SEARCH RESULTS FOR: Sinusitis

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)

Orbital Cellulitis: Pathogenesis and clinical findings

Orbital Cellulitis: Pathogenesis and clinical findings Authors: Amanda Marchak Reviewers: Jaimie Bird Dr. Rupesh Chawla* * MD at time of publication Staphylococcus aureus, Streptococcus pyogenes Note: Orbital cellulitis is an extremely serious infection. If not caught and treated early, it can lead to death. CT should be performed if suspected. Involves the orbit Panopthalmitisb Endopthalmitisc Blindness Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenza Local infection or break in skin Eye surgery or trauma Direct inoculation Sinusitis (more common) Periorbital cellulitis1,2 Hematogenous spread Contiguous spread of infection Pathogens reach orbital tissue (posterior to the orbital septum) Spreads to periorbital tissue (anterior to the orbital septum) Localized inflammation Conjunctival chemosisa Eyelid and periorbital edema Pain on palpation Induration Warmth Orbital Cellulitis Inflammation of orbital tissue Proptosis Spreads to surrounding structures Subperiosteal abscess Brain abscess Cavernous sinus thrombosis Meningitis Subdural empyema Orbital abscess Notes: Impinges on ocular muscles Impaired extra- ocular movements Pain with eye movement or opthalmoplegia Definitions: Impinges on nerves Afferent pupillary defect Decreased visual acuity Exposes cornea Corneal drying and scarring a. Chemosis: Edema of the bulbar conjunctiva b. Panopthalmitis: inflammation of all coats of the eye including intraocular structures. c. Endopthalmitis: inflammation of the interior of the eye. 1. See slide on Periorbital Cellulitis for how sinusitis can lead to the development of periorbital cellulitis 2. The micro-organism responsible for periorbital cellulitis varies depending on how the pathogen was introduced to the system. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2018 on www.thecalgaryguide.com

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

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

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

Tonsillitis Pathogenesis and clinical findings

Tonsillitis: Pathogenesis and clinical findings Authors: Taylor Krawec Amanda Marchak Reviewers: Nicola Adderley, Jim Rogers Emily J. Doucette, Danielle Nelson* James D. Kellner* * MD at time of publication Pathogen infiltrates tonsillar epithelium Microfold cells recognize pathogen & activate immune response Virus (most common) Group A Streptococci (GAS) (most common bacteria) Group B, C & G Strep, Fusobacterium necrophorum Age 5-15 (tonsils have ↑ role in immune function at this age) Tonsillitis Inflammation of the tonsils Infectious agent exposure Susceptible host Pathogen colonizes the oropharynx Acute suppurative disease Immune cells release proinflammatory cytokines & antibodies Inflammatory mediators ↑ vascular permeability of tonsils Leakage of protein & fluid into surrounding tissue Regional nodes receive ↑ lymph Enlarged anterior cervical nodes Sinusitis** Pharyngitis** Local spread of pathogen Acute otitis media** Pneumonia** Cervical lymphadenitis Bacteria spread from tonsils into lymphatic system & bloodstream Bacteremia F. necrophorum invades lateral pharyngeal space & soft tissue in neck Thrombosis forms in peritonsillar vein Thrombosis extends into internal jugular vein Lemierre’s syndrome Systemic inflammatory cytokines disrupt hypothalamic regulation Fever Additional immune cells are recruited to facilitate immune response Macrophages phagocytize pathogen Bacteria invade distant tissue & elicit local inflammatory response Hepatitis Osteomyelitis Infective endocarditis Bacteria illicit systemic response Sepsis Tonsillar tissue become swollen & irritated Tonsillar hypertrophy Localized collection of pus forms Immune cells cause inadvertent cellular injury & hemolysis Palatal petechiae Meningitis Products of immune response & cellular debris are deposited into tonsillar tissue Peritonsillar or Tonsillar retropharyngeal abscess** exudate ** See corresponding Calgary Guide slide Toxin-mediated disease Bacteria release exotoxins into bloodstream Inflammatory mediators & cytokines are overactivated (cytokine storm) Skin has local inflammatory response Toxic shock syndrome** Scarlet fever** Post-infectious disease Antibodies to GAS cross react with host tissue Acute rheumatic fever** Post-strep glomerulonephritis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 5, 2018; updated Mar 14, 2025 on www.thecalgaryguide.com

Cystic Fibrosis

Authors: Navdeep Goraya, Spencer Montgomery Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery*, Danielle Nelson* *MD at time of publication Reproductive Manifestations Incomplete development of Wolffian duct derivatives (vas deferens, epididymis, & seminal vesicles) Cystic Fibrosis (CF): Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (transmembrane chloride ion channel found in exocrine tissue) dysfunction Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Secretions accumulate in secretory passages throughout the body Inhibition of sperm transport (obstructive azoospermia) Male infertility Upper Respiratory Tract Manifestations Retained secretions in sinuses Failure to clear bacteria in sinuses Persistent neutrophilic inflammation triggers tissue remodeling & mucosal overgrowth Bacterial proliferation Nasal polyps Chronic sinusitis Pancreatic Manifestations Trapped digestive enzymes degrade pancreatic tissue Pancreatic tissue damage triggers inflammation, scarring & fatty tissue replacement Islet cell damage & destruction Cystic-fibrosis related diabetes (CFRD) Lower Respiratory Tract Manifestations Retained secretions in airways Bacterial proliferation in lower airway Airway infection & inflammation Chronic productive cough Signs of obstructive lung disease (lung hyperinflation on x-ray & abnormal pulmonary function tests) Bronchitis ± bronchiectasis** ↓ Production & secretion of pancreatic enzymes into GI tract (pancreatic insufficiency) Fat & protein malabsorption Failure to thrive ↓ Absorption of fat-soluble vitamins Steatorrhea (↑ fat in stool) Vitamin D deficiency Vitamin K deficiency** Rickets** Osteoporosis** Coagulopathies Hepatic Manifestations Delayed passage of bile through biliary tree ↑ Loss of bile acids in stool Inflammatory hepatic response ↑ Production of lithogenic bile (bile supersaturated with cholesterol) Biliary cirrhosis with portal hypertension Cholelithiasis** Gastrointestinal (GI) Manifestations ↓ Movement of intestinal contents In newborns: Meconium ileus In children/adults: Distal ileal obstruction syndrome (DIOS) ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates **See corresponding Calgary Guide slide Legend: Sign/Symptom/Lab Finding Complications Pathophysiology Mechanism Published Jan 21, 2013; updated Aug 20, 2025 on www.thecalgaryguide.com Reproductive Manifestations Degeneration of Wolffian duct derivatives (vas deferens, epididymis, & seminal vesicles) Inhibition of sperm transport (obstructive azoospermia) Male infertility Cystic Fibrosis (CF): Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Authors: Navdeep Goraya, Spencer Montgomery Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery*, Danielle Nelson* *MD at time of publication Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Secretions accumulate in secretory passages throughout the body Upper Respiratory Tract Manifestations Retained secretions in sinuses Failure to clear bacteria in sinuses Persistent neutrophilic inflammation triggers tissue remodeling & mucosal overgrowth Bacterial proliferation Nasal polyps Chronic sinusitis Lower Respiratory Tract Manifestations Retained secretions in airways Bacterial proliferation in lower airway Airway infection & inflammation Chronic productive cough Signs of obstructive lung disease (lung hyperinflation on x-ray & abnormal pulmonary function tests) Bronchitis ± bronchiectasis** Pancreatic Manifestations Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat & protein malabsorption ↓ Absorption of fat-soluble vitamins Failure to thrive ↓ Serum Vitamin D Osteoporosis** Trapped digestive enzymes degrade pancreatic tissue Tissue damage triggers inflammation, scarring & fatty tissue replacement Islet cell destruction Cystic-fibrosis related diabetes (CFRD) Hepatic Manifestations Delayed passage of bile through biliary tree Inflammatory hepatic response Cirrhosis** & portal hypertension Gastrointestinal Manifestations ↓ Movement of intestinal contents In newborns: Meconium ileus In children/adults: Distal ileal obstruction syndrome (DIOS) ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications **See corresponding Calgary Guide slide Published January 21, 2013 on www.thecalgaryguide.com Please only review slide 1 – slides 3-7 are previous draft versions. Thank you! Authors: Spencer Montgomery, Navdeep Goraya Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery*, Name Name* *MD at time of publication In the vas deferens in utero Cystic Fibrosis: Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Secretions accumulate in secretory passages throughout the body Degeneration of vas deferens, Wolffian ducts & associated structures Infertility in affected males In upper respiratory tract Retained secretions in sinuses Failure to clear bacteria in airways Persistent neutrophilic inflammation triggers tissue remodeling & mucosal overgrowth Bacterial proliferation Chronic sinusitis Nasal polyps In lower respiratory tract Chronic productive cough Retained secretions in airways Bacterial proliferation Airway infection & inflammation Signs of obstructive lung disease (lung hyperinflation on x-ray & abnormal pulmonary function tests) Bronchitis ± bronchiectasis** In pancreas Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat & protein malabsorption ↓ Absorption of fat- soluble vitamins Failure to thrive ↓ Serum Vitamin D Osteoporosis** Trapped digestive enzymes degrade pancreatic tissue Tissue damage triggers inflammation, scarring & fatty tissue replacement Islet cell destruction Cystic-fibrosis related diabetes (CFRD) In biliary tree Delayed passage of bile Inflammatory hepatic response Cirrhosis** & portal hypertension In GI tract ↓ Movement of intestinal contents In children/adults: Distal ileal obstruction syndrome (DIOS) In newborns: Meconium ileus ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 21, 2013 on www.thecalgaryguide.com Authors: Spencer Montgomery, Navdeep Goraya Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery*, Name Name* *MD at time of publication In the vas deferens in utero Cystic Fibrosis: Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Secretions accumulate in secretory passages throughout the body Degeneration of vas deferens, Wolffian ducts & associated structures Infertility in affected males In upper respiratory tract Retained secretions in sinuses Failure to clear bacteria in airways Persistent neutrophilic inflammation triggers tissue remodeling & mucosal overgrowth Bacterial proliferation Chronic sinusitis Nasal polyps In lower respiratory tract Chronic productive cough Retained secretions in airways Bacterial proliferation Airway infection & inflammation Signs of obstructive lung disease (lung hyperinflation on x-ray & abnormal pulmonary function tests) Bronchitis ± bronchiectasis** Trapped digestive enzymes degrade pancreatic tissue Inflammation Scarring & fatty tissue infiltration Islet cell destruction Type II Diabetes Mellitus** In pancreas Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat & protein malabsorption ↓ Absorption of fat- soluble vitamins Failure to thrive ↓ Serum Vitamin D Osteoporosis** In biliary tree Delayed passage of bile Inflammatory hepatic response Cirrhosis** & portal hypertension In GI tract ↓ Movement of intestinal contents In children/adults: Distal ileal obstruction syndrome (DIOS) In newborns: Meconium ileus ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 21, 2013 on www.thecalgaryguide.com In the vas deferens in utero Retained secretions in sinuses Cystic Fibrosis: Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Mutated CFTR proteins prevent Cl- reabsorption in sweat glands ↑ Secretion of Cl- into sweat ↑ Sweat Cl- concentration Mutated CFTR proteins in duct epithelial tissue of other parts of the body prevent diffusion of Cl- into secretions ↓ Cl- diffusion into peri-ciliary fluid ↓ Water composition of peri-ciliary fluid ↓ Clearance of mucociliary secretions Accumulation of secretions in secretory passages throughout the body obstructing these passages Authors: Spencer Montgomery, Navdeep Goraya Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery* *MD at time of publication Degeneration of vas deferens, Wolffian ducts & associated structures Infertility in affected males In upper respiratory tract Failure to clear bacteria in airways Bacterial proliferation Chronic sinusitis Nasal polyps In lower respiratory tract Chronic productive cough Retained secretions in airways Bacterial proliferation Airway infection & inflammation Signs of obstructive lung disease i.e. lung hyperinflation on x-ray & abnormal pulmonary function tests Bronchitis ± bronchiectasis Trapped digestive enzymes degrade pancreatic tissue Inflammation Scarring & fatty tissue infiltration Islet cell destruction Type II Diabetes Mellitus In pancreas Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat and protein malabsorption ↓ Absorption of fat- soluble vitamins Failure to thrive ↓Serum Vitamin D Osteoporosis In biliary tree Delayed passage of bile Inflammatory hepatic response Cirrhosis & portal hypertension In GI tract ↓ Movement of intestinal contents In children/adults: Distal ileal obstruction syndrome (DIOS) In newborns: Meconium ileus ↑ Retention of meconium ↑ Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 21, 2013 on www.thecalgaryguide.com In the vas deferens in utero Cystic Fibrosis: Pathogenesis, clinical findings, and complications Cystic Fibrosis Transmembrane Regulator (CFTR) autosomal recessive gene mutation on chromosome 7 CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) dysfunction Chloride channel no longer allows Cl- transport CFTR proteins in sweat glands reabsorb Cl- CFTR proteins in duct epithelial tissue of other parts of the body facilitate diffusion of Cl- into secretions ↓Reabsorption ↓Cl- diffusion into peri-ciliary fluid ↓Water composition of peri-ciliary fluid ↑Secretion of Cl- into sweat ↓Clearance of mucociliary secretions ↑Sweat Cl- concentration Accumulation of secretions in secretory passages throughout the body obstructing these passages Degeneration of vas deferens, Wolffian ducts & associated structures Authors: Spencer Montgomery, Navdeep Goraya Reviewers: Yan Yu, Kayla Nelson, Emily J. Doucette, Mark Montgomery* *MD at time of publication Infertility in affected males In upper respiratory tract Retained secretions in sinuses Nasal polyps Bacterial proliferation Chronic sinusitis In lower respiratory tract Chronic productive cough Retained secretions in airways Bacterial proliferation Signs of obstructive lung disease i.e. lung hyperinflation on x-ray & abnormal pulmonary function tests Airway infection & inflammation Bronchitis ± bronchiectasis Trapped digestive enzymes degrade pancreatic tissue Inflammation Scarring & fatty tissue infiltration Islet cell destruction Type II Diabetes Mellitus In pancreas Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat and protein malabsorption ↓Absorption of fat- soluble vitamins Failure to thrive ↓Serum Vitamin D Osteoporosis In biliary tree Delayed passage of bile Inflammatory hepatic response Cirrhosis & portal hypertension In GI tract ↓Movement of intestinal contents In children/adults: Distal ileal obstruction syndrome (DIOS) In newborns: Meconium ileus ↑Retention of meconium ↑Reabsorption of bilirubin Prolonged jaundice in neonates Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 21, 2013 on www.thecalgaryguide.com In the vas deferens in utero Degeneration of vas deferens, Wolffian ducts and associated structures Infertility in affected males Legend: Cystic Fibrosis: Pathogenesis, clinical findings, and complications Mutation of Cystic Fibrosis Transmembrane Regulator (CFTR) gene on chromosome 7 à Dysfunction of the CFTR protein (a transmembrane chloride ion channel that is found in exocrine tissue) Author: Spencer Montgomery Reviewers: Yan Yu, Kayla Nelson, Mark Montgomery* * MD at time of publication Chloride channel no longer allows Cl- transport In sweat glands, CFTR proteins are responsible for the reabsorption of Cl- In duct epithelial tissue of other parts of the body, CFTR proteins facilitate diffusion of Cl- into secretions Notes: • The CFTR mutation exhibits an autosomal recessive inheritance pattern • > 1700 different CFTR gene mutations are identified, ∆F508 mutation accounts for ~67% of cases in Caucasians. • Cystic fibrosis is diagnosed based presence of ↑ sweat chloride concentration, disease causing CFTR mutations, & symptoms of ≥ 1 associated organ system ↓ Cl- diffusion into peri-ciliary fluid → ↓water composition of peri-ciliary fluid In children/adults: Distal ileal obstruction syndrome (DIOS) ↓ reabsorption = ↑secretion of Cl- into sweat In GI tract ↓movement of intestinal contents ↓ clearance of mucociliary secretions In newborns: Meconium ileus ↑ retention of meconium → ↑ reabsorption of bilirubin Prolonged jaundice in neonates ↑ Sweat chloride concentration Accumulation of secretions in secretory passages throughout the body, obstructing these passages In biliary tree Delayed passage of bile → inflammatory hepatic response Cirrhosis & portal hypertension In upper respiratory tract In pancreas Trapped digestive enzymes degrade pancreatic tissue Nasal polyps Retained secretions in sinuses → bacterial proliferation Pancreas unable to secrete digestive enzymes into GI tract (pancreatic insufficiency) Fat and protein mal- absorption ↓ absorption of fat soluble vitamins Inflammation → scarring & fatty tissue infiltration → islet cell destruction Chronic sinusitis ↓ serum Vit. D Type II Diabetes Mellitus Failure to thrive Osteoporosis Published January 21, 2013 on www.thecalgaryguide.com In lower respiratory tract Chronic productive cough Retained secretions in airways → bacterial proliferation à Airway infection & inflammation Persistent respiratory tract infections Can progress to chronic bronchitis ± bronchiectasis (This is the biggest cause of death in CF) Pathophysiology Signs of obstructive lung dx: i.e. Lung hyperinflation (on x-ray), Abnormal pulmonary function tests Mechanism Sign/Symptom/Lab Finding Complications

Childhood Immunization Schedule

Alberta Health Services Childhood Immunization Schedule: Why we immunize Diphtheria** toxin Bacteria colonize upper respiratory epithelium & secrete exotoxin that enters local cells Sore throat, low grade fever, lymphadenopathy, stridor or wheeze, gray pseudomembrane in the airway ↑ Mortality from CNS, respiratory & cardiac disease Tetanus** toxin Pertussis** metabolites Polio virus Haemophilus influenzae type B Hepatitis B virus Streptococcus pneumoniae Rotavirus Neisseria meningitidis Measles** virus Mumps virus Rubella virus Varicella zoster virus** Human papillomavirus (HPV) Spores enter contaminated wounds & bacteria produce tetanospasmin to invade central nervous system (CNS) Muscle rigidity spasms, hyperreflexia, autonomic dysfunction, laryngeal spasms ↑ Mortality from respiratory obstruction & failure Bacteria attach to ciliated respiratory epithelial cells & release toxins Prolonged paroxysmal cough, inspiratory “whoop” sound, emesis, apnea, cyanosis, leukocytosis ↑ Risk of pneumonia, seizures & encephalopathy Virus invades oropharynx/GI tract & replicates in lymphoid tissue before hematogenous spread to motor neurons ↑ Risk of paralytic poliomyelitis & respiratory failure Bacteria colonize the nasopharynx & invade the bloodstream & CNS Virus invades hepatocytes via specific receptors & replicates within liver cells Bacteria colonize the nasopharynx & may invade the lungs, bloodstream, or meninges Virus invades mature enterocytes in the small intestine Bacteria colonize the nasopharynx & enter the bloodstream to cross the blood–brain barrier Virus invades respiratory epithelium & spreads to regional lymphoid tissue & bloodstream Virus infects upper respiratory tract (URT) & disseminates via viremia to salivary glands & other organs Virus invades URT & enters the bloodstream & regional lymphoid tissue Virus infects URT & lymphoid tissue before invading neural tissue Virus infects anogenital & oropharyngeal basal layer epithelium tissue Influenza virus Virus invades upper & lower respiratory epithelium Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)** Viral invasion of mucous membranes & may invade extrapulmonary tissues Legend: Muscle weakness, asymmetric reduction in tone, quadriplegia Fever, fatigue, shortness of breath, nausea, emesis, headache, stiff neck, altered mental status, otitis media** Fatigue, anorexia, nausea, jaundice, arthralgia, right upper quadrant pain Otitis media**, sinusitis, pneumonia**, meningitis**, bacteremia Gastroenteritis with emesis, fever, diarrhea, malaise & dehydration Fever, headache, neck stiffness, altered level of consciousness, purpuric rash Koplik spots, conjunctivitis, fever, rhinorrhea, cough, diarrhea, otitis media, pneumonia Parotitis, headache, fever, malaise, sensorineural hearing loss, orchitis, mastitis, oophoritis, pancreatitis Fever, lymphadenopathy, rash, congenital anomalies such as hearing loss, cataracts & cardiac defects ↑ Mortality from meningitis, pneumonia & sepsis ↑ Risk of cirrhosis, hepatic malignancy, & liver failure ↑ Mortality from respiratory, CNS & cardiac dysfunction ↑ Mortality from hypovolemic shock & CNS infection ↑ Mortality from sepsis, multiorgan failure & necrosis ↑ Mortality from pneumonia & encephalitis ↑ Mortality from meningitis & encephalitis ↑ Mortality from congenital rubella Vesicular & pruritic rash, fever, malaise, pneumonia, encephalitis, cellulitis ↑ Morbidity from necrotizing fasciitis, CNS, soft tissue & respiratory infections Often asymptomatic, or may present with painless anogenital warts ↑ Risk of anogenital & head & neck malignancy Fever, cough, myalgia, malaise, cough, headache, emesis, diarrhea, abdominal pain, febrile seizures ↑ Mortality from widespread multiorgan infection Fever, cough, fatigue, shortness of breath, anosmia, ageusia, pneumonia, multiorgan dysfunction ↑ Mortality from respiratory distress & multiorgan failure DTaP-IPV-Hib-HB vaccine Given at 2, 4 & 6 months old Protects against diphtheria, Tetanus, Pertussis, Polio, Haemophilus influenzae type B, & Hepatitis B DTaP-IPV-Hib vaccine Given at 18 months old Protects against diphtheria, Tetanus, Pertussis, Polio, & Haemophilus influenzae type B Pneumococcal conjugate vaccine Given at 2, 4 & 12 months old (additional 4th dose given at 6 months if at ↑ risk of invasive pneumococcal disease) Authors: McKayla Kirkpatrick, Stacey Holbrook Reviewers: Merry Faye Graff, Emily J. Doucette, Charissa Chen, Amanda Ang, Danielle Nelson* * MD at time of publication Tdap-IPV vaccine Given at 4 years old Tdap vaccine Given in Grade 9 Protects against diphtheria, Tetanus, Pertussis, & Polio Protects against diphtheria, Tetanus, & Pertussis HB vaccine Given in Grade 6 Protects against Hepatitis B virus Protects against Streptococcus pneumoniae Rotavirus vaccine Given at 2 & 4 months old Protects against rotavirus Meningococcal conjugate (MenconC) Given at 4 & 12 months old MenC-ACYW (Meningococcal type A, C, Y, W-135) in Grade 9 Protects against Neisseria meningitidis MMR-Var vaccine (e.g., Priorix-Tetra) Given at 12 & 18 months old Protects against measles, mumps, rubella & varicella Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications HPV vaccine Given in Grade 6 (2-3 doses over 6 months) Seasonal influenza vaccine Given annually starting at 6 months or older COVID-19 vaccine Given at 6 months or older Published Aug 19, 2015; updated Dec 31, 2025 on www.thecalgaryguide.com Protects against HPV Protects against influenza viruses predicted to circulate each fall & winter Protects against SARS-CoV2

Sinusitis

Septal deviation Turbinate hypertrophy Adenoid hypertrophy Polyps Tumors Foreign body Congenital &/or craniofacial abnormality Sinusitis: Pathogenesis and clinical findings Chemical irritants Cystic Fibrosis Viral upper respiratory tract infection Allergies Inflammation of paranasal sinuses Oxidative stress damages cilial structure Abnormally thick mucus secretions Direct toxic effect on cilia Inflammation creates edematous passageways Cilia unable to clear mucus from sinuses Obstruction of sinus ostia Mucus unable to drain through ostia Mucus overflows from the sinuses into the nasopharynx & down the posterior pharyngeal wall into the oropharynx Mucus accumulates leading to stasis in sinuses Nasal obstruction/ congestion Post-nasal drip Mucus irritates the back of the throat Odorant molecules fail to reach olfactory receptors ↑ Pressure on & irritation of sinus walls Immunodeficiency due to primary antibody deficiencies, HIV, fungal infections, immunosuppressive drugs, or diabetes Cough Halitosis Pharyngitis Throat clearing Hyposmia (decreased sense of smell) Local & recruited immune cells release inflammatory mediators ↑ Susceptibility to bacterial infection (Staphylococcus Dental root infection aureus, Group A Streptococcus) Commensal nasal bacteria (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenza, Moraxella catarrhalis) trapped in warm & moist environment Inflammatory response causes mucosal edema & ↑ mucus production Ear pain/ fullness Bacterial enzymes perforate maxillary sinus floor & Schneiderian membrane (separating sinus from dental roots) lining the maxillary cavity Facial pain/pressure Oral anaerobes move into sinuses Bacteria overgrow in sinuses Maxillary tooth pain Bacterial infection spreads to adjacent structures Mucopurulent discharge from nose Cranial cavity à Cavernous sinus thrombosis Bony eye cavity à Orbital cellulitis, edema, &/or subperiosteal orbital abscess Skull à Osteomyelitis of frontal bone Fever Fatigue Brain à Cerebral abscess Meninges à Subdural abscess Meningitis Spine à Epidural abscess Authors: Amanda Marchak Daniel Alayev Reviewers: Alua Kulenova Nicola Adderley Jim Rogers Danielle Nelson* * MD at time of publication Updated May 18, 2026 on www.thecalgaryguide.com Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications