SEARCH RESULTS FOR: heart failure

Left Heart Failure - Pathogenesis

Right Heart Failure

Left Heart Failure

Left Heart Failure - Physical Exam Findings

Left Heart Failure - Findings on History

Left Heart Failure: Pathophysiology (Neurohormonal Activation)

Left Heart Failure: Pathophysiology (Neurohormonal Activation) Frank Starling Mechanism • The Frank Starling mechanism of the heart represents the relationship between preload (EDV) and SV • As preload (EDV) increases, SV increases, because higher volumes of blood in the ventricles stretch the cardiac fibers and increases cardiac contraction during systole. However, volume overload causes reduced SV. Myocardial Dysfunction: • Left ventricular Compensatory 4, SV 4A, CO 4 Mechanisms 4, BP Important equations: • BP = CO x SVR • CO = SV x HR Cardiac hemodynamics: • Stroke volume is affected by three factors 1) Preload (end-diastolic volume (EDV)) 2) Afterload (resistance to LV ejection) 3) Contractility (inherent strength of contraction of LV myocytes) Definition of heart failure: • Myocardial dysfunction (systolic or diastolic) results in decreased CO, such that the heart cannot meet the body's metabolic demands or can only do so at elevated filling pressures Anti-diuretic hormone (ADH) activation: Arginine 4, BP 4 carotid sinus Vasopressin --• and aortic arch (V2) receptor baroceptors activation activation 4 I` ADH release RAAS System: 4, BP 4 t release of renin from the juxtaglomerular kidney cells due to renal hypoperfusion SNS System: In response to CO, 4 SNS t release of (catecholamines) norepinephrine and epinephrine Adrenal Glands: Aldosterone release Angiotensin II Type 1 receptor activation al receptor activation 13, receptor activation —• Renal Collecting Ducts: t H2O retention Renal Distal —• Tubules: t Na+ & H2O retention Heart: Activation of fibroblasts 4 collagen synthesis and hypertrophy Blood Vessels: Peripheral vasoconstriction 4 SVR Heart: Chronic p, receptor activation 4 Ca2+ overload myocyte apoptosis Heart: Increase HR to maintain normal CO Maladaptive Response: t preload (EDV), —• volume overload Abbreviations: • SV — Stroke volume • CO — Cardiac output • SVR — Systemic vascular resistance • BP — Blood pressure • RAAS — Renin-Angiotensin-Aldosterone System • SNS — Sympathetic nervous system tin systemic and pulmonary congestion via the Frank-Starling Mechanism Maladaptive 1` resistance Response: t BP, —• against LV afterload ejection 4 4, SV Maladaptive Response: Adverse LV remodelling Maladaptive Response: t myocardial oxygen demand and 4, diastolic time 4, contractility —• of the heart 4, coronary blood flow 4 myocardial ischemia Physical signs and symptoms of congestive heart failure (see relevant slide) Authors: Sunny Fong Reviewers: —• I Jack Fu Usama Malik Dr. Jason Waechter* *MD at time of publication

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Pathogenesis

Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Pathogenesis Acute Pulmonary Thromboembolic Event Mechanical breakdown, Fibrinolysis —5%: Incomplete thrombus resolution after 2 years (Etiology unknown) * Clot resolution (>90%) Hypothesis 1: Increased hypercoagulability Hypothesis 2: Impaired clot lysis Hypothesis 3: Impaired angiogenesis Hypothesis 4: Inflammatory thrombosis • Associated with 1` levels of • Fibrin more resistant to • Impaired VEG-F function (unknown if cause or effect) plasma Factor VIII plasmin-mediated lysis • Ventriculoatrial shunts • Infected pacemaker wires • Splenectomy • Inflammatory bowel disease Unresolved thromboemboli incorporates into blood vessel wall by fibrosis leading to fibrothrombotic organization Authors: Dinusha T. Senaratne Reviewers: Midas (Kening) Kang Usama Malik Natalie Morgunov* Lian Szabo* * MD at time of publication Legend: Webs, bands and slow blood flow In-situ thrombosis expanding the fibrotic thrombus and branch occlusion Abbreviations: BP: Blood pressure PE: Pulmonary embolism PH: Pulmonary hypertension RAD: Right atrial dilatation RHF: Right heart failure RVHD: Right Ventricular hypertrophy/dilatation RVP: Right ventricular pressure VEGF: Vascular endothelial growth factor Proliferation of vascular and inflammatory cells proximal to lesion sites Adaptive vascular remodeling BP in patent vessels of the pulmonary vasculature For signs and symptoms refer to PH slide ■ Progressive PH CTEPH (Chronic Thromboembolic pulmonary hypertension): Chronic occlusion of the pulmonary arteries due to intraluminal fibrosis of thromboembolic material from unresolved PE clots Pathophysiology Mechanism Progressive'(` RVP causes RAD and RVH/D Sign/Symptom/Lab Finding Progressive RHF Complications For signs and symptoms refer to RHF slide

Hyponatremia- Physiology

Hyponatremia: Physiology Authors: Mannat Dhillon Reviewers: Andrea Kuczynski Kevin McLaughlin* * MD at time of publication Abnormal Renal H2O Handling (hypo-osmolar serum) AKI/CKD Heart failure ↓ renal blood flow ↓ glomerular filtration GFR < 25 mL/min, ↓ urine dilution ↑ H2O retention Note: • Plasma [Na+] is regulated by water intake/excretion, not by changes in [Na+]. • Artifactual hyponatremia can be differentiated by a normal or hyperosmolar serum. Appropriate ADH secretion ↓ EABV Hypovolemia: losses via GI, renal, skin, 3rd spacing, bleeding Hypervolemia: heart failure, cirrhosis ↑ Na+/H2O absorption at PCT ↓ EABV, ↑ H2O retention Urine [Na+] < 20 mmol/L Hereditary: tubular disorders (Bartter, Gitlemann syndromes). Thiazide diuretics Inappropriate: SIADH, hypothyroidism, AI Normal EABV Anti-diuresis Primary polydipsia, eating disorder ↑ H2O or ↓ solute intake ↓ Osmoles Impaired desalination Block NCC ↑ H2O retention ↑ Na+/K+ excretion Hyponatremia Serum [Na+] < 135 mmol/L Urine osmolality > 100 mmol/L Urine osmolality < 100 mmol/L Cerebral edema, ↑ intracranial pressure, vasoconstriction If hypovolemic: ↓ JVP, ↓ blood pressure Lethargy, altered mental status Abbreviations: AKI: Acute Kidney Injury CKD: Chronic Kidney Disease GFR: Glomerular Filtration Rate H2O: Water PCT: Proximal Convoluted Tubule EABV: Effective Arterial Blood Volume NCC: Na+/Cl- Co-Transporter SIADH: Syndrome of Inappropriate ADH Secretion AI: Adrenal Insufficiency Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 11, 2019 on www.thecalgaryguide.com

Patent Ductus Arteriosus (PDA)- Pathogenesis and Clinical Findings

Patent Ductus Arteriosus (PDA)- Pathogenesis and Clinical Findings Sun Bishay Gagnon Adderley Ryznar waechter circulating PGE2 low arterial oxygen content genetic factors char syndrome patent birth aortic pressure pulmonary artery pressure continuous flow from aorta to pulmonary artery via the PDA left to right shunt continuous flow murmur precordial activity S1 S2 accentuated pulse volume load dilation dysfunction left atrium ventricle displaced apex dynamic left ventricular impulse grade pulmonary blood flow systemic blood flow exercise intolerance wide systemic pulse pressure pulmonary artery pressure vascular changes resistance difficulty feeding infants failure to thrive heart failure respiratory distress pulmonary hypertension reversal of shunt adult complications eisenmenger syndrome clubbing cyanosis

Takotsubo Cardiomyopathy- Pathogenesis and clinical findings

Takotsubo Cardiomyopathy- Pathogenesis and clinical findings emotional physical stresses other neurologic endocrine drug brain natriuretic peptide coronary artery disease takotsubo catecholamine release stimulation Beta receptors ionotropic effect alpha receptors coronary vessels metabolic contraction band necrosis edema inflammatory cell infiltration localized fibrosis coronary vasospasm microvascular dysfunction decrease oxygen supply relative to demand hypo-contraction ballooning left ventricular apex chest pain troponin BNP elevation ST ECG changes absence of obstructive CAD transient left ventricle systolic dysfunction dyskinetic apex Mitral regurgitation ventricular thrombus cardiac output low dyspnea syncope heart failure cardiogenic shock echocardiogram apex Gu gagnon Ryznar Waechter

Hyperkalemia- Physiology

Hyperkalemia: Physiology ↓ Renal Excretion ↑ Intake ↓ Intracellular Shift Acute and chronic kidney disease; CHF Principal Cell Dysfunction (TTKG < 7) ACEi/ARB; AI; heparin Hypovolemia (TTKG > 7) ↓ EABV ↓ distal flow of Na+ and H2O Urine [Na+] < 20 mmol/L Cell lysis ↑ osmolarity H2O efflux Solvent drag β2 inhibition α1 stimulation Digoxin ↓ A NAGMA ↓ insulin ↓ NHE1 activity Diabetic nephropathy; NSAIDs ↓ A: ↓ R K+ sparing diuretics; voltage- dependent RTA ↓ Na+/K+ ATPase activity ↓ GFR ↓ A: ↑ R ↑ A: ↑ R ↓ CCD K+ secretion ↑ K+ availability ↑ K+ release ↓ intracellular K+ influx Chronic: Desensitize voltage- gated Na+ channels and ↓ membrane excitability ECG: Peaked T-waves, ↑ PR interval, flat/absent P-wave, ↑ QRS, QRST “sine wave” Hyperkalemia Serum [K+] > 5.1 mmol/L Acute: ↑ extracellular [K+] makes the RMP less (-) Abbreviations: A: Aldosterone AI: Adrenal Insufficiency CCD: Cortical Collecting Duct CHF: Congestive Heart Failure EABV: Effective Arterial Blood Volume H+: Hydrogen ion K+: Potassium ion Na+: Sodium ion NAGMA: Normal Anion Gap Metabolic Acidosis NSAIDs: Non-steroidal anti-inflammatory drugs Note: Muscle weakness or paralysis, ↓ urinary acid excretion R: Renin RTA: Renal Tubular Acidosis RMP: Resting Membrane Potential TTKG: Transtubular Potassium Gradient • Pseudohyperkalemia should always be excluded; can be caused by thrombocytosis, leukocytosis or improper blood withdrawal technique. Authors: Mannat Dhillon Joshua Low Reviewers: Andrea Kuczynski Kevin McLaughlin* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 6, 2019 on www.thecalgaryguide.com

Torsades de Pointes (TdP)- Pathogenesis and Clinical Findings

Torsades de Pointes (TdP): Pathogenesis and Clinical Findings Drugs (e.g. Class 1A [quinidine], Class III [sotalol, amiodarone], TCAs, erythromycin, quinolones, anti-histamines) Sinus bradycardia, AV block Metabolic abnormality (hypo K+/Ca2+/Mg2+) Primary heart disease: ischemic, congestive heart failure, cardiomyopathy Acquired long QT syndrome Congenital long QT syndrome ↓ repolarizing current/ ­ depolarizing current in cardiomyocytes Mutated cardiac ion channels Author: Nicola Adderley Reviewers: Luke Gagnon Emily Ryznar *Saman Rezazadeh *George Veenhuyzen MD at time of publication* ↓ repolarizing current in cardiomyocytes ­ QTc interval Prolonged ventricular action potential duration Early after depolarization (EAD) triggering PVC Torsades de Pointes Illustrated changes to action potential: Normal cardiac action potential EAD Abbreviations: TCAs: tricyclic antidepressants AV: atrioventricular QTc: QT interval, corrected for heart rate PVC: premature ventricular contraction VF: ventricular fibrillation SR: sinus rhythm Polymorphic ventricular tachycardia initiated by PVC in the setting of QT interval prolongation and maintained by functional re-entry Non-sustained TdP Asymptomatic, palpitations, syncope (length-dependent) Illustrated changes to ECG Strip: OR Sinus rhythm restored Degeneration to VF Sudden cardiac death Prolonged repolarization Triggered beat (PVC) A BCDE A. Prolonged QT interval B. PVC C. PVC triggers TdP D. Non-sustained TdP E. Return to SR Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 10, 2019 on www.thecalgaryguide.com

Polyarteritis Nodosa (PAN): Pathogenesis and Clinical Findings

Polyarteritis Nodosa (PAN): Pathogenesis and clinical findings Environmental triggers Infectious/viral agents (commonly Hepatitis B) Medical Comorbidities Malignancies (most commonly hairy-cell leukemia) Immunogenetic Predisposition: patient is genetically predisposed to a dysregulated immune response Fever ↑ ESR and CRP Postulate 1 Viral antigen-antibody complexes deposit in vasculature, causing lesions and activating cellular inflammatory response Authors: Nela Cosic, Yan Yu* Reviewers: Sean Doherty Martin Atkinson* * MD at time of publication Palpable or necrotic purpura Malignant Hypertension Renal Insufficiency Myocardial ischemia Heart failure Diffuse myalgias Postulate 2 Viral replication causes direct injury to vascular endothelial cells ↑ Anti- endothelial cell autoantibodies (AECA) Altered cytokine profile (↑TNF-α, IL-1β, IFN-α, IL- 2)à↑ T-cell mediated immune response Weight metabolism Loss Autoimmune attack on various areas of the body Malaise and/or Arthralgias (knees, ankles, elbows, wrists) Orchitis: Testicular pain, erythema and/or swelling Small intestine perforation GI Manifestations Non-specific abdo pain GI hemorrhage Peripheral sensory changes: Distal mononeuropathy multiplex Polyarteritis Nodosa (PAN) Focal segmental necrotizing leukocytoclastic vasculitis of medium or small-sized arteries Inflammation of arteries damages the vascular endothelium of those arteries Inflammation predisposes formation of arterial thromboses Blockage of arteriesà tissue ischemia and possible necrosis (tissue cell death) ↑ basal Arterial aneurysms Inflamed subcutaneous arteries Inflamed renal artery àluminal narrowing and reduced blood flow to kidneys Inflamed coronary artery à luminal narrowing, occlusion, thromboses Segmental inflammation of muscular arteries, stimulating surrounding nociceptors. Muscle ischemia develops long-term. Ischemia/necrosis of the testicles Ischemia/necrosis of the small intestine Ischemic vasculitic nerve damage: Immune complex deposition within vessel walls of arteries traveling with nerves leads to persistent vascular inflammation and ischemia of associated nerve Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 18, 2019 on www.thecalgaryguide.com

Normocytic Anemia

Normocytic Anemia: Causes, Signs, and Symptoms Authors: Katie Lin Yan Yu Reviewers: Andrew Brack Jessica Tjong Man-Chiu Poon* Lynn Savoie* * MD at time of publication Aplastic anemia: hypo-proliferation of bone marrow RBC precursors Anemia of Chronic Disease Splenomegaly ↑ RBC sequestration within enlarged spleen Acute bleeding Hemolysis (infection, autoimmune, RBC structural defects) ↓ RBC production ↑ RBC destruction/elimination Normocytic Anemia: [Hgb] <120g/L in females, <140g/L in males, with the RBC mean corpuscular volume (MCV) still within the normal range: 80-100 fL RBCs that ultimately end up in the blood are still qualitatively normal/functional; there is a quantitative shortage of these RBCs in the blood relative to body needs Spurious/False normocytic anemia: Any fluid overload state (pregnancy, heart failure, kidney disease, etc.) can ↑ plasma volume which can dilute RBCs and cause apparent anemia, but the mean volume of each RBC is still normal Normocytic Anemia Heart needs to work faster to pump sufficient oxygenated blood to tissues ↑ Heart rate Reduced oxygen- carrying ability of blood Patient feels oxygen- deprived, needs to inhale more oxygen as compensation Dyspnea (shortness of breath) ↑ Respiratory rate (RR) Not enough oxygen being delivered to body tissues, including brain Fatigue Reduced absolute number of RBCs means less RBCs to color the blood red Pallor (especially conjunctival and palmar) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 27, 2019 on www.thecalgaryguide.com

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu disease)

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu disease): Pathogenesis and Clinical Findings Inherited or de novo mutation in the ACVRL1, ENG, or Smad4 genes Abnormal signalling within the transforming growth factor ß (TGF-ß) pathway Unclear mechanismsàInability of vascular mural cells to stabilize and remodel newly formed blood vessels Excessive proliferation of endothelial cells and ensuing overgrowth of blood vessels Authors: Tony Gu Reviewers: Brian Rankin Yan Yu* Laurie Parsons* * MD at time of publication Formation of friable telangiectasias (small dilated vessels apparent near the surface of skin or mucous membranes) Formation of Arteriovenous malformations (AVMs): Direct connection between arteries and veins without intervening capillary bed Nasal telangiectasias Epistaxis (nosebleeds) Gastrointestinal telangiectasias Gastrointestinal bleeding Mucocutaneous telangiectasias Cerebral AVMs Hepatic AVMs Left to right shunting of blood Heart works harder to perfuse tissues Heart failure Pulmonary AVMs Rupture High flow left to right shunting of blood (the steal effect) Cerebral ischemia No oxygenation at capillaries Hypoxemia ↑ erythropoietin production Secondary polycythemia No filtering from capillaries Hemorrhage, shock, death Venous emboli enter arteries (paradoxical embolism) Stroke Venous bacteria enter arteries Cerebral abscess Iron deficiency anemia ↓ serum iron is associated with ↑ coagulation factor VIII levels (mechanism unclear) Venous thromboembolism Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 28, 2020 on www.thecalgaryguide.com

Pulmonary Hypertension

Pulmonary Hypertension: Pathogenesis and Clinical Findings Left heart disease (heart failure, myocardial infarction) ↓ contractility and/or diastolic relaxation ↓ left ventricle cardiac output Backup of blood in left ventricle and atrium Backup of blood in pulmonary vasculature ↑ pulmonary capillary wedge pressure– estimate of blood pressure in left atrium Chronic Anemia ↓ plasma hemoglobin content ↓ oxygen carrying capacity per unit blood Compensatory ↑ in heart rate to maintain tissue oxygen supply ↑ cardiac output Lung disease (chronic obstructive pulmonary disease) Tissue breakdown and ↓ lung elasticity Chronic thromboembolism Pulmonary vessel disease (pulmonary arterial hypertension, scleroderma) Vascular obstruction/fibrosis ↓ lungs’ ventilation ability ↓ surface areaà↓ gas exchange Lung vasculature undergo reflexive, localized vaso- constriction, to shunt blood to better ventilated areas Chronic hypoxemia ↓ local alveolar partial pressure of oxygen ↓ blood vessel compliance ↑ Pulmonary vascular resistance (PVR) Impaired gas exchange across thickened vessel walls ↓ blood partial pressure of O2 and ↑ partial pressure of CO2 Insufficient O2 provision & CO2 removal from tissues Reflexive mechanisms trigger harder & faster breathing to compensate Vascular fibrosis due to chronically increased pressures ↓ circulation of blood to left heart and ↓ filling of left ventricle ↓ left ventricle cardiac output Elevated blood pressure in the lung arteries Pulmonary Hypertension ↑ right-ventricle afterload (pressure against which the heart contracts to eject blood) ↓ right ventricle cardiac output ↑ residual volume in right heart after cardiac contraction Backup of blood in systemic circulation ↑ blood volume in venous system Myocardial hypertrophy develops over time (eccentric & concentric) ↑ tissue volume ↑ myocardial oxygen demand Myocardial ischemia (supply/demand mismatch) ↑ risk of chest pain in times of ↑ oxygen demand Peripheral edema Formation of aberrant conduction pathways and ectopic electrical foci Dysrhythmias Palpitations ↓ tissue perfusion Fatigue Dyspnea ↓ brain perfusion Syncope Authors: Grant E. MacKinnon Davis Maclean Hannah Yaphe Reviewers: Yan Yu* Jason Weatherald* * MD at time of publication ↑ volume and blood pressure in capillaries Fluid pushed from vessels into interstitial space of tissues Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 8, 2020 on www.thecalgaryguide.com

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

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

Pneumoconioses

Pneumoconioses: Pathogenesis and Clinical Findings Authors: Austin Laing Reviewers: Yan Yu* Tara Lohmann* * MD at time of publication Bronchogenic carcinoma and mesothelioma Inhalation of asbestos (Asbestosis) Inhalation of carbonaceous dust (Carboconiosis) Inhalation of metal dust (Metaloconiosis) Inhalation of silica dust (Silicosis) “-Coniosis”: disease which comes from inhaling dust particles Internalized asbestos fibers disrupt cellular processes through a complex series of theorized mechanisms Inhaled dust particles (1-5μm in size) are trapped and deposited in the alveolar airspaces Alveolar macrophages ingest dust particles, which activates the macrophages and sometimes causes apoptosis Activated macrophages create an inflammatory microenvironment by releasing pro-inflammatory cytokines, chemokines and reactive oxygen species Inflammatory products (e.g. reactive oxygen species) damage alveolar epithelial cells, causing activation and release of inflammatory cytokines into the alveolar space Inhaled dust particles, inflammatory products & other pro- tussive mediators activate airway vagal afferent receptors Activated receptors stimulate the cough center located in the medulla oblongata Cough Alveolar capillaries vasoconstrict in response to hypoxia à↑ Pulmonary vascular resistance Pulmonary Hypertension Right heart must pump blood into lungs against higher pressure àcardiomyocyte growth (via sarcomeres formed in parallel within myofibrils)àconcentric hypertrophy of right heart Cor Pulmonale (right heart failure due to pulmonary hypertension) Asbestos fibers accumulate in the airspace and translocate to the pleural surface Macrophage apoptosis: ↓ alveolar macrophages Fibroblasts are recruited to the alveolar wall and are activated Activated fibroblasts produce and deposit collagen in the extracellular space between alveoli Thickening of tissue between alveoli and capillaries ↑ the diffusion distance of atmospheric and blood gasses ↓ Diffusion of CO2 from blood to alveoli and ↓ diffusion of O2 from alveoli to blood ↑ Respiratory rate to maintain minute ventilation due to ↓ lung volumes and diffusion limitations Dyspnea and Exertional Hypoxemia ↓ Innate immune response in the lungs Chest X-Ray: Nodular and reticulonodular opacities are seen in varying lung regions depending on the underlying inhaled dust Excessive collagen deposition ↓ lung compliance and ↓ lung expansion ↓ Diffusing capacity for carbon monoxide (DLCO) on pulmonary function test ↓ Arterial oxygen contentà ↑ deoxyhemoglobin and ↓ oxyhemoglobin ↑ Deoxyhemoglobin within the vasculature causes the skin and mucous membranes to appear blue Cyanosis ↑ Risk of respiratory infections. Mycobacterial infections (e.g. tuberculosis) associated primarily with silicosis ↓ Inhalation volume ↓ Expiratory volume Hypoxemia ↓Total lung capacity (TLC) and ↓ residual volume (RV) on pulmonary function test ↓Forced vital capacity (FVC) and ↓ forced expiratory volume in 1 second (FEV1) on pulmonary function test Note: Forced Vital Capacity: the volume of air that can forcibly be blown out after full inspiration Forced Expiratory Volume in 1 second: the volume of air that can forcibly be blown out in first 1 second, after full inspiration Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 12, 2021 on www.thecalgaryguide.com

Hypercortisolemia

Hypercortisolemia (Cushing’s Syndrome): Clinical Findings Cortisol is a net catabolic hormone affecting many body systems, serving to release energy into the blood in response to stress. Excess cortisol also impacts circulation and impairs immune function. Excess Serum Cortisol affects: Authors: Samin Dolatabadi, Yan Yu* Reviewers: Meena Assad, Amanda Henderson, Brooke Fallis, David Campbell* * MD at time of publication Bone and Calcium Metabolism Kidney and vasculature Excess cortisol in the renal tubule saturates the enzyme 11β- HSD2, which converts cortisol to cortisone Capacity of body to convert cortisol to cortisone is exceeded Excess cortisol can mimic aldosterone and bind to mineralocorticoid receptors (cortisone can’t bind to these receptors) ↑ Aldosterone effect → ↑ Na+ reabsorption from the cortical collecting duct into blood vessels Liver and Peripheral Tissue Cortisol ↑ gluco- neogenesis in liver, and ↑ insulin resistance by body tissue (unclear mechanisms) Hyper- glycemia Reproductive System Cortisol exerts negative feedback on hypothalamus à↓ gonadotropin releasing hormone (GnRH) secretion ↓ GnRH → ↓ LH/FSH → ↓ estrogen and testosterone production (especially important in females) Infertility, ↓ Libido, Irregular Menses Adipose Tissue Cortisol ↑ fat breakdown (lipolysis) Selective expression of cortisol receptor on different adipose tissuesàcentral, facial, dorsal fat is less broken down than in other areas (mechanism unclear) Combined with cortisol ↑ appetite: Skin & Connective Tissue ↑ Serum cortisol à↓ Fibroblast proliferation → ↓ Collagen synthesis Skin atrophy with loss of connective tissue Muscle ↑ Proteolysis & ↓ Protein synthesisà↓ muscle growth and function Immune System Normal serum cortisol protects against damaging effects of uncontrolled inflammatory and immune responses ↑ Serum cortisolà over-suppression of inflammation and impaired cell- mediated immunity ↑ Serum cortisol leads to ↓ Intestinal Ca2+ absorption and ↓ renal Ca2+ reabsorption ↓ Serum Ca2+ ↑ PTH secretion ↑ Serum cortisolà↑ RANKL:OPG ratio ↓ Osteoblast activity & ↑ Osteoclast activity Cardiac muscle Cardio- myopathy, Heart Failure Skeletal muscle, especially upper arms & thighs (for unclear reasons) Proximal Muscle Weakness Easy Bruising ↑ abdominal size stretches the fragile skin to become thinneràvenous blood of the underlying dermis becomes visible Purple Striae If hypertension is chronic Ca2+ resorption from bone into the blood Osteoporosis Supraclavicular & Dorsal Fat Pads Central Obesity Poor Wound Healing Susceptibility to infection Round Face (Moon Face) Abbreviations: • RANKL – Receptor activator of nuclear factor kappa-Β ligand • OPG – Osteoprotegerin • 11β-HSD2 – 11β-hydroxysteroid dehydrogenase type 2 Water follows Na+ into blood vessels to balance the osmotic pressure between the blood and renal tubules Water reabsorption → Expansion of blood volume Hypertension Both primary Cushing’s (e.g. adenomas that extend into zona reticularis of the adrenal cortex) and central/secondary Cushing’s (e.g. ↑ ACTH stimulation of zona reticularis) are associated with ↑ adrenal androgen secretion Removal of positively charged Na+ from tubular lumen creates a negative luminal environment K+ follows the electrical gradient and is secreted into tubular lumen ↓ Serum K+ concentration Hypokalemia Arrhythmia, Paralysis, Cramps (see Hypokalemia: Clinical Findings slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 17, 2021 on www.thecalgaryguide.com Hirsutism, Acne

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

COPD-发病机制

COPD: 发病机制 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: ! 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " title="COPD: 发病机制 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 慢性阻塞性肺疾病 (COPD) 如果出现在气道周围 气流阻塞 肺不能完全排空 气体，气体潴留 于肺泡(肺过度 充气) 总呼气时长大于 正常时长 呼气相延长 肺组织损伤 呼气时，将空气排出肺外 的弹性回缩力↓ 肺不能完全排空气体， 气体潴留于肺泡内 (肺过度充气) 肺容积↑，膈肌紧张 性收缩(膈肌平坦) 呼气时，胸膜腔正压挤压气道 à 气道阻塞↑ 肺泡通气↓ 血液氧合↓ (低 氧血症) 身体组织灌注 量↓ (比如脑、 肌肉) 疲劳; 运动耐量↓ 黏液生成↑ 清除黏液的上皮纤 毛细胞数量↓ (受 气道炎症损伤) 慢性咳嗽伴咳 痰 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 容积较大 的肺需要 更加努力 才能通气 呼吸肌必须 更用力才能 呼吸 听诊闻及狭窄气 道中的湍流气流 呼气喘鸣音 呼吸困难 气促，尤其是劳累 膈肌无法进一步收缩以 产生深呼吸 呼吸浅快 为了呼吸， 胸壁必须延 展得更大 桶状胸 晚期病人: 患者试图在较高的口 慢性疲劳导致 患者动用辅助呼吸肌和膈肌呼吸， 腔内气压下进行呼气， 活动耐量下降 从而使气道更开放 以改善气流 晚期病人:膈肌 “平坦” ，持续吸气进一步压 缩膈肌à 向内拉季肋部胸壁 胡佛征 (吸气时，胸廓下侧季肋部内收) 缩唇呼吸 肌肉无力 & 消瘦 端坐呼吸 (调动胸肌) 颈部肌肉收 缩(胸锁乳 突肌、斜角 肌) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Findings on Investigations Chronic Obstructive Pulmonary Disease (COPD) Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication Airflow obstruction Lung tissue damage ↓ ventilation of alveoli Blood perfusing ill- ventilated alveoli does not receive normal amounts of oxygen During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction) No elastic recoil to push air out of lungs Loss of lung parenchyma and vasculature ↓ surface area for gas exchange ↓ diffusion capacity (on spirometry) Hypoxemia: PaO2 < 70mmHg (on ABGs) Abbreviations: • FEV1: Forced expiratory volume in 1 second • FVC: Forced vital capacity • TLC: Total lung capacity • VC: Vital Capacity Investigations for COPD : • Spirometry (Pulmonary function test) Total expiration time takes longer than normal FEV1/FEV < 0.7 (on spirometry) Lungs don’t fully empty More air trapped within lungs (hyperinflation) More CO2 remains and diffuses into the blood Hypercapnia: PaCO2 > 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " />

COPD-临床表现

COPD: 临床表现 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: ! 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " title="COPD: 临床表现 作者: Yan Yu 审稿人:Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人:Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 /012 (如a1-抗胰蛋白酶缺乏) 阻止肺组织损伤的能力↓ +,-. (如长期吸烟、环境污染、感染) 肺内产生自由基 34*5 肺抗蛋白酶的失活 ↑氧化应激，炎性细胞因子，蛋白酶功能 支气管的持续、反复损伤 炎性细胞浸润， 杯状细胞增殖， 气道上皮纤毛 尤其中性粒细 黏液产生↑ 细胞死亡 气道弹性↓ (弹性回缩 肺实质的蛋白水解破坏↑ 维持气道开放 肺泡永久性异常 的结构支持↓ 扩张 胞 力) 肺气体潴留 气道狭窄与 肺过度 肺大泡 气道黏液潴留，成为感染 狭窄 病灶 塌陷 充气 肺气肿 (容易肺泡 破裂) 气道纤维化和 %&'()* 慢性阻塞性肺疾病(COPD) 临床表现 并发症 (参阅相关幻灯片) (参阅相关幻灯片) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Clinical Findings Lung tissue Chronic Obstructive Pulmonary Disease (COPD) damage ↓ elastic recoil to push air out of lungs on expiration Lungs don’t fully empty, air is trapped in alveoli (lung hyperinflation) ↑ lung volume means diaphragm is tonically contracted (flatter) If occurring around airways Airflow obstruction ↑ mucus production ↓ number of epithelial ciliated cells to clear away the mucus (the cells have been killed by airway inflammation) Chronic cough with sputum Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction ↓ ventilation of alveoli ↓ oxygenation of blood (hypoxemia) ↓ perfusion of body tissues (i.e. brain, muscle) Fatigue; ↓ exercise tolerance Total expiration time takes longer than normal Prolonged expiration More effort needed to ventilate larger lungs Respiratory muscles must work harder to breathe Turbulent airflow in narrower airways is heard on auscultation Expiratory Wheeze Diaphragm can’t flatten much further to generate deep breaths To breathe, chest wall must expand out more Dyspnea Shortness of breath, especially on exertion Breathes are rapid & shallow If end-stage: Chronic fatigue causes deconditioning Muscle weakness & wasting Barrel chest If end-stage: diaphragm will be “flat”. Continued Patient tries to expire against higher mouth air pressure, forcing airways to open wider Pursed-lip breathing Patient breathes with accessory muscles as well as diaphragm to try to improve airflow inspiratory effort further contracts diaphragmà pull the lower chest wall inwards Hoover’s sign (paradoxical shrinking of lower chest during inspiration) Tripod sitting position (activates pectoral muscles) Neck (SCM, scalene) muscles contracted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 慢性阻塞性肺疾病 (COPD) 如果出现在气道周围 气流阻塞 肺不能完全排空 气体，气体潴留 于肺泡(肺过度 充气) 总呼气时长大于 正常时长 呼气相延长 肺组织损伤 呼气时，将空气排出肺外 的弹性回缩力↓ 肺不能完全排空气体， 气体潴留于肺泡内 (肺过度充气) 肺容积↑，膈肌紧张 性收缩(膈肌平坦) 呼气时，胸膜腔正压挤压气道 à 气道阻塞↑ 肺泡通气↓ 血液氧合↓ (低 氧血症) 身体组织灌注 量↓ (比如脑、 肌肉) 疲劳; 运动耐量↓ 黏液生成↑ 清除黏液的上皮纤 毛细胞数量↓ (受 气道炎症损伤) 慢性咳嗽伴咳 痰 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 容积较大 的肺需要 更加努力 才能通气 呼吸肌必须 更用力才能 呼吸 听诊闻及狭窄气 道中的湍流气流 呼气喘鸣音 呼吸困难 气促，尤其是劳累 膈肌无法进一步收缩以 产生深呼吸 呼吸浅快 为了呼吸， 胸壁必须延 展得更大 桶状胸 晚期病人: 患者试图在较高的口 慢性疲劳导致 患者动用辅助呼吸肌和膈肌呼吸， 腔内气压下进行呼气， 活动耐量下降 从而使气道更开放 以改善气流 晚期病人:膈肌 “平坦” ，持续吸气进一步压 缩膈肌à 向内拉季肋部胸壁 胡佛征 (吸气时，胸廓下侧季肋部内收) 缩唇呼吸 肌肉无力 & 消瘦 端坐呼吸 (调动胸肌) 颈部肌肉收 缩(胸锁乳 突肌、斜角 肌) 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Findings on Investigations Chronic Obstructive Pulmonary Disease (COPD) Author: Yan Yu Reviewers: Jason Baserman Jennifer Au Naushad Hirani* Juri Janovcik* * MD at time of publication Airflow obstruction Lung tissue damage ↓ ventilation of alveoli Blood perfusing ill- ventilated alveoli does not receive normal amounts of oxygen During expiration, positive pleural pressure squeezes on airwaysà↑ obstruction) No elastic recoil to push air out of lungs Loss of lung parenchyma and vasculature ↓ surface area for gas exchange ↓ diffusion capacity (on spirometry) Hypoxemia: PaO2 < 70mmHg (on ABGs) Abbreviations: • FEV1: Forced expiratory volume in 1 second • FVC: Forced vital capacity • TLC: Total lung capacity • VC: Vital Capacity Investigations for COPD : • Spirometry (Pulmonary function test) Total expiration time takes longer than normal FEV1/FEV < 0.7 (on spirometry) Lungs don’t fully empty More air trapped within lungs (hyperinflation) More CO2 remains and diffuses into the blood Hypercapnia: PaCO2 > 45 (on ABGs) Ventilation- perfusion mismatch High A-a gradient (calculated from ABGs) Low, flat diaphragm, >10 posterior ribs (on frontal CXR) High TLC and VC (on spirometry) • • PaO2: partial pressure of O2 in arterial blood PaCO2: partial pressure of CO2 in arterial blood • In the setting of fever and productive cough, especially if lung field opacifications are seen on CXR: consider sputum gram stain and culture to rule out pneumonia. Air does not block X-ray beams, will appear black on X-ray film Chronic hypercapnia makes breathing centers less sensitive to the high PaCO2 stimulus for breathing, & more reliant on the low PaO2 stimulus (“CO2 retention”) Give O2 carefully to these patients (high PaO2 may suppress patients’ hypoxic respiratory drive, ↓ their breathing, & ↑↑↑ PaCO2) ↑ retrosternal air space (on lateral CXR) Hyper-lucent (darker) lung fields, ↓ lung markings (on frontal CXR) • Arterial Blood Gasses (ABGs) • Chest X-Ray (CXR): frontal and lateral Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"#$ 气流阻塞 肺泡通气↓ 呼气时，胸膜腔正压挤压气 道à 阻塞↑ 作者: Yan Yu 审稿人: Jason Baserman, Jennifer Au, Naushad Hirani*, Juri Janovcik* 译者:Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 慢性阻塞性肺疾病 (COPD) 肺组织损伤 没有弹性回缩力将 气体排出肺 肺实质与血管分布减少导 致气体交换面积↓ 弥散功能↓ (肺功能检查) 更多的CO2残留 并扩散到血液中 高碳酸血症: PaCO2 > 45 (动脉血气) 血流灌注通气不良的肺泡 时无法获得足够的氧气 总呼气时长较正常长 FEV1/FEV < 0.7 (肺功能检查) 肺无法完全排空 更多空气潴留在肺部 (肺过度充气) 低氧血症: PaO2 < 70mmHg (动脉血气) 通气-灌注不匹配 肺泡-动脉氧分压差↑ (可通过动脉血气分析计算得出) 横膈低平， 下移至第10肋后端 及以下部位 (胸部正位片) TLC与VC增大 (肺功能检查) 缩写: • • FEV1: 1秒用 • VC:肺活量 PaO2: 动脉血 力呼气量 氧分压 空气不会阻挡X射线， 在X光片上呈现为黑色 慢性高碳酸血症使呼吸中枢对PaCO2 刺激呼吸的敏感性下降 & 更依赖于低PaO2的刺激 (“二氧化碳潴留”) 给患者吸氧时需注意(高PaO2 可能会抑制患者低氧时对呼吸的 刺激，使呼吸驱动↓ & PaCO2↑↑↑ ) • FVC: 用力肺 • 活量 • TLC:肺总量 慢阻肺相关检查 : PaCO2: 动脉 血二氧化碳 分压 胸骨后间隙↑ (胸部侧位片) 肺纹理↓ • 肺功能检查 • 动脉血气分析(Arterial Blood Gasses, ABGs) • 胸部正侧位片 • 当患者发热和湿咳，特别是胸片上见肺野不清晰时: 肺透亮度↑, (胸部正位片) 考虑进行痰革兰氏染色及痰培养以排除肺炎可能 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com COPD: Complications Lung inflammation Chronic Obstructive Pulmonary Disease (COPD) Airway obstruction ↓ inhaled air in alveoli and terminal bronchioles Rupture of emphasematous bullae on surface of lung Inhaled air leaks into pleural cavity and is trapped there Pneumothorax Feeling a loss of control over one’s life, and hopelessness for the future Goblet cell proliferation, ↑ mucus production Death of airway epithelium ciliated cells ↓ oxygenation of the blood passing through the lungs Chronic hypoxemia Kidneys compensate by ↑ erythropoietin (EPO) production ↑ Hemoglobin and red blood cell synthesis Polycythemia (secondary) Hypoxic alveoli cause the pulmonary arterioles perfusing them to reflexively vasoconstrict Since most alveoli in the lungs are hypoxic, hypoxic vasoconstriction occurs across entire lung Vasoconstriction ↑ blood pressure within lung vasculature Pulmonary hypertension ↑ workload of the right ventricle (to pump against higher pressures) To compensate, the right ventricle progressively hypertrophies and dilates, but over time its output ↓ Cor pulmonale (Right heart failure in isolation, not due to Left heart failure) Mucus trapped in airways, serve as nidus for infection Acute exacerbation of COPD (AECOPD) Pneumonia The chronic, systemic inflammation in COPD is a hyper-metabolic state that consumes calories Macro-nutrient deficiency Trouble with respiration lead to inactivity and deconditioning Wasting, muscle atrophy More inactivity and deconditioning perpetuates the cycle Depression Author: Yan Yu Reviewers: Jason Baserman Naushad Hirani* Juri Janovcik* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 7, 2013 on www.thecalgaryguide.com COPD: !"# 肺部炎症 杯状细胞增殖， 气道上皮纤毛 粘液产生↑ 细胞死亡 黏液潴留呼吸道，成为感 染的病灶 慢性阻塞性肺疾病 (COPD) 气道阻塞à 吸入肺泡和终末细 肺大疱破裂 吸入的空气渗入 并潴留于胸腔 气胸 感觉生活失控，对未 来感到绝望 抑郁 作者: Yan Yu 审稿人: Jason Baserman, Naushad Hirani*, Juri Janovcik* 译者: Zihong Xie (谢梓泓) 翻译审稿人: Yonglin Mai (麦泳琳), Zesheng Ye (叶泽生) * 发表时担任临床医生 支气管的空气 ↓ 流经肺的血液进行气 缺氧的肺泡à灌注肺泡的肺小动 慢性阻塞性肺疾 病急性加重期 (AECOPD) 肺炎 体交换↓ 慢性低氧血症 肾脏合成促红细胞 生成素进行代偿↑ 血红蛋白与红 细胞合成↑ 红细胞增多症 (继发性) 脉发生反射性血管收缩 肺大部分肺泡缺氧à整个肺 都出现缺氧性血管收缩 肺血管收缩 à 肺血管压力↑ 肺动脉高压 ↑ 右心室负荷(泵血时对抗高压) 为了代偿，右心室逐渐肥大和扩张， 但随着病程进展，右心室输出量 ↓ 肺心病 (单独出现右心衰竭，非左心衰) COPD所致的慢性全身 呼吸困难导致活 性炎症会使机体处于高 动量减少和活动 代谢状态，消耗能量 耐量降低 宏量营养 素缺乏症 消瘦，肌肉萎缩 运动量下降和活动耐量 的降低造成恶性循环 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年1月7日发布于 www.thecalgaryguide.com " />

chronic-hypertension-complications

Chronic Hypertension: Complications Chronic Hypertension Long term Blood Pressure (BP) ≥ 135/85 (on ambulatory or home blood pressure measurement) in patients without diabetes, or BP ≥ 130/80 in patients with diabetes Authors: Samin Dolatabadi, Yan Yu* Reviewers: Meena Assad, Jessica Krahn Juliya Hemmett* * MD at time of publication ↑ Afterloadà ↑ Resistance to left ventricle ejection To overcome resistance and preserve cardiac output, the myocardium undergoes structural and functional changes Left ventricular hypertrophy and fibrosis Stiff ventricle ↓ Contractility of the left ventricle Impaired forward flow of blood from heart Chronic stress on the endothelium of systemic blood vessels ↑ Blood pressure in retinal circulation Hypertensive Retinopathy (See slide on Chronic Hypertensive Retinopathy: Pathogenesis and Clinic Findings) Smooth muscle of kidney’s afferent arterioles constricts to prevent transmission of ↑ blood pressure to glomerulus Overtime, smooth muscles of afferent arterioles hypertrophy from prolonged vasoconstriction Chronic stress and trauma on endothelial and smooth muscle cells of kidney Injury leads to excretion of cytokines and extracellular matrix such as fibrin and collagen into subendothelial layer Endothelial dysfunction (See slide on Atherosclerosis: Pathogenesis) Atherosclerosis Loss of normal arterial architecture in the brain due to stress of ↑ blood pressure Weakening of cerebral arteries Formation and rupture of microaneurysms Intracerebral Hemorrhage Accumulation of plaques in the walls of cerebral arteries ↓ Cerebral blood flow Ischemic Stroke Accumulation of plaques in the walls of coronary arteries ↓ Myocardial blood flow Oxygen supply- demand mismatch Coronary Artery Disease Thickening of arteriolar wall and narrowing of afferent arterioles ↓ Glomerular blood flow Glomerular and tubular ischemia Glomerular sclerosis and tubular atrophy Blood backs up into lungs ↓ perfusion of blood throughout the bodyà inability of the heart to meet metabolic demands Congestive Heart Failure Hypertensive Nephrosclerosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 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

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

obstructive-sleep-apnea-pathogenesis-and-clinical-findings

Obstructive Sleep Apnea: Pathogenesis and clinical findings Vascular Factors: During recumbent sleep, more bodily fluids enter the head and neck area (compared to when the patient is standing/sitting) ↑ volume of head/neck tissue surrounding the upper airwayà possible airway obstruction Authors: Ciara Hanly Austin Laing Alexander Arnold Reviewers: Steven Liu Amogh Agrawal Yonglin Mai (麦泳琳) Naushad Hirani* Yan Yu* *MD at time of publication Neuromuscular Factors: Sleep onset and/or the sleeping state reduces the drive of respiratory muscles to breathe ↓ Upper airway neuromuscular activityà↓ upper airway caliber, ↑ upper airway resistance, ↑ upper airway collapsibility during sleep Structural Factors: Obesity, tonsillar or adenoid hypertrophy, macroglossia, ↑ neck circumference, craniofacial abnormalities Excess pressure on upper airway, or deformity to that area, ↑ risk of upper airway collapse Polysomnography Absence of airflow but persistent ventilatory effort Hypopnea or Apnea Paradoxical breathing Chest wall draws in and abdomen expands during inspiration Ventilatory effort persists against closed airway No air entry due to collapsed upper airway ↑ Negative intrathoracic pressure ↑ Venous return to right atrium Stretching of right atrial myocardium à secretion of atrial natriuretic peptide (ANP) ANP inhibits epithelial Na+ channels (ENaC) in the collecting ducts of the kidney from reabsorbing Na+ à Na+ excretion ↑ Na+ excretionà↑ water excretion Nocturia Complete or partial upper airway obstruction during sleep ↑ PCO2 & ̄ PO2 in the lungsà ̄ diffusion gradient of CO2 & O2 between lungs & arteries ↑ PaCO2,, ̄ PaO2 Respiratory acidosis (↑ [H+] in blood)àactivation of vascular endothelial voltage gated K+ channels Cerebral blood vessel dilation to provide adequate O2 to brain Morning Headaches Activation of central (medulla oblongata) & peripheral (carotid body) chemoreceptors ↑ Respiratory drive à ↑ activation of respiratory muscles (ventilatory effort ) Transient arousal from sleep ↑ sympathetic nervous system activityà arterial vasoconstriction ↑ systemic vascular resistance Systemic Hypertension ↑ intraluminal pressure within blood vesselsàadaptive vascular endothelial and smooth muscle changes Artery walls thicken, harden and lose elasticityà ̄ perfusion to end organs (such as the brain) Ischemic stroke Hypoxia during the day and night ↑ pulmonary vascular resistance Pulmonary Hypertension Right heart pumps against higher pulmonary pressure àcardiomyocytes undergo concentric hypertrophy over time Cor Pulmonale (Right heart failure due to pulmonary hypertension, separate from left heart failure) Respiratory muscles overcome upper airway obstructionà airway patency restored Sleep fragmentation ̄ Daytime cognitive performance and attentiveness ↑ Risk of motor vehicle accidents Daytime Sleepiness Eg. Epworth Sleepiness Scale >10 Abbreviations: PCO2: partial pressure of carbon dioxide PO2: partial pressure of oxygen PaCO2: partial pressure of carbon dioxide in arteries PaO2: partial pressure of oxygen in arteries Ventilatory response overcompensatesà breathe out more CO2 than is required for homeostasisà ̄ PaCO2 ̄ respiratory driveà ̄ ventilatory effort Resuscitative Gasping Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 19, 2013, updated May 31, 2022 on www.thecalgaryguide.com 阻塞性睡眠呼吸暂停:发病机制及临床表现 作者:Ciara Hanly, Austin Laing, Alexander Arnold 审稿人: Steven Liu, Amogh Agrawal, Naushad Hirani*,Yan Yu* 译者: Zesheng Ye(叶泽生) 翻译审稿人: Yonglin Mai(麦泳琳) *发表时担任临床医生 神经肌肉因素: 睡眠状态下, 患者无法通过 适当增加上气道肌张力来维持气道通畅 上气道神经肌肉活动 ̄à上气道直径 ̄, 上气道 阻力↑, 睡眠时上气道塌陷 结构(解剖)因素: 肥胖、扁桃体或腺样体 肥大, 舌体肥大, 颈围增大, 颅面部畸形 上气道压力过大或上气道畸形, 上气道塌陷 的风险 ↑ 血管因素: 仰卧位睡觉引起 夜间嘴侧液体移位 周围组织与压力 ↑à上气道阻塞 多导睡眠描记术 没有气流，但持 续通气 呼吸浅慢或 呼吸暂停 反常呼吸 吸气时胸壁凹陷, 腹部膨隆 持续通气以抵抗气道 闭合 上气道塌陷导致空气进 入气道受阻 腹膜腔负压↑ 静脉血回流右心室阻力↑ 右心房心肌细胞拉伸 à心房利钠肽分泌 (ANP) ANP抑制肾集合管的上 皮Na+通道(ENaC)对 Na+重吸收à Na+排出 Na+排出量↑ à 水排出量 ↑ 睡眠时全部 或部分上呼 吸道阻塞 肺内PO2 ̄ 且 PCO2↑ à CO2 及 O2在肺和动脉 间的扩散梯度 ̄ ↑ PaCO2, ̄ PaO2 呼吸性酸中毒 (血液中 [H+] ↑) à激活血管内皮电压 门控 K+ 脑血管扩张为大 晨间头痛 脑提供足够的 O2 激活中央(延髓)和外周(颈动脉体)的化学感受器 呼吸驱动↑à呼吸肌活动 (呼吸做功 )↑ 短暂的睡眠唤醒 通道 交感神经系统活动↑ 全天缺氧 肺血管阻力↑ 肺动脉高压 右心泵血以抵抗肺 动脉高压à 随着时 间推移，心肌向心 性肥大 肺心病(区别于左 心衰，右心衰是肺 动脉高压所致) 呼吸肌克服上气道阻力à 气道 明显恢复 睡眠过程不连续 白天的认知功能 及注意力 ̄ 机动车辆事故风险↑ 白天嗜睡 à 动脉收缩 全身血管阻力↑ 高血压 血管内压力↑ à 血 管内皮和平滑肌发生 适应性改变 动脉壁增厚、硬化、失 去弹性à器官血液灌 注量 ̄ (如脑部) 缩写: PCO2:二氧化碳分压 PO2:氧分压 PaCO2:动脉二氧化 碳分压 PaO2:动脉血氧分压 通气过度 à呼出CO2 ↑ à PaCO2 ̄ 呼吸驱动 ̄à 呼吸做功 ̄ 复苏性鼾音 夜尿症 如:伊普沃斯嗜睡评分 >10 缺血性卒中 图注: 病理生理 机制 体征/临床表现/实验室检查 并发症 2013年8月19日发表 www.thecalgaryguide.com, 2022年5月31日更新

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

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

Coronary Artery Bypass Graft CABG Indications

Coronary Artery Bypass Graft (CABG): Indications Author: Breanne Gordulic Reviewers: Miranda Schmidt Ben Campbell Sunawer Aujla Angela Kealey* * MD at time of publication Symptomatic multivessel (≥ 3 vessels) coronary artery disease (MVCAD) or complex MVCAD Acute coronary syndrome (ACS) Left main coronary artery disease Multivessel (≥ 3 vessels) CAD and diabetes Cardiac surgery required for other pathology Multivessel CAD, LV dysfunction and congestive heart failure (CHF) Complex CAD includes stenosed vein grafts, bifurcation lesions, calcified lesions, total occlusions, ostial lesions STEMI initial treatment is PCI/thrombolysis CABG outcomes compared to percutaneous coronary intervention (PCI) in MVCAD include ↑ survival in diabetes, ↑ survival with LV dysfunction, ↓ repeat revascularization, ↓ myocardial infarction, ↓ stroke ↑ Risk of failure in complex CAD with PCI Rapid reperfusion to myocardium most important in STEMI to decrease myocardial damage CABG can be considered for residual stenoses 6-8 weeks later NSTEMI or unstable angina (UA) with MVCAD involving at least three vessels including the proximal left anterior descending (LAD) Left main coronary artery divides into left anterior descending (LAD) and left circumflex (LCx) which supplies 2/3 of myocardium ↑ Survival Myocardial infarction from left main artery occlusion Death Left main stenosis Ventricular dysrhythmias Ongoing ischemia LV dysfunction Hemodynamic instability ↑ risk of PCI CABG has mortality benefit ↓ Number of operations ↑ Risk of cardiovascular disease in diabetes Revascularization indicated along with other cardiac surgery Multivessel CAD with >90% stenosis and CHF LV ejection fraction <35% ↑ Risk of atherosclerosis from hyperglycemia and dyslipidemia CABG bypasses several atherosclerotic plaques in coronary arteries ↑ Durability ↑ Complete perfusion Valve stenosis or regurgitation Septal defect Aortic root or arch pathology Combination procedure Evidence of ischemia at rest Evidence of impaired LV function at rest ↓ All-cause mortality in CABG vs medical management Chronic obstructive pulmonary disease Abbreviations: • ACS- acute coronary syndrome. Acute reduction in blood flow to heart muscle resulting in cell death. • CAD- coronary artery disease. Narrowing or blockage of the coronary arteries by plaque • NSTEMI- myocardial infarction (heart attack) with no ST elevation on electrocardiogram • PCI- percutaneous coronary intervention. A balloon tipped catheter is used to open blocked coronary arteries; a stent may be placed. • STEMI- myocardial infarction with ST segment elevation on electrocardiogram Consider revascularization (restore blood flow to blocked or narrowed blood vessels) of coronary arteries to increase perfusion to myocardium (heart muscle) Coronary artery bypass graft recommended Assess surgical risk and comorbidities with evaluation by heart team that includes both a cardiac surgeon and interventional cardiologist (SYNTAX Trial) Individual management plan for patients with comorbidities that increase mortality Frailty Chronic Renal Failure ↑ Inflammation and deregulated angiogenesis affects all organ systems ↓ Physiologic reserve and ↓ ability to recover from acute stress ↑ Pneumonia ↑ Respiratory and Renal Failure ↑ Stroke ↑ In hospital mortality ↓ Survival two years after surgery Use Society of Thoracic Surgeons Score, EuroSCORE, or SYNTAX II Score to predict patient outcome with anatomy, disease severity, and preoperative characteristics Coronary Artery Bypass Graft Surgery to take healthy blood vessels from the body and connect them proximally and distally to blocked coronary arteries Cardiopulmonary bypass, fluid overload, ↑ renal vasoconstriction and ↓ renal oxygenation from rewarming Kidney injury ↑ End stage kidney disease Blood flow restored to ischemic myocardium ↓ Angina ↑ Quality of life ↑ LV function ↑ Survival Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 12, 2023 on www.thecalgaryguide.com

Mitral Regurgitation Pathogenesis and clinical findings

Mitral Regurgitation: Pathogenesis and clinical findings Coronary Artery Disease Authors: Juliette Hall, Victoria Nkunu Reviewers: Raafi Ali, Jack Fu, Usama Malik, Sina Marzoughi, Jason Waechter* * MD at time of publication (Ischemic Heart Disease & Myocardial Infarction) Myocarditis Left ventricular dilation displaces papillary muscles Dilation of the Tethering of mitral valve annulus chordae tendineae ↑ Volume and pressure in left atrium ↑ Volume pushed back into left ventricle Dilated left ventricle Apical impulse on palpation and auscultation ↓ Forward flow of blood out of heart Blood backs up into pulmonary circulation ↑ Intravascular hydrostatic pressure in pulmonary vessels Fluid extravasates out of vessels and into the lungs Papillary muscle rupture Mitral valve leaflets flail Mitral valve prolapse Structurally abnormal valve Connective tissue disorders Weak valve leaflets Rheumatic heart disease Dilatation of the mitral valve annulus, inflammation of leaflets Infective endocarditis Vegetations form on valve leaflets Mitral Regurgitation Blood consistently flows backward throughout systole Holosystolic murmur, radiates to axilla, ↑ with afterload (e.g. making a fist) Backflow of blood from left ventricle to left atrium due to impaired mitral valve closure S3 heart sound Myocardial remodeling ↓ Muscle efficiency ↓ Left ventricle systolic function ↓ O2 saturation, tachypnea, wheeze, ↑ work of breathing, crackles, frothy sputum (if severe) Congestive heart failure ↓ Stroke volume ejected into aorta ↓ Cardiac output ↓ Organ perfusion ↓ O2 to kidney Activation of renin-angiotensin- aldosterone system ↑ Reabsorption of water by kidneys ↑ Intravascular hydrostatic pressure systemically Peripheral edema Injury to kidney parenchyma ↓ ability for kidney to clear creatinine ↑ Serum creatinine Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 3, 2018, updated Oct 15, 2023 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

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