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SEARCH RESULTS FOR: pulmonary edema

Negative-Pressure-Pulmonary-Edema

Negative Pressure Pulmonary Edema: Pathophysiology Authors: Mackenzie Gault Reviewers: Arsalan Ahmad Melinda Davis* * MD at time of publication Notes: ET tube: Endotrachial tube Laryngospasm: spasm of vocal cords; may occur on extubation CXR: Chest X-Ray Hypoxia Detected by peripheral chemoreceptors Sympathetic stimulation ↓ ventilation to lungs Airway Obstruction Involuntarily biting ET tube or laryngospasm most common Patient tries to inspire forcefully against obstruction Highly negative intrathoracic pressure Acute ↑ in systemic venous return to right heart ↑ pulmonary blood volume ↑ pulmonary arterial + capillary pressure ↓ pulmonary interstitial pressure ↑ trans-capillary pressure gradient Fluid pushed out of pulmonary capillaries into the interstitium Negative Pressure Pulmonary Edema: Fluid in lungs caused by highly negative intrathoracic pressure alveolus capillary interstitium Frothy pink sputum CXR: diffuse bilateral infiltrates ↓ PO2 ↓ O2 Sats Fluid surrounds alveoli ↓ diffusion of alveolar O2 into pulmonary capillaries If severe: pressure and fluid build-up damages capillary and alveolar walls Fluid & red blood cells from capillaries enter alveoli and are coughed up Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 1, 2019 on www.thecalgaryguide.com

Maternal-complications-after-labor-and-vaginal-delivery

Maternal complications of labour and vaginal delivery Author: Yan Yu Reviewers: Kayla Nelson, Radhmila Parmar, Jemimah Raffe-Devine, Alina Constantin* * MD at time of publication Labour and vaginal delivery Detachment of placenta disrupts uterine blood vessels Intense pressure on vaginal walls during fetal passage and/or use of forceps or vacuumà physical damage vagina and perineum Urinary tract catheterization during labour Foreign tube inserted into bladder allows easier colonization of bladder & urinary tract by bacteria Urinary Tract Infections Passage of fetus distends pubo-vesicular and pubo- rectalis sling muscles Urethra /rectum no longer kinked enough to prevent high intra-abdominal pressures from forcing out urine or feces Stress incontinence (of bladder & bowel; usually temporary) Scar tissue forms at site of placental detachment After complete hemostasis (cessation of bleeding) and vessel healing, scar tissue is shed from uterus Lochia (vaginal discharge/ bleeding) & eschar (scar tissue) shedding Placental tissue may be retained in the uterus Uterus fails to contract fully to seal off uterine blood vessels Post-partum hemorrhage (See relevant slide) Foreign substances trigger systemic inflammatory response in mother Disseminated Intravascular Coagulation, DIC (see relevant slide) Rarely, torn blood vessels let amniotic fluid (with fetal cells & meconium) enter maternal circulation Amniotic fluid embolism (clumps of foreign fetal cells and meconium in maternal circulation) Viscous amniotic fluid can block maternal blood vessels Obstructing blood flow out of lungs Blood backs up before lungsàless preload for heart Damaged tissue & blood in the uterus Ample nutrients for bacteria to infect uterus Endometritis Uterine pain, radiating throughout the abdomen Pulmonary edema Hypotension Perineal tears (1st-4th degree); Hemorrhoids Perineal Pain Unilateral leg pain & swelling Dyspnea, Cough If profound Cardiac arrest Tissue damage activates blood coagulation factors ­ Coagulation in areas of hemostasis (e.g. veins) Deep Vein Thrombosis Post-partum fever (see relevant slide) Cardiovascular collapse Lack of perfusion to heart Note: Post-partum depression is commonly seen in at least 10% of newly-delivered mothers. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Initially published September 5, 2013 on www.thecalgaryguide.com Updated and re-published January 23, 2021

Summary of Acyanotic Congenital Heart Diseases

Summary of Acyanotic Congenital Heart Diseases (Left-to-Right Shunts) Authors: Gaya Narendran, Winnie Nagesh Reviewers: Jack Fu, Usama Malik, Yan Yu*, Deborah Fruitman* * MD at time of publication Asymptomatic M, ↑ respiratory tract infections, rarely: failure to thrive Left to Right Shunt ↑ flow from left to right heart Dilation of chambers exposed to ↑ flow Atrial Septal Defect (ASD) Presents later in childhood – often asymptomatic Note: These conditions tend to be acyanotic in presentation. Clinical severity will depend on the defect’s size, anatomic location and the presence of other cardiac anomalies. Please see relevant Calgary Guide slides for each heart condition for full explanation of their pathophysiology. Figures are hand-drawn by the authors. L to R physical communication between atria 1. Pressure in LA > pressure in RA à blood shunts from LA to RA 2. Dilation of RAàdilation of RV 3. ↑ pulmonary blood flow On exam: Systolic Ejection Murmur at LUSB, fixed split S2, RV heave, tachypnea CXR: +/- ↑ pulmonary vasculature Ventricular Septal Defect (VSD) 1. Pressure in LV > pressure in RV (after 4-6wks old) On exam: harsh pansystolic M +/- diastolic rumble at LLSB, +/- hepatomegaly, WOB, tachypnea, +/- ↓ perfusion signs e.g. pallor CXR: ↑ vascular markings, cardiomegaly, pulmonary edema Feeding difficulties, failure to thrive, congestive heart failure (CHF) L to R physical communication between ventricles 2. This causes blood in LV to flow to RV in systole 3. ↑ flow to RVà↑ flow to pulmonary arteriesà ↑ pulmonary blood flow 4. ↑ blood returning to LA & LVàLA & LV dilation Presents usually at 4-6 weeks as PVR falls to normal (after birth) Patent Ductus Arteriosus (PDA) 1. Pressure in aorta > pressure in pulmonary arteries (PA) à continuous flow from aorta to PA 2. ↑ bloodflow load in the PA 3. ↑ flow in PA/lung vasculature à ↑ return to left Note: Adult presentation or unrepaired large VSD may cause pulmonary HTN, leading to Eisenmenger’s Syndrome (see relevant slide) Vessel linking descending aorta & pulmonary arteries remains after birth On exam: Continuous machine-like murmur in sub-clavicular region, wide pulse pressure, tachypnea CXR: ↑ pulmonary vasculature, LV enlargement, cardiomegaly, prominent PA Asymptomatic M , less commonly: failure to thrive, congestive heart failure heart à Dilation of the LA and LV Typically presents later in infancy – dependent on shunt size. Presentation and management may differ in preterm infants. Atrioventricular septal defects (AVSD) Defect in the crux/ center of heart involving both atria and ventricles, with AV abnormalities on a spectrum 1. Pressure in left heart > pressures in right heart 2. Thus blood shunts left à right at atrial and ventricular levels 3. As PVR falls (as part of normal newborn development) à ↑ pulmonary blood flow, +/- AV regurgitation 4. ↑ pulmonary flow à ↑ return to left heart à Cardiomegaly On exam: Systolic Ejection Murmur at LUSB, hepatomegaly, mild O2 desaturation in children CXR: ↑ pulmonary vasculature, cardiomegaly defect Similar to VSD – may present earlier, dependent on severity of defect – associated with Trisomy 21 Abbreviations: AV: Atrioventricular valve; CHF: Congestive Heart Failure; CXR: Chest X-ray; LA: Left Atrium; LV: Left Ventricle; LUSB: Left Upper Sternal Border; LLSB: Left Lower Sternal Border; M : Murmur; PA: Pulmonary Artery; PVR: Pulmonary Vascular Resistance; RA: Right Atrium; RV: Right Ventricle; WOB: Work of Breathing Same as VSD; dependent on severity of Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 15, 2017, updated Oct 21, 2021 on www.thecalgaryguide.com

Renal Artery Stenosis

Renal Artery Stenosis: Pathogenesis and clinical findings Atherosclerosis: A collection of inflammatory cells, lipids, & Fibromuscular Dysplasia: A rare vascular condition characterized by fibrous connective tissue deposits on the renal artery wall abnormal cellular growth in arterial walls, especially renal & carotid arteries Narrowing (stenosis) of the renal artery Renal Artery Stenosis can be unilateral or bilateral Authors: Samin Dolatabadi, Yan Yu* Reviewers: Meena Assad, Jessica Krahn Timothy Fu, Brooke Fallis, Juliya Hemmett* * MD at time of publication ↓ Pressure perfusing the kidney ↑ RAAS (renin-angiotensin- aldosterone system) activation ↓ pressure gradient in glomerulus ↓ Glomerular filtration rate (GFR) ↑ Secretion of aldosterone Turbulent blood flow through area of stenosis Abdominal bruit on side of affected kidney(s) ↑ Secretion of Angiotensin IIà ↑ Systemic vasoconstriction Hypertension ↑ Expression of epithelial sodium channels in cortical collecting duct ↑ Blood volume within volume- constrained space of blood vessels ↓ Renal blood flowà ischemic renal injury Atrophy and fibrosis of affected kidney(s) Unilateral stenosis à Kidney size asymmetry (≥1.5cm difference) ↓ Positively charged Na+ in lumen à Electronegative lumen compared to the interstitial/tubular epithelial cells K+ follows the electrical gradient and is secreted into the electronegative tubular lumen ↓ Serum K+ concentration Hypokalemia *Note: In unilateral renal artery stenosis, the contralateral (normal) kidney can compensate for the increase in renal perfusion pressure caused by hypertension by increasing sodium excretion (pressure natriuresis), preventing flash pulmonary edema. ↑ NHE3 (Sodium Hydrogen Exchanger 3) activity in proximal collecting tubule ↑ Na+ and water reabsorption from renal tubular lumen into blood vessels Chronic left ventricle pressure overload àLeft ventricle hypertrophy (see Left Heart Failure: Pathogenesis Slide) Systolic dysfunction → ↓ left ventricle stroke volume Normally, ↑ in renal perfusion pressureà↑ Na+ excretion and water loss (pressure natriuresis) In bilateral renal artery stenosis*, ↓ GFRàinability for kidney to ↑ renal Na+ & water excretion à volume overload Acute increase in afterload or preload → sudden ↑ in left ventricular filling pressures → blood backup into lungs Pulmonary vasculature hypertension → ↑ fluid filtration across the pulmonary endothelium into interstitium and alveolar spaces Flash (rapid onset) pulmonary edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 30, 2021 on www.thecalgaryguide.com

presentation-of-sah

Subarachnoid Hemorrhage: Clinical Findings Sudden bleeding into space surrounding the brain (for pathogenesis, see Subarachnoid Hemorrhage: Pathogenesis) Authors: Jason An, M. Patrick Pankow Reviewers: Owen Stechishin, Dave Nicholl, Haotian Wang, Hannah Mathew, Ran (Marissa) Zhang, Yan Yu*, Cory Toth* * MD at time of publication Bleed into subarachnoid space Subarachnoid Hemorrhage (SAH) Posterior hypothalamus ischemia (↓ Blood flow and oxygen) Red blood cell lysis from energy depletion or complement activation Release of spasmogens (spasm inducing agents) Cerebral vasospasm (narrowing of arteries from persistent contraction) ↓ blood flow Cerebral ischemia Release catecholamines (hormones from the adrenal gland; e.g., epinephrine, norepinephrine) ↑ Intracellular calcium Release of antidiuretic hormone Antidiuretic hormone acts on the distal convoluted tubule and collecting duct in kidney to reabsorb water Dilution of serum sodium Hyponatremia (low blood sodium levels) Release of epileptogenic (potential seizure causing agents) into cerebral circulation Seizure Products from blood breakdown in cerebral spinal fluid Irritation of meninges (membranes surrounding the brain) Aseptic meningitis (non-infectious inflammation) Meningismus (neck pain + rigidity) Cerebral infarction (death of tissue) Obstructs cerebral spinal fluid flow and absorption at subarachnoid granulations Hydrocephalus (fluid build up in ventricles) ↓ Level of consciousness Reduced cerebral blood flow Dilation of cranial vessels to ↑ blood flow Rapid ↑ internal carotid artery intracranial pressure Refer to Increased Intracranial Pressure: Clinical Findings slide Internal carotid artery Pituitary ischemia Hypopituitarism [underactive pituitary gland, failing to produce 1+ pituitary hormone(s)] Refer to hypopituitarism slides Myocardial disruption Left ventricle dysfunction ↑ Pressure in left heart Blood forced backwards into pulmonary veins ↑ Pulmonary blood pressure Fluid from blood vessels leaks into lungs Dysrhythmias (disturbance in rate/rhythm of heart) causing ↓ cardiac output Syncope (loss of consciousness due to ↓ blood flow to the brain) Pulmonary edema (excess accumulation of fluid in lung) Cerebral hypoperfusion Sudden ↑in blood volume Vessels and meninges suddenly stretch Thunderclap Headache (worst headache of patient's life) Shortness of breath Reactive cerebral hyperemia (excess blood in vessels supplying the brain) Artery specific findings: Rapid ↑ internal carotid artery intracranial pressure Middle cerebral artery Posterior communicating artery Compression of outer CN3 Compression of inner CN3 Anterior communicating artery Nonreactive pupil Gaze palsy (eye deviates down and out) Diplopia (double vision) Ptosis (drooping of upper eyelid) Frontal lobe ischemia Avolition (complete lack of motivation) Ischemia of motor strip pertaining to the legs Bilateral leg weakness Motor strip ischemia Hemiparesis (weakness/ inability to move one side of the body) Ischemia of parietal association areas (brain regions integral for motor control of the eyes, the extremities and spatial cognition) Aphasia (impaired ability to speak and/or understand language)/ neglect Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 1, 2014, updated August 10, 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 Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome: Pathogenesis and clinical findings Acute respiratory distress syndrome (ARDS) is a clinical syndrome involving acute lung injury. It results in severe hypoxemia and bilateral Authors: David Olmstead Mao Ding Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* * MD at time of publication ↓ PaO2 (Partial pressure of oxygen in arterial blood ↓SpO2 (Peripheral oxygen saturation) Tachypnea (↑ RR) Tachycardia (↑ HR) Dyspnea Bilateral Opacity on chest radiograph ↓ PaO2, ↓SpO2 ↑ PaCO 2 ↑ PaO2, ↓PaCO2 Eupnea (normal breathing) ↓ O2 Requirements Depression, Anxiety, PTSD Neuromuscular Weakness Chronic Respiratory Dysfunction airspace disease in the absence of elevated left-heart pressures. Direct Lung Injury Causes include pneumonia and pulmonary sepsis (community- acquired, hospital-acquired, aspiration, viral), drowning, and chemical pneumonitis from aspiration or direct inhalational injury Indirect Lung Injury Causes include sepsis with a non-pulmonary source, trauma, severe burns, transfusion- related acute lung injury (TRALI) and pancreatitis Lung Tissue Inflammation Exudative: Neutrophils migrate into the alveoli in response to inflammatory stimulus Note: While the three phases of ARDS take place in sequence, all areas of the lung may not be in the same phase at the same time. For this reason, the processes can be thought of as overlapping. Proliferative: Body attempts to heal damage. If it is not successful, the tissue transitions to the fibrotic phase Neutrophil-containing pulmonary exudate interferes with surfactant function Neutrophil infiltration and proinflammatory cytokines lead to tissue edema, dysfunction and subsequent destruction of pulmonary epithelium Residual debris in alveoli are cleared by phagocytic cells Restoration of alveolar epithelial cells. Alveoli collapse in absence of working surfactant Damaged epithelium impairs gas exchange Pulmonary capillaries do not adequately absorb fluid The body’s attempts to heal lung tissue result in deposition of hyaline membranes in the alveoli Ventilation- Perfusion Mismatch Pulmonary Edema Impaired Gas Diffusion Functional epithelium is able to absorb fluid back into circulation ↑ useful surface area for gas exchange Clearing of CXR Impaired Function After Prolonged Illness Pulmonary Hypertension Fibrotic: Inadequate healing results in long-term pulmonary damage (rare) Fibroblast activity leads to deposition of collagen in alveoli and alveolar capillaries Fatigue Pulmonary Fibrosis Nail Clubbing (nails appear wider & swollen) Cough/Dyspnea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 6, 2018, updated Oct 10, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome: Note: Acute respiratory distress syndrome is a clinical Authors: David Olmstead Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* * MD at time of publication Pathogenesis and clinical findings Direct Lung Injury Causes include pneumonia and pulmonary sepsis (community-acquired, hospital-acquired, aspiration, viral), drowning, and chemical pneumonitis from aspiration or direct inhalational injury Indirect Lung Injury syndrome involving acute lung injury. It results in severe hypoxemia and bilateral airspace disease in the absence of elevated left-heart pressures. Causes include sepsis with a non-pulmonary source, trauma, severe burns, transfusion-related acute lung injury (TRALI) and pancreatitis Lung Tissue Inflammation Exudative: Neutrophils migrate into the alveoli in response to inflammatory stimulus Note: While the three phases of ARDS take place in sequence, all areas of the lung may not be in the same phase at the same time. For this reason, the processes can be thought of as overlapping. Proliferative: Body attempts to heal damage. If it is not successful, the tissue transitions to the fibrotic phase Neutrophil-containing pulmonary exudate interferes with surfactant function Neutrophil infiltration and proinflammatory cytokines lead to tissue edema, dysfunction and subsequent destruction of pulmonary epithelium Abbreviations: PaO2: Partial pressure of oxygen in arterial blood SpO2: Peripheral oxygen saturation. CXR: Chest radiograph. Residual debris in alveoli are cleared by phagocytic cells Restoration of alveolar epithelial cells. Alveoli collapse in absence of working surfactant Damaged epithelium impairs gas exchange Pulmonary capillaries do not adequately absorb fluid The body’s attempts to heal lung tissue result in deposition of hyaline membranes in the alveoli Ventilation- Perfusion Mismatch Pulmonary Edema Impaired Gas Diffusion ↓ PaO2, ↓SpO2 Tachypnea Tachycardia Dyspnea Bilateral Opacity on CXR ↓ PaO , ↓SpO 2 2 ↑ PaCO2 ↑ PaO2, ↓PaCO2 Eupnea ↓ O2 Requirements Clearing of CXR Depression, Anxiety, PTSD Neuromuscular Weakness Chronic Respiratory Dysfunction ↑ useful surface area for gas exchange Functional epithelium is able to absorb fluid back into circulation Impaired Function After Prolonged Illness Fibrotic: Inadequate healing results in long-term pulmonary damage (rare) Fibroblast activity leads to deposition of collagen in alveoli and alveolar capillaries Pulmonary Fibrosis Pulmonary Hypertension Cough/Dyspnea Nail Clubbing Fatigue Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 06, 2018 on www.thecalgaryguide.com

Complication of MI - Acute Mitral Regurgitation

Complication of MI: Acute mitral regurgitation Authors: Victória Silva Reviewers: Juliette Hall, Raafi Ali *Angela Kealey * MD at time of publication S3 Indicates rapid overfilling of ventricle S1 S2 S3 Calcified plaque formation (atherosclerosis**) commonly in the posterior descending artery Plaque ruptures Exposed plaque contentsàPlatelet adhesion and aggregation Artery becomes partially or completely occluded Mitral Regurgitation** (Back flow of blood from left ventricle to left atrium during systole) ↑ Left atrial pressure Blood from left atrium backs up into pulmonary venous system ↑ Pulmonary venous pressure ↑ Hydrostatic pressure in alveolar capillaries ↑ Fluid leak from alveolar capillaries to interstitium (pulmonary edema**) ↓ Gas exchange Attempt at physiologic compensation à ↑ Respiratory rate Tachypnea Holosystolic murmur Heard loudest over the mitral valve (5th intercostal space, mid-clavicular line), with radiation to the axilla ↑ Volume of blood to left ventricle during diastole ↓ Blood supply to the portion of the ventricle that supports the papillary muscle à↓ Muscle movement Left ventricle dysfunction ↓ Blood supply to the posterior medial papillary muscle Cell death (myocardial infarction) Papillary muscle ischemia (muscle is intact but cannot contract) ↑ Blood in right atriumà↑ Blood in superior vena cava ↑ Blood in internal jugular vein ↑ Jugular venous pressure (JVP) Redistribution of interstitial fluid when lying flat (reduced effect of gravity) ↓ Forward blood flow from left ventricle to aorta ↓ Stroke volume (SV) ↓ Cardiac output (CO) CO = SV x HR (heart rate) Sympathetic nervous system attempts to physiologically compensate ↑ Heart rate Tachycardia ↓ Blood pressure (BP) because BP = CO X SVR (systemic vascular resistance) Cardiogenic shock** Papillary muscle rupture Papillary muscle unable to provide adequate tension on mitral valve Mitral valve unable to stay closed during systole Orthopnea Difficulty breathing Dyspnea Paroxysmal nocturnal dyspnea **See corresponding Calgary Guide slides for more details Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com

Atrial Septal Defect Pathogenesis and Clinical Findings

Atrial Septal Defect (ASD): Pathogenesis and clinical findings Genetic syndromes (e.g., Holt- Oram, Noonan, and Down) Gene mutations (e.g., TBX5, GATA4, and NKX2-5) Authors: Ryan Wilkie George Tadros Reviewers: Julena Foglia Haotian Wang Shahab Marzoughi Tim Prieur* * MD at time of publication Spontaneous Abnormal formation of the septum of the atria Atrial Septal Defect (ASD) An abnormal connection between the left and right atria of the heart Following birth, lungs fill with air and resistance to blood flow in the lung vasculature ↓ Pressure within the right ventricle and right atrium ↓ Left atrial pressure exceeds right atrial pressure Blood passes from left to right through the ASD (left-to-right shunt) ↑ Blood flow through the right heart ↑ Blood flow through tricuspid valve Mid-diastolic murmur Right-sided heart dilation (enlargement of the right ventricle) Enlarged ventricle cannot pump blood effectively Congestive Heart Failure ↑ Blood flow through pulmonary valve and pulmonary vasculature Right ventricular heave (visible or palpable chest wall impulse around sternum) ↑ Right atrial wall stress Inspiration produces no net pressure change between communicating atria Delayed closure of pulmonary valve (relative to aortic valve) Morphologic changes in pulmonary vasculature from long standing exposure to high blood flow Pulmonary vascular resistanceáover time, may surpass systemic vascular resistance **Pulmonary Hypertension** Mid-systolic ejection murmur Heart is unable to pump enough blood to meet demand during activity (including feeding) ↑ Backup of blood in lungs ↑ Hydrostatic pressure in lung vasculature Pulmonary edema Damage to normal conduction of electrical signal from the atria to the ventricles ECG Changes: Prolonged PR and QRS intervals, right bundle branch block, right axis deviation Fixed split S2 (two distinct sounds are heard as part of S2) Reduced exercise capacity ↓ Eating Failure to thrive Fatigue Atrial arrhythmias (atrial fibrillation or flutter) Irregular beats are felt in the chest wall Palpitations Dyspnea ↓ Ability to clear foreign particles from interstitium due to presence of extra fluid Respiratory tract infections ** See Relevant Calgary Guide Slide ** Pulmonary Hypertension: Pathogenesis and clinical findings Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 1, 2014; updated Mar 21, 2024 on www.thecalgaryguide.com

Sickle Cell Disease Pathogenesis Clinical Findings and Complications

Sickle Cell Disease: Pathogenesis, Clinical Findings, and Complications DNA point mutation in chromosome 11 causes a substitution of glutamate to valine for the sixth amino acid of the β-globin chain Authors: Yang (Steven) Liu Priyanka Grewal Reviewers: Alexander Arnold Luiza Radu JoyAnne Krupa Yan Yu* Lynn Savoie* * MD at time of publication Hemoglobin S (HbS) variant formed instead of normal Hemoglobin A (HbA) Hb electrophoresis shows approximately 45% HbS, 52% HbA (ααββ), 2% HbA Hb electrophoresis shows approximately 90% HbS, 8% HbF, & 2% HbA . No HbA present (ααδδ), & 1% HbF (ααγγ;2 fetal hemoglobin) Heterozygous: point mutation in one of the two chromosomes (Hb AS) Sickle cell trait (asymptomatic unless severely hypoxic) Homozygous: point mutation in both chromosomes (Hb SS) Sickle cell disease An inherited blood disorder characterized by defective hemoglobin that leads to red blood cells sickling 2 Dehydration Hypoxemia Acidosis ↓ Volume of RBC cytoplasm ↓ O2 Saturation of Hb O morereadily 2 released from Hb in low pH environment ↑ Concentration of deoxygenated HbSinred blood cells (RBCs) Hydrophilic glutamate→ hydrophobic valine substitution makes HbS less soluble in the cytoplasm & more prone to polymerization & precipitation in its deoxygenated state ↑ Concentration of deoxygenated Hb in RBC leads to ↑ polymerization rate Polymerized & precipitated HbS forms long needle-like fibers RBC shape becomes sickled Sickle cells on peripheral blood smear Vaso-occlusion (sickled RBCs lodge in small vessels, blocking bloodflow to organs & tissues) Blockage of venous outflow Occlusion of vessels in lungs ↑ pulmonary blood pressure Fluid extravasates into interstitial tissue leading to pulmonary edema Acute chest syndrome (chest pain, hypoxemia (↓blood oxygen), etc.)** to the penis: to the spleen: Priapism (persistent, painful erection) Splenic Sequestration (blood pools in spleenà splenomegaly & hypotension) Extravascular hemolysis (macrophages in the spleen phagocytose sickled RBCs) Normocytic anemia ↑Marrow erythropoiesis (RBC production) to compensate for hemolysis Infarction of bone Pain crises If occurring in hands Dactylitis (inflammation of digits) Blockage of arteries ↓ oxygenation of organs & tissues Vaso-occlusion of the splenic artery Splenic infarction (↓ blood supply leads to tissue death) RBC inclusions (structures found in RBCs) not removed by spleen Howell-Jolly bodies (RBC DNA remnants) on blood smear Vaso-occlusion of other arteries (cranial, renal, etc) Stroke, renal failure ↑ RBC breakdown ↑ Unconjugated bilirubin released from RBC breakdown RBC precursors (reticulocytes) are released into the blood stream Reticulocytosis (increased number of immature red blood cells) on peripheral blood smear Patient’s RBC level becomes dependent on increased marrow activity Bone marrow infarction or viral infections (i.e. Parvovirus B19) suppresses bone marrow activity Aplastic crises (profound anemia) ** See corresponding Calgary Guide slide(s) ↑ Serum level of unconjugated bilirubin Some of the circulating unconjugated bilirubin deposits in the skin Jaundice (yellowing of skin) ↑ Conjugation of bilirubin in liver ↑Amounts of conjugated bilirubin released into bile Gallstone formation Cholelithiasis (presence of gallstones in the gallbladder) Spleen releases invasive encapsulated bacteria (eg. Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis) into circulation, which causes infections Meningitis Sepsis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 16, 2013, updated Apr 29, 2024 on www.thecalgaryguide.com

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