SEARCH RESULTS FOR: asthma

Asthma: Findings on Investigations

Asthma Exacerbation - Pathogenesis and Clinical Findings in Children

Asthma Acute Exacerbation: Pathogenesis and Treatment

Asthma Acute Exacerbation: Pathogenesis and Treatment Viral URI Allergen Pollution Other Triggers Activation of immune system: Epithelial chemokine activation, lymphocyte activation, macrophage activation, t leukotriene production Inflammation of lower airway • Dyspnea Air flows past inflamed airways causes t irritation Cough and wheezing Release of inflammatory mediators Mucosal edema causing turbulent air flow 7Ir Wheezing Notes • Asthma: Airway hyper-responsiveness causing airflow obstructions • Acute Exacerbation (Asthma): An episode of increased symptoms due to decreases in airflow Abbreviations • PCO2: Partial pressure of CO, in arterial blood • PEF: Peak expiratory flow • SABA: Short-acting beta-2 agonists • Sp02 : Blood oxygen saturation level Mild to moderate exacerbation: PEF 50% of predicted Titrate O2 toSpO2, 92%, give SABA & steroids ■ Good response: symptoms resolved, PEF > 80% [Treat at home with SABA as needed and steroids Dyspnea Bronchoconstriction 1` Residual volume and 1` PCO2 Respiratory failure 1` Air trapping causes '1' intra-alveolar pressure Severe exacerbation: PEF 50% of predicted Educate patient regarding medications, Loss of Pulsus inhaler technique & [consciousness paradoxus follow up with primary care provider I Legend: Pathophysiology Mechanism Titrate O2 to402 93%, give SABA, steroids & magnesium sulfate Sign/Symptom/Lab Finding {Worsening symptoms and/or respiratory failure: Do not delay intubation, send to ICU, give SABA, steroids & magnesium sulfate Authors: Luke Gagnon Reviewers: Midas (Kening) Kang Usama Malik Lian Szabo* * MD at time of publication 4, Delivery of oxygen rich air to alveoli 4, Oxygenation of blood Drowsy and confused Central cyanosis • Tachycardia Pneumothorax [Depending on 1 severity: Observation or place chest tube

Benzodiazepine (BZD) withdrawal: clinical findings and complications

Benzodiazepine (BZD) withdrawal: clinical findings and complications Abrupt cessation of chronic ingestion of BZDs Administration of BZD antagonist (flumazenil) on patients who have developed -* tolerance/dependence to BZD Withdrawal Seizure Negative physiological reactions BZD intake inhibition a mygd to f, • of a la Withdrawal symptoms Benzodiazepine Withdrawal GABA receptor activity (less inhibition alleviated by ingesting BZD Tolerance GABA BZD intake Conformational changes in the GABA receptor 1, receptor's Withdrawal Insomnia Pro-excitatory 4— state of excitatory neurotransmitters) 4— to the agent activity affinity for the agent A Activation of ACC and OFC Feelings of fear Activation of PAG Behavioural response of fight or flight Legend: Pathophysiology Mechanism Activation of hypothalamus '1` Cortisol CAD, T2DM, Stroke Sign/Symptom/Lab Finding Activation of PBN V t RR, SOB, Asthma, or a sense of being smothered Activation of LC t Sympathetic Activity t BP, t HR variability, tremor, and diaphoresis Authors: Usama Malik Reviewers: Sina Marzoughi Aaron Mackie* * MD at time of publication Notes: • The onset of withdrawal can vary according to the half-life of the BZD involved. Symptoms may be delayed up to three weeks in BZDs with long half-lives, but may appear as early as 24 to 48 hours after cessation of BZDs with short half-lives. Abbreviations: • ACC: Anterior Cingulate Cortex • BP: Blood Pressure • CAD: Coronary Artery Disease • HR: Heart Rate • LC: Locus Coeruleus • MI: Myocardial Infarction • OFC: Orbitofrontal Cortex • PAG: Periaqueductal Gray • PBN: Parabrachial Nucleus • RR: Respiratory Rate • SOB: Shortness of Breath • T2DM: Type 2 Diabetes I` atherosclerosis, cardiac ischemia, MI, or sudden death

gastroesophageal-reflux-disease-gerd-complications

Gastroesophageal Reflux Disease (GERD): Complications Esophageal stricture disease Esophagitis Esophageal adenocarcinoma Barrett’s esophagus GERD Reflux of gastric content into distal esophagus Damage to squamous esophageal epithelium Legend: Published March 30, 2019 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications thecalgaryguide.com Authors: Wendy Wang Reviewers: Yoyo Chan Sean Doherty Dr. Sylvain Coderre* * MD at time of publication Squamous esophageal epithelium undergoes metaplasia to become columnar epithelium This predisposes cells to premalignant changes (dysplasia) Collagen is deposited where ulcers heal Asthma/Chronic Cough Chronic Laryngitis Laryngeal and Tracheal Stenosis Extra-esophageal Complications Esophageal Complications Airway becomes irritated Fibroblasts proliferate and deposit granulation tissue in airway Tissue deposition leads to narrowing of laryngeal and tracheal space Damage to pharyngeal lining and airway Esophageal tissue repeatedly exposed to stomach acid Pro-inflammatory cells and cytokines are recruited to the area Definitions: • Metaplasia: abnormal change in the nature of a tissue • Pro-inflammatory cells and cytokines: Mediators of inflammation. Examples of cells include macrophages and T cells, cytokines include IL-17, IL-2, IL-4 Over time, collagen fibers contract Bronchoconstriction ↑ vagal tone ↑ bronchial reactivity Cough sensory nerve endings are stimulated Vagal reflex is activated Activation of cough center in brainstem ↑ inflammation of squamous epithelium Ulcers form in esophagus

Beta-Blockers-Mechanism-of-Action-and-Side-Effects

Beta-Blockers: Mechanism of Action and Side Effects Two classes of “Beta-Blockers” are used clinically: Non-cardio-selective: binds Cardio-selective: binds largely beta-1 and beta-2 receptors to beta-1 receptors Authors: Tegan Evans, Davis Maclean, Yan Yu* Reviewers:, Amanda Nguyen, P. Timothy Pollak*, Sean Spence* * MD at time of publication Beta blockers bind to beta 1 and/or beta 2-receptors of various tissues throughout body, and thus competitively inhibit binding of sympathetic adrenergic molecules (such as catecholamines from the adrenal medulla, e.g. epinephrine) to these receptors, ↓ their normal adrenergic tone Beta-2 receptor antagonism Beta-1 receptor antagonism Lungs Eyes Central nervous system Heart Kidneys ↓ cAMP (intracellular messenger) productionàcomplex, tissue-specific intracellular mechanisms resulting in a variety of effects in different tissues: Throughout body tissue Epinephrine (via cAMP) indirectly ↑ the activity of the Na+/K+ pump on cell membranes (a pump that moves 3 Na+ out of cells per 2 K+ moved into cells) Blocking epinephrine from binding the beta-2 receptor and producing cAMPà↓ activity of Na+/K+ pump à↓K+ moved into cells ↑ proportion of K+ now resides in extracellular fluid, detectable in serum (total body K+ remains the same) Hyperkalemia (see Calgary Guide: Hyperkalemia – Clinical findings) Blocking sympathetic hormonesà↓ relaxation of smooth muscle circumferentially wrapped around airways ↑ resting airway muscle toneà bronchoconstriction ↑ resistance to airflow Wheezing, dyspnea, chest tightness Exacerbation of underlying airway disease (e.g. asthma) ↓ ciliary epithelium’s production of aqueous humor (fluid that fills anterior chamber of the eye) Reduced intraocular pressure Blocking adrenergic response mediated by epinephrine and norepinephrine (e.g. the physiologic “fight- or-flight” response to stress) ↓ tremor, irritability, anxiety ↓ ability to produce adrenergic symptoms in response to hypoglycemia Hypoglycemia unawareness Coronary perfusion pressure = diastolic blood pressure in aorta – LV end diastolic pressure ↓ inotropy (contractility of cardiac muscle) ↓ chronotropy (heart rate and conduction velocity) ↓ renin releaseà↓ creation of angiotensin II & aldosterone + ↓ reabsorption of Na and H2O in nephron ↑ urinary Na+ & H2O loss ↓ total blood volume Decompensation of acute heart failure Dizziness and fatigue Hypotension (Blood pressure = cardiac output x systemic vascular resistance) ↓ O2 demand of myocardial tissue Bradycardia Inability to ↑ heart rate in response to stress (e.g. shock, sepsis) ↓ stroke volume ↓ cardiac output Beta blockers ↓ diastolic blood pressure, & thus may ↓ coronary perfusion pressure Before giving beta blockers, ensure blood pressure isn’t too low Otherwise, may worsen acute myocardial ischemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 14, 2021, updated Feb 7, 2021 on www.thecalgaryguide.com

asthma-pathogenesis

Asthma: Pathogenesis Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Ciara Hanly Yonglin Mai (􏰁􏰃􏰄) Naushad Hirani* * MD at time of publication Genetic factors (i.e. HLA gene mutations, defects in bronchial airway epithelium) Environmental factors (i.e. excess hygiene, fewer siblings, antibiotics within the first two years) Asthma: Defined as airway hyper-responsiveness causing variable and reversible airflow obstruction Atopy: predisposition to allergic hyper-sensitivity in airways First exposure to triggers* sensitizes helper T cells Stimulation of B-cells to produce IgE, which binds to mast cell surfaces Activated Helper-T cells & IgE-sensitized mast cells now line the airways Triggers of airway hyper- responsiveness include: Upper respiratory tract infections (URTIs) Allergens (pollen, animal dander, dust, mold, etc) Air pollution, cigarette smoke, other chemicals Drugs (aspirin, NSAIDs, Beta- blockers) Cold air Exercise Early response (0-2 hrs) Delayed response (3-4 hrs) Allergens cross-link IgEs on mast cells Activated mast cells & helper T cells release cytokines Mast cells release histamines, leukotrienes, and other inflammatory mediators Induce maturation of granular WBCs like eosinophils Eosinophils migrate into: Vascular permeabilityà edema of airway mucosa Goblet cell hyperplasia à­ mucus secretion Bronchial smooth muscle contraction Airway obstruction Second exposure to triggers Asthma Airways Bronchiole constriction Eyes Conjunctivitis Nose Rhinitis Note: Delayed response presents within 3-4 hrs, peaks within 6-8 hrs, and resolves within 24 hrs Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 17, 2012, updated Aug 19, 2021 on www.thecalgaryguide.com

copd-overview-and-definitions

Defining “Chronic Obstructive Pulmonary Disease (COPD)” Author: Yan Yu Reviewers: Jason Baserman, Jennifer Au, Ciara Hanly, Zesheng Ye (叶泽生), Yonglin Mai (麦泳琳)*, Naushad Hirani*, Juri Janovcik* * MD at time of publication Cystic Fibrosis Multisystem disease due to CFTR gene mutation, that presents in the lungs as bronchiectasis Bronchiectasis, Cystic Fibrosis, etc COPD Systemic disease, largely manifesting as an airflow-obstructing respiratory disorder; can manifest in the form of any of the following disorders: Emphysema Lung tissue destruction & abnormal, permanent enlargement of lung acini: airspaces distal to terminal bronchioles Chronic Bronchitis Chronic, productive cough for a total duration of 3 months per year, over 2 continuous years Asthma Asthma that does not remit completely with treatment (thus, chronic airflow obstruction) is defined as asthma-COPD overlap syndrome (ACOS) Emphysema Bronchiectasis Destruction and widening of large airways, resulting in mucus hyper-secretion and recurrent infections Chronic Bronchitis Most common COPD manifestations (most patients suffer from a combination of emphysema and chronic bronchitis) Clinically, COPD is seen as: • Progressive, partially reversible airflow obstruction and lung hyperinflation (causing respiratory symptoms like cough, sputum production, and dyspnea) • Post-bronchodilator spirometry results: FEV1/FVC ratio <0.7 (FEV1 is not a defining feature of COPD, but a marker of severity) • ↑ frequency & severity of acute exacerbations • Systemic manifestations such as deconditioning and muscle weakness Chronic Obstructive Pulmonary Disease (COPD) Asthma Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013, updated October 5, 2021 on www.thecalgaryguide.com

Pneumonie: Pathogenese und klinische Befunde

Pneumonie: Pathogenese und klinische Befunde Autoren: Laura Byford-Richardson Rezensenten: *Yan Yu, Sadie Kutz, Natalie Morgunov, *Kerri Johannson Übersetzung: Sarah Schwarz Übersetungsprüfung: Gesche Tallen* *MD zum Zeitpunkt der Veröffentlichung Anmerkungen: • Pathogene können Bakterien, Viren, Pilze oder Parasiten sein • Die Pneumonie ist eine Entzündung der unteren Atemwege (im Gegensatz zur Entzündung der oberen Atemwege z.B. die Bronchitis) und kann unterteilt werden in: Ambulant erworbene, nosokomial (im Krankenhaus) erworbene Pneumonie Die Immunantwort variiert je nach eingedrungenem Erreger (z.B. Pneumokokken verursachen ein lobär betontes, H. influenzae ein interstitiell betontes Entzündungsbild) Rauchen unterdrückt die Funktionsfähigkeit der neutrophilen Granulozyten und schädigt das Lungenepithel Chronische Lungenerkrankungen z.B. COPD, Asthma oder Lungenkrebs zerstören das Lungengewebe und bieten Krankheitserregern mehr Angriffsfläche für Infektionen Durch Immunsuppression z.B. bei HIV, Sepsis, Glucocorticoid- oder Chemotherapie wird die Immunantwort eingeschränkt Systemisch kommt es zu einer inflammatorischen Immunantwort Durch systemische Zytokinfreisetzung wird die hypothalamische Thermoregulation beeinträchtigt Erregersexposition durch Inhalation, Aspiration, Kontakt- oder hämatologische Übertragung Anfällige Person und/oder virulenter Erreger Proliferation des Erregers in unteren Atemwegen und Alveolen Lokal reagiert das Alveolarepithel mit einer Chemokinausschüttung um neutrophile Granulozyten an den Entzündungsort zu mobilisieren LOBÄR betont: Lokal begrenzte Akkumulation von neutrophilen Granulozyten und Plasmaexudat in Alveolen INTERSTITIELL betont: Zelluläre Infiltrate (Immunzellen und Immunzellfragmente) in den Alveolarwänden (zwischen Alveolen und Kapillaren) Fieber Anmerkungen: Schüttelfrost Irritation der Atemwege mit Hustenreiz Flüssige Infiltrate in Alveolen führen zur Schleimbildung Produktiver Husten Das Exudat vermindert die Röntgenstrahlendur chlässigkeit, entzündete Areale erscheinen im Röntgenbild heller/weiß. Verschattung im Röntgen Alveolen sind durch Flüssigkeitsansamml ungen blockiert Verdickung der Alveolarwände, Diffusionsstrecke ↑ Irritation der Alveolarwände mit Hustenreiz Bei ausschließlich interstitieller Infiltration -> Husten ohne Schleimproduktion Trockener Husten • Andere Symptome der Pneumonie sind: Brustschmerzen, Nutzung der Atemhilfsmuskulatur, auskultatorisch Rasselgeräusche, Müdigkeit • Diese Symptome sind jedoch unspezifisch O2 und CO2- Austausch vermindert Hypoxie Periphere & zentrale Chemorezeptoren werden aktiviert, Atemfrequenz ↑ Luftnot Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 26. September 2016 auf www.thecalgaryguide.com

Asthma: Pathogenese

Asthma: Pathogenese Autor: Yan Yu Rezensenten: Jason Baserman Jennifer Au Ciara Hanly Yonglin Mai (麦泳琳) Naushad Hirani* Übersetzung: Sarah Schwarz Übersetzungsprüfung: Dr. Gesche Tallen * MD zum Zeitpunkt der Veröffentlichung Genetische Faktoren (z.B. Mutationen im HLA- Gen, Defekte im bronchialen Endothel) Umwelteinflüsse (z.B. übermäßige Hygiene, wenige Geschwister, Antibiotikaeinnahme in den ersten 2 Lj.) Asthma: Eine chronisch-entzündliche Erkrankung welche durch hyperreagible Atemwege zu variablen, reversiblen Obstruktionen führt Trigger für Hyperreagibilität der Atemwege: Atopie: Neigung zu allergischen Überempfindlichkeitsreaktionen der Atemwege Erstexposition gegenüber des Triggers Sensibilisierung der T-Helferzellen Stimulation der B-Zellen zur IgE Produktion, welche an Mastzellen binden und diese aktivieren Aktivierte T-Helferzellen und Mastzellen säumen die Atemwege Infektionen des oberen Respirationstrakts Allergene (Pollen, Haus- staub, Tierhaar etc.) Luftverschmutzung, Zigarettenrauch, Chemikalien Medikamente (ASS, NSAR, Beta-Blocker) kalte Luft Bewegung Mastzellen setzen Histamine, Leukotriene und andere Entzündungsmediatoren frei Induzieren Zellreifung eosinophiler Granulozyten Eosinophile migrieren in: Gefäßpermeabilität ↑, Schleimhautödem in Bronchien Becherzellhyperplasie, Schleimsekretion ↑ Kontraktion der Bronchialmuskulatur Zweitkontak t mit dem Trigger Frühe Reaktion (0-2 h) Verspätet e Reaktion (3-4 h) Allergene binden an IgEs auf Mastzellen Aktivierte T- Helferzellen & Mastzellen setzen Zytokine frei Obstruktion der Atemwege Asthma Bronchokonstriktion Konjunktivitis Beachte: Verspätete Reaktionen beginnen nach 3-4h, erreichen ihren Höhepunkt nach 6-8h und klingen nach 24h ab Atemwege Augen Nase Rhinitis Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 17. Dez. 2012, aktualisiert: 19. Aug. 2021 auf www.thecalgaryguide.com

哮喘急性发作-发病机制和治疗

哮喘急性发作: 发病机制和治疗 病毒性上呼吸道感染 接触变应原 环境污染 其他诱因 作者: Luke Gagnon 审稿人:Midas (Kening) Kang，Usama Malik，Lian Szabo* 译者:Yonglin Mai (麦泳琳) 翻译审核人:Zesheng Ye (叶泽生) * 发表时担任临床医生 下呼吸道炎症 免疫系统激活:气道上皮趋化因子、淋巴细胞和巨噬细胞激活, 白三烯产生↑ 炎症介质释放 哮喘轻中度急性发作: PEF ≥ 预计值50% 疗效良好: 症状缓 解, PEF ≥ 80% 患者日常在家 服用糖皮质激 素及必要时使 用SABA 支气管狭窄 残气量↑ 及PaCO2↑ 气体潴留↑，肺 泡内压力 ↑ 奇脉 气体通过 发炎的呼 吸道产生 的刺激↑ 咳嗽和喘息 Notes 呼吸 困难 黏膜水肿会导 致气流湍急 喘息 吸O2使SpO2 ≥ 92%, 给予SABA & 糖皮质激素 治疗 重度急性发作: PEF ≤预计值 50% 呼吸困难 呼吸急促 呼吸衰竭 意识丧失 ↓ 向肺泡传送 空气氧含量 血氧饱和度↓ • • Asthma哮喘: Airway hyper- responsiveness causing airflow obstructions气道高反应性引起气流受 限 Acute Exacerbation (Asthma)哮喘急性 发作: An episode of increased symptoms due to decreases in airflow气流减少而 引起一系列症状加重 Abbreviations • PaCO2动脉二氧化碳分压:Partial pressure of CO2 in arterial blood • PEF最大呼气流量/呼气流量峰值: Peak expiratory flow • SABA短效beta-2受体激动剂: Short- acting beta-2 agonists • SpO2血氧饱和度: Blood oxygen saturation level 昏睡 气胸 中枢性紫绀 心动过速 患者宣教: 正确服用药物，使用 药物吸入装置 &全科医生密切医学随 访 吸 O 使 SpO ≥ 2 2 症状恶化和/或呼吸衰竭 :及时气 管插管, 送往ICU, 给予SABA, 糖皮 质激素 & 硫酸镁 取决于气胸严 重程度: 密切观 察或者置入胸 腔引流管 93%, 给予 SABA, 糖皮质激素 & 硫 酸镁 图注: 病理生理 机制 体征/症状/实验室检查 并发症 2018年 2月6日发布于 www.thecalgaryguide.com

Asthma clinical findings

Asthma: Clinical Findings Asthma Episodic airway constriction and airflow obstruction, due to hyper- responsiveness to certain triggers (see slide on asthma pathogenesis) Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Yonoglin Mai (麦泳琳) Naushad Hirani* * MD at time of publication Variable, sporadic airway obstruction in response to triggers Associated allergic eosinophil response Eosinophils infiltrate: Skin If severe: ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) During expiration, positive pleural pressure squeezes on airwaysà↑↑ airway obstruction Heart rate ­ to improve perfusion of tissue Tachycardia Respiratory centers ­ rate of breathing to compensate Tachypnea Gas is trapped within alveolià hyperinflates lungs Ventilating larger lungs needs more effort Patients need to voluntarily contract their expiratory muscles faster and more forcefully to effectively expire Narrower airways àturbulent airflow, heard on auscultation Expiratory Wheeze (high-pitched expiratory sound) Nose Rhinitis/ sinusitis Runny nose, sneezing, etc Atopic dermatitis Skin rash, hives Eyes Conjunctivitis Red itchy eyes, visual blurring Episodic dyspnea (shortness of breath) Chest tightness During severe attacks: Note: Asthma attacks often have two phases: • An immediate attack (within 0-2 hours of the trigger, due to acute release of histamine from mast cells) • A delayed attack (due to eosinophil infiltration of airways, presents within 3-4 hours after exposure to the trigger, peaks within 6-8 hours, and resolves within 24 hours). Keep the possibility of a delayed attack in mind when treating patients in Emergency! Note: Symptoms often worse at night or early in the morning. Note: Asthma should be suspected in children experiencing dyspnea with multiple episodes of Upper Respiratory Tract Infections or Croup. Patient compensates by activating accessory respiratory muscles to ↑ thoracic volume Visible contraction of neck muscles (Scalene, sternocleidomastoids) ↑↑↑ airway obstruction on expiration, lungs take more time to empty Prolonged expiratory phase of breathing Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 17, 2012 and updated Dec 4, 2021 on www.thecalgaryguide.com

Chronic Cough Pathogenesis_2021

Chronic Cough: Pathogenesis ACE Inhibitors Protussive mediator accumulation (bradykinin, substance P) Infection IP; likely chronic ↑ cough receptors commonly pertussis- related or post-viral Asthma ↑ EDN ↑ MBP levels in RT Neoplasm Bronchiectasis COPD GERD Allergic Rhinitis ↑ sputum production and accumulation Damage from chronic inflammation causes poor mucus clearance Inhalants trigger ↑ cytokines ↑ mucus Aspiration of refluxed microdroplets Irritation by post- nasal drip ↑ inflammatory mediators in RT Mechanical obstructions (i.e. mediastinal masses, neoplasms) Foreign body Presence irritation of irritants Stimulation of sensory nerve receptors expressed on nerve endings penetrating the epithelia of the upper RT Abbreviations: • RT: respiratory tract • IP: indefinite pathophysiology • GERD: Gastro-esophageal reflux disease • EDN: Eosinophil-derived neurotoxin • MBP: Major basic protein • COPD: Chronic Obstructive Pulmonary Disease Complications: Syncope, insomnia, hemoptysis, rib fractures Slowly adapting receptors Respond to mechanical forces during breathing Stimulation of the vagus nerve Activation of nucleus tractus solitarius in central respiratory generator (brainstem) Generation of efferent cough signal Chronic cough: Cough of over 8 weeks duration with no dyspnea or fever C-fibre receptors Respond to chemical stimuli (bradykinin, capsaicin, acid/alkaline solutions, mannitol, hypertonic saline, and other inhaled irritants) Authors: Arsalan Ahmad Lance Bartel Reviewers: Midas (Kening) Kang Usama Malik Ciara Hanly Yonglin Mai (麦泳琳) Yan Yu*, Eric Leung* * MD at time of publication Rapidly adapting receptors Responds to mechanical stimuli, such as physical obstruction of the airways Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 06, 2018, updated Dec 4, 2021 on www.thecalgaryguide.com

哮喘-发病机制

哮喘-发病机制

哮喘-临床表现

哮喘-临床表现

哮喘-检查结果

哮喘-检查结果

adult-pneumonia-pathogenesis-and-clinical-findings

Adult Pneumonia: Pathogenesis and clinical findings Author: Laura Byford-Richardson Reviewers: Tara Shannon, *Yan Yu, Sadie Kutz , Natalie Morgunov, *Kerri Johannson, *Julie Carson *MD at time of publication Smoking à suppressed neutrophil function and damaged lung epithelium Chronic lung conditions e.g. COPD, asthma, lung canceràdestroys lung tissue and offers pathogen more niduses for infection Immune suppression e.g. HIV, sepsis, glucocorticoids, chemotherapyà suppression of immune response Systemic inflammatory response towards invading microbe Systemic cytokine release leads to a disruption in hypothalamic thermoregulation Exposure to a pathogen via inhalation, aspiration, contiguous Notes: or hematological mechanism Susceptible host and/or virulent pathogen Proliferation of microbe in lower airways and alveoli Local response by alveolar epithelial cells release chemokines into surrounding tissue to recruit neutrophils to the site of inflammation • Pathogens can be bacteria, viruses, fungi and parasites • Pneumonia is a lower respiratory tract infection (in contrast to upper respiratory tract infections such as bronchitis) and can be further classified by location of exposure: community, health- care, hospital acquired Inflammatory response varies depending on type of invading pathogen (i.e. S. Pneumonia causes a lobar pattern and Influenza A & B cause an interstitial pattern) LOBAR: Accumulation of neutrophils and plasma exudate from capillaries into alveoli specific to a lung area/lobe INTERSTITIAL: Accumulation of infiltrates (i.e. inflamed cellular debris) in the alveolar walls (i.e. space between the alveolar spaces and bloodstream) Fever Notes: • Other signs and symptoms of pneumonia exist such as chest pain, accessory muscle use, crackles on auscultation and fatigue • These signs and symptoms are less specific to the ones outlined on this slide Irritation and attempted clearance of airways Fluid infiltrates are inside alveoli, airway clearance leads to phlegm production Productive Cough Fluid build up does not allow X-rays to pass through à white opacity on plain film at site of fluid buildup Consolidation on CXR Alveolar sacs blocked by fluid accumulation Thickening of alveolar walls ↑ diffusion distance between alveoli & capillaries Irritated alveolar walls trigger cough reflex Since fluid infiltrates are NOT in the alveoli, attempts to empty the alveoli through coughing doesn’t lead to production of fluid Dry Cough Chills/Rigors ↓ Exchange of CO2 and O2 Hypoxemia Triggers peripheral and central chemoreceptors to ↑ respiratory drive Dyspnea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 26 2016, updated Feb 9, 2022 on www.thecalgaryguide.com

asthma-how-treatments-work-and-common-side-effects

Asthma: How Treatments Work and Common Side Effects • Relievers: Used as needed to ↓ symptoms during attacks • Controllers: Used daily to ↓ frequency and severity of attacks Note: Please see slide on Asthma: Pathogenesis • Exacerbation: Used emergently in acute exacerbation Short-acting Beta Agonists (Reliever) Long-acting Beta Agonists (Controller) Short-acting Muscarinic Antagonists (Exacerbation) Long-acting Muscarinic Antagonists (Controller) Magnesium Sulfate (Exacerbation) Monoclonal Antibodies (Controller) Leukotriene Receptor Antagonists (Controller) Inhaled Corticosteroids (ICS) (Controller) Systemic Corticosteroids (Exacerbation) Binding to beta-2 adrenergic receptors and subsequent intracellular signal cascade in bronchial smooth muscle Off-target binding occurs in other systemic cells Inhibition of muscarinic acetylcholine receptors in airway muscle cells ↓ Activation of the inositol triphosphate (IP3) intracellular pathway (IP3 pathway normally functions to mobilize intracellular Ca2+ stores) Inhibition of Ca2+ channels on airway smooth muscle surface ↓ Influx of Ca2+ Binding and inactivation of inflammatory signal molecules (IgE, IL-5) Inhibition of leukotriene receptors in lung and immune cells Steroid binds to nuclear receptors within cells ↓ Gene expression/synthesis of immune mediators (ex. cytokines) Stimulation of Na/K ATPase (which transports K into cells) Hypokalemia Palpitations Tachycardia Muscle cramps Tremor Authors: Chunpeng Nie Reviewers: Sravya Kakumanu, Ben Campbell, *Tara Lohmann * MD at time of publication ↓ Activation of mast cells (by ↓ IgE) and eosinophils (by ↓ IL-5/leukotrienes) ↓ Release of inflammatory cytokines by these cells (↓ Type 2 inflammatory response in airways) ↓ Permeability of airway vasculature ↓ Microvascular leakage into airway Inadvertent sympathetic nervous system activation Bronchial smooth muscle cells have ↓ Ca2+ release from intracellular stores (i.e. from sarcoplasmic reticulum) ↓↓ Cytoplasmic Ca2+ Myosin (muscle protein) unable to be activated for muscle contraction ↓ Smooth muscle contraction in bronchioles Bronchodilation ICS cause ↓ immune cell activity in the oropharynx Susceptibility to infection and irritation of the oropharynx from inhaled particles and pathogens Hoarseness Thrush Systemic corticosteroids cause ↓ immune cell activity in whole body ↑ Susceptibility to any infection Many other side effects Similar effects on other muscles in the body outside bronchi Dry mouth Urinary retention Constipation ↓ Mucosal edema ↓ Airway Mucus Airflow improvement ↑ Peak flow, ↑ Oxygenation, ↓ Dyspnea Legend: Pathophysiology Mechanism Treatment Effect Complications Published October 9, 2022 on www.thecalgaryguide.com

Acute Laryngitis

Acute Laryngitis: Pathogenesis and clinical findings Infectious Author: Charmaine Szalay-Anderson Reviewers: Shayan Hemmati, Sunawer Aujla, Derrick Randall*, Viral (most common) Malaise Fever Fungal Atopy (asthma, allergy) Non-infectious Gastroesophageal Reflux Trauma or damage to larynx Smoking Yan Yu* * MD at time of publication Environmental Pollution/Inhalants Bacterial (S. pneumoniae, H. influenzae, M. catarrhalis) Systemic immune response Spread of infection to larynx through upper respiratory tract Infection of the vocal folds and surrounding tissue Mechanical (vocal misuse/ trauma) (Area in the neck that contains the structures for voice production, anatomically anterior to the esophagus, inferior to the pharynx and superior to the trachea) Irritation of the vocal folds and surrounding tissue Inflammatory cascade triggered Acute Laryngitis Symptoms for <3 weeks Acute injury to vocal folds Vocal fold lesions (i.e., vocal polyps) Laryngeal inflammation Neutrophils and macrophages release inflammatory cytokines Local laryngeal inflammationà↑ vascular permeability ↑ Secretion of mucous leading to airway congestion Cough reflex initiated to clear airway congestion Cough Edema of vocal folds and surrounding tissue Dysphagia (difficulty swallowing) Dysphonia (difficulty speaking) Odynophagia (painful swallowing) Swelling impairs vocal cord vibration Frank aphonia (loss of voice) Progressive worsening of edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 24, 2023 on www.thecalgaryguide.com

Kindliche Asthma Exazerbation: Pathogenese und klinische Befunde bei Kindern

Kindliche Asthma Exazerbation: Pathogenese und klinische Befunde bei Kindern

Asma Eksaserbasi Patogenesis dan temuan klinis pada anak

Asma Eksaserbasi: Patogenesis dan temuan klinis pada anak

تشدید آسم حاد بیماریزایی و درمان

تشدید آسم حاد: بیماریزایی و درمان

آسم بیماریزایی

آسم: بیماریزایی

آسم یافتھ ھای بالینی

آسم: یافتھ ھای بالینی

آسم یافتھ ھای تحقیقاتی

آسم: یافتھ ھای تحقیقاتی

Death Cardiovascular Respiratory and Neurologic Mechanisms

Death: Cardiovascular, Respiratory and Neurologic Mechanisms Mitochondria in tissues unable to utilize O2 Reduced hemoglobin in blood to carry O2 Low oxygen content in blood (CaO2) Hypoxemia (Type I Respiratory Failure): low dissolved oxygen in blood (PaO2) Lungs can’t oxygenate blood fast enough Lungs can’t rid blood of CO2 fast enough Hypercapnia / hypercarbia (Type II Respiratory Failure): elevated dissolved CO2 in blood (PaCO2) Cerebral vasodilation Toxins: e.g. cyanide, pesticides, arsenic Severe anemia Distributive problems: Systemic inflammation (sepsis, anaphylaxis, pancreatitis), adrenal insufficiency, vasodilatory drugs Obstructive problems: Cardiac tamponade*, tension pneumothorax* or massive pulmonary embolism* Hypovolemic* problems (low blood volume): Hemorrhage, dehydration, widespread skin disruption or burns Cardiac valve dysfunction Myocardial infarction* or cardiomyopathy Cardiac arrhythmia or heart block Disturbed electrical activity in cardiomyocytes Peripheral metabolic disturbances Hypokalemia*, Hyperkalemia* Acidosis* (including renal failure) Hypothermia* Toxins* (e.g. cocaine, beta blockers, tricyclics) Severe thyroid derangement Inappropriate systemic vasodilation Adjacent forces impair heart filling Low cardiac preload Low stroke volume (SV; depends on valves, contractility, preload) Decreased systemic vascular resistance (SVR) Low blood pressure (BP = CO x SVR) Decreased cardiac output (CO = SV x HR) Disseminated intravascular coagulationàwidespread thrombi that occlude blood flow (also causes hemorrhage, see relevant box at left) Methemoglobinemia: some hemoglobin gets stuck in a state that can’t carry O2 Hemoglobin has reduced capacity to carry or release O2 Drugs: e.g. dapsone, nitrates Carbon monoxide poisoning Circulatory collapse / shock: inadequate perfusion of tissue with blood Respiratory collapse: blood has insufficient useable O2 content Ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) Hypoxia*: inadequate O2 delivery or utilization in tissues Hypoxia creates metabolic disturbances that impair cardiac cells. Alternatively, any of the preceding conditions marked with (*) can directly trigger cardiac arrest first Pulseless Electrical Activity (PEA): organized activity on ECG with no cardiac output (can be preceded or mimicked by pseudo-PEA, in which there is still some output on ultrasound) Low atmospheric pressure or oxygen content Severe lung disease Asthma, COPD, interstitial lung disease, congestive heart failure, pulmonary hypertension, pulmonary embolism, lung collapse / atelectasis Acute respiratory distress syndrome Pneumonia, aspiration pneumonitis, inhalational injury, systemic inflammation, drowning Severe hypoventilation Respiratory fatigue, advanced COPD, chest wall disorders, neuromuscular disorders, upper airway obstruction, toxins (e.g. opioids, botulism) Can degenerate at any time Asystole: no cardiac electrical activity or output Death Respiratory arrest: cessation of breathing Inability to protect airway Decreased level of consciousness Note This is a broad overview of the many scenarios that can result in death. For detailed explanations of the various disease mechanisms, refer to the corresponding slides. * = reversible causes of cardiac arrest (Hs and Ts) Author: Ben Campbell Reviewers: Yan Yu* Huma Ali* * MD at time of publication Bradycardia (low heart rate, HR) Unopposed parasympathetic stimulation of heart (can also cause vasodilation, see Distributive problems) Disruption of spinal cord sympathetic control Injury to cervical or upper thoracic spinal cord Irreversible cessation of cardiac, respiratory, and brain function Prolonged seizure initially causes increased cardiovascular activity, until the system fatigues Disruption of respiratory control center in medulla Expanding skull contents squeeze brainstem (herniation) Increased intracranial pressure Edema from intracranial hemorrhage, trauma, brain mass Edema, inflammation, hypoxia and/or metabolic derangements cause diffuse neuron dysfunction Central nervous system infection Dementia, particularly with delirium Massive ischemic stroke Seizure activity prevents or alters breathing Metabolic disturbances that affect the central nervous system Hypoglycemia Hypocalcemia, hypercalcemia Hyponatremia, hypernatremia Uremia Acute liver failure (hyperNH4) Many drugs / toxins Withdrawal (e.g. EtOH) Status epilepticus Brainstem lesion (e.g. stroke, neoplasm, inflammatory) Nervous System Insult Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 11, 2023 on www.thecalgaryguide.com Respiratory System Insult Cardiovascular System Insult Cardiogenic problems

آسم-چگونگی-اثر-درمان-ھا-و-عوارض-جانبی-ر

آسم: چگونگی اثر درمان ھا و عوارض جانبی رایج آنھا

Pediatric Pneumonia Pathogenesis and Clinical Findings

Pediatric Pneumonia: Pathogenesis and clinical findings Authors: Jasmine Nguyen Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Annie Pham Eric Leung* Jean Mah* * MD at time of publication Immunological: unvaccinated, primary immunocompromise, pre-existing illness (e.g. HIV, measles), malnutrition Environmental: smoke, air pollution, mold, crowded housing Recent hospitalization or antibiotic-use Physiological: neonates, low-birth weight, underlying lung disease These factors make the host more susceptible to infection Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to infection/proliferation of microbial pathogens at the alveolar level Exposure to pathogen via inhalation, hematogenous, direct exposure, or aspiration Epithelial cells in respiratory tract release cytokines that recruit neutrophils & plasma proteins to infection site, initiating a local inflammatory response Cytokines released into the bloodstream (e.g. TNF, IL-1) initiate a systemic inflammatory response ↑ Vascular permeability Accumulation of exudate, cellular debris, serous fluid, fibrin, or bacteria in the airway spaces ↑ Respiratory drive Tachypnea ↑ Excitability of the peripheral somatosensory system Circulating cytokines induce prostaglandin synthesis Airway irritation as cilia are unable to efficiently clear fluid buildup Crackles, ↓ breath sounds Fluid, protein, or inflammatory cells leak into pleural space Pleural effusion Pulmonary edema Fluid buildup in interstitial spaces ↑ gas diffusion distance Bacteria enter the bloodstream (if bacterial pneumonia) Sepsis Fluid buildup in the alveoli ↓ available surface area for gas diffusion ↓ Efficiency of gas exchange Intra- and extracranial arteries dilate Headache ↑ Thermo-regulatory set-point of the hypothalamus Fever Myalgia Hypoxemia Malaise Cough Fluid accumulation in the pleural space prevents full lung expansion ↑ Work of breathing (tracheal tug, paradoxical abdominal breathing, subcostal/suprasternal indrawing) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 28, 2018; updated Aug 25, 2024 on www.thecalgaryguide.com Pediatric Pneumonia: Pathogenesis and clinical findings Authors: Jasmine Nguyen Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Annie Pham Eric Leung* * MD at time of publication Immunological: unvaccinated, primary immunocompromise, pre-existing illness (e.g. HIV, measles), malnutrition Environmental: smoke, air pollution, mold, crowded housing Recent Hospitalization: length of stay, recent antibiotics, mechanical ventilation Physiological: neonates, low-birth weight, underlying lung disease (ciliary dysfunction, asthma, cystic fibrosis, bronchiectasis) Host is more susceptible to infection Exposure to pathogen: inhalation, hematogenous, direct, aspiration Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to infection/proliferation of microbial pathogens at the alveolar level Notes: • Additional findings in pediatric pneumonia may include increased irritability, nausea/vomiting, diarrhea, otitis, and headache • Viral pathogens most common in children <2yrs; bacterial pathogens most common in children >2yrs Local inflammatory response: epithelial cells release cytokines in response to infection, which recruit neutrophils and plasma proteins to site of infection ↑ Vascular permeability causes accumulation of plasma exudate, cellular debris, serous fluid, fibrin, or bacteria in the airway spaces Systemic inflammatory response: Cytokine release (eg. TNF, IL-1) ↑ respiratory drive Airway irritation as cilia are unable to efficiently clear fluid buildup Crackles, ↓ breath sounds Fluid, protein, or inflammatory cells leak into pleural space Pleural effusion Pulmonary edema Fluid buildup in interstitial spaces increases gas diffusion distance Fluid buildup in the alveoli decreases available surface area for gas diffusion ↓ efficiency of gas exchange Bacteria invade into the bloodstream (if bacterial pneumonia) Sepsis Hypoxemia Circulating cytokines induce prostaglandin synthesis, which raise the thermoregulatory set-point of the hypothalamus paradoxical abdominal breathing, subcostal/suprasternal indrawing) Fever Cough Fluid accumulation in the pleural space prevents full lung expansion, resulting in ↓ lung volumes Tachypnea ↑ Work of breathing (tracheal tug, Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Month Day, Year on www.thecalgaryguide.com Pediatric Pneumonia: Pathogenesis and clinical findings Immunological: immunization status, immune compromise Environmental: second-hand smoke, air pollution Hospitalization: length of stay, recent antibiotics, mechanical ventilation Neonates, immunocompromise, underlying lung disease (ciliary dysfunction, Cystic Fibrosis, bronchiectasis) Authors: Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Eric Leung* * MD at time of publication Additional findings in pediatric pneumonia may include nausea, otitis, headache Viral pathogens most common in children <2yrs; bacterial pathogens most common in children >2yrs Interstitial pattern: suspect Mycoplasma pneumoniae, Influenza A + B, Parainfluenza Lobar pattern: suspect S. pneumonia, H. influenzae, Moraxella, S. aureus Systemic inflammatory response: Cytokine release (eg. TNF, IL-1) Exposure to pathogen: inhalation, hematogenous, direct, aspiration Susceptible host and/or virulent pathogen Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to proliferation of microbial pathogens at the alveolar level Notes: • • • • Local inflammatory response: neutrophils recruited to site of infection (LOBAR or INTERSTITIAL PATTERN, depending on pathogen) by epithelial cytokine release Irritation of contiguous structures and/or referred pain (mechanism unclear) Acute abdominal pain Cough Accumulation of plasma exudate (from capillary leakage at sites of inflammation), cell-debris, serous fluid, bacteria, fibrin ↑ respiratory drive Disruption of hypothalamic thermoregulation Fever/chills Irritation of airways and failure of ciliary clearance to keep up with fluid buildup Crackles, ↓ breath sounds Fluid buildup in spaces between alveoli (INTERSTITIAL PATTERN) Interstitial opacity on CXR Fluid buildup in alveoli (LOBAR PATTERN) ↓ efficiency of gas exchange (↑ diffusion distance in INTERSTITIAL, ↓ surface area in LOBAR) Hypoxemia Tachypnea Lobar consolidation on CXR Respiratory accessory muscle use (chest indrawing, paradoxical breathing, muscle retractions) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 28, 2018 on www.thecalgaryguide.com gin

Transient Tachypnea of the Newborn

Transient Tachypnea of the Newborn: Pathogenesis and clinical findings Cesarean delivery without labour Author: Tanis Orsetti Reviewers: Annie Pham Michelle J. Chen Dr. Jean Mah* * MD at time of publication Smoking during pregnancy Uncontrolled maternal asthma Uncontrolled maternal diabetes Dilution of surfactant ↑ Surface tension in alveoli ↓ Expansion/contraction of lungs (↓ pulmonary compliance) ↑ Work of breathing Maternal factors leading to impaired fetal lung development Lack of labour-induced hormone changes (i.e. cortisol, catecholamines) ↓ Alveolar fluid reabsorption through epithelial aquaporin channels ↑ Alveolar fluid in lungs Disruption of laminar flow in airways ↑ Resistance to airflow ↑ Lung expansion to compensate Limited surface area for gas exchange in the alveoli ↓ Ventilation Fluid buildup in the major bronchi in the perihilar region Prominent perihilar streaking on chest x-ray ↑ Intrathoracic pressure pushes the diaphragm down Blunting of costophrenic angle on chest x-ray Hyperinflation of lungs Expanded lung fields on chest x-ray ↑ Deoxygenated hemoglobin in the bloodstream Blue/purple discoloration of the skin particularly around the lips & fingers (cyanosis) ↓ Oxygenated hemoglobin in the bloodstream ↑ Nasal passage size allows for more air to enter the lungs with each breath Nasal flaring Scalene/intercostal/ sternocleidomastoid /abdominal muscle activation to assist with breathing Accessory muscle use ↓Oxygen saturation (SpO2) Neonate takes more breaths to compensate for limited oxygenation Respiratory rate > 60 breaths/minute (tachypnea) Transient Tachypnea of the Newborn Temporary respiratory condition in newborns characterized by impaired lung function and rapid breathing Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 4, 2024 on www.thecalgaryguide.com

Pulsus Paradoxus

Pulsus Paradoxus: Pathogenesis and Clinical Findings Inspiration: Diaphragm and intercostal muscles contract Author: Yan Yu, Victória Silva, Layla Al-Yasiri Reviewers: Sean Spence, Laura Craig, Juliette Hall, Raafi Ali, George Tadros. Shahab Marzoughi Nanette Alvarez* * MD at time of publication Vascular pathology (rare) Thoracic cavity expands Lungs expand and intrathoracic pressure ↓ Physiologic: ↑ Venous return to right (R) heart ↑ R heart preload (volume of blood inside the ventricle right before it contracts) ↑ Blood pools in the right side of the heart Obstructive lung diseases (e.g., COPD**, asthma**) Hyperinflated lungs ↑ Stretching of pulmonary vessels at rest On inspiration, ↑↑ stretching of pulmonary vessels ↑↑ Blood pools within pulmonary vasculature ↓↓ Flow to L heart Pathologic: Constrictive pathologies (e.g., cardiac tamponade**, constrictive pericarditis**) Decreased pericardial compliance Constriction of ventricles On inspiration, ↑ venous return to R heart (normal) R ventricle unable to fully expand due to ↓ compliance Septum bows into L ventricle L ventricle unable to fully expand ↓↓ Filling of L heart ↓↓ L ventricular end diastolic volume ↓↓ L heart stroke volume ↓↓ Cardiac output Pulsus Paradoxus Exaggerated ↓in systolic BP on inspiration (>10mmHg) Air flows into the lungs Pulmonary vessels are physically stretched/pulled ↑ Blood pools in pulmonary vessels ↓ Return of blood to left (L) heart ↓ L heart preload ↓ L heart stroke volume ↓ Cardiac output Obstruction of superior or inferior vena cava (e.g., clot) ↓↓ Venous return to R heart at rest ↓↓ Right heart filling ↓↓ Blood flow to pulmonary arteries Pulmonary embolism** Clot occludes pulmonary arteries/ arterioles ↓↓ Flow to pulmonary veins At rest, ↓↓ flow to L heart On inspiration, ↓↓↓ flow to L heart ↓ Systolic blood pressure (BP) of < 10mmHg on inspiration BP = cardiac output x systemic vascular resistance **See corresponding Calgary Guide slides Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 21, 2013; updated Dec 3, 2024 on www.thecalgaryguide.com