Part 1: Week 1-2 of Discussion Board Self Defense Mechanisms: Case Presentation RT is a 24-year-old male who presents to the office several hours after receiving a bee sting. RT relates a 3-hour history of an increasing itching throat and “tightness” with breathing. A previous allergy is noted on RT's chart to bee stings. RT’s arm is very swollen with a localized area of redness containing a bee stinger. The site is also very tender and warm to touch on exam. The following questions will provide a framework for the online discussion:  What type of hypersensitivity is most likely?  Describe the cellular pathophysiology that has resulted in the local inflammation.  What effect will the kinin system have on the course of inflammation and the level of pain? Initial Post #1 An altered immune response to an antigen that causes disease or harm to an individual is referred to as a hypersensitive reaction. Hypersensitivity reactions can be classified by the immunologic mechanism that causes diseases (Rogers & Brashers, 2023). There are four distinct mechanism types, which are listed below. The four mechanisms are interrelated, and in most hypersensitivity reactions, several mechanisms can function simultaneously or sequentially (Rogers & Brashers, 2023). 1. Type I: Immunoglobulin E (IgE) mediated reactions 2. Type II: Tissue-specific reactions 3. Type III: Immune complex-mediated reactions 4. Type IV: Cell-mediated reactions RT is most likely experiencing a type one hypersensitivity reaction, which antigen specific IgE and the product of tissue mast cells mediate. In a type one IgE-mediated reaction, T helper two cells produce elevated levels of interleukin-4, leading to B-cell activation and subsequent plasma cell production of the IgE antibody (Rogers & Brashers, 2023). IgE binds to mast cell receptors, resulting in their immediate degranulation and release of histamine, leukotrienes, and other inflammatory mediators (Rogers & Brashers, 2023). Type one hypersensitivity reactions have two distinct phases. When first exposed, there is an initial phase marked by vasodilation, vascular leakage, and smooth muscle spasms, depending on the region (Chen et al., 2017). Eosinophils facilitate damage to mucosal epithelial cells. Subsequent exposure is characterized by infiltration of the tissues with more eosinophils and other inflammatory leukocytes, resulting in prolonged epithelial cell damage and mucus secretion (Rogers & Brashers, 2023). The kinin system is also known as the third plasma protein system. Bradykinin is the final product of the kinin system, which causes dilation of the blood vessels. Additionally, bradykinin acts in concert with prostaglandins to induce pain, trigger smooth muscle cell contraction

(bronchoconstriction), and increase vascular permeability (Rogers & Brashers, 2023). The role of bradykinin in a type one hypersensitivity reaction like RT is experiencing is to contribute to tissue hyperresponsiveness, local inflammation, and hypotension. Bradykinin triggers pain by stimulating primary sensory neurons directly, releasing substance P, neurokinin, and calcitonin gene-related peptides (Bekassy et al., 2021). References Bekassy, Z., Lopatko Fagerstrom, I., Bader, M., & Karpman, D. (2021). Crosstalk between the renin-angiotensin, compliment, and kallikrein-kinin systems in inflammation. Nature Reviews Immunology. https://doi-org.proxy.westernu.edu/10.1038/s41577-021-00634-8 Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2017). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204–7218. https://doi-org.proxy.westernu.edu/10.18632/oncotarget.23208 Rogers, J. L., & Brashers, V. L. (Eds.). (2023). McCance & Huether’s pathophysiology: the biologic basis for disease in adults and children (9th edition.). Elsevier. Response Post #1 Hello Connie, Thank you for your detailed discussion board post on the self-defense mechanism’s case presentation. I agree that RT is most likely experiencing a type one hypersensitivity reaction mediated by antigen-specific immunoglobulin (IgE). IgE is generally at low concentrations in the circulation, and it has specialized functions to mediate many common allergic responses and defenses against infections (Rogers & Brashers, 2023). In RT’s case, a bee sting allergy is a common hypersensitivity mainly brought on by the production of IgE in response to relatively harmless environmental antigens. In people with a severe allergy, monoclonal antibodies are employed to prevent the actions of IgE. Skin tests and blood IgE measurements are just two of the several procedures available to identify allergic reactions. Reactivity to a specific allergen can be assessed by injecting an allergen intradermally or epicutaneously onto the skin under controlled conditions in small dosages. A local wheal and flare reaction at the injection site may happen within a few minutes if the person is allergic to a particular allergen. Various immunoassays can be used to detect IgE antibodies in serum, and these essays can be used to measure circulating levels of total IgE or circulating levels of specific IgE antibodies against selected allergens (Rogers & Brashers, 2023). References Rogers, J. L., & Brashers, V. L. (Eds.). (2023). McCance & Huether’s pathophysiology: the biologic basis for disease in adults and children (9th edition.). Elsevier.

Response Post #2 Hi Michelle, Thank you for your detailed discussion board post. Type one hypersensitivity reactions call for sensitization against a specific environmental antigen, which produces immune memory B cells and T cells specific to that antigen. Individuals genetically predisposed to this type of hypersensitivity reaction generate an inappropriate immunoglobulin (IgE) mediated response to what would otherwise be an innocuous exposure (Rogers & Brashers, 2023). As you stated, anaphylaxis is the most serious and potentially fatal side effect of a type one hypersensitivity reaction that RT may experience. Anaphylaxis could potentially trigger hypotension, dyspnea, hypoxia, and distributive shock. In a prospective study, the likelihood of an annual recurrence of anaphylaxis was shown to be approximately 18% in over 300 patients (Barakat et al., 2021). Consequently, it is critical to provide patients who exhibit anaphylaxis symptoms with proper patient education. The acronym "SAFE" can be used in counseling to help patients remember the actions they must do if an anaphylactic reaction occurs again. SAFE stands for seeking support, allergen identification and avoidance, follow-up for specialty care, and epinephrine for emergencies (Barakat et al., 2021). In RT's case, he should also consult with a specialist, such as an allergist or pulmonologist, if supplementary therapy does not control his symptoms. Overall, great post! Thank you for sharing, Michelle! Best regards, Carly Piña References Barakat, L., Torres, M. J., Phillips, E. J., Caminati, M., Chang, Y.-S., Caimmi, D., Sanchez- Borges, M., Rosenwasser, L., Didier, A., de Blay, F., Fontaine, J.-F., Bosse, I., Lefevre, S., Bassani, C., De Filippo, M., Asontegui, I., Morais-Almeida, M., Ebisawa, M., Martin, B., & Tanno, L. K. (2021). Biological treatments in allergy: prescribing patterns and management of hypersensitivity reactions. The Journal of Allergy and Clinical Immunology. In Practice, 9(3), 1396. https://doi- org.proxy.westernu.edu/10.1016/j.jaip.2020.10.044 Rogers, J. L., & Brashers, V. L. (Eds.). (2023). McCance & Huether’s pathophysiology: the biologic basis for disease in adults and children (9th edition.). Elsevier. Part 2: Week 2-3 of Discussion Board Self Defense Mechanisms: Case Presentation RT is a 24-year-old male who presents to the office several hours after receiving a bee sting. RT relates a 3-hour history of an increasing itching throat and “tightness” with breathing. A previous allergy is noted on RT's chart to bee stings. RT’s arm is very swollen with a localized

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