SEARCH RESULTS FOR: obstruction

lower-urinary-tract-infections-complications

Predisposing Factors: Immunocompromised state, diabetes, elderly, female (short urethra), stagnant urine (anatomical variant, obstruction, neurogenic bladder, urinary reflux) Bacterial entry (Less Common): Indwelling catheter, surgical inoculation, hematogenousspread, trauma (Staphylococcus, Enterococcus, Candida) Fecal bacteria access urethra (E. coli, Proteus, Klebsiella) Impairment of body's natural defense systems, or stagnant urine, allow for bacterial accumulation Portal of entry bypasses body's physical defenses (gravity and repetitive outward urine flow) Bacterial fimbriae and pili allow them to ascend urethra and adhere to epithelium Lower Urinary Tract Infection (LUTI): Pathogenesis and clinical findings Suprapubic Tenderness Bacterial colony irritates urinary epithelium Urgency: Sensation of need to urinate quickly or impending incontinence Stimulation of inflammatory response Stimulation of urinary reflex Pathogens use enzymes to reduce nitrate to nitrite Delirium in Elderly Frequency: Repetitive need to urinate Unique response of altered fluid status, electrolytes and mental status, likely as a result of increased inflammatory cytokines Lower Urinary Tract Infection (“Cystitis”): Infection of bladder or distal tract by capable bacteria colonizing epithelium and causing symptoms Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 16, 2014 on www.thecalgaryguide.com Author: Brett Edwards Reviewers: Riley Hartmann Jan Rudzinski Haotian Wang Steve Vaughan* * MD at time of publication Usual Pathogens (“KEEPS”): K – Klebsiella E – E. coli (90%) E – Enterococcus, Enterobacteriaceae P – Proteus, Pseudomonas S – Staph. saprophyticus, Serratia Urine Findings: ↑ Colony Count (>107 CFU/L) ↑ WBC (>10 WBC/μL) (+) Bacterial culture (+) Nitrites, Leukocyte Esterase (+) Foul, turbid urine +/- Hematuria (rare)

lower-urinary-tract-infection-pathogenesis-and-clinical-findings

Predisposing Factors: Immunocompromised state, diabetes, elderly, female (short urethra), stagnant urine (anatomical variant, obstruction, neurogenic bladder, urinary reflux) Bacterial entry (Less Common): Indwelling catheter, surgical inoculation, hematogenousspread, trauma (Staphylococcus, Enterococcus, Candida) Fecal bacteria access urethra (E. coli, Proteus, Klebsiella) Impairment of body's natural defense systems, or stagnant urine, allow for bacterial accumulation Portal of entry bypasses body's physical defenses (gravity and repetitive outward urine flow) Bacterial fimbriae and pili allow them to ascend urethra and adhere to epithelium Lower Urinary Tract Infection (LUTI): Pathogenesis and clinical findings Suprapubic Tenderness Bacterial colony irritates urinary epithelium Urgency: Sensation of need to urinate quickly or impending incontinence Stimulation of inflammatory response Stimulation of urinary reflex Pathogens use enzymes to reduce nitrate to nitrite Delirium in Elderly Frequency: Repetitive need to urinate Unique response of altered fluid status, electrolytes and mental status, likely as a result of increased inflammatory cytokines Lower Urinary Tract Infection (“Cystitis”): Infection of bladder or distal tract by capable bacteria colonizing epithelium and causing symptoms Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 16, 2014 on www.thecalgaryguide.com Author: Brett Edwards Reviewers: Riley Hartmann Jan Rudzinski Haotian Wang Steve Vaughan* * MD at time of publication Usual Pathogens (“KEEPS”): K – Klebsiella E – E. coli (90%) E – Enterococcus, Enterobacteriaceae P – Proteus, Pseudomonas S – Staph. saprophyticus, Serratia Urine Findings: ↑ Colony Count (>107 CFU/L) ↑ WBC (>10 WBC/μL) (+) Bacterial culture (+) Nitrites, Leukocyte Esterase (+) Foul, turbid urine +/- Hematuria (rare) WBCs onsite release enzymes Cytokines released systemically Fever, Malaise, ↑WBC (>11 x 109 cells/L) (Rare in LUTI)

Pulsus Paradoxus

Yu Yan - Pulsus Paradoxus - FINAL.pptx Lungs are hyperinflated, and vascular beds are more expanded? BP on inspiration (<10mmHg)Pulsus ParadoxusThrombi in the pulmonary arteries ? blood filling pulmonary vasculatureLegend:Published January 21, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceLaura CraigNanette Alvarez** MD at time of publication? ? ? forward blood flow from lungs into left heartWith cardiac pathology external to myocardium(Cardiac tamponade, or rarely with constrictive pericarditis)? Right heart filling, ? blood flow into lung vesselsMore blood returns to R heart ? more blood enters and pools in pulmonary vasculature? blood returns to the left heart, ? its fillingWith obstructive lung diseases (i.e. COPD)With vascular pathology (rare):InspirationNormally:? lung volume ? ? intra-vascular volume within pulmonary blood vessels ? ? lung capacitance for blood, ? R heart afterloadPulsus Paradoxus:Exaggerated ?in systolic BP on inspiration (>10mmHg)? left heart stroke volume/cardiac outputOn inspiration, ? ? ? blood enter lungs and pools within pulmonary vasculature? ? ? left heart stroke volume/cardiac outputAbnormally:On inspiration, as pulmonary intra-vasculature volume expands and blood pools within, flow into the left heart ? ? ? Pulmonary embolism? venous return to R heartVena cava obstructionBy thrombi, or external compression by masses/ fibrosis (from obesity, pregnancy) As ? blood fills R heart on inspiration, external constraints on myocardium ? cardiac expansion, interventricular septum is pushed into LVThere is no room in the pericardial sac for the LV to expand and maintain normal end diastolic volume (i.e. ? LV filling) 98 kB / 233 words

localized-pitting-edema

Localized Pitting Edema: Pathogenesis Central venous catheter insertion -11I• Insufficient venous valves Foreign body irritates the endothelium, causing endothelial injury 1` pro-fibrotic gene activation & pro-inflammatory factors Smooth muscle proliferation & thickening of the venous endothelial layer Central vein stenosis 1` in venous blood pooling, causing venous congestion -1111. Venous insufficiency 1` in venous blood • pressure Extrinsic compression (i.e. tumor) Authors: Sunny Fong Reviewers: Joseph Tropiano Adam Bass* * MD at time of publication Central vein thrombosis Deep vein thrombosis T in venous pressure is transmitted to the capillaries 1` in capillary hydrostatic pressure T in fluid extravasation from plasma into the interstitial space distal to site of obstruction or insufficiency Localized Pitting Edema: Edema fixed at a specific anatomical site Venous obstruction causes'` blood pooling distal to site of obstruction Starling's Equation: Net filtration gradient = LpS x ((Pap — Pint) Olcap LpS = Porosity or permeability of the endothelial layer Pup = Capillary hydrostatic pressure Pint = Interstitial hydrostatic pressure ncap = Capillary oncotic pressure flint = Interstitial oncotic pressure Note: An increase in net filtration gradient (eg. Increased capillary hydrostatic pressure or decreased capillary oncotic pressure) can lead to the formation of edema

pathogenesis-of-select-causes-of-constipation-in-adults-and-in-elderly

Pathogenesis of Select Causes of Constipation in Adults and in Elderly Authors: Reviewers: Lina Cadili Peter Bishay Joseph Tropiano Kirles Bishay* *MD at time of publication Mechanical Metabolic Endocrine Neurological Myogenic Pelvic Floor IBS-C Drugs (ex. Bowel (ex. (ex. (ex. Multiple (ex. Dyssynergia (ex. Opioid Obstruction, Stricture) Hypercalcemia) Hypothyroid-ism) Sclerosis) Scleroderma) Analgesics) Mechanical I`Ca2+ = 4, Na+ Thyroid Demyelination Collagen Puborectalis Disturbance in obstruction in permeability in hormone of CNS neurons deposits into muscle and the gut-brain the bowel neurons deficiency colonic mucosa, leading to external anal sphincter fail interaction fibrosis of the gut wall to relax Interrupted 4, Excitability Possible Dysfunction of Narrowed Mechanism flow of bowel contents and tone of bowel smooth mechanisms: hormone autonomic nerves that anorectal angle and unknown, many Atrophy of the muscle receptor supply smooth muscle '`pressure of pathways changes, involuntary wall of the colon anal canal neuromuscular disorders, myopathy from bodily functions 1, Peristalsis of infiltration of 4, Ability of the Evacuation Visceral the bowel colon to contract of feces is hypersensitivity Abbreviations: the intestinal wall 4, Digestion less effective and 4, colonic and colonic motility motor • IBS-C: Irritable Bowel Syndrome with predominant constipation • CNS: Central Nervous System 4, Peristalsis of response after a meal the bowel Opioids bind to Lt-opioid receptors on gut wall Inhibition of excitatory neural pathways within the enteric nervous system 1, Peristaltic contractions 1 l• Colonic transit time

Pituitary Mass Effects

Pituitary Mass Effects Note: pituitary tumors are almost always a benign adenoma. Pituitary adenomas are very common -approximately 1 in 6 individuals. These are usually asymptomatic and are found incidentally. Symptomatic pituitary adenomas that require treatment are much less common and affect approximately 1 in 1000 individuals. Pituitary tumor Note: typically (but not always) the anterior hormones will be lost in the following order; GH, LH, FSH, TSH, ACTH, PRL. This order (with the exception of prolactin) is the order of least-essential to most-essential hormones needed for survival. A good mnemonic to remember the order the hormones are is, 10mm on MRI) vomiting Giant adenoma Extension into hypothalamus —1■• Damage to hypothalamic cells Hypothalamic (>40mm on MRI) dysfunction Obstruction of dopamine Superior tumor growth Impingement of the optic chiasma Bitemporal Loss of pituitary hemianopsia hormones ICP Suprasellar extension Occlusion of ventricles Obstruction of CSF Flow Hydrocephalus Lateral tumor growth Impingement of cranial nerves 3, 4, 5 (V1/V2) and 6 4 Pituitary stalk impingement Diplopia Inferior tumor growth Erosion into sphenoid sinus CSF leak into throat Post-nasal Obstruction of ADH drip Communication between sinus and brain Migration of bacteria from sinus flora Hyper-Diabetes Meningitis prolactinemia insipidus Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 1 2017 on www.thecalgaryguide.com " title="Pituitary Mass Effects Note: pituitary tumors are almost always a benign adenoma. Pituitary adenomas are very common -approximately 1 in 6 individuals. These are usually asymptomatic and are found incidentally. Symptomatic pituitary adenomas that require treatment are much less common and affect approximately 1 in 1000 individuals. Pituitary tumor Note: typically (but not always) the anterior hormones will be lost in the following order; GH, LH, FSH, TSH, ACTH, PRL. This order (with the exception of prolactin) is the order of least-essential to most-essential hormones needed for survival. A good mnemonic to remember the order the hormones are is, "Go Look For The Adenoma Please". Legend: Note: for pituitary masses of all sizes, it is important to determine whether the pituitary tumor is secreting (70%) or non-secreting (30%) as secreting tumors can be targeted with medication. The most common secreting tumors secrete prolactin (most common), growth hormone, and ACTH. Authors: Chris Oleynick Reviewers: Amyna Fidai Laura Byford-Richardson Joseph Tropiano Hanan Bassyouni* * MD at time of publication Microadenoma Small size is unlikely to cause mass effects (<10mm on MRI) Asymptomatic Macroadenoma Large size may press on surrounding structures, causing mass effects Headaches Stretching of the meninges Activation of mechanoreceptors Nausea and (>10mm on MRI) vomiting Giant adenoma Extension into hypothalamus —1■• Damage to hypothalamic cells Hypothalamic (>40mm on MRI) dysfunction Obstruction of dopamine Superior tumor growth Impingement of the optic chiasma Bitemporal Loss of pituitary hemianopsia hormones ICP Suprasellar extension Occlusion of ventricles Obstruction of CSF Flow Hydrocephalus Lateral tumor growth Impingement of cranial nerves 3, 4, 5 (V1/V2) and 6 4 Pituitary stalk impingement Diplopia Inferior tumor growth Erosion into sphenoid sinus CSF leak into throat Post-nasal Obstruction of ADH drip Communication between sinus and brain Migration of bacteria from sinus flora Hyper-Diabetes Meningitis prolactinemia insipidus Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 1 2017 on www.thecalgaryguide.com " />

Ischemia: Pathogenesis of Cellular Injury and Death

Ischemia: Pathogenesis of Cellular Injury and Death 4, Cardiac Output Obstruction of Blood Flow 4, Oxygen Carrying Capacity Inadequate oxygenation of body tissues • lschemia • 4, oxygen availability to body tissues with inadequate oxygen supply • Hypoxia/Anoxia 4, cellular oxidative phosphorylation Authors: Tiffany Yuen Reviewers: David Lincoln Erin Davison Usama Malik Dr. P. Timothy Pollak* * MD at time of publication Anaerobic respiration • vir Failure to resynthesize energy-rich phosphates & phosphocreatine Catabolism of ATP -> AMP Altered ATP-dependent ionic membrane pump Intracellular accumulation of intracellular Ca2+ intracellular hypoxanthine & H2O Conversion of hypoxanthine Activation of phospholipases & Cellular Edema production of free fatty acids -> toxic oxygen species Reperfusion and re-introduction Phospholipases and free fatty acids degrade cellular membranes of molecular oxygen Legend: Pathophysiology Mechanism Cellular Injury and/or Cellular Death Sign/Symptom/Lab Finding Complications 4, pH Lactic acidosis • 1` Fe decompartmentalization Mitochondrial injury 1` free-radicals NADH degradation 4, ATP levels Nuclear damage

Bronchogenic Carcinoma - Pancoast Tumors Pathogenesis and clinical findings

Bronchogenic Carcinoma - Pancoast Tumors Pathogenesis and clinical findings Abbreviations: • NSCLC- Non Small Cell Lung Cancer • SCLC — Small Cell Lung Cancer • RLN — Recurrent Laryngeal Nerve • SVC — Superior Vena Cava • RA — Right Atrium • STM — Superior Tarsal Muscle Chest pain Pleural rubs Shoulder pain SCLC (less common) Endothoracic fascia 1— Parietal pleura • 1— Upper ribs Large Cell Carcinoma Adenocarcinoma Squamous Cell Carcinoma Primary Bronchogenic Carcinoma Pancoast tumor: Local/metastatic growth in ipsilateral lung apex Disruption of structures adjacent to superior pulmonary sulcus NSCLC (more common) Invasion of airways ► causing obstruction (later stages) Author: Bradley Stebner Daniel Meyers Midas (Kening) Kang Reviewers: Natalie Morgunov Sadie Kutz Usama Malik Kerri Johannson* *MD at time of publication Notes: • Pancoast Tumor: Malignant lesion occupying the superior pulmonary sulcus (lung apex) Bronchogenic carcinoma: primary malignant neoplasm arising from epithelium of bronchus or bronchiole Pancoast tumors can be caused by primary or metastatic pulmonary neoplasms (described here) as well as infectious foci Hemoptysis Compression of C8 and T1 nerves • Disruption of paravertebral sympathetic chain Shoulder • Weakness in intrinsic Horner's • 4, sympathetic to to iris muscle Syndrome 4, sympathetic radial to eccrine sweat gland Pain (ulnar hand muscles nerve) 4, sympathetic innervation STM Paresthesia in 4th /5th digits and arm/forearm medial Ptosis Mi o sis Anhidrosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Compression of SVC SVC Syndrome • 4, venous return to RA 4, Cardiac output to lungs Dyspnea Disruption of RLN 1 Hoarse voice 4, venous drainage from upper thoracic cavity Retention of fluid in upper limb •)r Facial and limb swelling

Asthma Acute Exacerbation: Pathogenesis and Treatment

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

Bronchiectasis Pathogenesis and clinical findings

Bronchiectasis: Pathogenesis and clinical findings Acquired immunodeficiency Lymphoma, HIV, transplant Autoimmune Lupus, inflammatory bowel disease, rheumatoid arthritis Congenital/Genetic Cystic fibrosis, A1AT deficiency, Marfan, immunoglobulin deficiency, Kartagener syndrome, Young syndrome Endobronchial obstruction Neoplasm, foreign body, lymph node compression Other Inhalation exposure (smoke, ammonia), MAC complex infection, COPD, allergic bronchopulmonary aspergillosis, chronic infections Irreversibly dilated bronchi Chronic bronchial infection and inflammation 1 Easily collapsible airways I Bronchiectasis (persistent and progressive damage to lungs) Chronic cough (mucopurulent) Defect in immunity and/or mucus clearance Persistent bacteria in airway (commonly Pseudomonas/Staph aureus) Inflammatory response Rhinosinusitis Abbreviations: • A1AT — Alpha-1-antitrypsin • COPD — Chronic Obstructive Pulmonary Disease • HIV — Human Immunodeficiency Virus • MAC — Membrane Attack Complex • VQ— Ventilation/Perfusion ratio Legend: Pathophysiology Mechanism Fever Sign/Symptom/Lab Finding Failure to thrive (children) Authors: Rebecca (Becky) Phillips Reviewers: Midas (Kening) Kang Usama Malik Eric Leung* * MD at time of publication Notes: • Can be focal (single lobe/segment) or diffuse (both lungs) • Mainly in elderly • 1% prevalence in children Tissue damage Epithelial destruction of airways Further impairment of bacterial clearance Persistent inspiratory adventitious sounds (crackles > wheezing) Complications Structural damage to bronchial walls Obstructive pulmonary function tests Hemoptysis Chest pain VQ mismatch and 4, gas exchange 4, oxygenation Digital clubbing (rare) Fatigue Dyspnea Cyanosis (uncommon)

Lung cancer clinical findings and paraneoplastic syndromes

Lung cancer: clinical findings and paraneoplastic syndromes Note: most presentations of lung cancer are very subtle with non-specific symptoms and signs (i.e. fever, weight loss, general malaise) Obstruction of proximal airway Inability to clear inhaled pathogens Postobstructive pneumonia Cough, fever, dyspnea Local tumor growth Spread of tumor to pleural surface Chest Pleural discomfort effusion • Obstruction or compression at local site Uncontrolled abnormal cell growth in one or both lungs 4 Lung Cancer Airway invasion Hemoptysis Lambert-Eaton syndrome (Production of auto-antibodies against Calcium channels) Muscle weakness I` effort to Compression at the Compression Superior vena ventilate the laryngeal nerve of brachial cava lungs nerve plexus compression Impaired innervation to the vocal cords Dyspnea Shortness of Arm/shoulder/ Face/arm breath Voice hoarseness neck pain edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Authors: Yoyo Chan Reviewers: Midas (Kening) Kang Usama Malik Leila Barss* * MD at time of publication Tumor secretes biologically active substances Paraneoplastic Syndromes 4 Associated symptoms with malignant diseases TGF131 extracellular matrix protein Fingers clubbing PTHrP T calcium release from bones Hypercalcemia Serum calcium >2.6 mmol/L ADH 1 SIADH T water reabsorption 1 Hyponatremia Serum sodium <135mEq/L Abbreviations: • ACTH: Adrenocorticotropic hormone • ADH: Anti-diuretic hormone • PTHrP: Parathyroid hormone-related protein • SIADH: Syndrome of inappropriate antidiuretic hormone production • TGFI31: Transforming growth factor beta 1 1` ACTH cortisol release and production Cushing's syndrome (symptoms and signs caused by prolonged cortisol exposure) Muscle weakness, hyperglycemia, severe hypokalemia

Benign Prostatic Hyperplasia: Pathogenesis and medications

Benign Prostatic Hyperplasia: Pathogenesis and medications Aging Testosterone Testosterone metabolized into DHT by type II 5- a-reductase in prostate DHT binds to androgen receptor in prostate cell nuclei Hyperplasia of the prostate Prostate encapsulated by fibromuscular tissue, therefore grows inwards Prostatic urethral compression and bladder outlet obstruction Legend: a-1 blockers (e.g. tamsulosin) Note: MoA not fully established PDE-5 inhibitors (e.g. tadalafil) Bladder and prostate smooth-muscle a-1 receptor antagonism —110. Relaxation of bladder outlet and prostate smooth-muscle Authors: Michael Korostensky Reviewers: Alex Tang Usama Malik Dr. Jay Lee* * MD at time of publication Acronyms: 5-ARI = 5-a reductase inhibitors COX = cyclooxygenase DHT = dihydrotestosterone GnRH = gonadotropin-releasing hormone LUTS = lower urinary tract symptoms PDE-5-mediated cGMP degradation in prostate smooth-Improved urinary outflow muscle and associated vascular supply Relaxation of prostate smooth-muscle MoA = mechanism of action NSAID = nonsteroidal anti-inflammatory drugs PDE-5 = phosphodiesterase-5 -NO 5-ARIs (e.g. dutasteride) LHRH receptor antagonists (e.g. cetrorel ix) P3-adrenergic agonists (e.g. mirabegron) anticholinergics (e.g. oxybutynin) NSAIDs 1` Bladder pressures Pathophysiology Mechanism 5-a-reductase activity 1, Conversion of testosterone into DHT 4, Progression of LUTS 1, Testosterone secretion from testicular Leydig cells 1, LH secretion from pituitary GnRH antagonism DHT production Relaxation of detrusor Bladder muscle 1` capacity Improved LUTS Acetylcholine antagonism at muscarinic receptors Relaxation of bladder outlet smooth-muscle 1` volume to first detrusor contraction 4, Prostaglandin release Analgesia and 4, Prostatic ,f, COX activity ► inflammation —110. Bladder smooth-muscle hyperplasia (detrusor thickening) /1` Sensitivity (i.e. overactive detrusor) -1110. 1, Volume to first detrusor contraction LUTS

Mixed Urinary Incontinence Pathogenesis and clinical findings

Mixed Urinary Incontinence: Pathogenesis and clinical findings Abbreviations: • BOO — Bladder Outlet Obstruction • BPH — Benign Prostatic Hyperplasia • CNS — Central Nervous System • IAP — Intra-abdominal pressure • OAB — Over-Active Bladder • PVR — Post Void Residual • SUI —Stress Urinary Incontinence • UTI — Urinary Tract Infection • UUI — Urge Urinary Incontinence Mixed Urinary Incontinence 47 Urinary leakage accompanied by both urgency and t intra-abdominal pressure Urgency Urinary Incontinence (UUI) 4, Urinary leakage preceded by a sudden, strong urge to void Overflow Incontinence vir Overfilling of the bladder from obstruction; BOO (tumour, stone, BPH, urethral or bladder neck stricture) Detrusor Overactivity Ilr OAB (idiopathic), CNS lesion (neurogenic), inflammation/ infection (cystitis, UTI), diabetes mellitus 4. Bladder Wall Compliance Progressive t in intravesicle pressure during bladder filling pushing urine from the bladder Authors: Braden Millan Reviewers: Alex Tang Usama Malik Jay C. Lee* * MD at time of publication Stress Urinary Incontinence (SUI) + Episodic involuntary urinary leakage with sudden l• in intra-abdominal pressure 4. Urethral hypermobility, intrinsic sphincter deficiency, or a poorly coapting urethra 4, 4, Pelvic floor muscle and ligament strength causing 4. tone of vesicoureteral sphincter unit; 4, urethral strength and associated striated and smooth muscle; iatrogenic Legend: Failure to Void Weak Stream (+ dribbling), Intermittent, Straining, '1` PVR if a complication of urinary retention; obstruction visible on cystoscopy Failure to Store Frequency, Urgency, Nocturia, Dysuria if SUI or UUI not caused by obstruction Pathophysiology Mechanism Urodynamic Studies SUI — 4, urethral closure pressure with 11` IAP/Bladder Volume and urinary leakage UUI — involuntary detrusor contraction and/or detrusor sphincter dyssynergia Incontinence, 4, Quality of Life, UTI's

Periorbital Cellulitis: Pathogenesis and Clinical Findings

Periorbital Cellulitis: Pathogenesis and Clinical Findings Authors: Amanda Marchak Reviewers: Jaimie Bird Dr. Rupesh Chawla* * MD at time of publication Staphylococcus aureus, Streptococcus pyogenes (most common organisms) Note: Also referred to as preseptal cellulitis Dacryoadenitisa Conjunctivitisb Acute chalazionc Dacryocystitisd Hordeolume Streptococcus pneumoniae, Moraxella catarrhalis, non-typable Haemophilus influenza (most common organisms) Abrasion Insect bite Burns Trauma Local infection Contiguous spread of infection Sinusitis Otitis media Hematogenous spread Local break in skin Micro-organisms enter Definitions: Note: Eye exam should reveal normal: - extra-ocular movements and globe position - pupillary reflex and visual acuity If any are abnormal, the presentation is no longer considered periorbital cellulitis, as the infection has likely spread beyond the preseptal compartment/orbital septum. If the eye cannot be assessed, the patient NEEDS a CT scan. Pathogens reach dermis and subcutaneous periorbital tissue Periorbital Cellulitis a. Dacryoadenitis: infection of the lacrimal glands b. Conjunctivitis: inflammation of the conjunctiva c. Chalazion: a benign, painless bump or nodule inside the upper or lower eyelid which results from healed internal hordeolums that are no longer infectious. d. Dacryocystitis: an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of lacrimal sac. e. Hordeolum: localized infection or inflammation of the eyelid margin involving hair follicles of the eyelashes or meibomian glands. Spreads beyond preseptal compartment/orbital septum Involves the orbit Orbital cellulitis See slide on Orbital Cellulitis: Pathogenesis and clinical findings Localized inflammation Pain on palpation Induration Warmth Eyelid and periorbital edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Sinusitis: Pathogenesis and clinical findings

Sinusitis: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Abbreviations URTI – Upper respiratory tract infection Nasal obstruction/ congestion Hyposmia Headache Facial pain/pressure Maxillary tooth pain Ear pain/ fullness Osteomyelitis of frontal bone Chemical irritants Cystic Fibrosis Direct toxic effect on cilia Viral URTI Allergies Inflammation of paranasal sinuses Edematous passageways Septal deviation Adenoid hypertrophy Polyps Turbinate hypertrophy Tumors Foreign body Dysfunctional cilia Congenital and/or craniofacial abnormality Obstruct sinus ostia Cilia unable to clear mucus from sinuses Mucus unable to drain through ostia Post-nasal drip Mucus overflows from the sinuses Cough Mucus accumulates in sinuses Occupies a larger volume Applies ↑ pressure to sinus walls Mucopurulent discharge Bacterial1 overgrowth in sinuses Bacterial infection spreads to adjacent structures Halitosis Pharyngitis Throat clearing Dental root infection Immunodeficiency Note: Irritates the back of the throat Perforation of the Schneiderian membrane2 Passage of bacteria into the sinuses Fever Fatigue Subperiosteal orbital abscess Orbital abscess Orbital edema ↑ susceptibility to bacteria 1. The most common bacteria are Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis. Staphylococcus aureus and Group A Streptococcus may be seen, but are less common. However, in cases of dental root infection, oral anaerobes become more common, while Pseudomonas species are associated with foreign bodies. 2. The Schneiderian membrane is the membranous lining of the maxillary cavity. Cavernous sinus thrombosis Meningitis Cerebral abscess Subdural abscess Epidural abscess Periorbital or orbital cellulitis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

Vesicoureteric reflux (VUR): Pathogenesis and clinical findings

Vesicoureteric reflux (VUR): Pathogenesis and clinical findings Authors: Nicola Adderley Reviewers: Emily Ryznar *Lindsay Long * MD at time of publication Abnormal function Abnormal anatomy Neurogenic bladder (e.g. cerebral palsy, constipation, spinal injury, iatrogenic) Non-neurogenic bladder (neuropsychological) Lower urinary tract abnormality (posterior urethral valves, meatal stenosis) Bladder outlet obstruction ↑ pressure distorts UVJ Upper urinary tract abnormality (ureters) UVJ abnormality Incomplete closure of UVJ during bladder contraction Abbreviations • UVJ - ureterovesicular junction • UTI – urinary tract infection Failure of bladder sphincter to relax during bladder contraction Vesicoureteric reflux (VUR): Back flow of urine from the bladder into one or both ureters +/- kidneys Migration of lower urinary tract bacteria to kidneys Bacterial invasion of renal parenchyma Upper UTI (pyelonephritis) Incomplete emptying of bladder during Abnormal ↑ pressure in bladder Bladder dilates Dilated bladder on U/S urination Bacteria in bladder are not cleared during urination voiding habits ↑ bladder capacity Renal scarring ↓ functional renal tissue *Chronic kidney disease (↓ GFR, hypertension, proteinuria) Flank tenderness Fever, dysuria, urgency, frequency Lower UTI (cystitis) Urinary stasis Cloudy, foul- smelling urine Urethral stricture Notes Urgency, dysuria, frequency • First febrile UTI in an infant should trigger a work-up for VUR • High likelihood of spontaneous resolution • *Late complication of severe VUR Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 19, 2018 on www.thecalgaryguide.com

Microangiopathic Hemolytic Anemia: Pathogenesis and clinical findings

Microangiopathic Hemolytic Anemia: Pathogenesis and clinical findings Authors: Jocelyn Law Reviewers: Naman Siddique Emily Ryznar Lynn Savoie* * MD at time of publication Atypical HUS Mutation or antibody attack of complement proteins HELLP Anti-angiogenic factors in maternal blood Damaged placental vasculature Typical HUS STEC releases Shiga Toxin Malignant Hypertension DIC (See DIC Slide) ↓ Inhibition of complement Immune inflammatory ↑ Pressure in ↑ Extrinsic clotting pathway activation TTP (See TTP-HUS Slide) Disruption of endothelial cell activation perfusion/ischemia response metabolism vasculature ↑Thrombin Deficient Placental under- renal afferent ↑ Complement pathway activation MAC-mediated cell lysis Cytokine release Endothelial injury Shear stress on endothelium production ↑ Fibrin clot production and deposition in small vessels ADAMTS13 protease enzyme ↓ Cleavage and ↑ accumulation of VWF multimers Abbreviations: • HELLP - Hemolysis, Elevated Liver Enzymes, Low Platelets • HUS - Hemolytic-Uremic Syndrome • DIC - Disseminated Intravascular Coagulation • TTP - Thrombotic Thrombocytopenic Purpura • MAC - Membrane Attack Complex • STEC - Shiga Toxin-Producing Escherichia coli • VWF - Von Willebrand Factor Pro-thrombotic Environment (see Virchow’s Triad Slide) Platelet aggregation Mechanical obstruction of the vessel lumen Hypercoagulable state Thrombocytopenia ↑ RBC production in bone marrow ↑ Reticulocytes Hemoglobin released from damaged RBCs Shearing of RBCs Anemia Binds to haptoglobin Conversion to bilirubin in liver ↓ Free haptoglobin ↑Indirect bilirubin Shistocytes Jaundice Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 13, 2018 on www.thecalgaryguide.com

Venous insufficiency- Signs and symptoms

Venous insufficiency- Signs and symptoms vein veins blood flow interruption venous system valve incompetence reflux venous obstruction venous return backflow blood hypertension hydrostatic transmural pressure in postcapillary vessels capillary dilatation vessel permeability extravasation RBCs interstitial hemoglobin released degraded hemosiderin deposits hemosiderosis brown discolouration high pressure superficial venous circulation varicose veins tortuous dilated superficial veins distended veins compress somatic nerves achy pain protein-rich exudate edema peripheral ankle edema tissue perfusion metabolic exchange stasis dermatitis dermal fibrosis lipodermatosclerosis fibrotic thickened skin pruritus chronic inflammation risk of thrombus local ischemia embolus skin integrity venous ulcer risk of infection Adderley gagnon Waechter

Biliary Atresia (BA)- Pathogenesis and clinical findings

Biliary Atresia (BA)- Pathogenesis and clinical findings Intrauterine environment genetic factors abnormal bile duct development toxic inflammatory response viral immunologic injury to bile duct epithelia pathophysiology poorly understood histology consistent with obstruction on liver biopsy biliary atresia progressive idiopathic fibre-obliterative disease extra-hepatic biliary tree biliary obstruction on intra-operative cholangiogram (diagnostic) partial complete bile duct obstruction delivery of bile acids to small intestine pressure in bile duct absorption of fat and soluble vitamins vitamin K+ deficiency coagulopathy INR PTT bruising petechiae acholic pale stool failure to thrive elimination of bilirubin conjugated direct bilirubin jaundice pruritus excreted urine dark urine diaper yellow pressure bile duct GGT backs up in liver cholestatic hepatitis firm enlarged liver fibrosis cirrhosis ALT AST Horwitz Adderley McKenzie

Crohn's Disease

Inflammatory Bowel Disease: Clinical findings in Crohn’s Disease Authors: Yan Yu Amy Maghera Reviewers: Jennifer Au Danny Guo Jason Baserman Jessica Tjong Kerri Novak* * MD at time of publication Behavioural Factors: Smoking, over-sanitation Genetic Susceptibility Environmental Factors Diet, bacteria/viruses, drugs, vitamin D Systemic immune response primarily against the GI tract. (Unclear mechanism, mediated by cytokine release and neutrophil inflammation) Inflammation of the GI tract lining - Inflammation is “transmural”, spanning the entire thickness of the intestinal wall from luminal mucosa to the serosa. - The inflammation occurs anywhere in the GI tract from the oral mucosa to the anal mucosa (from ‘gums to bum’) in skip lesion pattern. Atrophy, scarring of the intestinal villi Inflammatory cytokines destroy the mucosa epithelial cells of the GI tract wall, causing cell apoptosis and ulceration ↑ permeability of the blood vessels supplying the GI tract wall Chronic inflammation impairs healing responses Dysregulated wound healingàexcess extracellular matrix deposition Fibrosis leads to scar tissue and thickening of all layers of the GI tract Strictures Inflammation is systemic, affecting: Joints Arthropathy Erythema Impaired absorption of nutrients Weight loss Prolonged GI bleeding Anemia Transporter proteins responsible for Na+ reabsorption gradually disappear from the epithelium More sodium (and thus water) is retained in the GI tract lumen Microperforations can penetrate through the intestinal wall Anal fistulae (“holes” connecting the anus to the skin, bladder, peritoneum, small bowel, etc.) Continued inflammation and/or infection can lead to: Leakage of fluid out of capillaries into the GI tract Luminal edema and swelling Narrowing of GI lumenàbowel obstruction Skin Mouth Eyes Liver nodosum, pyoderma gangreno- sum >5 canker sores Uveitis Iritis, scleritis Sclerosing cholangitis ↓ fat absorption Fatty acids (negatively charged) bind Ca2+, freeing oxalate from Ca2+ ↑ oxalate absorbed into blood & filtered by kidney Calcium oxalate kidney stones Diarrhea Abdominal cramping and pain (see Bowel Obstruction page for full mechanism Anal abscesses Inflammatory masses Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

Signs and Symptoms of Pulmonary Embolism

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

Secondary Polycythemia

Secondary Polycythemia: Pathogenesis Authors: Noriyah Al Awadhi, Yan Yu, Peter Duggan* Reviewers: Crystal Liu, Kara Hawker, Paul Ratti, Man-Chiu Poon*, Lynn Savoie* * MD at time of initial publication Chronic lung disease (ILD, COPD) Poor lung function Renal artery stenosis ↓ blood flow to kidney Kidney senses ↓ O2 High affinity Hb or CO poisoning Hb does not easily unload O2 Tissues become hypoxic Tumors (e.g. renal, hepatic, lung) Secretes EPO in an unregulated way, as a “paraneoplastic syndrome” High altitude Obstructive sleep apnea Episodic airway obstruction during sleep Intermittent hypoxia Cyanotic heart disease Shunting of blood Venous and arterial blood mixes Poorly oxygenated blood ↓ O2 partial pressure ↑ EPO production independent of O2 (inappropriate response) ↑ EPO production due to hypoxia (appropriate response) Abbreviations: • Hb- Hemoglobin • EPO- Erythropoietin • ILD- Interstitial Lung Disease • COPD- Chronic Obstructive Pulmonary Disease “Endogenous causes” of high EPO Secondary Polycythemia “Exogenous causes” of high EPO Testosterone therapy Iatrogenic EPO (results in ↑ EPO synthesis administration within the body) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published May 5, 2019 on www.thecalgaryguide.com

Ulcerative Colitis

Inflammatory Bowel Disease: Clinical Findings in Ulcerative Colitis Authors: Yan Yu Amy Maghera Reviewers: Jennifer Au Danny Guo Jason Baserman Crystal Liu Danielle Chang Kerri Novak* * MD at time of initial publication Inflammation is systemic, affecting: Environmental Factors Diet, bacteria/viruses, drugs Genetic Susceptibility Behavioral Factors: In UC, smoking and appendectomy are actually protective (unknown reason) Immune response against the GI tract. (Unclear mechanism, but thought to be mediated by cytokine release and neutrophil infiltration) Inflammation of the GI tract epithelial lining - Starting at the rectum and moves up the colon and is continuous (does not invade the small intestine) - Inflammation affects the mucosal and submucosal only Diarrhea, abdo pain and cramping causing avoidance of food Weight loss Apoptosis of GI tract mucosa Transporter proteins responsible for Na+ reabsorption gradually disappear from the epithelium Ulceration, into the anus, and more severe Prolonged Bleeding - GI and anus Anemia, often iron deficiency Inflammation ↑ permeability of the blood vessels supplying the GI tract wall Fluid leak out of capillaries into GI tract wall, causes edema and swelling Swelling narrows the GI tract lumen, causing bowel obstruction Inflammation, ulceration, or infection at the anus (all involve the RECTUM!) Anal irritation stimulates autonomic and somatic nerves leading up to the brain, causing the pt to want to defecate Tenesmus, urgency, frequency (feeling or urgency to defecate, but little stool is produced) Joints Skin Arthroplasty/ joint pain Erythema nodosum, pyoderma gangrenosum Mouth >5 canker sores More sodium (and thus water) is retained in the GI tract lumen Bloody Diarrhea, usually bloody due to anal bleeding and ulceration bleeding Abdominal Cramping and pain (see Bowel Obstruction page for full mechanism) Eyes (uvea, iris, sclera) Liver Blood Uveitis Iritis, scleritis Sclerosing Cholangitis Autoimmune hemolytic anemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published May 5, 2019 on www.thecalgaryguide.com

intraventricular-hemorrhage-in-preterm-infants-clinical-findings-and-complications

Intraventricular hemorrhage (IVH) in preterm infants: Clinical findings and complications Authors: Alexa Scarcello Reviewers: Nicola Adderley, Emily Ryznar, Yan Yu*, Jennifer Unrau* * MD at time of publication Volpe Grading Grade I: germinal matrix hemorrhage with no or minimal IVH (<10% of ventricular area) Grade II: IVH (10-50% of ventricle) Grade III: IVH (>50% of ventricle; usually distends lateral ventricle) Grade IV/Intra-parenchymal echodensity (IPE): periventricular hemorrhagic infarction Inflammation/dysfunction of arachnoid villi ↓ absorption of CSF 2° to obstruction of arachnoid villi Communicating hydrocephalus (IVH grades II-IV) Venous congestion Venous infarction Periventricular hemorrhagic necrosis Destruction of periventricular motor tracts Cerebral palsy Rapid significant blood loss ↓ intravascular blood volume Hypotension ↓ bloodflow to the brain to support brain function Intraventricular Hemorrhage (IVH) hemorrhage in periventricular subependymal germinal matrix Ultrasound: blood in germinal matrix, ventricles, or cerebral parenchyma Sudden ↓ hematocrit Blood irritates contiguous structures Variable neurologic findings; including altered level of consciousness, hypotonia, apnea, etc Neuro- developmental abnormalities (varying severity) See slide - Hydrocephalus: Clinical Findings in Pediatrics This mechanism leads to three different possible clinical manifestations: 1. Silent Presentation (most common) 2. Stuttering/Saltatory Course: non-specific findings - hypotonia, apnea, altered level of consciousness, bradycardia, and ↓ Spontaneous movements 3. Catastrophic Deterioration (least common) Stupor or coma, decerebrate posturing, seizures, bradycardia, metabolic acidosis, bulging fontanelles, abnormal pupillary reflexes, inappropriate ADH secretion Notes • Incidence & severity are inversely proportional to gestational age • 50% occur within 1st day of life, 90% by 3rd day • As explained in the flow chart, the postnatal clinical presentations of IVH fall into three categories (1-3) • Symptoms of catastrophic bleeds are uncommon and usually caused by rapid significant blood loss with subsequent neurologic findings 2° to meningeal irritation, inflammation, and potential mass effect/acute hydrocephalus; severe bleeds may also occur in the absence of clinical findings attributable to IVH Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 27, 2019 on www.thecalgaryguide.com

Appendicitis

Appendicitis: Pathogenesis and Clinical Findings Authors: Yan Yu Wayne Rosen* Reviewers: Wendy Yao Laura Craig Noriyah AlAwadhi* * MD at time of publication Dull, crampy, diffuse peri- umbilical pain Pt may develop fever, diarrhea, constipation, vomiting or anorexia as inflammation worsens Focal, intense, persistent RLQ pain, abdominal guarding and peritoneal signs (i.e. percussion and rebound tenderness Epidemiology Dx of healthy adults: • Men > women • Commonly 10-30 years old, can present at any age • Most common cause of acute abdomen (5% prevalence in all ethnicities) The appendix is anatomically located in the RLQ; appendicitis may be confused with disorders of surrounding structures: Gynecological Diseases • RuleoutpregnancywithHCG pregnancy test • Rupturedovariancyst • Ectopicpregnancy • Mittelschmerz(mid-cycle pain) Gastro-intestinal Diseases • Meckel’sdiverticulum (presents identically to appendicitis; surgically located 2 feet from ileocecal valve; mostly seen in children) • Diverticulitis(presentsasleft sided appendicitis) Non-GI Abdominal Issues • Mesentericadenitisinkids <15: swollen mesenteric lymph nodes • Renalcolic Obstruction of appendiceal lumen (by fecalith, fibrosis, neoplasia, foreign bodies or lymph nodes in kids) Appendix distension and spasms ↑ lumen pressure, ↓ blood flow to appendix Ischemia, tissue necrosis, loss of appendix structural integrity Bacterial invasion of the appendix wall, causing transmural inflammationandnecrosis Stretching of visceral peritoneum, stimulation of autonomic nerves T9-T10 Progression of inflammation over several days (variable length of time) Irritation of parietal peritoneum, stimulation of somaticnerves If appendix not surgically removed Perforation of colon wall, causing peritonitis, abscesses or death Note: Symptoms hugely variable. Only 30% present with classic history. Diagnosis is mostly clinical. Further investigations: CBC: Leukocytosis (due to inflammatory response) CT: Gold standard test. Thickened visceral membrane with enhancing (white) rim due to ↑ blood flow Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 27, 2019 on www.thecalgaryguide.com

Acute GI Related Abdominal Pain

Acute GI-Related Abdominal Pain: Pathogenesis and Characteristics Authors: Yan Yu Wayne Rosen* Reviewers: Laura Craig Danny Guo Julia Heighton Maitreyi Raman* * MD at time of publication Peritoneal cavity Visceral peritoneum (innervated by autonomic nerves) Bowel stretching, pulling, contracting Abdominal pain type: Diffuse, non-localized Dull, crampy, periodic Not associated with movement Patient may writhe around, trying to get rid of the pain Mesentery Intestinal lumen Parietal peritoneum (innervated by somatic nerves) Cross-section of the GI tract Cuts, structural damage, and inflammation in the bowel Important Notes • Acute abdominal pain can also result from non- gastrointestinal causes, such as kidney stones, female reproductive tract issues, and urinary tract issues. For simplicity’s sake, only the GI-related acute abdominal pain disorders are listed here. • The DDx of visceral abdominal pain is broad. Please consult relevant sections of the Calgary Black Book for the DDx. • Keep in mind that visceral abdominal pain can also be caused by the “acute abdomen” diseases (if the diseases are presenting in their initial phases). • • • • • • Abdominal pain type: Sharp, well-localized Excruciatingly painful, persistent Associated with movement of bowels Patient often lies still to avoid abdominal vibration Peritoneal signs Abdominal guarding, pain with abdominal vibration (coughing, shaking, percussion, palpation) Transition from diffuse to localized pain can indicate disease progression (e.g. from visceral to parietal peritoneal inflammation) Note: bowel obstruction may or may not present as acute abdominal pain Bowel Infarction Appendicitis Diverticulitis Acute Cholecystitis Acute Pancreatitis Perforated Ulcer DDx of an “acute abdomen”: A sudden, non-traumatic disorder of the abdomen that needs urgent diagnosis and treatment. Each topic will be further explored in their respective slides. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 27, 2019 on www.thecalgaryguide.com

Colorectal Carcinoma pathogenesis and clinical findings

Colorectal Carcinoma: Pathogenesis and clinical findings Obstipation Nausea & vomiting Tenesmus Rectal pain Hematochezia Hydronephrosis (swelling of kidney) ↓ appetite Local bleeding Abdominal Abscess Weight loss Acute blood loss Iron deficiency anemia Classification of tumours/abnormal growths: 1. Adenoma–abenigntumorfromglandular structures 2. Carcinoma–cancerarisingfromtheepithelial tissue of the skin or the lining of internal organs 3. Sarcoma–cancerarisingfromconnectivetissue Mechanical bowel Obstruction Ribbon (thin) stool In rectum Mass effect Tumor ↓ bowel lumencaliber Backed up contents mayberegurgitated Cancerinvadesrectal sphincters, muscles, vessels&nerves Compressing ureters, urine backs up into kidney Compressing stomach Abdominal distension/pain Invades blood vessels Inflammatory Bowel Disease Smoking Abdominal radiation Tubular adenomas (pre- cancerous polyps) Obesity Local growth of tumor Cell line mutations Idiopathic Uncontrolled cell division in the colon and rectum Hereditary syndromes Colorectal Carcinoma (Develops over time) Outside bowel serosa Bowel perforation Bowel to bowel/local organ fistulisation Host immune cells release cytokines to combat cancer Bowel contents leak Metabolic abnormalities, ↑energy use Tumor Spread Mechanisms: 1. Hematogenous 2. Lymphatic 3. Contiguous 4. Transperitoneal Tumor cells spread distally Friable vessels supply tumor Metastatic Disease Vessels Rupture Occult bleeding & melena (black stools) depletes stores of iron Authors: Karly Nikkel Reviewers: Michael Blomfield Tony Gu Yan Yu* Edwin Cheng* * MD at time of publication Tumors develop in liver, lungs, brain, peritoneum and lymph nodes Hematochezia (passage of fresh blood in stool) Slow, chronic blood loss Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 25, 2019 on www.thecalgaryguide.com

Negative-Pressure-Pulmonary-Edema

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

Incisional-Hernia

Incisional Hernia: Pathogenesis and clinical findings Penetration of abdominal wall from prior surgery, in combination with: Dead and injured cells from incision Small blood vessels rupture Plasma seeps out of vessels and collects together Nutritional deficiency ↓ absorption of fat soluble vitamins Chronic illness Cirrhosis Diabetes Malignancy Immuno- suppressive therapy Ascites Heavy lifting Multiple complex mechanisms (including hyper- glycemia & immune dysfunction) that ↑ risk of infection Post-op wound Infection Obesity Chronic constipation Chronic cough Pregnancy ↓ clotting factors Vigorous cough Severe Hypertension Seroma Post-op hematoma Bulging fluid separates High risk Sutures unsuitable Poor surgical for tension technique ↑ intraabdominal pressure Fascial Incision separates Notes: fascial incision surgeries* High Risk Surgeries* Connective tissue disorder Suboptimal fascial closure • • • Emergency surgeries Midline incisions Acute abdominal surgeries ↓ wound healing/collagen synthesis Fascial defect at previous incision site Incisional Hernia: Protrusion of tissues through prior fascial incision • Deep wound infection = most common cause of incisional hernias • Diagnosis on physical exam +/- CT scan if patient is obese • Treatment = surgery Bulge at prior incision site Palpable fascial defect Bowel and other abdominal contents protrude through defect Mechanical bowel obstruction (see relevant slide) Constipation /obstipation Contents unable to be pushed back through defect (incarceration) Vascular supply is compromised to herniated contents Contents become ischemic (strangulated) Prolonged pressure on skin & bowel over time Ulceration & ischemia ↓ blood flow to skin layers Discoloration of skin Bulge ↑ with coughing/straining Ulcers extend through bowel wall Authors: Karly Nikkel Meaghan Ryan Reviewers Michael Blomfield Tony Gu Yan Yu* Edwin Cheng* *MD at time of publication Colo-enteric fistula Bowel Perforation Abdominal Pain Abdominal Distension Nausea/ Vomiting Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 13, 2019 on www.thecalgaryguide.com

Varicocele

Varicocele: Pathogenesis and clinical findings Authors: Luc Wittig Ryan Brenneis Reviewers: Alec Mitchell Darren Desantis* * MD at time of publication Notes: • 90% present as left sided. • Primary varicocele ache and scrotal venous distention can be relieved by superincumbent positioning (increases venous return). • Small varicoceles can be identified by preforming the Valsalva maneuver (decreases venous return). • Unilateral right varicoceles are uncommon and should be investigated for underlying pathology causing obstruction. Primary Anatomically: the left spermatic vein drains into the left renal vein Nutcracker Effect: The left renal vein can get pinched by the abdominal aorta and superior mesenteric artery Backup of blood in left renal vein ↑ pressure in left spermatic vein Secondary Renal cell carcinoma or retroperitoneal masses Inferior vena cava thrombus External compression of spermatic vein Obstruction of blood flow ↑ spermatic vein pressure Vein valve leaflet failure & retrograde bloodflow back towards testicle Dilation of pampiniform plexus and scrotal vein plexus Varicocele ↑ scrotal blood volume ↑ volume in a closed space ↑ pressure and distension of scrotal layers ↑ scrotal vein plexus pressure Compliant veins distend, becoming visible through scrotum Blood heats up the structures it flows through Scrotal hyperthermia Unsuitable environment for spermatogenesis Loss of germ cell mass Bag of Worms Sign Dull ache/heaviness Decreased fertility Testicular atrophy Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 26, 2019 on www.thecalgaryguide.com

vomiting-pathogenesis

Vomiting: Pathogenesis Authors: Julena Foglia Reviewers: Varun Suresh Matthew Harding Haotian Wang *Yan Yu *Eldon Shaffer *MD at time of publication Intracranial: Trauma, Infection, Tumor, Stroke ↑ Intracranial pressure Mechanism Unknown Irritation of GI mucosa: Inflammation, Distention, Chemotherapy, Radiation Activates receptors in gut mucosa GI Disease: Upper: GERD, PUD, Cancer Lower: Ischemia, obstruction, IBD Mechanical pharyngeal stimulation Signal travels via vagal and sympathetic afferent nerves Metabolic: Pregnancy, Diabetes, Uremia, Thyroid disease, Hypercalcemia Pain, Smells, Foul Sights, Memories Sensory inputs to cortical region Cerebral Cortex Vomiting (Emetic) Center Toxins circulating in bloodstream: Chemotherapy, Opioids Offending substance travels through circulation and binds to receptors in the CTZ, outside the blood brain barrier Abbreviations: GERD: Gastroesophageal Reflux Disease PUD: Peptic Ulcer Disease IBD: Inflammatory Bowel Disease CTZ: Chemoreceptor Trigger Zone CNX: Cranial Nerve Ten H1: Histamine Receptor M1: Muscarinic Receptor Disrupted inner ear balance: Motion Sickness Activation of H1 & M1 receptors in vestibular center traveling via Cerebellum Stimulates Solitary Tract Nucleus (Medulla) (Medulla) Vagus Nerve (CNX) and enteric nervous system activation, resulting in: Gastric relaxation, ↓ pylorus tone, retrograde duodenal peristalsis Downward diaphragm contraction, abdominal & chest wall muscles contract: ↑ intra-gastric pressure Vomiting (Forceful expulsion of material from stomach and intestines) Upper and lower esophageal sphincter relaxation and glottis closure Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-published February 16, 2020 on www.thecalgaryguide.com

Marfan-Syndrome

Marfan Syndrome: Pathogenesis and Clinical Findings Inherited or acquired mutation in TGFBR1/2 gene (TGF-β receptor) Dural ectasia (widening of the dural sac) Diminished and disorganized dural elastic fibres Abnormalities in connective tissues Tear in the aortic intima (innermost layer of aorta) Aortic dissection Type A (tear in ascending aorta) > Type B (tear in descending aorta) Back pain Sensory and motor deficits Ectopia lentis (lens dislocation) Development of lung bullae and blebs Rupture of bullae/blebs Pneumothorax ** Abnormal properties of lens + cornea ** Scoliosis ** Myopia Tall stature Chest wall (pectus) Inherited (autosomal dominant) or de novo mutation in FBN1 gene Distortion of neural roots Thinning of ciliary zonules of the eye Weakness and rupture of alveolar tissue Production of aberrant or reduced fibrillin-1 Formation of unstable microfibrils in extracellular matrix of connective tissues ** inactivate TGF-β1 ↑ production of matrix metalloproteinases ↑ cellular signaling cascades ↑ production of growth factors in the endocardium Cell proliferation and apoptosis suppression in mitral valve leaflets Change in valvular architecture Mitral prolapse Mitral regurgitation ↑ degradation of extracellular matrix Thinning of the aortic media Weakness of the aortic wall Inability of fibrillin- 1 to sequester and ↑ TGF-β1 signalling Abbreviations • TGF-β: Transforming growth factor beta (a cytokine) Notes **The underlying mechanisms are unclear Authors: Tony Gu Reviewers: Amanda Nguyen Davis Maclean Yan Yu* Michelle Keir* * MD at time of publication Aortic root dilation Aortic valve leaflets stretched outwards, unable to fully close Aortic regurgitation Aneurysmal dilation of the abdominal & thoracic aorta Aortic rupture Stroke Blood enters and pressurizes a ‘false lumen’ Obstruction of aortic branches End organ malperfusion ** deformities ** Joint hypermobility Thumb sign: Thumb tip extends from palm of hand when thumb is folded into closed wrist Wrist sign: thumb and fifth finger of the hand overlap when grasping opposite wrist Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 28, 2020 on www.thecalgaryguide.com

acute-pancreatitis-complications

Acute pancreatitis: Complications Inflammation causes vasodilation and vasculature leakage Mild, (85%): Interstitial edematous pancreatitis Local accumulation of fluid in the pancreas <2 weeks after onset Acute peripancreatic fluid collection (not encapsulated) Walled off by fibrous & granulation tissue >2 weeks after onset Pancreatic pseudocyst (completely encapsulated) Peritoneal irritation à pain Large cyst can (very rarely) compress surrounding bowel Acute Pancreatitis Inflammatory cytokines are released from damaged pancreas If recurrentàchronic pancreatitis (see relevant slide) Inflammation damages pancreatic exocrine cellsàInappropriate release of pancreatic enzymes into surrounding tissue & vasculature àdigesting pancreatic parenchyma Authors: Nissi Wei, *Yan Yu Reviewers: Dean Percy, Miles Mannas, Varun Suresh, Brandon Hisey, *Kerri Novak, *Sylvain Coderre * MD at time of publication complete resolution (most cases) Necrotic tissue is vulnerable to infection (esp. Gram neg GI bacteria) inflammation & necrosis activate cytokine cascade Severe, necrosis (15%): Necrotizing pancreatitis Local infection Severe pancreatic inflammation shifts body fluid into retroperitoneal spaceàintravascular volume depletion Systemic Inflammatory Response Syndrome (SIRS) (see relevant slide) Organ failure (may be sole feature on presentation) Stagnant fluid can more easily become infected Infection spreads to bloodstream Cardiac failure Hypovolemic shock Renal failure Local accumulation of fluid & necrosis in the pancreas < 4 weeks after onset: Acute necrotic collection (not encapsulated) Walled off by fibrous & granulation tissue > 4 weeks after onset walled-off necrosis (completely encapsulated) When treated with excess fluid resuscitation: Intra- abdominal hypertension Respiratory failure (ARDS) Disseminated intravascular coagulation (DIC) Bowel obstruction Gastric outlet (see relevant slide) obstruction Infected pancreatic necrosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 20, 2016, updated September 7, 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

Tumour-Lysis-Syndrome

Tumour Lysis Syndrome High sensitivity to treatment Highly proliferative malignancy with ↑cell-turnover Large tumour mass Author: Joshua Yu Reviewers: Hannah Yaphe Davis Maclean Tejeswin Sharma Yan Yu* *Peter Duggan *ManChiu Poon *Lynn Savoie *Juliya Hemmett * MD at time of publication High serum phosphate High serum Advanced uric acid Age Volume depletion Pre-existing renal disease Patient risk factors Initiation of cancer treatment Massive tumour cell lysis and release of cellular contents into circulation overwhelms homeostatic mechanisms Tumour properties (hematologic malignancies most common) Though rare, aggressive tumours can spontaneously lyse without treatment Intracellular potassium released into bloodstream Intracellular phosphate released Hyperphosphatemia ↑ serum phosphate Intracellular lactate dehydrogenase (LDH) released ↑ serum LDH Intracellular nucleic acids released Nucleic acids metabolized to uric acid Hyperuricemia ↑ serum uric acid Hyperkalemia ↑ serum potassium (see Hyperkalemia: clinical findings) Uric acid (a crystallizing substance) ↑ precipitation of calcium phosphate ↑ filtration of poorly soluble uric acid into acidic environment of renal tubules Serum phosphate binds serum calcium, forming solid calcium phosphate precipitate crystals High levels of calcium phosphate ↑ uric acid precipitation Uric acid precipitates as crystals and deposits in kidney tubules and collecting ducts Tubular injury and/or intraluminal obstruction Endothelial dysfunction in renal vasculature Renal inflammation, vasoconstriction, and impaired renal vascular autoregulation Decreased renal filtration Acute Kidney Injury (see Acute Kidney Injury Overview) Crystal deposition in the heart Depletion of soluble calcium Hypocalcemia Calcium phosphate crystals deposit in kidneys Main mechanism of Acute Kidney Injury Cardiac Arrythmias ↓ serum calcium (see Hypocalcemia: clinical findings) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 25, 2020 on www.thecalgaryguide.com

Small-Bowel-Obstruction-findings-on-X-Ray

Small Bowel Obstruction: Findings on X-Ray Authors: Evan Allarie Shelley Spaner* Reviewers: Davis Maclean Yan Yu* * MD at time of publication See Calgary Guide – Mechanical Bowel Obstruction and Ileus: Pathogenesis and clinical findings Bowel contents cannot pass the obstruction Buildup of bowel contents (gas, fluid) proximal to the obstruction Gas rises above the fluid If exclusively or mostly accumulation of fluid (and not gas) occurs Any small amounts of gas/air present (not enough to create an air-fluid level) will rise and become trapped in valvulae conniventes (small bowel folds) Small bowel loops are anatomically central compared to large bowel Bowel contents physically push on the bowel walls, dilating them Dilated bowel loops are “central” in location on the x-ray Dilated bowel loops (>3cm) Valvulae Conniventes Visible: Anatomical folds of the small bowel that becomes more apparent when small bowel is distended & allows differentiation from large bowel Air-fluid level (on erect/upright study) - Dark area above level = Gas/Air - Bright/white area below level = Fluid ‘Gasless’ abdomen (not seen here): Refers to the lack of gas/air (dark on X-ray) in the bowel loops - only fluid (bright/white on X- ray) is seen in bowel loops String of pearls sign (not seen here): Small gas bubbles seen arranged in a “string of pearls” pattern instead of a large air fluid level Image Credit: Alberta Health Services Repository Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 25, 2020 on www.thecalgaryguide.com

Fat-Embolism-Syndrome

Fat Embolism Syndrome: Pathogenesis and clinical findings Panniculitis (conditions causing inflammation of subcutaneous fat) Non-trauma related (rare) Long bone fracture Pelvic fracture Orthopedic Trauma Intraosseous access Soft tissue injuries Chest compressions Bone marrow transplant Pancreatitis Diabetes mellitus Fat from bone marrow is disrupted and leaks into bloodstream via damaged blood vessels Fat globules obstruct dermal capillaries Capillaries rupture Blood leaks into the skin Petechial rash Non-Orthopedic Trauma (less common) Fat from injured adipose tissue is released from adipocytes into bloodstream Metabolic disturbance mobilizes stored fat and moves it into circulation Fat Embolism Syndrome the presence of fat globules in circulation Fat globules damage blood vessel walls Platelets stick to damaged areas Platelet aggregation ↑ circulating free fatty acids ↑ inflammatory cytokines (TNF, IL1, IL6) ↑ serum C Reactive Protein (an acute phase reactant) C reactive protein binds to lipid vesicles in circulation ↑ formation of lipid complexes in the blood Obstruction of cerebral vasculature ↓ blood flow and oxygen delivery to brain tissue Neurological findings: ranging from ↓ level of consciousness to seizures Notes: Large quantities of fat globules can obstruct pulmonary vasculature Blood clots form throughout the body Disseminated intravascular coagulopathy Back up of blood into right heart àRight ventricular dysfunction ↓ pulmonary arterial blood flow à↓ gas exchange in the lungs Higher CO2 & lower O2 levels in blood àdetected by chemoreceptors Chemoreceptors stimulate respiratory centre in the brain to ↑ rate of respiration Dyspnea / Tachypnea Authors: Tabitha Hawes Reviewers: Hannah Koury, Alyssa Federico, Davis MacLean, Mehul Gupta, Yan Yu*, Jeremy Lamothe* * MD at time of publication • Underlined findings indicate classic triad of symptoms (petechial rash, neurologic findings, dyspnea/tachypnea) • Clinical presentation of fat embolism syndrome is variable and may present with any or all of these findings ↓ pumping of blood into systemic circulation Hypotension Obstructive shock Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 19, 2021 on www.thecalgaryguide.com

Complications-Accouchement-Vaginale

Complications maternelles de l’accouchement par voie vaginale Autheur: Yan Yu Rédacteurs: Kayla Nelson, Radhmila Parmar, Jemimah Travail et accouchement par voie vaginale Pression intense sur les parois vaginales pendant le passage du fœtus et/ou utilisation de forceps ou d'un aspirateur endommagent le vagin et le périnée. Raffe-Devine, Alina Constantin* Traducteurs: Brianna Ghali, Philippe Couillard* * MD at time of publication Le détachement du placenta perturbe les vaisseaux sanguins de l'utérus. Sondage des voies urinaires pendant le travail Un tissu cicatriciel se forme au niveau du décollement du placenta. Après l'hémostase complète (arrêt du saignement) et la cicatrisation des vaisseaux, le tissu cicatriciel est éliminé de l'utérus. Lochies (pertes/ saignements vaginaux) et perte d'escarres (tissu cicatriciel) Le tissu placentaire peut être retenu dans l'utérus. L'utérus ne se contracte pas complètement pour fermer les vaisseaux sanguins utérins. Hémorragie post- partum (Voir la diapositive correspondante) Les substances étrangères déclenchent une réaction inflammatoire systémique chez la mère Coagulation intravasculaire disséminée, CIVD (voir diapositive correspondante) Dans de rares cas, des vaisseaux sanguins déchirés laissent le liquide amniotique (contenant des cellules fœtales et du méconium) pénétrer dans la circulation maternelle. Embolie de liquide amniotique (amas de cellules fœtales et de méconium dans la circulation maternelle) Le liquide amniotique visqueux peut bloquer les vaisseaux sanguins maternels Obstruction de la circulation du sang dans les poumons Bas debit cardiaque avec reduction de la précharge. Tissus endommagés et sang dans l'utérus Des nutriments pour que les bactéries infectent l'utérus. Endométrite Douleur utérine, irradiant dans tout l'abdomen Œdème pulmonaire Hypotension Manque de perfusion au cœur Arrêt cardiaque Le passage du fœtus distend les muscles pubo- vésiculaires et pubo-rectaux. L'urètre/ rectum ne sont plus suffisamment courbés pour empêcher les fortes pressions intra- abdominales de forcer l'urine ou les selles. Incontinence de stresse (de la vessie et des intestins ; généralement temporaire) Remarque: la dépression post-partum est couramment observée chez au moins 10 % des mères qui viennent d'accoucher. Déchirures périnéales (1er-4e degré) ; Hémorroïdes Douleur périnéale Douleur et gonflement unilatéral de la jambe Dyspnée, Toux Les lésions tissulaires activent les facteurs de coagulation du sang. ­ Coagulation dans les zones d'hémostase (par exemple, les veines) Thrombose veineuse profonde La fièvre du post- partum (voir la diapositive correspondante) L'insertion d'un tube étranger dans la vessie facilite la colonisation de la vessie et des voies urinaires par les bactéries. Infections des voies urinaires Si grave Effondrement cardio-vasculaire Légende: Pathophysiologie Méchanisme Signe/Symptôme/Résultat Laboratoire Complications Publié 19 juin 2013 à www.thecalgaryguide.com

cystic-fibrosis-findings-on-chest-x-ray-and-lung-window-ct-scan

Cystic Fibrosis: Findings on Chest X-Ray and Lung Window CT Scan CFTR mutationàabnormal transmembrane Cl- transport in exocrine tissueà Author: Sean Kennedy Reviewers: Matthew Harding, Amogh Agrawal, Yan Yu, Ciara Hanly, Aman Wadhwani, Zesheng Ye (􏰃􏰄􏰁), Mark Montgomery* * MD at time of publication Collapsed alveoli appears white on x-ray Peribronchial Cuffing secretions become more viscous. (See relevant slide for CF pathogenesis.) As early as at birth, secretions collect in bronchial lumen, delaying mucociliary clearance Mucus plugs and obstructs bronchial lumen Air trapped distal to obstruction and cannot leave lungs Lung Hyperinflation Diaphragm domes below 10th posterior rib and 6th anterior rib on PA CXR Flattened hemidiaphragm, enlarged retrosternal space on lateral CXR With time, pulmonary capillaries gradually absorb gases in alveoli distal to obstruction àalveolar collapse (Atelectasis) Collapsed alveoli more solid and radiodense than airà↓X-ray penetration Adjacent structures may shift towards atelectasis on CXR In first few years of life, retained bronchial secretions serve as nidus for recurrent bacterial colonization and infection Late findings at 10- 30 years oldà secretion accumulation blocks inhaled air to affected lung segments àchronic hypoxia Inflammatory response (cytokines, nitric oxide and radical oxygen species) leads to bronchial and peribronchial destruction Hypoxia induces pulmonary capillary vasoconstriction Some airways are blocked more than others Leakage of fluid into bronchial walls & peri- bronchial regions. Inflammatory cytokines destroy elastic components of bronchi Accumulation of inflammatory exudate in bronchi Pulmonary artery hypertension à Blood backs up in pulmonary arteries Some segments of lung underventilated Fluid around bronchial walls is more radiodense than air à↓X-ray penetration àappears white Bronchiectasis: dilated, thickened, untapered bronchi on CXR/CT Fluid/mucus in bronchi is more radiodense than air, thus appearing white on imaging Edematous bronchi viewed end on are thickened and appear ring-like on CT/CXR Tramlines (AKA Tramtracking) Bronchus wider than corresponding blood vessel on CXR/CT Advanced bronchiectasis is saccular in appearance Mucus-filled bronchi form tubular opacities giving appearance of white fingers on CXR/CT Signet Ring Sign Bronchiectatic Cavities Mucoid Impaction (AKA Finger in glove sign) ↑ Blood dilates pulmonary arteries Blood backs up in right ventricle, dilating it Pulmonary arteries look wider on CXR. Main pulmonary artery >30 mm diameter on CT Right Ventricle Enlargement on CXR/CT Underventilated lung segments appear as lower intensity (darker) than normal ventilated segments which appear as normal intensity (brighter) Mosaic Changes on CT(non- contrast Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 13, 2013, updated Aug 18, 2021 on www.thecalgaryguide.com

asthma-pathogenesis

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

copd-overview-and-definitions

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

Ectopic Pregnancy

Ectopic Pregnancy: Pathogenesis and Clinical Findings In vitro fertilization Tubal disorders leading to infertility and unknown procedural causes Previous ectopic pregnancy Underlying tubal disorder leading to previous ectopic Pelvic inflammatory disease (PID) Endometriosis Tubal surgery or disorders Age >35 Risk factor accumulation over time Smoking Impairment in tubal motility; impaired immunity (risk factor for PID) Tubal scarring leading to adhesions, obstruction, and alteration of tubal function Ectopic Pregnancy: Implantation of developing blastocyst outside the uterine cavity, most commonly in fallopian tube (other locations: interstitial > cornual > cervical > ovarian > abdominal) Embryo releases human chorionic gonadotropin (β-hCG), which supports corpus luteum to continue producing progesterone On transvaginal ultrasound: Extrauterine gestational sac with a yolk sac or embryo Embryo & trophoblast deathàloss of hormone support for the decidua (modified endometrial lining) Progesterone maintains the endometrial lining, preventing it from shedding Missed period Penetration of ovum into muscular wall of fallopian tube Tubal distention àTubal rupture Intra-abdominal hemorrhage Pregnancy cannot survive without the uterine endometrium Maternal blood extrudes through fimbriae of fallopian tubes and into peritoneal cavity Lower abdominal pain (including peritonitis in cases of hemoperitoneum) Hemoperitoneum (blood in the peritoneal cavity) Sloughing of decidua out of the uterus through the vagina Vaginal bleeding (usually in first trimester) Cessation of human chorionic gonadotropin (β-hCG) release from embryo β-hCG plateaus or decreases Authors: Jemimah Raffé-Devine Tahsin Khan Yan Yu* Reviewers: Brianna Ghali Bishwas Paudel Mackenzie Grisdale Christina Schweitzer Ron Cusano* Jadine Paw* * MD at time of publication Syncope ↓ Level of consciousness Positive β-hCG, but rising <35% over 2 days Discriminatory zone: β-hCG >2000 + absence of intrauterine pregnancy Hypotension Shock Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 1, 2017, updated Oct 19, 2021 on www.thecalgaryguide.com

Summary of Cyanotic Congenital Heart Diseases

Summary of Cyanotic Congenital Heart Diseases (CHD) Authors: Winnie Nagesh, Gaya Narendran, Deborah Fruitman* Reviewers: Austin Laing, Yan Yu* * MD at time of publication Right heart normally carries deoxygenated blood to the pulmonary circulation while the left heart carries oxygenated blood to the systemic circulation. Cyanosis can be due to varied pathophysiology, most involve a R-L shunt (described below) Typically presents in the newborn period but depends on the severity and the type of lesion Tetralogy Of Fallot (TOF) Main features: 1.VSD, 2. Overriding aorta, 3. RVH, 4. Pulmonary Valve stenosis 1. VSD causes equal systolic pressure in R and L ventricles 2. Pulmonary Valve stenosisàRight Ventricle Outflow Tract Obstructionà↓ pulmonary blood flow (degree depends on severity of obstruction) 3. RVàLV flow across VSD Presents in the 1st days to weeks, depending on severity of pulmonary valve stenosis On exam: LUSB SEM; loud S2; hypoxemia (degree depends on severity of Right Ventricle Outflow Tract Obstruction) CXR: “boot-shaped” heart, decreased pulmonary vasculature Presents at birth On exam: Often no murmur, no respiratory distress, severe cyanosis/hypoxemia CXR: “egg on a string”, normal pulmonary vasculature Presents in the 1st days to weeks as CHF symptoms develop On exam: Systolic ejection click, Single S2 , SEM, mild hypoxemia due to mixing of blood, +/- tachypnea, hepatomegaly (CHF symptoms) CXR: normal or ↑ pulmonary vasculature Presentation varies based on the degree of the outflow tract obstruction On exam: +/- Holosystolic murmur at LLSB (from VSD), or SEM if outflow tract obstruction, +/- severe cyanosis dependent on severity of pulmonary stenosis CXR: normal or ↓ pulmonary vasculature Presents in early infancy (earlier and more severe presentation if obstructed) On exam: +/-split S2, SEM LUSB, tachypnea, mild cyanosis CXR: cardiomegaly with ↑ pulmonary vasculature Note: see relevant Calgary Guide slides for each heart condition for full explanation of their pathophysiology. Figures are hand-drawn by the authors. Transposition of the Great Arteries (TGA) Aorta is the outflow for RV and pulmonary artery is the outflow for the LV (parallel circulation) Truncus Arteriosus 1. Single vessel (truncus) fails to divide into pulmonary artery and aorta, 2. Single outlet overriding VSD Tricuspid Atresia Tricuspid valve fails to develop normally with a hypoplastic right heart and VSD 1. Deoxygenated blood pumped from RVàaortaà systemic circulation, bypassing the lungs. 2. Oxygenated blood pumped from LVàPA 1. RV + LV pumped through VSDàoverriding truncal artery 2. Mixed deoxygenated and oxygenated blood enters systemic, pulmonary and coronary circulations 1. Blood cannot enter RV due to lack of tricuspid valve 2. Deoxygenated blood pumped from RAàASDàLA and mixes with oxygenated blood 3. Mixed blood enters systemic circulation Total Anomalous Pulmonary Venous Return (TAPVR) Pulmonary veins return blood to systemic venous circulation (most common type of supracardiac congential heart disease) 1. Oxygenated blood flows through pulmonary veinsàenters Superior or Inferior Vena CavaàRight atrium (all systemic & pulmonary venous blood returns to the RA, resulting in mixing of blood) 2. Blood follows pressure gradient, flows from RAàLA via ASD 3. Flow from LAàLVàAortaàSystemic Circulation Abbreviations: VSD: Ventral Septal Defect; RVH: Right Ventricular Hypertrophy; RV: Right Ventricle, LLSB: Left Lower Sternal Border, LUSB: Left Upper Sternal Border; SEM: Systolic ejection Murmur; RVOTO: Right Ventricle Outflow Tract Obstruction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 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 " />

哮喘急性发作-发病机制和治疗

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

Asthma clinical findings

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

Chronic Cough Pathogenesis_2021

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

mechanical-bowel-obstruction-and-ileus-pathogenesis-and-clinical-findings

Mechanical Bowel Obstruction and Ileus: Pathogenesis and clinical findings Anti-motility Diabetic Sepsis drugs gastroparesis Nerves coordinating bowel peristalsis are disrupted Ileus: functional bowel ‘blockage’, no peristalsis Post- operation Hernia (no past surgery) Post-abdominal surgery Authors: Yan Yu, Wayne Rosen* Reviewers: Nicole Burma, Jason Baserman, Jennifer Au, Maitreyi Raman* * MD at time of publication Adhesions Note: • Complete obstruction typically presents with acute abdominal pain and related symptoms • Incomplete obstructions can present with either acute or Congenital abnormality GI neoplasms If partial obstruction: ↓ frequency of bowel movements Since gas/air sounds hollow to percussion Abdomen tympanic to percussion Mechanical obstruction: physical blockage of bowel lumen Inflammatory bowel disease (IBD) Gas (from swallowed air, bacterial fermentation, & CO2 made via HCO3- neutralization) & ingested gastro- intestinal (GI) contents accumulate before obstruction Accumulated GI contents contain salts and other osmotically active solutes that osmotically draw water into the GI tract Continued ↑ bowel distention & ↑ luminal pressure over time ↑ pressure squeezes shut intestinal blood vesselsà↓ bowel perfusion chronic abdominal pain If complete obstruction: Obstipation (no flatus) & absent bowel movements Irritation of autonomic nerves in visceral peritoneum Lower effective arterial blood volumeàdehydration Continued peristalsis proximal to obstruction continues to push GI contents against the obstruction If obstruction is proximal (closer to mouth), higher luminal pressure may force regurgitation of GI contents Bloating, cramping, anorexia Diffuse visceral abdominal pain Flat/low jugular venous pressure (JVP), resting tachycardia, orthostatic hypotension Severe abdominal pain (may come in waves), peritonitis, guarding, rigidity Hyperactive bowel sounds (proximal to obstruction) or absent bowel sounds (ileus) Nausea/vomiting Bowel ischemia and infarction, tissue necrosis, possible perforation +/- bacterial invasion (see relevant slides) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published December 15, 2021 on thecalgaryguide.com

obstruccion-del-intestino-delgado-hallazgos-en-los-rayos-x

obstruccion-del-intestino-delgado-hallazgos-en-los-rayos-x

obstruccion-intestinal-mecanica-e-ileo-patogenesis-y-hallazgos-clinicos

obstruccion-intestinal-mecanica-e-ileo-patogenesis-y-hallazgos-clinicos

Langerhans Cell Histiocytosis

Langerhans Cell Histiocytosis: Pathogenesis and clinical findings Precursor cells differentiateàClonal expansion of abnormal (constitutive MAPK activation) CD1a+/CD207+ (Langerhans cell phenotype surface receptors) dendritic cells in tissue(s) Somatic BRAFV600E mutation: BRAF is a kinase in the MAPK pathway Other somatic (non- reproductive cell) mutations Idiopathic (unknown cause) Mutation(s) can occur in one of these precursor cell types* Hematopoietic stem cell (earliest cell of blood cell differentiation) in bone marrow Committed dendritic cell (type of myeloid antigen-presenting cell) precursor in bone marrow or blood Committed dendritic cell precursor in tissue Constitutive activation of the MAPK pathway (signalling pathway that regulates variety of cellular processes) in one of these precursor cell types *Note: Based on the “misguided myeloid differentiation” modelàthe earlier the mutation(s) occur in the myeloid cell differentiation pathway, the more severe the disease. Langerhans Cell Histiocytosis Accumulation of abnormal CD1a+/CD207+ dendritic cells (Langerhans Cell Histiocytosis cells or LCH cells) with an inflammatory background in one or more organs Authors: Ran (Marissa) Zhang Reviewers: Mehul Gupta Kiera Pajunen Yan Yu* Lynn Savoie* * MD at time of publication ↑ recruitment & activation of T cells, macrophages, eosinophils in tissue(s) around the body ↓ CCR7 & CXCR4 (chemokine receptors) expression on LCH cellsàinhibits migration of LCH cells to lymph nodes ↑ BCLXL (an apoptosis regulator protein) expression on LCH cellsà inhibits apoptosis of LCH cells Immune cell infiltration & ↑ pro-inflammatory chemokine/cytokine release à dysregulated local & systemic inflammation Accumulation of LCH cells in tissue(s) around the body Inflammatory lesion (an area of abnormal tissue) formation in one or more organs: In pituitary stalk Mass effectà obstruction of antidiuretic hormone (complex mechanisms) In liver Invasion & accumulation of cells foreign to liverà expands liver Chronic local inflammation Scarring of bile ducts ↓ bilirubin clearance from liveràbuildup into serum ↑ serum bilirubin Jaundice In cortical bone Cytokine production à↑ osteoclast (cells that break down bone) activity ↑ rate of bone loss Osteolytic bone lesions In bone marrow Unclear mechanism but likely due to macrophage activation ↑ phagocytosis (ingestion & destruction) of blood cells In spleen Invasion & accumulation of cells foreign to spleen Forms aggregates that expand the red pulp (functions as the blood filter in spleen) Splenomegaly In skin Unclear mechanisms Variable presentations: most commonly pinpoint erythematous (red) papules or erythematous plaques with crusting & scaling Hepatomegaly • BRAF- B-Raf proto-oncogene, serine/threonine kinase • CCR7- C-C motif chemokine receptor type 7 • CD1a- Cluster of differentiation 1A • CD207- C-type lectin domain family 4 member k • CXCR4- C-X-C chemokine receptor type 4 • LCH- Langerhans Cell Histiocytosis • MAPK- Mitogen-activated protein kinase Diabetes Insipidus Abbreviations: • BCLXL- B-cell lymphoma-extra large Anemia, thrombocytopenia &/or neutropenia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 13, 2022 on www.thecalgaryguide.com

NSAIDs and the Kidney mechanism of action and side effects

NSAIDs and the Kidney: Mechanism of Action and Side Effects Authors: Kyle Moxham Mehul Gupta Reviewers: Emily Wildman Yan Yu* Adam Bass* *MD at time of publication Concurrent use of angiotensin- converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) AECi and ARBs act to ↓ renin- angiotensin-aldosterone system (RAAS) activation Reduced angiotensin (AT) 2 activity at its receptors on efferent arteriole of the nephron Net vasodilation of efferent arterioles ↓ in glomerular pressure ↓ blood perfusing kidney tissueà↑ hypoxemia & renal ischemia Pre-existing ↓effective arterial blood volume (EABV) from dehydration, GI loss, diuretics, CKD, CHF, cirrhosis, etc. Decreased EABV triggers endogenous renal autoregulation, resulting in norepinephrine (NE) mediated vasoconstriction of afferent arteriole of the nephron Net ↓ in renal blood flow and ↓ in glomerular pressure ↓ volume of blood filtered by the glomeruli per unit time Non-steroidal anti-inflammatory drugs (NSAIDs) Inhibition of Cyclooxygenase COX-1 (expressed in kidney) and COX-2 (expressed in kidney and sites of inflammation) ↓ Renal prostaglandin (PG) synthesis: local hormones involved in renal homeostasis NSAID induced nephrotoxicity: associated with chronic usage independent of dosage (see Calgary Guide slide on NSAIDs and the Kidney: NSAID induced nephrotoxicity) ↓ intrarenal PG reduces inhibitory effects of PG over ADH in cortical colleting duct (CCD) of the kidneyà↓ antagonism on ADH activity ↑ ADH activity causes insertion of more aquaporins (water channels) in the collecting duct of renal tubules Net ↑ in volume of water reabsorbed into the blood ↓ vasodilatory effect of PG at the afferent arteriole of the nephron ↓ Glomerular filtration rate (GFR) ↓ PG signalling results in ↓ renin secretion at juxtaglomerular apparatus Low renin levelsà↓ conversion of angiotensinogen into its AT1 form and, by extension, ACE mediated conversion of AT1 to AT2 ↓ ACE 2 signalling leads to ↓ levels of aldosterone in the serum ↓ Na+ and K+ channel insertion on apical surface and ↓ Na/K ATPase activity on basolateral surface of principal cells ↓ K+ excretion into urine, and ↓ Na+ reabsorption back into the blood, at the late DCT and collecting duct of the kidney Pre-renal Acute Kidney Injury (AKI): kidney injury due to renal hypoperfusion Prolonged and/or severe ischemia causes cell death and aggregation of tubular epithelial cells of the kidney with subsequent inability to reabsorb luminal Na+ Renal dehydration predisposes precipitation of uromodulin protein Renal tubules mold uromodulin into cylindrical structures known as “casts”. Casts that contain only uromodulin protein are known as “hyaline casts” Hyaline cast seen on urinalysis Hypoperfusion of the kidney activates the renin- angiotensin- aldosterone system (RAAS) ↑ amount of sodium (Na) reabsorbed from the filtrate (less Na excreted) Fractional excretion of Na <1% Papillary necrosis: ureteral passage of sloughed ischemic tissue causing ureteral obstruction Acute tubular necrosis: a type of kidney injury causing damage to the tubules Hypertension Post-renal AKI: a type of kidney injury due to obstruction of the urinary tract Distal distal obstruction of the urinary tract causes fluid to accumulate within the kidneysàenlarging the kidneys Renal Ultrasound shows hydronephrosis (enlarged kidneys) Damaged tubule epithelial cells slough into the tubular lumen Epithelial cell breakdown in the tubular lumen releases uromodulin & other proteins, which aggregate into “casts” (cylindrical imprints of the renal tubule). The varied protein content of these casts result in them having a coarse, granular appearance Damaged tubular epithelial cells are unable to properly reabsorb sodium ↓ amount of sodium (Na) reabsorbed from filtrate into the blood (more Na excreted) Fractional excretion of Na >2% True excess of free water relative to Na+ in the blood Excess free water ↑ venous hydrostatic pressure (see Calgary Guide slide on edema for full mechanisms) Pitting Edema Hyperkalemia Hyponatremia Coarse granular casts seen on urinalysis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 29, 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

ascending-cholangitis-pathogenesis-clinical-findings

Ascending Cholangitis: Pathogenesis and clinical findings Authors: Brandon Hisey, Neel Mistry Reviewers: Alec Campbell, Vina Fan, Ben Campbell, Kelly Burak*, Eldon Shaffer* * MD at time of publication Reflux of biliary contents into the vascular system (cholangiovenous reflux) Bacteria ascends into biliary tract from duodenum via Sphincter of Oddi Gallstone in the common bile duct Stricture of biliary/hepatic ducts Biliary / pancreatic duct malignancy Biliary obstruction (partial bile duct obstruction) ↓ Excretion of bilirubin into bileà ↑ bilirubin in blood ↑ Serum bilirubin Deposition of bilirubin in the skin and mucous membranes Jaundice*† Parasites in bile duct (E.g. Clonorchis) Complication of endoscopic retrograde cholangiopancreatography (ERCP) Bile accumulates in biliary tract Bile duct dilation on ultrasound Sludge (bile precipitants) impact bile ducts worsening obstruction Obstruction & detergents in bile inflame ductal mucosa. Inflammation then spreads to adjacent structures Stimulates phrenic (C3-C5) and foregut autonomic nerves (T5-T8) Dull right upper quadrant pain*† radiating to back and right shoulder ↑ Intra-biliary pressure Impaired forward flowà ↑ backflow of bile Impaired bile secretion damages ductal epithelium of the biliary tract Damaged ductal epithelium leaks ALP and GGT (enzymes) into blood ↑ Serum ALP and GGT ↑ Permeability of bile ductules Reduced flushing of bile out to duodenum Inflammatory response triggered Fever*† ↑ WBCs Tachycardia Hypotension† Confusion† Oliguria Bacterial translocation from biliary tract into blood Bacteremia Massive systemic inflammatory response Septic Shock (see Distributive Shock slide) * Charcot’s triad ~20% of cases | † Reynolds’ pentad ~7% of cases Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published November 18, 2015; Updated August 31, 2022 on www.thecalgaryguide.com

chronic-pancreatitis-complications

Chronic pancreatitis: Complications Hypothesis: Cytokines stimulate hypersecretion of secretory proteins (lithostathine, GP2) from acinar cells in exocrine pancreas (early in disease course) Proteins precipitate and form aggregates within pancreatic ducts Accumulation of protein aggregates and localized fibrosis block pancreatic ducts Rupture of acinar cells near blocked ducts → release of intracellular enzymes and fluid Accumulation of enzyme- rich fluid within pancreas Intra-pancreatic pseudocysts (differ from pseudocysts in acute pancreatitis, which are primarily extra-pancreatic) Chronic Pancreatitis Recurrent episodes of acute pancreatitis leading to irreversible fibroinflammatory pancreatic damage Inflammatory cytokines are continuously released from damaged pancreas over years Cytokines damage endothelium of intra- and peri-pancreatic blood vessels (including splenic vein, which runs posteriorly behind pancreas and allows for its venous drainage) Thin and weakened vessel walls balloon outwards from pressure of blood flow Pseudoaneurysms Venous stasis (low blood flow) → ↑ concentration of clotting factors Obstruction of peripancreatic ducts Author: Ashar Memon Reviewers: Yan Yu*, Kiana Hampton, Sylvain Coderre* * MD at time of publication Exocrine insufficiency (↓ secretion of digestive enzymes, e.g., Lipase, into gastro-intestinal tract) ↓ digestion of foods and absorption of nutrients (including fats) ↓ absorption of fat-soluble vitamin D Metabolic bone disease (a group of disorders of decreased bone mineralization) Blood vessels dilate and swell from increased blood flow Gastric varices Cytokines perpetually activate pancreatic stellate cells (stellate cells produce proteins that remodel extra- cellular matrix) Pancreatic stellate cells increase amounts of collagen and other extra- cellular matrix molecules in pancreas → Fibrosis Pancreatic proteolytic enzymes (e.g., trypsin) in fluid-filled pseudocysts digest walls of adjacent blood vessels Fibrotic tissue and pseudocysts compress peripancreatic structures (including splenic vein) Cytokines stimulate apoptosis of hormone- producing pancreatic Islet cells (e.g., beta cells) Endocrine insufficiency (↓ production and secretion of pancreatic hormones) Damaged endothelial cells of splenic vein trigger coagulation cascade (See Calgary Guide slide on Coagulation Cascade) Splenic vein thrombosis ↑ resistance to blood flow through splenic vein Cytokines stimulate apoptosis of acinar cells in exocrine pancreas Malnutrition ↓ secretion of insulin ↓ cellular uptake and metabolism of glucose → hyperglycemia Diabetes mellitus Collateral blood vessels develop around stomach so blood can circumvent splenic vein and relieve splenic vein hypertension Duodenal obstruction Biliary obstruction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 18, 2022 on www.thecalgaryguide.com

Granulomatosis with Polyangiitis Pathogenesis

Granulomatosis with polyangiitis: Pathogenesis Author: Oswald Chen Reviewers: Ben Campbell *Liam Martin * MD at time of publication Drugs Thiol- and hydrazine-containing medications (e.g., hydralazine, propylthiouracil, allopurinol) Environmental exposures Silica dust, cigarette smoke, infections (Staphylococcus aureus) Genetic factors Alpha-1 antitrypsin deficiency, proteinase 3 gene mutation ↑ Production of cytokines and antineutrophil cytoplasmic antibodies (ANCAs) (mechanism unknown) Cytokines bind to endothelial cells (that line blood vessels) and neutrophils, priming them Proteinase 3 (PR3), an enzyme that degrades extracellular matrix proteins, migrates from neutrophil granules to neutrophil cell surface Circulating ANCAs bind to PR3 on neutrophils PR3 stimulates maturation of dendritic cells in lungs Dendritic cells present antigen (PR3) to naïve CD4+ T cells in peripheral lymph nodes T cells differentiate into type 1 and type 17 helper T cells (Th1 and Th17 cells) Th1 and Th17 cells secrete cytokines (interferon γ (INF-γ) and tumor necrosis factor α (TNF-α)) in lungs Secreted cytokines trigger macrophage maturation Formation of granulomas (giant cells with central necrosis surrounded by plasma cells, lymphocytes, and dendritic cells) primarily in lungs and upper airways ANCA-activated neutrophils release proinflammatory cytokines, attracting more neutrophils to endothelium (blood vessel wall) ANCA-activated neutrophils undergo firm adhesion to endothelium ANCAs stimulate ↑ secretion of proteolytic enzymes and reactive oxygen species from neutrophils Endothelial damage and tissue injury Granulomatosis with polyangiitis (GPA) ANCA-associated vasculitis affecting medium and small-sized arteries, associated with necrotizing granulomas Constitutional symptoms with involvement of multiple organ systems (see slide on clinical findings) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2022 on www.thecalgaryguide.com Granulomatosis with polyangiitis: Clinical findings Inflammation-mediated endothelial damage and granuloma formation (see slide on pathogenesis) Granulomatosis with polyangiitis (GPA) Author: Oswald Chen Reviewers: Ben Campbell *Liam Martin * MD at time of publication ANCA-associated vasculitis affecting medium and small-sized arteries, associated with necrotizing granulomas Constitutional symptoms Fever, unintentional weight loss, night sweats, arthralgias Skin involvement Inflammation of cutaneous vessels Systemic inflammation obstructing blood flow, with granulomatous lesions primarily in upper airways and lungs Ear, nose, and throat involvement ↑ C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (markers of inflammation) Necrotizing granulomas on biopsy of affected tissue Positive PR3-ANCA/c-ANCA blood test (antibodies present in ~90% of patients, described in GPA Pathogenesis slide) Renal involvement Inflammation of renal vessels Rupture of basement membrane (layer that filters blood from glomerular capillaries into Bowman’s capsule) Pauci-immune glomerulonephritis (see Nephritic Syndrome slide) Rapidly progressive glomerulonephritis Eye involvement Inflammation of ocular tissue Conjunctivitis Scleritis/ episcleritis (painful red eye) Lower respiratory tract involvement Inflammation of pulmonary vessels Vessel occlusion and ischemia Skin necrosis Vessels burst and blood pools under skin Round and retiform (net- like) palpable purpura of lower extremities Granulomatous destruction of nasal cartilage Collapse of nasal bridge Saddle nose deformity Inflammation of paranasal sinus and nasal cavity vessels ↓ Perfusion of lungs Dyspnea Damage to interstitial capillaries Hemoptysis Diffuse alveolar hemorrhage Rhinitis/ sinusitis Granulomatous obstruction of eustachian tube Otitis media (see Otitis Media slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2022 on www.thecalgaryguide.com

Granulomatosis with polyangiitis: Clinical findings

Granulomatosis with polyangiitis: Clinical findings Inflammation-mediated endothelial damage and granuloma formation (see slide on pathogenesis) Granulomatosis with polyangiitis (GPA) Author: Oswald Chen Reviewers: Ben Campbell *Liam Martin * MD at time of publication ANCA-associated vasculitis affecting medium and small-sized arteries, associated with necrotizing granulomas Constitutional symptoms Fever, unintentional weight loss, night sweats, arthralgias Skin involvement Inflammation of cutaneous vessels Systemic inflammation obstructing blood flow, with granulomatous lesions primarily in upper airways and lungs Ear, nose, and throat involvement ↑ C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (markers of inflammation) Necrotizing granulomas on biopsy of affected tissue Positive PR3-ANCA/c-ANCA blood test (antibodies present in ~90% of patients, described in GPA Pathogenesis slide) Renal involvement Inflammation of renal vessels Rupture of basement membrane (layer that filters blood from glomerular capillaries into Bowman’s capsule) Pauci-immune glomerulonephritis (see Nephritic Syndrome slide) Rapidly progressive glomerulonephritis Eye involvement Inflammation of ocular tissue Conjunctivitis Scleritis/ episcleritis (painful red eye) Lower respiratory tract involvement Inflammation of pulmonary vessels Vessel occlusion and ischemia Skin necrosis Vessels burst and blood pools under skin Round and retiform (net- like) palpable purpura of lower extremities Granulomatous destruction of nasal cartilage Collapse of nasal bridge Saddle nose deformity Inflammation of paranasal sinus and nasal cavity vessels ↓ Perfusion of lungs Dyspnea Damage to interstitial capillaries Hemoptysis Diffuse alveolar hemorrhage Rhinitis/ sinusitis Granulomatous obstruction of eustachian tube Otitis media (see Otitis Media slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2022 on www.thecalgaryguide.com

Inhalational Injury

Inhalation Injury: Pathogenesis and complications Authors: Marshall Thibedeau, W Fraser Hill, Paloma Arteaga Juarez Reviewers: Spencer Yakaback, Tony Gu, Dami Omotajo, Ben Campbell, Yan Yu*, Michael Liss*, Duncan Nickerson*, Donald McPhalen* * MD at time of publication Smoke Inhalation Suspect if patient found unconscious, history of fire in a confined space and presence of facial burns Convective heat transfer Exposure to chemical irritants Tracheobronchial injury Injury stimulates vasomotor and sensory nerves of the trachea and bronchi Neuropeptides from neurons are released into local circulation and activate nitric oxide Inhalation of toxins Lack of O2 in an enclosed space Asphyxiation (O2 deprivation in lungs) Acute hypoxemia Loss of consciousness Death Upper airway injury (above vocal cords) Cell lysis & necrosis Local release of inflammatory substances ↑ Vascular permeability à edema of tissues in upper airway Damage to lower respiratory tract cilia ↓ Mucus clearance from alveoli Parenchymal injury (delayed reaction dependent on severity of burn) Alveolar epithelial and endothelial barrier irritation/damage Inflammatory response Carbon monoxide poisoning Cyanide poisoning Cyanide binds to mitochondrial cytochrome oxidase a3 CO binds more strongly to hemoglobin than O2 ↑ Carboxyhemoglobin in blood, ↓ free hemoglobin available to bind O2 in the lungs ↑ Affinity for O2 on remaining binding sites in hemoglobin (i.e. hemoglobin binds O2 more strongly and is slow to release it) ↓ O2 delivered to tissues Inhibition of cytochrome c oxidase Mucous obstructs airways Air retained distal to the obstruction is resorbed from nonventilated alveoli Regions without gas collapse i.e atelectasis ↑ Risk of infection ↓ Mitochondrial respiratory chain function Impaired oxidative phosphorylation & cellular energy production Cellular dysfunction in high metabolic tissues Nitric oxide acts as a vasodilator in alveolar arterioles Loss of hypoxic vasoconstriction (constriction of arterioles in alveoli due to ↓ O2) Reactive inflammation & bronchoconstriction Stridor Complete airway obstruction ↑ Vascular permeability leading to fluid leakage into interstitium and alveoli Blood flow to poorly ventilated alveoli is maintained Ventilation/perfusion (V/Q) mismatch (regions of lung not effectively ventilated despite being well perfused by blood) Acute Respiratory Distress Syndrome See ARDS Pathogenesis slide Hypoxemia Lower airway edema Wheezing Coughing Impaired brain function Muscle weakness Impaired heart function Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published November 10, 2019; Updated on February 12, 2023 on www.thecalgaryguide.com

Large Bowel Obstruction: Findings on Abdominal X-ray

Large Bowel Obstruction: Findings on Abdominal X-ray Authors: Shayan Hemmati Reviewers: Reshma Sirajee, Tara Shannon, *Stephanie Nguyen, *MD at the time of publication Radiopaedia, rID:18015 Common causes of obstruction are colorectal carcinoma (60-80%) and cecal or sigmoid volvulus (11-15%) Obstruction from mechanical causes such as physical blockade of bowel lumen or twisting of the large bowel Bowel Obstruction *See Mechanical Bowel Obstruction and Ileus: Pathogenesis and clinical findings Large bowel contents cannot pass the obstructionàgas buildup in colon from swallowed air, bacterial fermentation, CO2 from acid + bicarbonate reaction Colon intraluminal pressure overcomes venous and lymphatic pressure Impaired venous outflowàbowel wall edema/thickening ↑ Vascular resistance eventually impedes arterial inflowàbowel wall ischemia Ischemia can progress to bowel infarction and necrosis Large bowel loops are anatomically peripheral to the small bowel Evacuation of gas and water reabsorption distal to obstruction If ileocecal (IC) valve incompetent or sufficient pressure buildup in large bowel can overcome IC valve ↑ intraluminal pressure Gas dissects into bowel wall from mucosal disruption Pneumatosis coli (air within bowel wall) Bowel wall perforation (especially when cecum diameter > 10-12cm) Dilated large bowel loops located peripherally (highlighted yellow) Collapsed distal colon (few or no air-fluid levels in the large bowel as water is reabsorbed) Small bowel dilatation (> 3 cm) Colonic dilatation (> 6 cm) Cecum dilatation (> 9 cm) Haustra (anatomical folds of the large bowel) become visible as it is distended Pneumoperitoneum (sub-diaphragmatic air on erect chest x-ray) Release of gas into peritoneum PA Radiopaedia, rID:17957 PA Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 16, 2023 on www.thecalgaryguide.com

Central Retinal Vein Occlusion

Central Retinal Vein Occlusion: Pathogenesis and clinical findings Authors: Graeme Prosperi-Porta Mina Mina Reviewers: Stephanie Cote Usama Malik Mao Ding Johnathan Wong* *MD at time of publication Hypercoagulable state (pathologic state where there is an exaggerated tendency for the blood to clot) ↓ Anticoagulation (e.g., Protein C or S def) and/or ↑ coagulation (e.g., malignancy, Polycythemia Vera) Non-ischemic (perfused) CRVO Glaucoma (a disease characterized by ↑ intraocular pressure) Optic disc drusen (calcified nodules located within the optic disk – the most anterior part of the optic nerve) Diabetes Dyslipidemia Hypertension Vasculitis (inflammation of blood vessels; e.g., sarcoid, Systemic Lupus Erythematosus) Endothelial damage Pupillary responses do not vary between both eyes when a light is shone in one eye at a time Relative afferent pupillary defect (RAPD) mild or absent Lost vascular wall integrity Normal retinal electrical response to a light stimuli Normal electro- retinography (ERG) with b- wave >60% Few scattered Intra-retinal hemorrhages ↓ In retinal electrical response to a light stimuli Pupils respond differently to a light stimulus shone in one eye at a time Severe ↓ in visual acuity (Snellen acuity of <20/400) Visual field deficits ↓ b-wave amplitude (<60%) on ERG RAPD present ↑ Pressure compromises retinal vein outflow Central retinal atherosclerosis (build-up of fat & cholesterol plaque in arteries) & hardening Atherosclerotic changes in the central retinal artery compress the central retinal vein (since they are both held together in region of the optic disc) Venous stasis (stagnation of blood flow) ↑ Likelihood of thrombus formation Central Retinal Vein Occlusion (CRVO) A common retinal vascular disease characterized by blockage of the main vein that drains blood from the retina CRVO classified based on the degree of perfusion (as seen through retinal angiography) Ischemic (nonperfused) CRVO ↑ Intraluminal venous pressure Dilated tortuous retinal veins Normal visual fields Vascular wall integrity lost Four-quadrant hemorrhages described as “blood and thunder” on fundus exam Obstruction due to thrombus ↓ Retinal capillary perfusion causes ischemia Hypoxia in the retinal tissues ↑ Release of vascular endothelial growth factor to revascularize diseased tissue & overcome hypoxic conditions Angiogenesis (formation of new blood vessels) Intraretinal infarcts “Cotton wool spots” on fundus exam Venous capillary fluid/protein leakage Mild retina, macula and disc edema Moderate ↓in visual acuity often (Snellen acuity >20/400) New vessel proliferation can occur in the anterior chamber of the eye This change can block the outflow path of the aqueous humor in the eye Neovascular glaucoma Neovascular vessels are structurally different in comparison to regular retinal vasculature Neovascular vessels are more fragile ↑ Likelihood of rupture Vitreous hemorrhage Neovascular vessels lack tight junctions ↑ Fluid leakage Retina, macula and disc edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First Published June 28, 2017, updated March 4, 2023 on www.thecalgaryguide.com

Benzodiazepine Mechanism of Action

Benzodiazepine: Mechanism of action Anesthetic composed of a fused benzene and diazepine ring that is administered orally or intravenously to produce a sedative or hypnotic effect Ex. Lorazepam, Midazolam, Diazepam Binds to Gamma- aminobutyric acid (GABAA) receptor in vascular smooth muscle and the central nervous system (CNS) APs inhibited in vascular smooth muscle Vascular smooth muscle relaxes Vasodilation ↓ Blood pressure Authors: Victoria Silva Travis Novak Reviewers: Billy Sun Mao Ding Melinda Davis* *MD at time of publication ↑ Frequency of chloride channel opening Hyperpolarization of nerve membrane Action potential (AP) inhibited APs inhibited in the medulla oblongata (the respiratory center) ↓ Respiratory drive: the body fails to ↑ depth and rate of respirations when arterial CO2 ↑ General CNS inhibition Anti-convulsion (Seizures are caused by a burst of uncontrollable, electrical activity in the brain) APs inhibited in the thalamus and hypothalamus (play a role in memory) APs inhibited in the limbic system (the behavioral and emotional response centers in the brain) Hypotension ↓ Cerebral blood flow ↓CO2 diffusion from arterial blood to alveoli ↓O2 diffusion from alveoli to arterial blood Pharyngeal muscle relaxation ↑ Arterial CO2 ↓ Arterial O2 Airway obstruction Amnesia ↑ PaCO2 ↓ PaO2 ↓ Anxiety Anxiolysis Hypercapnia Hypoxemia In high doses: Depression of arousal and loss of consciousness Induction of general anesthesia (No analgesic effect) ↓ Intracranial pressure Benzodiazepine reversal: Temporary cessation of breathing Apnea Flumazenil competitively binds to GABAA Flumazenil reverses the binding of benzodiazepine to GABAA ↓ Frequency of chloride channel opening Depolarization of nerve membrane Benzodiazepine reversal Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 09, 2018, updated April 25, 2023 on www.thecalgaryguide.com

diverticulosis-vs-diverticulitis-distinguishing-features

Diverticulosis vs. Diverticulitis: Distinguishing features Authors: Sahil Prabhnoor Sidhu, Vadim Iablokov, Vina Fan Reviewers: Brandon Hisey, Laura Byford-Richardson, Raafi Ali Dr. Sylvain Coderre* * MD at time of publication Local inflammation Diverticulitis Inflammation of diverticuli Conditions causing inherent weakness in bowel wall, i.e. aging, Ehlers-Danlos syndrome, Marfan syndrome Risk factors (i.e. low fiber diet, obesity, inactivity, smoking) contributing to reduced gut motility ↑Intraluminal pressure in the colon Herniation of colonic mucosa and submucosa through circular muscle at points of weakness to form outpouchings Diverticulosis Presence of outpouchings in the colon (diverticuli) Note: In Western populations, most diverticulosis is left-sided, whereas in Asian populations, these outpouchings are more often right-sided. Mucosal abrasion or micro-perforation by ↑ intraluminal pressure or dense food particles Bacterial overgrowth, dysbiosis and passage into the lamina propria Feces collects in diverticuli Gut bacteria metabolize undigested material and produce gas Stretching of colon Bloating wall irritates and visceral afferent flatulence nerves Episodic abdominal discomfort and cramping Blood vessels in the mucosa and submucosa (vasa recta) are stretched over the diverticuli, and may rupture from ↑ pressure Diverticular bleed Painless hematochezia (passage of fresh blood from the rectum) Inflammatory cytokines activate clotting factors Clotting of blood in vessels supplying diverticula Inflammatory cytokine release (IL-6, TNF-α) Cytokines enter systemic circulation Edema in the bowel wall Irritation of adjacent parietal peritoneum and somatic nerves Left lower quadrant (LLQ) pain, guarding Small abrasions are walled off by pericolic fat and mesentery ↑WBC Fever Inflammation may spread to nearby organs, leading to ulceration and abnormal connections between organs Pericolic abscess No hematochezia Local ischemia and focal necrosis resulting in loss of integrity of the bowel wall Perforation Generalized peritonitis Colonic obstruction (rare) Fistulae (rare): i.e. colovesical, coloenteric Stricture/fibros is formation with healing Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 12, 2016; Updated July 30, 2023 on www.thecalgaryguide.com

Anesthetic Considerations for Obese Patients

Anesthetic Considerations In Patients With Obesity Pathophysiology Driving Anesthetic Management Goal Anesthetic Intervention Excess body fat in mouth and pharynx ↑ Total body fat & fat-free mass ↑ Mallampati score ↑ Neck circumference Loss of muscle tone in pharynx & tongue following neuromuscular blocking drugs Airway access difficulty & ↑ Intubation time ↑ Respiratory rate ↓ Time to desaturation Hypoventilation while supine ↓ Functional residual capacity ↑ Gastric aspiration risk ↑ Dosage requirements of lipophilic drugs ↑ Drug metabolism & clearance ↑ Energy cost of weight-bearing activity ↑ Basal metabolic rate ↓ Total respiratory compliance Excess weight compresses lungs Airway obstruction ↑ Oxygen required ↓ Functional residual capacity ↑ Work of breathing Secure a patent airway & avoid hypoxemia Optimize positioning Maintain oxygenation & lung protection Aspiration prophylaxis Achieve optimal anesthetic dosing for altered distribution Optimize anesthetic dosing for altered metabolism & clearance Intubate via endotracheal tube, avoid supraglottic airway device Consider video laryngoscopy Use head-elevated laryngoscopy positioning (“sniffing” position) Pre-oxygenate to ↑ oxygen reserve during intubation Avoid supine positioning, in place of alternate positioning (i.e., reverse trendelenburg) Lung-protective ventilation (↓ tidal volume, optimize oxygen levels, positive end expiratory pressure & recruitment maneuvers) Pre-operative fasting, gastric ultrasound to assess volume Rapid sequence induction to reduce aspiration risk Adjust drug dosages based on individual recommendations to account for altered distribution, metabolism & clearance Excess body fat on chest wall Excess intra- abdominal fat ↑ Gastric volume Excess body fat ↑ Circulating blood volume Obesity- related restrictive lung disease ↑ Load compressing chest wall BMI ≥30 kg/m2 Note: effects vary with the severity of obesity ↑ Pressure on diaphragm and lungs ↓ Outward chest wall force ↑ Abdominal pressure ↑ Fat acts as a reservoir for lipophilic drugs ↑ Fat storage in hepatocytes ↑ Cardiac output ↑ Pressure on gastric contents ↑ Distribution half-life of lipophilic drugs ↑ Volume of distribution for lipophilic drugs ↑ Hepatic cytochrome transcription ↑ Glomerular filtration rate and hepatic blood flow Authors: Brianna Rosgen Reviewers: Kayleigh Yang Ran Marissa Zhang Karl Darcus* * MD at time of publication Legend: Pathophysiology Mechanism Goal Anesthetic Intervention Published Nov 8, 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

Mechanical Ventilation mechanisms of action and complications

Mechanical Ventilation: Mechanisms of Action and Complications Authors: Madison Amyotte Reviewers: Victória Silva, Mao Ding Eric Leung* * MD at time of publication Mechanical ventilation is a form of life support that helps a patient breathe (ventilate) when they cannot breathe on their own. Invasive: Delivery of positive pressure to the lungs via endotracheal or tracheostomy tube Mechanical ventilation Pressure support ventilation (PSV): Set inspiratory pressure & flow. Patient initiates all breaths unassisted Non-invasive: Delivery of oxygen into the lungs via positive pressure through the mouth No endotracheal or tracheostomy tube Assist/control ventilation (AC): Set respiratory rate & tidal volume (amount of air delivered to the lungs with each breath). Patient can trigger additional assisted breaths Synchronized intermittent mandatory ventilation (SIMV): Set tidal volume & respiratory rate. Patient can trigger additional unassisted breaths 02 mask delivery Continuous positive airway pressure (CPAP) Provides continuous positive ventilatory pressure Bilevel positive airway pressure (BIPAP) Provides positive pressure with two different pressure levels for inhalation and exhalation ↑ Swallow non- inspiratory flow Aspiration Acute rise in airway pressure Barotrauma Patient- triggered breath Ventilator senses negative pressure from inflation of the lungs Time-triggered breath Respiratory rate set at x breaths per min Patient-triggered breath Ventilator senses negative pressure from inflation of the lungs Tidal volume determined by patient’s strength & lung compliance Time-triggered breath Respiratory rate set at x breaths per min Delivery of set tidal volume, inspiratory flow rate & pattern Complete patient- triggered breaths Ventilator senses negative pressure from inflation of the lungs Breathes assisted by set inspiratory pressure Inspiratory flow drops below set inhalational negative pressure threshold Pressure support terminates as exhalation cycle begins Combined with SIMV Inspiratory pressure added to patient triggered breaths Patient can overcome resistance of the endotracheal tube or ↑ volume of spontaneous breathes Delivery of set tidal volume, inspiratory flow rate & pattern Airways remain open & clear of obstruction Forced air into nasal passages Nose bleeds (epistaxis) Maximum tidal volume reached Exhale valve opens Patient exhales actively or passively until set end expiratory pressure in the lungs is reached (PEEP) to prevent alveolar collapse Patient exhales until PEEP reached Patient achieves optimal ventilation throughout respiratory cycles Mouth breathing Dry mouth (xerostomia) Increased work of breathing & muscle fatigue Prolonged weaning & extubation Breath stacking ↑ Volume and pressure in lungs Lung tissue injury (barotrauma) Microorganisms colonize artificial airway Ventilator associated pneumonia if ventilation >48 hrs Tachypnea ↓ CO2in circulation Respiratory alkalosis Legend: Pathophysiology Mechanism Sign/symptom/lab finding Complications Published Nov 25, 2023 on www.thecalgaryguide.com

Anesthetic Considerations One Lung Ventilation

Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Shunt: Non- dependent lung unventilated Perfusion but no ventilation to collapsed lung Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch causes ↑ hypoxemia Increase FiO2 to 1 to maintain SpO2 ≥ 90% Increased FiO2 can allow for toleration of shunt Optimize cardiac output and shunt fraction to maximize PaO2 Author: Aly Valji Reviewers: Jasleen Brar Ryden Armstrong* * MD at time of publication Relative indications Surgical exposure for pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Double lumen tube (gold standard) Endotracheal tube (ETT) with two lumens (bronchial and tracheal) Insert longer side to a mainstem bronchus, shorter side ends in distal trachea Absolute Indications Isolation of healthy from contaminated lung (unilateral infection, hemorrhage) Control unilateral disruption of ventilation (bronchopleural fistula, unilateral bullae) Video assisted thoracoscopic surgery Unilateral lung lavage Airway Technique Anesthetic Technique General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Intraabdominal contents push up on diaphragm ↓ Functional residual capacity (FRC) ↑ Atelectasis if closing capacity > FRC ↑ Hypoxemia Optimize Altered gravitational forces on thorax ↓ Compliance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure ↑ Perfusion to dependent lung. ↑ Ventilation to nondependent lung (prior to lung isolation) Collapse of nondependent lung using lung isolation causes ↓ ventilation to this lung Optimize tidal volume (6-8 mL/kg), respiratory rate (maintain PaCO2 35-40 mmHg), PEEP (5-10 cm H2O) based on clinical picture Univent tube Single lumen ETT with movable endobronchial blocker in wall Blocker steered after intubation into a mainstem bronchus with fiberoptic bronchoscope Endotracheal tube in mainstem bronchus Single lumen ETT pushed into a mainstem bronchus Bronchial blocker Shaft with an inflatable balloon on distal end Inserted through single lumen ETT into a mainstem bronchus, after intubation positive end- expiratory pressure (PEEP) of 5-10 cm H2O Recruitment of dependent, atelectatic lung with positive pressure Optimize FiO2 ↓ Absorptive atelectasis (from ↑ partial pressure O2 and ↓ N2) Cuff inflated in a mainstem bronchus to isolate respective lung. Placement should be verified using fiberoptic bronchoscope if possible after positioning ↓ Atelectasis and ↑ FRC ↓ Hypoxemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Management Published December 5, 2023 on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Shunt: Non- dependent lung unventilated Perfusion but no ventilation to collapsed lung Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO2 to 1 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung ↓ V/Q mismatch Author: Aly Valji Reviewers: Jasleen Brar Dr. Armstrong* * MD at time of publication Relative indications Surgical exposure for pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Double lumen tube (DLT) Two endotracheal tubes (ETT) bonded together Insert longer side to a mainstem bronchus, shorter side ends in distal trachea Absolute Indications Isolation of healthy from contaminated lung (unilateral infection, hemorrhage) Control unilateral disruption of ventilation (bronchopleural fistula, unilateral bullae) Video assisted thoracoscopic surgery Unilateral lung lavage Airway Technique Anesthetic Technique General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Intraabdominal contents push up on diaphragm ↓ Functional residual capacity (FRC) ↑ Atelectasis if closing capacity > FRC ↑ Hypoxemia Optimize Altered gravitational forces on thorax ↑ Elastance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure ↑ Perfusion to dependent, ventilated lung ↓ Ventilation- perfusion (V/Q) mismatch ↓ Hypoxemia Optimize tidal volume (6-8 mL/kg), respiratory rate (maintain PaCO2 35-40 mmHg), PEEP (5-10 cm H2O) based on clinical picture Univent tube Single lumen ETT with movable endobronchial blocker in wall Blocker steered after intubation into a mainstem bronchus with fiberoptic bronchoscope Endotracheal tube in mainstem bronchus Single lumen ETT pushed into a mainstem bronchus Bronchial blocker Shaft with an inflatable balloon on distal end Inserted through single lumen ETT into a mainstem bronchus, after intubation positive end- expiratory pressure (PEEP) of 5-10 cm H2O Recruitment of dependent, atelectatic lung with positive pressure Optimize FiO 2 ↓ Absorptive atelectasis (from ↑ partial pressure O2 and ↓ N2) Cuff inflated in a mainstem bronchus to isolate respective lung. Placement should be verified using fiberoptic bronchoscope if possible after positioning ↓ Atelectasis and ↑ FRC ↓ Hypoxemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Management Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Author: Aly Valji Reviewers: Jasleen Brar Name* * MD at time of publication Non-dependent lung unventilated Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO2 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Indications Anesthetic General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Relative indications Surgical exposure for pulmonary resection, mediastinal, esophageal, vascular, thoracic spine surgery Absolute Indications Isolation of healthy from contaminated lung (Unilateral infection or hemorrhage) Control unilateral disruption of ventilation (Bronchopleural fistula, unilateral bullae) Video assisted thoracoscopic surgery Unilateral lung lavage Intraabdominal contents push up on diaphragm ↓ FRC ↑ Atelectasis if closing capacity > FRC ↑ Hypoxemia Altered gravitational forces on thorax Shaft with an inflatable balloon on distal end. Inserted through a single lumen ETT after intubation into a mainstem bronchi Single lumen ETT pushed into a mainstem bronchus Optimize positive end-expiratory pressure (PEEP)) Recruitment of dependent, atelectatic lung with positive pressure ↑ Elastance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure ↑ Perfusion to dependent, ventilated lung ↓ Ventilation- perfusion (V/Q) mismatch ↓ Hypoxemia Optimize tidal volume, respiratory rate, PEEP based on clinical picture Bronchial blocker Endotracheal tube in mainstem bronchus Technique Univent tube Double lumen tube (DLT) Optimize FiO2 ↓ Absorptive atelectasis (from ↑ partial pressure O2 and ↓ N2) Single lumen ETT with movable endobronchial blocker housed in wall of ETT. Blocker maneuvered after intubation into a mainstem bronchus Two endotracheal tubes (ETT) bonded together. Longer side goes into a mainstem bronchus, shorter side ends in distal trachea ↓ Atelectasis and ↑ FRC ↓ V/Q mismatch Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Author: Aly Valji Reviewers: Jasleen Brar Name* * MD at time of publication Non-dependent lung unventilated Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO to 2 maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung ↓ V/Q mismatch Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Indications Anesthetic General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Comorbidity: Likely underlying pulmonary disease Pre-operative evaluation Pulmonary function testing Overall clinical picture, forced expiratory volume (FEV1), and diffusion capacity (DLCO) Multidisciplinary determination of fitness for surgery Pulmonary hemorrhage Whole lung lavage Unilateral infection Bronchopleural fistula Isolation of affected lung from unaffected lung Pulmonary resection Mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Operative lung deflated to expose surgical site Intraabdominal contents push up on diaphragm ↓ FRC ↑ Atelectasis if closing capacity > FRC ↑ Hypoxemia Optimize positive Altered gravitational forces on thorax Contraindications ↑ Elastance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure ↑ Perfusion to dependent, ventilated lung ↓ Ventilation- perfusion (V/Q) mismatch ↓ Hypoxemia Optimize tidal volume, respiratory rate, PEEP based on clinical picture Bilateral lung ventilation dependency Hemodynamic instability Severe hypoxia Severe COPD Severe pulmonary hypertension Potentially unable to tolerate one lung ventilation Intraluminal airway obstruction/mass Known difficult airway Risk of dislodging mass and inability to secure airway Pursue more advanced airway techniques end-expiratory pressure (PEEP) Recruitment of dependent, atelectatic lung with positive pressure Optimize FiO2 ↓ Absorptive atelectasis (from ↑ partial pressure O and ↓ N ) 2 2 ↓ Atelectasis and ↑ FRC Post-operative pain management Thoracotomy or VATS procedure causing ↑ pain along thoracic dermatomes Epidural Paravertebral block Anesthetic injected into epidural space Anesthetic injected into paravertebral spaces Bilateral spinal nerve blockade below desired spinal level Ipsilateral spinal nerve and sympathetic chain blockade in thoracic dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Author: Aly Valji Reviewers: Jasleen Brar Name* * MD at time of publication Non-dependent lung unventilated Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung Right to left intrapulmonary shunt with some perfusion to non- dependent lung V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO2 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung ↓ V/Q mismatch Indications Anesthetic General anesthetic with neuromuscular blockade ↓ Inspiratory muscle tone Comorbidity: Likely underlying pulmonary disease Pre-operative evaluation Pulmonary function testing Overall clinical picture, forced expiratory volume (FEV1), and diffusion capacity (DLCO) Multidisciplinary determination of fitness for surgery Anesthetic injected into epidural space Anesthetic injected into paravertebral spaces Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated Pulmonary hemorrhage Whole lung lavage Unilateral infection Bronchopleural fistula Isolation of affected lung and unaffected lung Pulmonary resection Mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Operative lung deflated to expose surgical site Intraabdominal contents push up on diaphragm ↓ FRC ↑ Atelectasis ↑ Hypoxemia Optimize positive end- expiratory pressure (PEEP) Recruitment of dependent, atelectatic lung with positive pressure ↓ Atelectasis and ↑ FRC Altered gravitational forces on thorax Contraindications ↑ Elastance of dependent lung ↑ Airway pressure required ↑ Risk of lung barotrauma due to ↑ pressure Optimize tidal volume, respiratory rate, PEEP based on clinical picture ↑ Perfusion to dependent, ventilated lung ↓ Ventilation- perfusion (V/Q) mismatch ↓ Hypoxemia Bilateral lung ventilation dependency Hemodynamically unstable Severe hypoxia Severe COPD Severe pulmonary hypertension Unable to tolerate one lung ventilation Intraluminal airway obstruction/mass Known difficult airway Risk of dislodging mass and inability to secure airway Pursue more advanced airway techniques Post-operative pain management Thoracotomy or VATS procedure causing ↑ pain along thoracic dermatomes Epidural Paravertebral block Bilateral spinal nerve blockade below desired spinal level Ipsilateral spinal nerve and sympathetic chain blockade in thoracic dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Mechanical separation of the lungs to allow for individualized ventilation of only one lung Author: Aly Valji Reviewers: Name* * MD at time of publication Indication Contraindications Comorbidity: Likely underlying pulmonary disease Positioning: Lateral decubitus position (patient on their side) with dependent lung ventilated General anesthetic with neuromuscular blockade Post-operative pain management Pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Pulmonary hemorrhage, whole lung lavage, bronchopleural fistula, or unilateral infection Operative lung deflated to expose surgical site Isolation of affected lung and unaffected lung Dependency on bilateral lung ventilation, hemodynamically unstable, severe hypoxia, severe COPD, or severe pulmonary hypertension Unable to tolerate one lung ventilation Intraluminal airway obstruction/mass or known difficult Pursue more advanced Risk of dislodging mass and inability to secure airway Multidisciplinary determination of fitness for surgery airway Pulmonary function testing Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung airway techniques Overall clinical picture, forced expiratory volume (FEV1), and diffusion capacity (DLCO) Pre-operative evaluation Non- dependent lung not ventilated Altered gravitational forces on thorax Intraabdominal contents push up on diaphragm ↓ Inspiratory muscle tone Likely procedure is thoracotomy or VATS causing ↑ pain along thoracic dermatomes Right to left intrapulmonary shunt with some perfusion to non- dependent lung still present V/Q mismatch from shunt causes ↑ hypoxemia Increase FiO2 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for shunt to non- dependent lung ↓ V/Q mismatch ↓ Hypoxemia Intervention: Optimize tidal volume, respiratory rate, PEEP based on clinical picture ↓ Atelectasis and ↑ FRC ↑ Perfusion to dependent, ventilated lung ↑ Elastance of dependent lung ↓ FRC ↓ Functional residual capacity (FRC) ↓ Ventilation-perfusion (V/Q) mismatch ↑ Airway pressure required ↑ Atelectasis ↑ Hypoxemia ↑ Risk of lung barotrauma due to ↑ pressure Intervention: Optimize positive end-expiratory pressure (PEEP) Recruitment of dependent, atelectatic lung with positive pressure Epidural Paravertebral block Anesthetic injected into epidural space Bilateral spinal nerve blockade below desired spinal level Anesthetic injected into Ipsilateral spinal nerve and sympathetic chain blockade in thoracic paravertebral spaces dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic Considerations: One-lung ventilation Author: Aly Valji Reviewers: Name* * MD at time of publication One lung ventilation: mechanical separation of the lungs to allow for individualized ventilation of only one lung Indication Pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Pulmonary hemorrhage, whole lung lavage, bronchopleural fistula, or unilateral infection Exposure of surgical site by deflation of operative lung Isolation of affected lung and unaffected lung Dependency on bilateral lung ventilation, Contraindications hemodynamically unstable, severe hypoxia, severe COPD, or severe pulmonary hypertension Intraluminal airway obstruction/mass or known difficult airway Pursue more advanced airway techniques Unable to tolerate one lung ventilation Risk of dislodging mass and inability to secure airway Likely underlying Pre-operative Pulmonary pulmonary disease evaluation function testing Overall clinical picture, forced expiratory Determination of volume (FEV1), and diffusion capacity (DLCO) fitness for surgery Right to left intrapulmonary shunt as some perfusion to non- dependent lung is still present ↑ Perfusion to dependent, ventilated lung ↑ Elastance of dependent lung ↓ FRC Non- dependent lung not ventilated Hypoxic vasoconstriction decreases but does not stop perfusion to non- dependent lung V/Q mismatch from shunt increases hypoxemia Intervention: Increase FiO2 to maintain SpO2 ≥ 90% Vasodilation of dependent lung vasculature to compensate for non-dependent lung ↓ V/Q mismatch ↓ Hypoxemia Intervention: Optimize tidal volume, respiratory rate, PEEP ↓ Atelectasis and ↑ FRC Positioning: Lateral position with dependent lung ventilated Altered gravitational forces on thorax ↓ Ventilation-perfusion (V/Q) mismatch General anesthetic with neuromuscular blockade Intraabdominal contents push up on diaphragm ↑ Airway pressure required ↑ Atelectasis ↑ Hypoxemia ↑ Risk of lung barotrauma Intervention: Optimize positive end-expiratory pressure (PEEP) Recruitment of dependent, atelectatic lung from PEEP ↓ Inspiratory muscle tone ↓ Functional residual capacity (FRC) Post- operative pain management Thoracotomy or VATS causes pain along thoracic dermatomes Epidural Paravertebral block Bilateral spinal nerve blockade below desired Anesthetic injected into epidural space spinal level Anesthetic injected into Ipsilateral spinal nerve and sympathetic chain blockade in paravertebral spaces thoracic dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com Anesthetic considerations: one-lung ventilation Author: Aly Valji Reviewers: Name* * MD at time of publication One lung ventilation: mechanical separation of the lungs to allow for individualized ventilation of only one lung Indication Pulmonary resection, mediastinal, esophageal, vascular, thoracic spine, or cardiac valve surgery Pulmonary hemorrhage, whole lung lavage, bronchopleural fistula, or unilateral infection Exposure of surgical site by deflation of one lung Isolation of one lung from other Dependency on bilateral lung ventilation, Contraindications hemodynamically unstable, severe hypoxia, severe COPD, or severe pulmonary hypertension Intraluminal airway obstruction/mass or known difficult airway Pursue more advanced airway techniques Unable to tolerate one lung ventilation Risk of dislodging mass and inability to secure airway Pre-operative evaluation given likely Pulmonary Forced expiratory volume (FEV1) Determination of underlying pulmonary disease function testing Diffusion capacity (DLCO) fitness for surgery Non- dependent lung not ventilated Hypoxic vasoconstriction decreases but does not stop perfusion of non- dependent lung Vasodilation of dependent lung pulmonary vasculature Right to left intrapulmonary shunt causes V/Q mismatch ↑ Perfusion to dependent, ventilated lung ↑ Elastance of dependent lung ↓ FRC ↑ Hypoxemia Intervention: Increase FiO2 to maintain SpO2 ≥ 90% ↓ V/Q mismatch ↓ Hypoxemia Intervention: Optimize tidal volume, respiratory rate, PEEP ↓ Atelectasis and ↑ FRC Positioning: Lateral decubitus with dependent lung ventilated Altered gravitational forces on thorax ↓ Ventilation-perfusion (V/Q) mismatch General anesthetic with neuromuscular blockade Intraabdominal contents push up on diaphragm ↑ Airway pressure required ↑ Atelectasis ↑ Hypoxemia ↑ Risk of lung barotrauma Intervention: Optimize positive end-expiratory pressure (PEEP) Recruitment of dependent lung ↓ Inspiratory muscle tone ↓ Functional residual capacity (FRC) Post- operative pain management Thoracotomy or VATS causes pain along thoracic dermatomes Epidural Paravertebral block Bilateral spinal nerve blockade below desired Anesthetic injected into epidural space spinal level Anesthetic injected into Ipsilateral spinal nerve and sympathetic chain blockade in paravertebral spaces thoracic dermatomes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complication/Intervention Published MONTH, DAY, YEAR on www.thecalgaryguide.com

Zenkers Diverticulum Pathogenesis and Clinical Findings

Zenker’s Diverticulum: Pathogenesis and Clinical Findings Author: Juliette Hall Reviewers: Sunawer Aujla *Dr. Derrick Randall Illustrator: Erica Lindquist * MD at time of publication Functional pharyngo- esophageal motility disorders. Increased upper esophageal sphincter (UES) resting pressure Inadequate relaxation of the cricopharyngeal muscle of the UES during swallowing Lack of synchronization between UES and hypopharynx during swallowing Outflow obstruction in the esophagus Increased intrabolus pressure with swallowing Increase in hypopharyngeal pressure Note: the pathogenesis of Zenker’s Diverticulum is multifactorial, but this mechanism is thought to be a significant contributor Herniation of the esophagus at a weak point between the inferior pharyngeal constrictor muscle and the cricopharyngeal muscle (Killian’s triangle) Zenker’s Diverticulum Acquired mucosal herniation between the horizontal and oblique fibers of the cricopharyngeus muscle Inability of the the upper esophageal sphincter to completely open Dysphagia Extrinsic compression of the cervical esophagus by the diverticulum Esophageal Obstruction Diverticulum compresses recurrent laryngeal nerve Impaired innervation to the intrinsic muscles of the larynx and other contributing factors False diverticulum retains food and saliva Feeling of needing to clear throat Palpable lump in the neck Halitosis (bad smelling breath) Secretions and food spontaneously empty into the bronchial tree Splashing of the fluid that has accumulated in large diverticula Cricoid Cartilage Cricopharyngeal muscle of the UES Thyroid Gland Boyce’s sign (gurgling sound heard as air passes through the diverticulum) Zenker’s Diverticulum Weight loss and malnutrition Aspiration Cough reflex Chronic cough Regurgitation Hoarseness Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com

Bacterial Tracheitis

Bacterial Tracheitis: Pathogenesis and Clinical Findings Authors: Fasika Jembere Reviewers: Simran Sandhu Mao Ding Danielle Nelson * MD at time of publication Recent upper respiratory viral infection Age typically <6 years old (more common in males) Children at higher risk due physiologic narrowing of airway Recent upper respiratory viral infection (often in Fall/Winter; respiratory virus season) Damage to airway mucosa Activation of systemic inflammatory response Inflammatory cytokines release into systemic circulation ↑ Thermo-regulatory set- point at the hypothalamus ↑ Work of breathing to adequately ventilate lungs Respiratory distress (nasal flaring, grunting) Activation of local inflammatory response Results in thick mucopurulent secretions, ulcerations, and shedding of tracheal mucosa Mucopurulent discharge secretion of fluid contains mucus and pus ↑ Production of mucous results in more accumulation Predisposition to bacterial infection Bacterial pathogen invades trachea Ex: S. aureus (common), S. pyogenes, M. catarrhalis, or H. influenzae Often high fever Trachea is narrowed with purulent debris Upper airway obstruction causes turbulent airstreams Hoarse voice Tachypnea Stridor (with inhalation & exhalation; may be biphasic) Tracheal tenderness ↓ Mucous clearance from the airways Excess airway mucous triggers cough reflex Cough (may be barky) ↑ Use of accessory respiratory muscles (sternocleidomastoid and scalene muscles) Toxic appearance (lethargy, cyanosis) ↓ Level of consciousness (due to hypoxia & hypercarbia) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 11, 2024 on www.thecalgaryguide.com

Epiglottitis

Epiglottitis: Pathogenesis and clinical findings Infectious cause: Bacterial (Staphylococcus aureus, Streptococcus pneumoniae, Neisseria meningitidis, or most commonly Haemophilus influenzae in unimmunized children), viral or fungal Authors: Alisha Ebrahim Reviewers: Simran Sandhu Mao Ding Michelle J. Chen Danielle Nelson* * MD at time of publication Infectious agent invades the bloodstream and/or the epithelial layer of the epiglottis, aryepiglottic folds and adjacent structures, allowing for spread Non-infectious cause: Ingestion of toxin or foreign body, thermal injury, or trauma The potential space between the squamous epithelial layer and the epiglottal cartilage fills with inflammatory cells such as neutrophils and eosinophils Exudate of inflammatory cells spreads through the lymphatic and blood vessels in the lingual surface of the epiglottis and periepiglottic tissues Fluid and inflammatory cells accumulate between the squamous epithelial layer and epiglottal cartilage Swelling of the entire supraglottic larynx Tripod/sniffing position (Anxious- looking and sitting with trunk leaning forward, neck hyper-extended and chin pushed forward to maximize airway diameter) Stridor (High-pitched sound that is produced by obstruction in the larynx or just below) Stertor (Low-pitched noise created in the nose or the back of the throat) Retraction of the intercostal and suprasternal muscles Tachypnea (Rapid breathing) Increased weight and mass of the epiglottis Epiglottis curls posteriorly and inferiorly Ball-valve effect (Airflow obstructed during inspiration as epiglottis is pulled over airway but not during expiration as epiglottis moves back into position) ↓ Diameter of upper airway Epiglottis obstructs the esophagus Dysphagia (Difficulty swallowing) Cyanosis (Blue tint to skin) Turbulent inspiratory airflow Aspiration of oropharyngeal secretions Hypoxemia (Low oxygen levels in blood) ↓ Air entry to lungs Airway obstruction ↑ Work of breathing Drooling Pain when swallowing Muffled/”hot potato” voice Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 5, 2024 on www.thecalgaryguide.com

Acute Otitis Externa Complications

Acute Otitis Externa (Swimmer’s Ear): Complications Acute Otitis Externa (AOE) Authors: Charmaine Szalay-Anderson Vaneeza Moosa Reviewers: Shayan Hemmati Shahab Marzoughi Ben Campbell Justin Lui* * MD at time of publication Spread to subcutaneous tissue Chronic otitis externa (>6 weeks) Chronic inflammation of the outer ear Fibroblast activation for collagen and extracellular matrix components production for tissue repair Excess accumulation of tissue Ear canal fibrosis (thickening) Ear canal stenosis (narrowing) Damage/obstruction to ear canal structures with impaired fluid drainage & pressure buildup Inflammation of the outer ear Recurrent or non-resolving acute otitis externa Dissemination of infection Spread to connective tissue and cartilage Perichondritis (inflammation of ear cartilage) Spread of Pseudomonas aeruginosa in an immunocompromised host or due to antibiotic resistance Rapid infectious spread through soft tissue to mastoid and/or temporal bone Malignant (necrotizing) otitis externa *can be life threatening Inflammation of connective tissue and bony structures Spread to tympanic membrane Myringitis (inflammation of tympanic membrane) Swelling and thinning of tissue Tympanic membrane perforation (tear) Immune reaction with inflammation Dead white blood cell, bacteria & tissue debris accumulation in the ear canal Pus formation with purulent otorrhea (discharge from ear) Localized pus accumulation Abscess Ear canal blockage Periauricular/ pinna (outer ear) cellulitis Facial cellulitis Erosion of temporal bone decreasing bony sound conduction Permanent conductive hearing loss Direct toxicity of pathogens to surrounding nerves Cranial nerve (CN) VII (facial) palsy (+/- CN X, XI, XII) Out-of- proportion primary otalgia (ear pain) Sensation of fullness in the ear Temporary hearing loss Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 4, 2022; updated Feb 7, 2024 on www.thecalgaryguide.com

Angioedema Bradykinin Mediated

Angioedema – Bradykinin Mediated: Pathogenesis and clinical findings Drug Induced Angiotensin converting enzyme inhibitor, dipeptidyl peptidase-4 inhibitor, or neprilysin inhibitor use Hereditary Type II Acquired Thrombolytic use Activate factor XII Factor XII initiates bradykinin synthesis Type I Type III Gain of function gene mutation in bradykinin cascade activators (factor XII) & precursors (kininogen), triggered by ↑ systemic estrogen Rheumatologic disorders & B- cell lymphoproliferative disease Complement cascade activation results in ↑ C1 protease production C1 esterase inhibitor is utilized to neutralize C1 protease, with its consumption exceeding its synthesis Plasma cell proliferation (i.e., dyscrasia/ monoclonal gammopathy) Immunoglobulin G antibodies act against C1 esterase inhibitor to render it non-functional Genetic or spontaneous mutation in C1 esterase inhibitor gene C1 esterase inhibitor deficiency C1 esterase inhibitor dysfunction Inhibition of angiotensin converting enzyme, dipeptidyl peptidase-4, or neprilysin induced metabolism of bradykinin ↓ Bradykinin (peptide hormone) degradation in plasma Misfunctioning C1 esterase inhibiter is unable to inactivate bradykinin cascade members ↓ C1 esterase inhibiter results in inadequate inactivation of bradykinin cascade members ↑ Bradykinin protein production in plasma Cutaneous Tissue Mucosal Tissue Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous layer Systemic bradykinin excess Bradykinin-2 receptor binding on endothelial and vascular smooth muscle cells Hyperpermeability pathway activation, with the transcription of some signalling molecules taking hours Released pro-inflammatory mediators act on venules & arterioles in subcutaneous & submucosa tissues Relaxation of vascular smooth muscle Dissociation of endothelial cell junctions ↑ Capillary blood flow ↑ Vascular permeability ↑ Plasma release into interstitial tissues (specific regions of the body hypothesized to be affected due to local differences in endothelial structure and its response to permeability inducing stimuli) Dilation & ↑ permeability of vasculature results in fluid release into surrounding tissues Mucosal Layer Muscularis mucosae Submucosal layer Muscularis externa Intestinal edema (Fluid buildup in Intestine tissues) Intestinal swelling (↑ intra-abdominal pressure) Laryngeal edema (Fluid buildup in larynx) Swelling in larynx ↓ air flow into & out of lungs Asphyxia (body is deprived of oxygen) Dyspnea (difficult in breathing) Author: Aaron Varga Reviewers: Tracey Rice Sunawer Aujla Shahab Marzoughi Maharshi Gandhi Jori Hardin* Yan Yu* * MD at time of publication Peripheral edema (Fluid buildup in extremities such as the hands, ankles, and feet) Ascites, bowel obstruction, &/or hypovolemic shock Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 21, 2024 on www.thecalgaryguide.com

Apnea of Prematurity

Apnea of Prematurity: Pathogenesis, Signs & Symptoms, and Complications Physiologic immaturity from birth at < 37 weeks gestation Authors: Akaya Blair Reviewers: Dasha Mori Michelle J. Chen Danielle Nelson* * MD at time of publication ↓ Synaptic connection & poor myelination Fetal brain areas responsible for breathing are poorly developed Immature neurologic respiratory function Immature mechanical respiratory function Poor hypopharyngeal muscle tone (soft upper airway helps with size and compliance of airway) Nasal obstruction (e.g. anatomic and/or iatrogenic [suctioning, NG tubes]) Neonate is reliant on nose breathing Airway is unable to remain open (patent) Laryngeal/tracheal abnormalities (e.g. tracheomalacia, laryngeal edema, tracheal stenosis) Anatomical narrowing leading to ↑ airway resistance ↑ Risk of mechanical airway obstruction Disruption of central respiratory drive ↓ Sensitivity to increased CO2 in the ventral medulla oblongata Disruption of peripheral respiratory reflex pathways ↓ Sensitivity to CO2 levels in peripheral carotid bodies and aortic bodies Large head size forces neck into flexion when laying supine Immature airway sensitive to collapse when in flexion ↑ Hypotonia (decreased muscle tone) in REM sleep ↓ Signaling to brainstem Brainstem unable to mount appropriate ventilatory response to insufficient oxygen Upper airway collapse Apnea of prematurity Respiratory pauses >20 sec or pauses <20 sec with bradycardia (<100 beats per minute), central cyanosis, and/or oxygen saturation <85% in neonates born at <37 weeks gestation and with no underlying disorders causing apnea. Most apneas in apnea of prematurity are central or mixed. ↓ Breathing rate Bradycardia (<100 bpm) ↓ Oxygen to brain Poor neurodevelopmental outcomes (e.g. cognitive function, brain adaptive potential and plasticity) Hypoxemia (↓blood oxygen levels where SpO2 <85%) ↓ Oxygen and hemoglobin to mucous membranes (e.g. lips) & fingers and toes (periphery) Central & peripheral cyanosis (bluish discoloration) ↓ Oxygen to retina Abnormal growth of blood vessels in eyes Retinopathy of prematurity (changes in visual acuity and possible blindness) Death/impairment in cell function from lack of oxygen ↑ Risk of infant mortality Imbalanced oxygen intake and CO2 output in lungs Body transiently ↑ HR to unsuccessfully try to compensate for ↓ tissue oxygenation Respiratory failure Respiratory rate >60 ↓ Heart rate ↓ Blood pressure Head bobbing Abdominal breathing Skin mottling Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 21, 2024 on www.thecalgaryguide.com

Post-Renal Acute Kidney Injury AKI

Post-Renal Acute Kidney Injury (AKI): Pathogenesis and clinical findings Blood clot or cellular debris Foreign body Neurogenic bladder Obstruction intrinsic to urine excretion system Nephrolithiasis (kidney stones) Anatomical defect(s) Intra- abdominal adhesions Retroperitoneal fibrosis (scar-like tissue) Benign or malignant masses Prostate cancer Benign prostatic hyperplasia ↓ Urine flow across point of obstruction Obstruction extrinsic to urine excretion system Urine buildup distends urine collecting system (hydronephrosis) Compression of renal vasculature due to mass effect ↑ Volume/pressure proximal to obstruction ↑ Intratubular pressure ↓ Pressure gradient between glomerular afferent arteriole and Bowman’s space Casts occlude tubules ↓ Filtration of plasma into nephrons ↓ Glomerular Filtration Rate (GFR) Obstruction is relieved ↓ Intratubular pressure Rapid GFR ↑ Rapid diuresis of fluid and electrolytes Dilated pelvicalyceal system on ultrasound ↓ Urine output ↓ Venous drainage and arterial supply Local ischemia and inflammation of kidney Impaired resorption, excretion, and fine tuning by tubules Acute Tubular Necrosis (ATN) with granular casts ↓ Urine output ↓ Clearance of free water and solutes ↑ Intravascular volume ↑ Serum creatinine ↓ Medullary solute concentration, ischemia, ↓ response of collecting ducts to antidiuretic hormone Lasts > 24hrs Post-obstructive diuresis causes hypovolemia and electrolyte derangements Authors: David Campbell, Matthew Hobart Reviewers: Raafi Ali, Luiza Radu Huneza Nadeem, Marissa Zhang, Julian Midgley* * MD at time of publication Resolves < 24hrs in euvolemia Physiologic post- obstructive diuresis ↑ Na+ and Cl- delivery to distal convoluted tubule is sensed by macula densa Secretion of adenosine by macula densa Adenosine constricts afferent arterioles ↓ GFR ↓ Renal clearance of drugs and waste products ↑ Venous hydrostatic pressure ↑ Volume in arterial system overwhelms pressure regulation mechanisms Hypertension Fluid extravasation from veins and capillaries Generalized Edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 25, 2024 on www.thecalgaryguide.com

Overview of Ischemic Heart Disease

Ischemic Heart Disease (IHD): Pathogenesis of the various types of IHD Authors: Sean Spence Vaneeza Moosa Reviewers: Tristan Jones Jason Baserman Yan Yu Michelle J. Chen Frank Spence* * MD at time of publication ↑ Serum low-density lipoprotein (LDL) ↑ Availability of lipids that deposit in arterial wall ↓ Serum high-density lipoprotein (HDL) ↓ LDL removal from coronary artery walls (transport of LDL to liver is impaired) Atherosclerosis Conditions predisposing to vessel wall endothelial cell dysfunction (e.g. metabolic syndrome, smoking, hypertension, physical inactivity) Vessel wall vulnerable to infiltration by LDL and immune cells Arterial wall degeneration, characterized by fat deposition (atheromatous plaque) in and fibrosis of the inner layer of arteries Stable atheromatous plaque in coronary arteries Fibromuscular cap (formed by smooth muscle cells) overlying fatty plaque contents remains intact & plaque contents are not released into vessel lumen Plaque serves as a fixed lumenal obstruction to blood flow If vessel stenosis (narrowing) is significant (≥70%) myocardial oxygen demand starts to exceed supply (especially with exertion) Heart experiences a predictable & transient reduction in blood flow (myocardial ischemia) Unstable atheromatous plaque in coronary arteries The fibromuscular cap overlying fatty plaque ruptures Thrombogenic plaque contents (especially tissue factor) are exposed to the coagulation factors in the vessel lumen Activation of platelets & the clotting cascade at the site of rupture Thrombus forms over already partially occlusive plaque and further partially or completely occludes lumen ↓ Perfusion (blood flow) of myocardium Cardiomyocytes experience a transient decrease in blood flow (transient ischemia) Unstable Angina Cardiomyocytes experience death (infarction) Myocardial Infarction (MI) Stable Angina Acute Coronary Syndromes (ACS) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 8, 2013; updated Mar 30, 2024 on www.thecalgaryguide.com

Circle of Willis Anatomy and Physiology

Circle of Willis: Anatomy & physiology Ischemic stroke Ischemic stroke Inadequate blood flow & oxygenation of brain tissue Occlusion or narrowing of A2 segment Supplies medial portions of frontal & parietal lobes (lower extremity regions of motor/sensory cortices) Anterior Cerebral Artery (ACA) Ischemic stroke (brain damage due to ischemia) Inadequate blood flow & oxygenation of brain tissue Occlusion or narrowing Supplies midbrain, thalamus, & occipital lobe Posterior Cerebral Artery (PCA) Vertebral Arteries (VA) Inadequate blood flow & oxygenation of brain tissue Occlusion or narrowing Supplies lateral portions of frontal, temporal & parietal lobes (upper extremity & facial regions of motor/sensory cortices) Middle Cerebral Artery (MCA) P2 segment A1 segment Supplies the MCA & ACA A2 segment Collateral circulation redistributes blood flow to maintain continuous blood supply Occlusion or narrowing of vessels within the Circle of Willis Anterior Communicating Artery (Acomm) Weakness in the blood vessel walls Aneurysm formation causes mass effect (displacement) on nearby structures Supplies BA & PCA, lateral medulla & cerebellum via posterior inferior cerebellar artery (PICA), & upper spinal cord via anterior spinal artery (ASA) Basilar Artery (BA) Supplies occipital lobe, cerebellum & brainstem Thromboembolism (blood clot obstruction) Inadequate blood flow & oxygenation of brain tissue Ischemic stroke Damage to the ventral pons Locked-in syndrome (quadriplegia, loss of voluntary breathing & speaking, intact cognition & blinking) Internal Carotid Arteries (ICA) Posterior Communicating Artery (Pcomm) Weakness in the blood vessel walls Aneurysm formation causes mass effect (displacement) on nearby structures Oculomotor nerve (cranial nerve III): double vision & absent pupil response to light Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 5, 2018, updated Apr 29, 2024 on www.thecalgaryguide.com P1 segment Ruptured aneurysm: subarachnoid hemorrhage Inadequate blood flow & oxygenation of brain tissue Hemorrhagic stroke (brain damage due to bleeding) Optic nerve (cranial nerve II): ↓ visual acuity Frontal lobe: headache & psychological changes Authors: Josh Kariath, Rafael Sanguinetti Reviewers: Andrea Kuczynski, Luiza Radu Gary Klein* * MD at time of publication

Benzodiazepines mechanism of action

Benzodiazepines: Mechanism of action Sedative-hypnotic, anxiolytic & anti-convulsive agents composed of a fused benzene and diazepine ring that is administered orally or intravenously to produce desired effect (ie., lorazepam, midazolam, diazepam) Authors: Tracey Rice Usama Malik Amy Fowler Reviewers: Sara Cho Keira Britto Luiza Radu Brienne McLane* Aaron Mackie* * MD at time of publication Benzodiazepine binds to gamma-aminobutyric acid (GABAA) receptors in vascular smooth muscle & the central nervous system (CNS) ↑ Opening of chloride channels Influx of chloride ions into the neuron Hyperpolarization of nerve membrane causing it to be more negative The cell membrane falls below the normal resting potential Medulla oblongata inhibition ↓ Respiratory drive; ↓ depth & rate of respirations Temporary cessation of breathing leads to reduced oxygen supply to the brain ↓ Level of consciousness Pharyngeal muscle relaxation leading to obstruction Hypoventilation and/or apnea General CNS inhibition ↓ Neuronal activity ↓ Electrical brain activity ↓ Seizure activity & hypnotic effect Thalamic & hypothalamic inhibition Disruption of short & long- term memory consolidation Limbic system inhibition ↓ Fear emotions (panic & phobia) Anxiolytic effect (↓ Anxiety) Smooth muscle inhibition Smooth muscles become relaxed &/or less spastic Vasodilation ↓ Preload Hypotension ↓ Cerebral blood flow Pre-syncope or syncope Anterograde amnesia ↓ Visuospatial ability, speed of processing & verbal learning Confusion ↓ Deep stage of non-REM sleep & delayed REM sleep Rapid sleep Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 21, 2024 on www.thecalgaryguide.com

Acute Otitis Media Pathogenesis and Clinical Findings in Children

Acute Otitis Media in Children: Pathogenesis and clinical findings Congenital conditions (e.g. Down Syndrome, Pierre Robin syndrome) Exposure to tobacco smoke Impaired macrophage function in nasopharynx Lack of immunizations Lack of breastfeeding Infant does not receive antibodies from breast milk Overcrowding Age 6 – 16 months Immune system deficiencies Close proximity of kids & ↓ sanitation (e.g. daycare) ↑ Infection risk Upper Respiratory Tract Infection (i.e. bacterial (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis), viral) Immature Eustachian tube anatomy which facilitates pathogen transmission to middle ear Author: Jody Platt Stephanie de Waal Reviewers: Yan Yu Elizabeth De Klerk William Kim Annie Pham Michelle J. Chen Danielle Nelson* * MD at time of publication Abnormal anatomical structure (e.g. cleft palate) ↑ Nasopharyngeal streptococcus pneumoniae Lack of immunity to pathogens ↑ Colonization of nasopharynx with bacterial pathogens Inflammation & edema of respiratory mucosa including the nose, nasopharynx, and Eustachian tube Obstruction of the Eustachian tube Air from middle ear resorbs into circulation which creates a low-pressure environment Negative pressure gradient pulls viral/bacterial pathogens into middle ear Degenerating white blood cells, tissue debris, and microorganisms accumulate & develops into purulent effusion Inflammation & infection of middle ear Complications of acute otitis media** ↑ Pressure in middle ear Stretching of tympanic membrane Helper T cells & macrophages release cytokines into the bloodstream Cytokines trigger hypothalamus to ↑ thermoregulatory set-point Effusion behind tympanic membrane Effusion obstructs visualization of ossicles Neutrophils infiltrate middle ear & phagocytose pathogens Pus accumulates behind the tympanic membrane Blood vessels of the tympanic membrane vasodilate Bulging tympanic membrane Otalgia (ear pain) Discomfort disrupts daily activities in young children Fever Irritable Poor feeding Tympanic membrane erythema Painful blisters on tympanic membrane (e.g. Bullous myringitis) Can persist for up to 3 months after infection resolves Loss of tympanic membrane landmarks (i.e. handle of malleus, light reflex) ** See corresponding Calgary Guide slide Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 28, 2013; updated Aug 25, 2024 on www.thecalgaryguide.com

Cystocele

Cystocele: Pathogenesis & Clinical Findings Authors: Emily Cox Reviewers: Riya Prajapati Michelle J. Chen Dr. Rebecca Manion* * MD at time of publication Obesity Pregnancy Chronic constipation Chronic cough Vaginal childbirth Vacuum-assisted or forceps-assisted vaginal birth Pelvic surgeries (e.g. hysterectomy) Connective tissue disorders (e.g. Marfans, Ehlers- Danlos Syndrome) Genetic susceptibility (e.g. Type III collagen gene abnormality Menopause Visceral fat places pressure on pelvic floor structures Growing fetus places pressure on pelvic floor structures Straining and bearing down on pelvic floor Muscle tearing and damage Disruption of nerves, loss of bladder structural support, and disruption of fascia and muscles Collagen impairment Depletion of ovarian follicles leading to ↓ in estrogen production ↑ Intra-abdominal pressure Transfer of intra- abdominal pressure to pelvic floor Pelvic floor muscles and pelvic floor fascia become weakened Pelvic tissue and muscular atrophy Loss of tissue function and structure support that collagen provided ↓ Stimulation of collagen production ↓ Estrogen levels Pelvic Organ Prolapse Quantification (POP-Q) System: Grade 1: Bladder descends 1 cm above the hymen Grade 2: Bladder descends to ≤ 1 cm above or below hymen Grade 3: Bladder descends past the hymen but 2 cm less than total vaginal length Grade 4: Complete vaginal prolapse Mechanical obstruction of bladder and urethra Urinary retention Descended bladder creates pressure in vagina Pressure/bulging sensation Symptoms of voiding dysfunction (e.g. incomplete emptying/frequency/ urgency/nocturia) Vaginal intercourse puts pressure on descended bladder Activates pain receptors Dyspareunia (painful sex) for some patients Cystocele Descent of bladder through anterior vaginal wall Hydronephrosis/ hydroureter Recurrent UTI Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 5, 2024 on www.thecalgaryguide.com

Ptosis

Ptosis: Pathogenesis and Clinical Findings Neurogenic causes of low Mechanical causes of low eyelid position Mass lesion of the upper eyelid (Chalazion, hemangioma, malignancy, etc.) Gravitational effect from excess eyelid weight Traumatic causes of low eyelid position Direct injury limits function of LPS or conduction of generated force to the tarsal plate Laceration of the LPS limiting its function or transection of the levator aponeurosis eyelid position Congenital causes of eyelid drooping Fibrofatty replacement of the LPS muscle at birth Reduced levator function Insult to the oculomotor nerve (CNIII) (e.g., compressive, microvascular, demyelinating) CNIII innervates levator palpebrae superioris, the main muscle responsible for upper eyelid elevation Insult to the sympathetic innervation (e.g., Horner’s syndrome) Ocular sympathetic innervate the Muller muscle, which provides approximately 2mm of the upper eyelid’s height Neuromuscular or myogenic causes of low eyelid position (e.g., myasthenia gravis) LPS muscle myopathy or defect at its neuromuscular junction that limits the elevation of the eyelid Aponeurotic causes of low eyelid position Involutional change (disinsertion) of the levator aponeurosis which connects the LPS to the tarsal plate Ptosis (also called blepharoptosis) Abnormally low position of the upper eyelid ↓ distance between the central corneal light reflex (as produced by an examiner’s penlight) and the level of the center of the upper-eyelid margin ↓ Margin-Reflex Distance (Normal: 4-6mm) Obstruction of the pupil/visual axis Decreased or occluded superior visual field ↓ distance between the upper eyelid margin and the lower eyelid margin ↓ Palpebral Fissure Height (Normal: 10-12mm) Flattening of the peripheral cornea by eyelid pressure Induced with-the-rule astigmatism Authors: Mina Mina Reviewers: Aicha Djaoutkhanova Shahab Marzoughi William Trask* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 18, 2024 on www.thecalgaryguide.com

Acute Diverticulitis

Acute Diverticulitis: Pathogenesis and clinical findings Low fiber diet Authors: Candace Chan Yan Yu Wayne Rosen* Reviewers: Laura Craig Noriyah AlAwadhi Danny Guo Erica Reed Maitreyi Raman* Claire Song Shahab Marzoughi * MD at time of publication ↓ Colonic motility ↑ Stool transit time Formation of small dry stool Stool build-up and ↑ strain with bowel movements ↑ Pressure in the colonic lumen Constipation (difficulty passing stool) Obstipation (inability to pass any feces) Inherent weakness in the muscle layers of the colonic wall associated with immature collagen fibers and diminished wall elasticity Mucosal and submucosal layers of the colon wall push through a weak spot of the circular muscle layer Formation of diverticulum (sac-like protrusion of the colonic wall) Continued stress on diverticula causes micro- perforations of the diverticulum Inflammation of diverticula Mesentery and pericolic fat (fat surrounding the colon) attempt to wall off inflammation or perforations Stool bacteria escapes the colon Formation of abscess (accumulation of pus in response to the bacteria ) Pro-inflammatory cytokine release from nearby adipose tissue Hypothalamic thermoregulatory center increases core temperature set point Fever Irritation of parietal peritoneum Inflamed vessels are more permeable and fluid leaks from colonic vessels into the abdominal cavity Chronic low-grade inflammation triggers activation of pro-fibrotic factors and fibroblasts Excess production of extracellular matrix proteins Stimulation of somatic nerves sends pain signals to the brain Lower left quadrant abdominal pain Peritoneal signs (abdominal guarding, rigidity, rebound tenderness) ↓ Total circulating blood volume ↑ heart rate ↓ Jugular venous pressure Orthostatic hypotension (low blood pressure when standing after sitting/lying down) Gastrointestinal strictures and/or colonic obstruction Accumulation of micro- perforations further weakens intestinal wall Complete bowel perforation (medical emergency) Development of an abnormal connection (fistula) through the bladder, vagina, skin, or gut Abscesses Accumulation of fibrotic tissue narrows the intestinal lumen Fibrosis of colon Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published Oct 4, 2024 on thecalgaryguide.com