SEARCH RESULTS FOR: pulmonary embolism

Signs and Symptoms of Pulmonary Embolism

Signs and Symptoms of Pulmonary Embolism Authors: Dean Percy Yan Yu Reviewers: Tristan Jones Julia Heighton Man-Chiu Poon* Lynn Savoie* * MD at time of publication Notes • One of the most under- diagnosed conditions, typically asymptomatic, with tachycardia often being the only sign • Consider DVT and PE as one disease: if PE is suspected, look for signs and symptoms of DVT • Absence of DVT does not rule out PE Virchow’s Triad: hypercoagulable state, venous stasis, vessel injury (*see Suspected DVT) Deep Vein Thrombosis – popliteal, femoral, iliac veins Clot migrates to IVCàright atrium of heartàright ventricleàpulmonary vasculature Large clots (saddle emboli) are lodged in pulmonary arteries Small clots are lodged in pulmonary arterioles Saddle embolus (pulmonary artery obstruction) Back-up of blood into right heart Right heart strain ↓ CO2 delivery to the lungs for exhalation Less CO2 exhaled, CO2 builds up in the blood, triggers medullary chemoreceptors to ↑ respiratory rate Well-ventilated (V) areas of lung do not receive adequate blood supply (Q); vice versa V/Q mismatch On V/Q scan Signals brain to ↑ heart rate Ischemic tissue becomes inflamed and adheres to pleura Pleural friction rub Sandpaper-like sound heard on auscultation Pleuritic chest pain Focal, localized chest pain that occurs with each breath Clot ↓ pulmonary arterial/arteriolar blood flow ↓ delivery of deoxygenated blood to alveoli for oxygenation Low O2 in blood (↓ O2 saturation) is detected by aortic/carotid chemoreceptors Signals brain to ↑ respiratory rate If circulation to lung periphery is cut off, sub-pleural lung tissue can become ischemic and infarct Irritation of somatic sensory nerve endings on the parietal pleural membrane Pain stimulates adrenergic response Tachycardia Dyspnea/shortness of breath (SOB) Most sensitive indicator of PE, but not very specific Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

virchows-triad-and-deep-vein-thrombosis-dvt

Suspected Deep Vein Thrombosis (DVT): Authors: Dean Percy Yan Yu Reviewers: Tristan Jones Ryan Brenneis Man-Chiu Poon* Maitreyi Raman* * MD at time of publication Pregnancy, Oral Contraceptives (OCP) Pathogenesis and Complications Platelet Activation Increased clot formation Hypercoagulable State ↑ ability for the blood to coagulate upon stimulation Inherited Disorders Congenital defect in coagulation (ie. Factor V Leiden, Factor II mutation, Protein S/C deficiency) ↑ blood clotting ability Estrogen promotes hypercoagulability, especially in presence of other risk factors Notes: • Venous thrombus causes pulmonary embolism, arterial thrombus causes stroke • Previous DVT is risk factor for current DVT Trauma/Surgery Malignancy Abnormal release of coagulation-promoting cytokines Systemic injuryà activation of coagulation cascade Hypertension Bacteria Artificial Valve Physically damages blood vessel walls Adhere/invade vessel wall Abnormal surface Vessel Injury Exposes tissue factor on damaged cells and subendothelium for vWF binding Virchow’s Triad Venous Stasis Low blood flow rate over site of vessel injury, concentrating blood clotting factors at that site Fat contains more aromatase, converts more androgens to estrogen Sedentary lifestyle, poor venous return Obesity Clot formation typically occurs in leg veins Deep, large veins allow for blood pooling (stasis, hypercoagulability) Venous return from legs often against gravity (stasis) Valves in leg veins prone to backflow (stasis) ↓ muscle motion = ↓ venous blood flow Fracture, immobilization, bedrest, long vehicle/airplane ride Destruction of vein valve by clot Venous Insufficiency Clot prevents blood from returning to heart. Blood accumulating in the leg results in unilateral leg edema and venous inflammation (redness, warmth, tenderness) 1. 2. 3. Clot embolizes to the lungs Thromboembolus -*Pulmonary embolism (acute life threatening complication) -Chronic thromboembolic pulmonary hypertension Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published September 1, 2019 on thecalgaryguide.com

Congenital-Thrombophilia

Congenital Thrombophilia: Pathogenesis and Complications Authors: Brian Yu Chieh Cheng, Yan Yu* Reviewers: Mehul Gupta, Hannah Yaphe, Tejeswin (Jovey) Sharma, Man-Chiu Poon* *MD at time of publication Group I Hereditary deficiencies of coagulation inhibitors Group II Hereditary disorders with ↑ levels or function of coagulation factors Antithrombin (AT) deficiency AT inhibits thrombin & activated coagulation e.g. factor X (FXa) Autosomal dominant mutation of the SERPINC1 gene causes ↓ production of AT ↓ AT concentrations allows thrombin & FXa to promote secondary hemostasis Protein C (PC) deficiency Protein S (PS) deficiency Factor V Leiden Autosomal dominant point mutation of the Factor V gene Single nucleotide substitution (G1691A) results in mutated form of FVa protein FVa becomes resistant to aPC & PS inactivation FVa is broken down at ↓ rate Prothrombin mutation Autosomal dominant point mutation of the Prothrombin gene Single nucleotide substitution (G20210A) of the gene’s 3’ untranslated region Accumulation of prothrombin mRNA & protein copies of prothrombin ↑ concentration of prothrombinà ↑ conversion to thrombin ↑ clotting factor quantity or function due to mutations intrinsic to these clotting factors Activated Protein C (aPC) & PS combine to inhibit activated clotting Factors V & VIII (FVa & FVIIIa) Autosomal dominant mutation of the PROC & or PROS1 gene ↓ production of PC and/or PS ↓ aPC & PS concentrationsà less breakdown of FVa & FVIIIa, ↑ blood’s clotting ability ↑ clotting factor function due to ↓ inhibition or breakdown of clotting factors Congenital Thrombophilia An inherited abnormality / imbalance of blood coagulation factors that increases the risk of thrombus formation ↑ generation of thrombin ↑ clotting tendency, especially in veins where blood flow is slower/prone to stasis (see Calgary Guide slide on Virchow’s Triad) Venous Thromboembolism Deep Vein Thrombosis Pulmonary Embolism Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 15, 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

overdiagnosis-in-medicine-causes-and-complications

Overdiagnosis in Medicine: Causes and Complications Expectation that negative experiences represent a symptom of pathology rather than a part normal human experience Profit-motivated industries (e.g pharmaceutical companies) ↑ The number of diagnosed individuals serves to ↑ profits by expanding consumer base for treatments Authors: Davis Maclean Reviewers: Ben Campbell Eddy Lang* *MD at time of publication Unintended consequences of disease screening programs Direct to consumer testing (e.g home medical genetics testing kits) Note: Misdiagnosis ≠ Overdiagnosis Misdiagnosis refers to making an incorrect diagnosis in a symptomatic patient. Defensive medical practices Increased testing to ‘rule out’ pathology and reduce legal liability ↑ Availability of diagnostic tests Technological advancements leading to ↑ sensitivity of diagnostic tests Common public perceptions of health and healthcare Public overestimation of benefit and underestimation of risk modern medical interventions Assumption that more medical information (e.g testing) results in better health ↑ Number of findings on diagnostic tests (e.g Imaging and lab work) Medicalization of normal life experiences Overdetection: Identification of an abnormality that would not have caused any symptoms or harm in the patient’s lifetime if left undiscovered (e.g detection of subsegmental pulmonary embolism) Overdefinition: Lowering thresholds for classification of diseases and what is considered abnormal without net benefit for those diagnosed (this includes people with symptoms but who are more likely to be harmed than benefit from a diagnosis) Overdiagnosis: making an accurate diagnosis in an patient where making the diagnosis does not produce a net benefit for the patient Overtreatment: treatment that occurs in absence of evidence for net benefit to the patient Treatment side effects ↓ Quality of life (e.g nausea and fatigue secondary to chemotherapy) Overtreatment and overutilization are common consequences of overdiagnosis, but can happen in the absence of overdiagnosis Overutilization: ↑ Use of health services and systems without evidence of net benefit ↑ Health system spending Unnecessary testing Testing-related complications (e.g infection of surgical biopsy site) ↑ Risk for other Illness (e.g ↑ risk of infection in the setting of immunotherapy) Indirect costs: (e.g time off work for medical appointment, travel costs) ↑ Individual costs Direct costs: paying for additional tests and treatment (e.g medications) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 30, 2022 on www.thecalgaryguide.com

postpartum-puerperal-fever-pathogenesis-and-complications

Postpartum (Puerperal) Fever: Pathogenesis and complications Author: Lindey Felske Reviewers: Brianna Ghali Ran (Marissa) Zhang Ingrid Kristensen* * MD at time of publication Breast Feeding Delayed gastric emptying in pregnancy ↑ Risk of aspiration during delivery Inhalation of gastric contents Chemical burn of the airways from gastric acid Tissue injury Chemokines released by alveolar cells recruit neutrophils Accumulation of neutrophils and plasma exudate in alveoli Aspiration Pneumonia Delivery (Vaginal or Cesarean Section) Tissue damage: Urinary tract catheterization Foreign body can: Introduce bacteria into bladder Provide a biofilm surface for bacterial adhesion Cause mucosal irritation Invasion of bacteria into urinary tract mucosa • • • • Perineal tear/episiotomy (perineal incision) Abdominal incision site Uterine damage Retained products of conception (RPOC) Bacteria enter open tissue Production of antimicrobial peptides and proinflammatory mediators in epidermis Cellulitis Necrosis of RPOC (good medium for bacterial growth) Post-operative pain Hypoventilation from shallow breathing Low volume in alveoli Alveolar collapse Endogenous cervicovaginal flora migrate into the uterine cavity Infiltration of bacteria into endometrium Endometrial TLR4 receptors recognize the endotoxin of Gram-negative bacteria Secretion of proinflammatory cytokines (IL-6, IL-8) and prostaglandin E(2) Activation of coagulation cascade Coagulation in areas of hemostasis (e.g., deep veins) Deep vein thrombosis Dislodged DVT travels to pulmonary arteries Pulmonary embolism • • • Skin openings in breasts (milk ducts +/- cracks) Bacteria from skin and/or saliva enter body Milk backup from blocked duct or poor breastfeeding technique Milk stasis provides environment for bacterial growth Upregulation of IFN- γ, and IL-12A cytokines in milk ducts Mastitis Collection of inflammatory exudate Breast abscess Cytokine expression and inflammatory cell infiltration Sloughing of urinary tract lining to reduce bacterial load Atelectasis Maternal fever (> 38.0°C) within 6 weeks of delivery Urinary tract infection Endometritis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 4, 2022 on www.thecalgaryguide.com The image part with relationship ID rId4 was not found in the file.

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

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

Pulmonary Embolism Pathogenesis and Clinical Findings

Pulmonary Embolism: Pathogenesis and Clinical Findings Virchow’s Triad Body attempts to break down clot Fibrinogen breakdown products in blood Lab: Positive D-Dimer D-Dimer only performed if clinical suspicion of PE low (Well’s Criteria) Authors: Mackenzie Gault Mao Ding Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* *MD at time of publication Hypercoagulable State Blood clot develops (commonly in deep veins of legs) Venous stasis = Deep Vein Thrombus (95% of PE) Vessel injury Ultrasound: Presence of Clot in Deep Vein of Leg Clot dislodges & migrates to inferior vena cava (IVC)àright atrium of heartàright ventricleàlodges in pulmonary arteries/arterioles Pulmonary Embolism (PE) Thromboembolic blockage of pulmonary vasculature ↓ perfusion to lung parenchyma Clot occludes pulmonary arteries/ arterioles ↑ dead space ventilation and V/Q mismatching Blood pumped from RV to pulmonary arteries cannot pass clot ↑ pulmonary and right ventricle (RV) pressure RV Strain ↑ RV workload, ↓ right coronary artery perfusion Computed Tomography- Pulmonary Angiogram (CTPA): Filling Defect (*see Radiology slide for CTPA findings) Echo: ↑ RV size + ↓ RV function ECG: S1Q3T3 Pattern (McGinn-White Sign: a large S wave in lead I, a Q wave in lead III and an inverted T wave in lead III together indicate acute right heart strain Lab: ↑ Brain natriuretic peptide (BNP) Chest Pain Tachycardia Dyspnea (shortness of breath) Pleuritic chest pain (worsens during breathing) Ischemia of lung tissue distal to clot X-Ray: usually normal, except Hampton’s Hump (↑ opacity in pleural based area), a rare but specific sign of PE) Air flow/ventilation to lungs unaffected VQ Scan (performed when CT contrast is contraindicated): Ventilation- perfusion ratio (V/Q) mismatch Chemoreceptors detect ↑ CO2 and ↓ O2 Signal brain to ↑ breathing rate Tachypnea (rapid breathing) ↓ Arterial O2 Lab: ↑Troponin BP: Hypotension Lab: ↑ Lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 7, 2018, updated Oct 15, 2023 on www.thecalgaryguide.com Pulmonary Embolism: Pathogenesis and Laboratory Findings Virchow’s Triad Authors: Mackenzie Gault Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson * * MD at time of publication Body attempts to break down clot Fibrinogen breakdown products in blood Positive D-Dimer ↓ perfusion to lung parenchyma Vessel injury = Deep Vein Thrombus (95% of PE) Ultrasound: Presence of Clot in Deep Vein of Leg Notes: Hypercoagulable State Venous stasis Blood clot develops (commonly in deep veins of legs) Clot dislodges, migrates to IVCàright atrium of heartà right ventricleàlodges in pulmonary artery Pulmonary Embolism (PE): Thromboembolic blockage of pulmonary vasculature Clot occludes pulmonary artery/ arterioles • D-Dimer is only performed if clinical suspicion of PE low (Well’s Criteria) • CT-PA is the current diagnostic test for PE • V/Q Scan is performed when CT contrast is contraindicated • X-Ray is usually normal in PE (Except Hampton’s Hump, a rare but specific sign of PE) Ischemia of lung tissue distal to clot X-Ray: Hampton’s Hump pleural based area of ↑ opacity Air flow/ ventilation to lungs unaffected Pleuritic Chest Pain + Dyspnea VQ Scan: V/Q Mismatch ↑ dead space ventilation and V/Q mismatching Chemoreceptors detect ↑ CO2 and ↓ O2 Signal brain to ↑ breathing rate Tachypnea ↓ Arterial O2 Blood pumped from RV to pulmonary arteries cannot pass clot ↑ pulmonary and RV pressure RV Strain CT-PA: Filling Defect Echo: ↑ RV size + ↓ RV Function ECG: S1Q3T3 Pattern Lab:↑ BNP Chest Pain Tachycardia ↑ RV work load, ↓ right coronary artery perfusion Abbreviations: • BNP – Brain Natriuretic Peptide • CT-PA – Computed Tomography-Pulmonary Angiogram • ECG – Electrocardiogram • IVC – Inferior Vena Cava • RV – Right Ventricle • V/Q – Ventilation-Perfusion ratio ↑ Troponin Hypotension ↑ Lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 07, 2018 on www.thecalgaryguide.com

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

Eisenmenger Syndrome

Eisenmenger Syndrome: Pathogenesis and clinical findings Ventricular septal defect Patent ductus arteriosus Authors: George S. Tadros Reviewers: Stephanie Happ Shahab Marzoughi Kim Myers* * MD at time of publication Atrial septal defect Blood shunted from systemic to pulmonary circulation Long-standing “left-to-right” shunt with too much pulmonary blood flow ↑ Flow of blood through the pulmonary circulation (from right ventricle to pulmonary arteries) ↑ Shear stress and circumferential stress on the pulmonary arteries and arterioles Atrioventricular septal defect Truncus arteriosus (Only one common artery arises from the heart rather aorta and pulmonary artery) Long-standing “right-to-left” shunt with too much pulmonary blood flow Structural changes occur in pulmonary arteries and arterioles to adapt to ↑ flow and pressure Hypertrophy of the smooth muscles (media) of pulmonary arteries and arterioles Thickening of the intima (innermost layer) of pulmonary arteries and arterioles ↑ Pulmonary vascular resistance (pressure in the pulmonary arteries) Pressure within the right ventricle gradually ↑ Right ventricular pressure is equal to, or exceeds left ventricular pressure Shunt changes from left-to-right to right-to-left “Right-to-Left” Shunt De-oxygenated blood originating from the right ventricle bypasses the lungs and goes into systemic circulation ↓ Oxygen delivery to tissue across the body Pulmonary hypertension (mean pulmonary artery pressure at rest ≥ 25mmHg) Right ventricular hypertrophy (enlarging) Hypertrophied right ventricle cannot contract effectively Right ventricle loses ability to pump blood efficiently Right heart failure Megakaryocytes (platelet precursors) are shunted away from the capillary beds of the lungs, where they usually get fragmented into platelets Chronic central cyanosis (generalized bluish discoloration) Induction of vascular endothelial growth factor (VEGF) in fingers Terminal digit clubbing (uniform swelling of the fingers and toes) Hypoxemia (<90% O2 saturation) Thrombocytopenia (↓ platelet count) Spontaneous bleeding events Body tries to compensate for ↓ O2 by ↑ oxygen-carrying capacity of the blood Polycythemia (↑ in red cell count) and ↑ hemoglobin concentration ↑ blood viscosity Hypercoagulable and prothrombotic state Not enough O2 to meet the body’s demands Fatigue Epistaxis (nose bleeds) Minor (non-life-threatening) Major (life-threatening) Pulmonary hemorrhage Dental bleeds Menorrhagia (heavy periods) Pulmonary Embolism (clot in pulmonary vessels) Stroke Deep vein thrombosis (clot in deep veins) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 5, 2024 on www.thecalgaryguide.com

Open Fractures

Open Fractures: Mechanisms, clinical features and complications Direct, high-energy force (e.g. vehicle collisions, gunshot) or low-energy force on diseased bone Force applied to bone exceeds strength of bone resulting in periosteal stripping and subsequent soft tissue and neurovascular destruction Open Fractures Also known as “compound fractures” and classified with the Gustilo-Anderson classification system (Types I, II, III), these are fractures in which the skin is penetrated and bone is exposed to the external environment. Comminuted fractures have ≥ 2 breaks in the bone. Inside-out (bone) or outside-in (external) penetration of skin to create a wound Skin tearing creates vacuum-like effect pulling debris into wound Minimal comminution Bone penetrates skin to create a wound < 1 cm in diameter (Type I) Smaller wound creates minimal opportunities for pathogen entry and contamination Moderate comminution Bone penetrates skin to create a wound 1-10 cm in diameter (Type II) Moderate wound creates some opportunity for pathogen entry and contamination Extensive comminution Bone penetrates skin to create a wound > 10 cm in diameter (Type III) Large wound creates ample opportunity for pathogen entry and extensive contamination Type IIIA (adequate soft tissue for bone coverage) Type IIIB (soft tissue damage with periosteal stripping) Type IIIC (vascular injuries, potential amputation) Displacement/shortening/ angulation/rotation of fracture fragment Improper bone healing Bone deformity Authors: Meaghan MacKenzie Holly Zahary Loreman Nojan Mannani Reviewers: Annalise Abbott Usama Malik Michelle J. Chen Dr. Prism Schneider* Dr. Jared Topham* * MD at time of publication Pain & lack of mechanical load bearing axis Inability to weight bear Decreased mobility promotes stasis of venous blood flow & intravascular vessel wall damage Deep vein thrombosis Potential progression to pulmonary embolism Bleeding or inflammation within fascia Muscle atrophy Compartment syndrome (↑ pressure in muscle) ** Open wound exposes bone Infiltration of debris & contaminants Infection of soft tissues or bone (osteomyelitis) Initial injury damages blood vessels Initial injury damages nerves ↓ Sensation distal to injury ↓ Limb function & proprioception ↓ Pulses distal to injury Amputation ↓ Blood flow to bone Avascular necrosis (bone tissue death) Limb ischemia ↓ Blood flow & oxygen delivery to tissues Compartment syndrome** Delayed union (bone healing) on serial radiographs Non-union (bone fails to heal) on serial radiographs **See corresponding Calgary Guide slide on Acute Compartment Syndrome Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 16, 2017; updated Nov 21, 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

Polycythemia Vera Complications

Polycythemia Vera (PV): Complications High numbers of cells & platelets ↑ blood viscosity Polycythemia Vera Hematological disorder in which JAK2 mutations in hematopoietic cells result in increased RBC production. See corresponding Calgary Guide slide “Polycythemia Vera: Pathogenesis” ↑ Blood cell volume Presence of increased numbers of platelets creates a hypercoagulable and prothrombotic state ↑ Risk of venous & arterial thrombosis ↑ Systemic vascular resistance Impaired/“sluggish” blood flow ↓ Perfusion to small vessels and ↓ oxygen delivery to throughout body Arterial clots in arms and legs or in vessels leading to brain prevent oxygen delivery to cells Systemic hypertension ↑ Turnover of hematopoietic cells (RBCs, WBCs, platelets) Fatigue Transient visual disturbances Neurological symptoms (e.g. headache, dizziness, tinnitus, concentration problems) Breakdown of nucleic acids during cell turnover ↑ uric acid levels in blood Lysing cells release lactate dehydrogenase (LDH) into bloodstream ↑ Spleen activity to filter and dispose of old blood cells Splenomegaly Authors: Caitlin Bittman Noriyah Al Awadhi Yan Yu Peter Duggan* Reviewers: Maharshi Gandhi Kevin Zhan Michelle J. Chen Paul Ratti Merna Adly Crystal Liu Kareem Jamani* Man-Chiu Poon* Lynn Savoie* * MD at time of publication Extramedullary hematopoiesis Pancytopenia Clots in the portal vein, splenic vein, & mesenteric vein are unusual & highly suggestive of PV Clots in cardiac arteries prevent O2 delivery to cardiac tissue Myocardial infarction Venous blood moves more slowly and is less pressurized compared to arterial blood. Combined with hypercoagulable state, clots are likely to form in deep veins (usually of the legs) Deep vein thrombosis Clot breaks off and travels through the inferior vena cava & right heart into the pulmonary arteries Pulmonary embolism Stimulation fibroblasts in the bone marrow Uric acid accumulates & precipitates in blood Hyperuricemia ↑ Serum LDH Limb ischemia Ischemic stroke & transient ischemic attacks Erythromelalgias (burning pain in the extremities and erythema due to poor perfusion and transient microvascular occlusion) Compensatory vasodilation in the capillaries of the skin Plethora/rusted or “ruddy” complexion, particularly noticeable on the face, palms, nailbeds, & mucous membranes Gout Uric acid stones Advanced Disease Progression Abnormal blood cells produced in PV release various growth factors and cytokines Production of excess collagen and other fibrous materials Hematopoietic cells in bone marrow replaced with fibrous tissue over time Bone marrow increasingly unable to produce healthy blood cells Myelofibrosis (rare type of chronic blood cancer; considered late-stage progression of PV characterized by bone marrow fibrosis) Bone marrow failure Chronic bone marrow hyperactivity leads to exhaustion and/or damage of hematopoietic cells Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 7, 2012, updated Feb 22, 2025 on www.thecalgaryguide.com

Obstructive Shock

Obstructive Shock: Pathogenesis, complications & clinical findings Cardiac tamponade** ↑ Pericardial cavity pressure due to fluid filling potential space Pericardial pressure exceeds cardiac venous filling pressure & compresses heart chambers ↓ Venous return to right atrium & left atrium Pulmonary embolism** Obstruction of pulmonary blood flow ↑ Right ventricle afterload (pressure the ventricle contracts against) ↓ Right ventricle stroke volume (blood volume ejected per beat) ↓ Blood return to left atrium Underfilled left ventricle Obstructive shock ↓ systemic blood flow due to a physical obstruction of the heart’s pumping function Insufficient organ perfusion Tension pneumothorax** ↑ Pressure in the pleural cavity Intrathoracic pressure exceeds venous filling pressures & compresses heart chambers ↓ Venous return to right atrium & left atrium Author: Ryan Dion Sergio F. Sharif Dean Percy Reviewers: Yan Yu Tristan Jones Jason Waechter* * MD at time of publication ** See corresponding Calgary Guide slides ↓ Preload (degree of left ventricular filling) as left ventricle receives low levels of blood ↓ Cardiac output (volume of blood ejected from the ↓ Blood pressure (BP) heart/min) Baroreceptors in carotid sinus & aortic arch detect low blood pressure Skin Reflexive release of catecholamines via sympathetic nervous system Blood supply diverted away from peripheral tissues to vital organs Tachycardia Hypotension Cold extremities Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Brain ↓ Cerebral blood flow causes cerebral hypoxia Altered consciousness Heart ↓ Coronary artery perfusion Myocardial ischemia** Complications Blood backs up into venous system Kidneys ↓ Blood flow to kidneys Prerenal acute kidney injury ** ↑ Pressure distends veins ↑ Jugular venous pressure Pressurized fluid leaks out of veins into tissue Fluid enters pulmonary perivascular spaces Fluid impedes normal gas exchange in lungs Tachypnea (↑ respiratory rate) Dyspnea Published July 7, 2013; updated Sept 28, 2025 on www.thecalgaryguide.com