DB 2 – Advanced Pathophysiology

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Electrical Engineering

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Dec 6, 2023

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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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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 can you predict will be the course of this episode? Future events?  What are the potential systemic adverse effects of this type of hypersensitivity reaction?  What medications are used for this condition and what are the mechanism of action at the cellular level?  What might be the adverse effects and/or drug interactions encountered with medications to treat his condition? Initial Post #2 RT is experiencing a type one hypersensitivity reaction, which is mediated through immunoglobulin (IgE) antibodies that are bound to the surface of mast cells. When IgE interacts with the antigen, mast cells activate and quickly degranulate, releasing histamine, serotonin, and other inflammatory mediators (Rogers & Brashers, 2023). RT may experience vasodilation, decreased blood pressure, and bronchoconstriction during this episode due to serotonin and histamine being released in considerable numbers. A potential adverse effect of a type one hypersensitivity reaction includes widespread activation of mast cells, resulting in a systemic response to antigens that can trigger anaphylactic shock. Eosinophils, prostaglandins, leukotrienes, and platelet-activating factors are also produced by activated mast cells (Rogers & Brashers, 2023). Prostaglandins and leukotrienes are powerful bronchospastic agents that can instigate respiratory insufficiency and anaphylaxis. Emergent treatment is imperative due to anaphylaxis’s rapid onset and potential cause of death. Unless there is a significant obstruction or airway irritation, it is advised that the offending agent be removed as soon as possible, and that the patient be placed supine with their lower extremities elevated. Intubation may be required right away if there is acute respiratory distress or noticeable stridor. Medications for this condition include epinephrine intramuscular auto injector or 1:1,000 solution, bronchodilators, antihistamines, and corticosteroids (Barakat et al., 2021). In RT’s case, epinephrine should be administered immediately. Epinephrine is a naturally occurring catecholamine obtained from animal adrenal glands and can be prepared synthetically. The mechanism of action of epinephrine is that it acts directly on alpha and beta receptors, which is the most potent activator of alpha receptors. On a cellular level, epinephrine stimulates the breakdown of glycogen to glucose in both liver and muscle cells by first stimulating an increase in intracellular cyclic adenosine monophosphate (Sánchez et al., 2022). The glucose released from liver glycogen enters the general circulation, whereas the glucose liberated from muscle glycogen is utilized for rapid adenosine triphosphate synthesis and production of lactate (Sánchez et al., 2022). Adverse effects encountered with epinephrine to treat RT’s condition include hypertension, myocardial infarction, tachyarrhythmias such as ventricular fibrillation, bronchial and pulmonary edema, urinary retention, tissue necrosis with repeated injections, metabolic acidosis, elevated serum lactic acid level, transient elevations of blood glucose, and possible cerebrovascular accident (Rogers & Brashers, 2023). When dealing with type one hypersensitivities, it is necessary to consult with experts like pulmonologists or allergists, mainly if adjuvant medications are not effective in controlling symptoms. RT would benefit from working with

pharmacists to provide more comprehensive medication usage counseling and instruction on emergency self-treatment prescriptions such as epinephrine auto injectors if RT is stung by a bee again. 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. Sánchez, T. S., Fuentes, J. G., Ochoa, H. M., Reyes, Y. B., Martínez, Y. J., Rodriguez, R. P., & Neto, A. P. (2022). Bee and wasp stings cause type I hypersensitivity reactions, mechanism, and treatment. Asia Pacific Journal of Medical Toxicology, 11(4), 163–165. Response Post #3 Hi Connie! Thank you for your thorough discussion board post. I agree with you that RT’s reaction will worsen if not treated with medications to stop the reaction. Treatment for allergic conditions begins with avoiding the offending agent. Patients who experience severe symptoms even when they avoid the allergen and who do not respond well to additional treatment may benefit from allergen immunotherapy, which includes allergy injections, desensitization, or hypo-sensitization (allergy shots). Before starting immunotherapy, the patient must have a verified history of an IgE-mediated allergy, such as asthma, rhinitis, conjunctivitis, dermatitis, bee sting allergy, or a drug allergy (Bil et al., 2021). For the first treatment doses, specific allergens are given in a clinical setting with a gradual increase in subclinical dosages. There are three possible delivery routes: mucosal, sublingual immunotherapy (SLIT), subcutaneous immunotherapy (SCIT), or intra-lymphatic immunotherapy (ILIT) (Chabot et al., 2022). Desensitization aims to induce mast cells to produce immunoglobulin G (IgG) antibodies rather than immunoglobulin E (IgE). Isotype switching is the term for this method, which typically lasts three years. About 67% of patients respond well to desensitization therapy, which is typically more advantageous for younger patients and those sensitive to a monovalent allergen (Chabot et al., 2022). Before immunotherapy begins, patients must be provided with epinephrine autoinjectors and instructed on how to use them properly. Up to 98% of patients can avoid systemic allergic responses to bee stings with venom immunotherapy (Chabot et al., 2022). In RT’s case, he may benefit from ILIT to reduce a potentially fatal reaction from occurring and lessen the fear brought on by being allergic to bee stings. Overall, excellent discussion board post! Thank you for sharing, Connie!

Best regards, Carly Piña References Bil, M. B., Braschi, C., Piga, M. A., Antonicelli, L., & Martini, M. (2021). Safety and adherence to venom immunotherapy during COVID-19 pandemic. Journal of Allergy and Clinical Immunology in Practice , 9 (2), 702–708. https://doi- org.proxy.westernu.edu/10.1016/j.jaip.2020.11.030 Chabot, A., Senti, G., Erdmann, I., Prinz, B. M., Wüthrich, B., Šošić, L., Kündig, T. M., & Johansen, P. (2022). Intralymphatic immunotherapy (ILIT) with bee venom allergens: a clinical proof-of-concept study and the very first ILIT in humans. Frontiers in Allergy , 3 , 832010. https://doi-org.proxy.westernu.edu/10.3389/falgy.2022.832010

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