SEARCH RESULTS FOR: pleural effusion

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Authors: Lauren D. Lee, Harry C. Liu* Reviewers: Mehul Gupta, Brian Rankin, Julia Chai, Stephen Williams Yan Yu* Laurie Parsons* *MD at time of publication Pathogenesis and clinical findings Genetic susceptibility Certain HLAs (e.g., HLA-B*58:01, HLA-B*57:01, and HLA-A*31:01) HLA alleles encode for MHC structure and may influence how specific drugs/drug metabolites interact with T cell receptors and MHC proteins on antigen-presenting cells Exposure to offending drug E.g., Aromatic anticonvulsants (lamotrigine, carbamazepine, and phenytoin), allopurinol, and sulfonamides Drug-specific CD4+ and CD8+ T cells produce tumor necrosis factor-alpha and interferon gamma ↑ activated T-cells 2-6 weeks after drug exposure Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Latent Viral infection Latent viruses (HHV-6, HHV- 7, CMV, and EBV) concealed in regulatory T-cells Reactivation of latent viruses may be contributory or secondary to T cell activation by drugs Eosinophilia +/- atypical lymphocytes T helper type 2 cells recruit and activate eosinophils by releasing cytokines Activated leukocytes create a humoral immune and allergic response Dysfunction of regulatory T cells, resulting in failure to control unwanted immune responses against “self” Autoimmune processes with single- or multi-organ involvement CMV- Cytomegalovirus EBV- Epstein-Barr Virus HHV- Human Herpesvirus HLA- Human Leukocyte Antigens MHC – Major Histo- compatibility Complex Endocrine system mechanism of dysfunction unclear but may be linked to autoreactive T cells Autoimmune Type 1 thyroiditis diabetes Lymphadenopathy Fever Facial edema Liver lobular inflammation, dispersed foci of necrotic hepatocytes, granulomatous infiltrates consisting of eosinophils Hepatitis Kidney Interstitial edema and infiltrates of lymphocytes, histiocytes, eosinophils, and plasma cells Acute interstitial nephritis Lung increased pulmonary infiltrate and edema Morbilliform Skin Eruption Spongiosis Epidermal layer Dermal- Epidermal Junction Dermal layer Interface dermatitis Skin eruption (morbilliform to diffuse erythema with follicular accentuation) Interstitial pneumonitis Pleural effusion Eosinophilic infiltration Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 19, 2021 on www.thecalgaryguide.com

complications-of-pulmonary-embolism

Complications of Pulmonary Embolism Authors: Sravya Kakumanu, Dean Percy, Yan Yu Reviewers: Tristan Jones, Ciara Hanly, Jieling Ma (马杰羚), Ben Campbell, Dr. Man-Chiu Poon*, Dr. Lynn Savoie*, Dr. Tara Lohmann * * MD at time of publication IF CHRONIC: Unresolved clot after 2 years leading to fibrosis of pulmonary vasculature Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (<5% of PE cases) Venous Stasis Hypercoagulable state Vessel Injury Virchow’s Triad (*See Suspected Deep Vein Thrombosis slide) Deep Vein Thrombosis Clot migrates from deep limb veins à femoral àiliac veins ACUTE/MASSIVE PE: Clot obstructs pulmonary arterial or arteriolar flow Lung infarction (tissue death) from ischemia Inflammatory cells migrate to site and release cytokines ↑ Permeability of blood vessels Permeability-driven (exudate) fluid leakage into pleural space Pleural Effusion Clot migratesàinferior vena cava àright atrium (RA) of heartà right ventricle (RV) à gets lodged in pulmonary arteries/arterioles Pulmonary Embolism (PE) ↑ RV afterload ↑ RV pressure and expansion Well-ventilated (V) areas of lung do not receive adequate blood supply (Q) V/Q Mismatch Leftward shift of ventricular septum ↓ Left ventricle filling in diastole ↓ Cardiac output Obstructive Shock Impaired heart filling Pulseless Electrical Activity (ECG activity in absence of palpable pulse) Back up of pressure in systemic venous system ↑ Pressure in capillaries draining parietal pleura Pressure-driven (transudate) fluid leakage into pleural space For signs and symptoms, see the Obstructive Shock slide For signs and symptoms refer to CTEPH slide Chronic ↑ RV afterload ↑ Stretching of myocytes causing RV hypertrophy and dilation ↓ RV ejection fraction Right Heart Failure “Cor Pulmonale” For signs and symptoms, see the Right Heart Failure slide Failure to oxygenate blood Type I Respiratory Failure Hypoxemic: patient has ↓ blood [O2] IF MASSIVE PE (less common): ↑ Alveolar dead space Failure to ventilate Type II Respiratory Failure Hypercapnic: patient has ↑ blood [CO2] Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 7, 2012, updated Mar 31, 2022 on www.thecalgaryguide.com

pleural-effusions-pathogenesis-and-anterior-posterior-chest-x-ray-findings

Pleural Effusions: Pathogenesis and Anterior-Posterior Chest X-Ray Findings Decubitus chest x-ray view causes fluid to accumulate on ipsilateral side. (Most sensitive view for small effusions) Excess fluid accumulation within pleural space that is gravity- dependent/free- flowing Large accumulation of fluid pressing against lung tissue and mediastinum Fluid layering (i.e. opacification) between lung and chest wall Author: Sravya Kakumanu Reviewers: Reshma Sirajee, Tara Shannon *Stephanie Nguyen, *Shelley Spaner * MD at time of publication Transudative pleural effusion *See Pathogenesis and Clinical Findings of Transudative Pleural Effusions slide Exudative pleural effusion *See Pathogenesis and Clinical Findings of Exudative Pleural Effusions slide Fluid accumulation at bottom of pleural space in anterior- posterior chest x- ray Lung atelectasis (lung collapse) Fluid is denser than air and appears white on x-ray ↓ Pressure and occupied space in thoracic cavity Meniscus sign (concave line above opacification) Opacification of affected pleural space Blunting of costophrenic angles Diaphragmatic silhouette sign (sharp diaphragm edge obscured by fluid) Mediastinal shift towards atelectic lung Contralateral mediastinal shift (when no lung atelectasis) Contralateral tracheal deviation Pleural infections ↑ Inflammation at infection site à↑ permeability of parietal pleura endothelium Bacterial invasion into pleural space from pulmonary parenchyma ↑ Migration of neutrophils and release of inflammatory cytokines in pleural space Inflammation ↑ activation of coagulation cascade and ↓ fibrinolytic activity ↑ Deposition of fibrin clots/membranes within pleural space creating septations Loculated pleural effusion/empyema (fluid stuck within septations within the pleural space) Opacification does not follow gravity Effusion does not move in decubitus view Pleural thickening (whitening of lung perimeter from fibrin deposition - more visible on CT scan) More rounded margins with chest wall/fissures Note: ~175-500mL of fluid may need to accumulate before being visible on an Anterior-Posterior Chest X-Ray Image credit: https://radiopaedia.org/cases/pleural-effusion-7 Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 22, 2022 on www.thecalgaryguide.com

exudative-pleural-effusions-pathogenesis-and-lab-findings

Exudative Pleural Effusions: Pathogenesis and Lab Findings Authors: Sravya Kakumanu Reviewers: Ben Campbell *Tara Lohmann * MD at time of publication Chylothorax Damage to thoracic duct Leakage of lymphatic fluid into pleural space Pulmonary embolism Clot obstructs blood flow to lung Infarcted lung tissue Lung infection (e.g. pneumonia, tuberculosis) Lung infection signals inflammatory response Systemic Lupus Rheumatoid Erythematosus (SLE) arthritis (RA) Autoimmune antibodies localize to pleura Pleural tumors (primary or secondary from metastatic cancer) Inflammatory cells migrate to affected site and release cytokines ↑ Permeability of pleural capillaries ↑ Fluid leakage across capillaries Exudative Pleural Effusion Cancer invades lymphatic drainage of pleural space (PS) ↓ Drainage of pleural fluid (PF) from pleural space If infectious etiology Tumor invasion = inflammatory response See Pleural Effusions: X-ray Findings and Physical Exam Findings of Lung Diseases slides ↑ Permeable pleural capillaries allow ↑ protein and cell leakage into pleural space If pleural tumour: Release of cancer cells into pleural space Cancer cells on PF cytology 60-75% sensitive for malignancy If rheumatoid arthritis: Release of auto-antibodies into pleural space Auto-antibodies initiate inflammatory response in pleural space ↑ Inflammatory cells have ↑ glucose metabolism in pleural space Sterile PF with mildly elevated white blood cells, normal pH, normal glucose ↑ Inflammation at infection site damages endothelium of pleura Pleural Infection Stage I: Simple Parapneumonic Effusion ↑ Inflammatory cells and bacterial cells in pleural space have ↑ glucose metabolism in pleural space Bacterial invasion from infected parenchymaà pleural space < 40mg/dL glucose in PF ↑ Activation of coagulation cascade and ↓ fibrinolytic activity ↑ Deposition of fibrin clots/membranes within pleural space creates loculated effusion (compartmentalized effusion due to septations in pleural space) ↑ Production of lactate dehydrogenase (LDH) (LDH maintains NAD+ supply during ↑ glucose metabolism) ↑ CO2 production pH of PF < 7.20 ↑ CO2 production pH of PF < 7.20 < 3.3mmol/L glucose in PF Pleural Infection Stage II: Complicated Parapneumonic Effusion Loculated effusion OR bacteria present OR ↓ pH + ↓ glucose ↑ Fibroblast proliferation creates thickened pleura ↑ Pus in pleural space Pleural Infection Stage III/Empyema: Loculated effusion and pus in pleural space PF/serum protein ratio ≥ 0.5 PF/serum LDH ratio ≥ 0.6 Light’s Criteria: Any criteria can be met to be an exudative pleural effusion PF LDH ≥ 2/3 upper limit of normal Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 9, 2022 on www.thecalgaryguide.com

transudative-pleural-effusions-pathogenesis-and-lab-findings

Transudative Pleural Effusions: Pathogenesis and Lab Findings Authors: Sravya Kakumanu Reviewers: Ben Campbell, *Yan Yu, *Tara Lohmann * MD at time of publication Cirrhosis Cirrhotic liver ↑ pressure in hepatic veins Ascites: Leakage of fluid from hepatic capillariesàperitoneal cavity Negative intrathoracic pressure on inspiration and ↑ intra-abdominal pressureàfluid leakage from abdominal space into pleural space across diaphragmatic defects L heart failure (most common) Left ventricle unable to pump sufficient blood into systemic circulation Backup of blood in pulmonary veins ↑ Hydrostatic pressure in pulmonary veins Pulmonary embolism R ventricle unable to pump blood due to clot in pulmonary artery Backup of blood in systemic veins ↑ Hydrostatic pressure in veins draining parietal pleura Nephrotic syndrome Damaged glomerulus has ↑ permeability to plasma proteins in blood ↑ Loss of proteins through urine ↓ Oncotic pressure in systemic capillaries (including within parietal pleura) Normally, permeable pleural capillaries do not allow protein leakage into the pleural space ↑ Interstitial fluid leakage across intact pulmonary or pleural capillaries into pleural space Transudative Pleural Effusion Absence of bacteria and inflammatory cells in pleural space No increase in cellular activity in pleural space Normal levels of glucose metabolism in pleural space = low lactate dehydrogenase (LDH) (LDH increases when glucose metabolism, particularly glycolysis, increases to maintain supply of NAD+) Large accumulation of pleural fluid (PF) pressing against lung tissue and mediastinum Lung atelectasis (lung collapse) See Pleural Effusions: X- ray Findings and Physical Exam Findings of Lung Diseases slides PF/serum protein ratio < 0.5 PF LDH < 2/3 upper limit of normal Light’s Criteria: All three criteria must be met to be a transudative pleural effusion PF/serum LDH ratio < 0.6 See Hypoxemia: Pathogenesis and Clinical Findings slide for pathophysiology and signs of hypoxemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 9, 2022 on www.thecalgaryguide.com

ventilator-associated-pneumonia-pathogenesis-and-clinical-findings

Ventilator-Associated Pneumonia: Pathogenesis and Clinical Findings Respiratory failure or inability Risk factors: e.g. immunocompromised, poor swallowing to maintain airway ability, weakened respiratory muscles, chronic disease Insertion of endotracheal tube (ETT) for invasive mechanical ventilation to maintain respiration Paralytics and sedatives lead to inhibition of cough reflex Damage to cilia on epithelial cells of trachea during insertion of ETT ↓ Mucociliary clearance Insertion of nasogastric (NG) tube for feeding Constant opening by NG tube ↓ esophageal sphincter function Introduction of oropharyngeal microbes during intubation Severe acute illness impairs phagocytosis and dysregulates T- cells (mechanism unclear) Medications, chronic disease, or severe acute illness can weaken immune system Desensitization of pharyngoglottal adduction reflex (PAR) (PAR normally induces closure of epiglottis to protect the airway when swallowing) ↑ Reflux of gastric contents Accumulation of subglottic secretions containing microbes Microbial colonization on inside of ETT Development of biofilm on inside of ETT Dislodgement of biofilm into lower airway ↑ Age or chronic disease can weaken respiratory function Micro aspirations of subglottic and gastric contents Impaired mechanisms to remove microbes from airway Positive pressure pushes microbes down Fever/rigors ↑ White blood cell count Introduction of pathogenic microbes to airway Susceptible patient (not required for infection) Septic shock See Distributive Shock slide Sepsis Microbes descend airway and infect lungs Ventilator-Associated Pneumonia (VAP) Occurs > 48-72 hours after intubation ↑ Inflammatory response at infection site promoting immune cell extravasation and cytokine release Cytokine signalling ↑ permeability of capillaries leading to ↑ fluid leakage into interstitium and alveoli Authors: Sravya Kakumanu Reviewers: Ben Campbell *Tara Lohmann *Bryan Yipp * MD at time of publication Acute respiratory distress syndrome See ARDS pathogenesis slide Pleural effusion Lung consolidation on chest x-ray (CXR) ↑ Sputum production to clear fluid on CXR (Note: In patients with Acute Respiratory Distress Syndrome (ARDS), look for VAP consolidation in non- within alveoli/airways (may be Positive microbial culture from sputum dependent/upper regions of the lung where ARDS consolidation would be unexpected to extend to) purulent in worse infections) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 2, 2022 on www.thecalgaryguide.com

chest-exam-findings-of-lung-pleural-diseases

Chest Exam Findings of Lung & Pleural Diseases Note: Please see slides on pathogenesis of Transudative and Exudative Pleural Effusions, Primary and Tension Pneumothorax, Adult Pneumonia, Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, and Kidney Disease Authors: Sravya Kakumanu Reviewers: Ben Campbell, *Tara Lohmann, *Yan Yu * MD at time of publication Interstitial Lung Disease Pneumothorax Rupture of visceral pleura Build-up of air within pleural space Pleural Effusion Atelectasis Consolidation ↑ Hydrostatic pressure pushes fluid into pleural space ↑ Capillary permeability = fluid leaks into pleural space ↓ Oncotic pressure = fluid moves into pleural space Bronchus obstructed Scarring/infiltration of lung tissue Surfactant dysfunction (ex. ARDS) Loss of contact between visceral and parietal pleura (ex. effusion, pneumothorax) Parenchymal compression (ex. loculated effusion, mass) ↑ Hydrostatic pressure pushing fluid into alveoli (ex. cardiogenic pulmonary edema) ↑ Capillary permeability allowing fluid to move into alveoli (ex. pneumonia) Idiopathic Connective tissue diseases Sarcoidosis, Amyloidosis Chronic medical diseases (ex. COPD, heart failure, kidney disease, etc) Occupational or environmental exposures (ex. silicosis, organic dusts, metals, gases, aerosols, etc) Accumulation of fluid in pleural space Collapse of alveoli Accumulation of fluid within alveoli Pulmonary fibrosis (scarring of alveoli bilaterally) Breath Sounds Lung unable to inflate fully Fluid in pleural space Collapsed lung unable to inflate Airspace filled with fluid and unable to fill with air dampens sound ↓ Breath sounds ipsilaterally Scarred alveoli unable to expand to fill with air ↓ Breath sounds bilaterally (may not be noticeable) Chest Rising on Inspiration Chest cavity filled with air, but lung Lung unable to inflate fully Scarred alveoli unable to expand to fill with air unable to inflate fully ↑ Chest size, ↓ Rising ipsilaterally ↓ Chest rising ipsilaterally ↓ Chest rising bilaterally (may not be noticeable) Percussion Sound resonates through air in pleural space Ipsilateral hyperresonance on percussion Sound unable to resonate through pleural fluid Sound unable to resonate through compacted lung tissue Ipsilateral dullness on percussion Sound unable to resonate through fluid-filled alveoli Diffuse scarring of alveoli No notable changes on percussion Tracheal Deviation Air pushes trachea Fluid pushes trachea ↓ Pressure within chest wall pulls trachea No pushing or pulling of trachea Contralateral tracheal deviation Ipsilateral tracheal deviation No tracheal deviation Adventitious Lung Sounds Alveoli not impacted (i.e. not collapsed or fluid-filled) Sudden opening of collapsed alveoli filling with air Fine inspiratory crackles Air movement through fluid-filled alveoli Coarse inspiratory crackles Fluid-filled alveoli can’t dampen breath sounds from larger central airways Bronchial breath sounds all over consolidated area (harsh, ↑ pitch with expiratory phase > inspiratory; only normal when heard centrally over trachea + bronchi) Scarred inelastic alveoli suddenly open on inspiration Fine inspiratory crackles No crackles No abnormal breath sounds Severe pneumothorax or effusion pushing against lung parenchyma Other sounds Amplification of patient voice through fluid-filled alveoli Tactile fremitus (↑ vibrations felt by hand placed on chest wall when patient speaks) *Whispers also sound louder on auscultation Fluid-filled alveoli only allow certain sound frequencies to be audible Egophony (“E” sounds like “A” on auscultation) Legend: Pathophysiology Mechanism Physical Exam Findings Complications Published October 9, 2022 on www.thecalgaryguide.com

Acute Pulmonary Embolism on CTPA

Acute Pulmonary Embolism: Computed Tomography Pulmonary Angiogram (CTPA/CTPE) Virchow’s Triad: Hypercoagulability, venous stasis, vascular endothelial injury Image Source: European Society of Radiology Image: Polo mint sign on axial CTPA. Image Source: Journal of The Indian Academy of Echocardiography Image: Railway sign on axial CTPA. Image Source: Moore et al. 2018 Image: Pleural effusion and pulmonary infarction on axial CTPA. Authors: Aly Valji, Nameerah Wajahat, Omer Mansoor Reviewers: Reshma Sirajee, Sravya Kakumanu, Victória Silva, Mao Ding Vincent Dinculescu* *MD at time of publication Deep Vein Thrombosis (DVT): Majority of pulmonary embolism (PE) arise from DVT: Clot travels via inferior vena cava → right atrium → right ventricle → pulmonary arteries/arterioles See “Virchow’s Triad and Deep Vein Thrombosis” for full pathogenesis Polo Mint Sign Clot visualized in short axis, Filling defect entirely surrounded by IV contrast creating a circle (polo mint) Railway Sign Clot visualized in long axis, Filling defect surrounded by IV contrast on two sides creating the appearance of a railway track Type I or II Ventilation/Perfusion respiratory failure (V/Q) mismatch Reverse Halo Sign Pulmonary infarction leads to wedge shaped opacity with a rim of consolidation (black arrows) surrounding “ground glass” (red arrows) Pulmonary Embolism: Clot in pulmonary arteries See “Signs and Symptoms of Pulmonary Embolism” for full presentation Saddle Embolus: Large clot over the pulmonary trunk bifurcation Lobar/Segmental/Subsegmental Embolus: Clot within the pulmonary arteries of the lungs Blockage of pulmonary arteries = ↓ Blood flow, ↑ Right heart pressure ↓ Gas exchange b/w lungs and blood Ischemia of lung tissue → infarction → inflammation of dead tissue ↑ Right heart filling and expansion Left heart filling impaired ↓ Cardiac output due to ↓ Left heart filling “Massive PE” = sustained systemic hypotension or bradycardia (SBP < 90 mmhg, HR < 40 bpm) Saddle Embolus Filling defect due to blockage of bifurcation. IV contrast appears white, and embolus appears grey Pleural Effusion Exudative Pleural Effusion Tissue inflammation → ↑ blood vessel permeability = Leakage of fluid into pleural space Transudative Pleural Effusion ↑ Hydrostatic pressure from right heart congestion = Pushes fluid into pleural space Image Source: Samra et al. 2017 Image: Saddle embolus on axial CTPA. Legend: Pathophysiology Mechanism Radiographic Findings Complications Published March 28, 2023 on www.thecalgaryguide.com

Acute Respiratory Distress Syndrome ARDS CXR findings

Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Author: Iffat Naeem Direct or indirect lung injury causing acute respiratory distress syndrome (see Acute Respiratory Distress Syndrome slide for pathogenesis and clinical findings) Activation of dysregulated inflammatory cascade Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Bilateral infiltrate that can present in all regions of lung Air bronchograms Silhouette sign Reviewers: Victória Silva, Mao Ding Tara Lohmann* *MD at the time of publication Edema not due to a cardiogenic cause Damage to alveolar epithelium Necrosis of epithelial cells Erosion of alveolar basement membrane ↑ Alveolar epithelium permeability Damage to lung capillary endothelium Release of inflammatory cytokines Neutrophils migrate into alveoli Fluid-filled alveoli show as white/grey opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and widespread damage to alveoli and interstitium that show as white/grey opacities ↑ Capillary endothelium permeability Alveolar edema Degradation of alveolar- capillary barrier Proliferative phase Alveolar epithelium attempts to recover Chronic phase Can either resolve or progress to fibrotic thickening and scaring of alveoli ↑ Leakage of fluid from capillaries into alveoli and lung interstitium Pulmonary fibrosis (scarring) ‘White lung’ appearance Image credit: Radiopaedia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Direct or indirect lung injury causing acute Author: Iffat Naeem Reviewers: Victória Silva respiratory distress syndrome* Activation of dysregulated inflammatory cascade Bilateral infiltrate that show as white/grey can present in Damage to alveolar epithelium Necrosis of epithelial cells Erosion of alveolar basement membrane ↑ Alveolar epithelium permeability Damage to lung capillary endothelium Fluid-filled alveoli opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and all regions of lung Release of inflammatory cytokines Neutrophils migrate into alveoli Alveolar edema Air bronchograms ↑ Capillary endothelium permeability Degradation of alveolar-capillary barrier Proliferative phase Alveolar epithelium attempts to recover Chronic phase Can either resolve or progress to fibrotic thickening and scaring of alveoli ↑ Leakage of fluid from capillaries into alveoli and lung interstitium Silhouette Sign widespread Pulmonary damage to alveoli ‘White lung’ appearance fibrosis (scarring) and interstitium that show as white/grey opacities *See corresponding Calgary Guide slides for more details Image credit: Radiopaedia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Direct or indirect lung injury causing acute respiratory Author: Iffat Naeem Reviewers: Victória Silva distress syndrome* Activation of dysregulated inflammatory cascade Bilateral infiltrate that show as white/grey can present in Damage to alveolar epithelium Necrosis of epithelial cells Denudation of alveolar basement membrane ↑ epithelium permeability Degradation of alveolar-capillary barrier Alveolar epithelium attempts to recover through (proliferative phase) Damage to lung capillary endothelium Fluid-filled alveoli opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and all regions of lung Air bronchograms Release of proinflamm atory cytokines Neutrophil migration into airspace Alveolar Edema ↑ capillary endothelium permeability ↑ leakage of fluid from vasculature into airspace and lung interstitium Can either resolve or progress to fibrotic Silhouette Sign widespread Pulmonary damage to alveoli ‘White lung’ appearance thickening and scaring of Fibrosis alveoli (chronic phase) and interstitium that show as white/grey opacities Image credit: Radiopaedia *See corresponding Calgary Guide slides for more details Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Author: Iffat Naeem Reviewers: Victória Silva Acute Lung Injury (see ‘ARDS: Pathogenesis and Clinical findings’ slide) causing impaired oxygenation Lung injury not due to cardiogenic cause (see ‘ARDS: Pathogenesis and Clinical findings’ slide) Alveolar endothelium damage promotes inflammatory marker release Exudative phase (1-6 days): neutrophils adhere to damaged endothelium and release pro- inflammatory mediators Accumulation of intra-alveolar fluid that is rich in neutrophils, macrophages, and red blood cells Proliferative phase (7-14 days): proliferation of alveolar epithelial Fibroblasts deposit collagen tissue in alveolar walls and spaces Can either resolve or progress to fibrotic thickening and scaring Alveolar Edema Fluid-filled alveoli show as white/grey opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli Bilateral infiltrate present in all regions Air bronchograms results in lack of Silhouette Sign differentiation of heart borders Diffuse alveolar damage ‘White lung’ appearance Image credit: Radiopaedia *See corresponding Calgary Guide slides for more details Legend: (chronic phase) Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Lung injury not due to a cardiogenic cause Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings

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