SEARCH RESULTS FOR: sepsis

Bronchopulmonary Dysplasia (BPD)- Pathogenesis and clinical findings

Bronchopulmonary Dysplasia (BPD)- Pathogenesis and clinical findings Adderley Mitchell antenatal post-natal prematurity intrauterine growth restriction genetic predisposition maternal smoking chorioamnionitis pregnancy induced hypertensive disorders post natal mechanical ventilation sepsis O2 toxicity patent ductus arteriosus insult to lungs pro inflammatory cytokines disruption pulmonary vascular alveolar development reduced pulmonary vascular resistance vascular growth and altered vasoreactivity dysmorphic capillary beds remodelling of pulmonary arteries artery hypertension suboptimal repair abnormal remodelling interstitial fibrosis diffuse haziness interstitial thickening cxr impaired pulmonary gas exchange hypoxia signs of respiratory distress retractions wheezes crackles DLCO airway resistance obstructive lung disease FEV1 separation and alveolar hypoplasia functional alveoli surface area gas exchange

Sepsis, and Septic Shock- Pathogenesis and Clinical Findings

Sepsis, and Septic Shock: Pathogenesis and Clinical Findings Authors: Daniel J. Lane Simonne Horwitz Reviewers: James Rogers Emily Ryznar Braedon McDonald* Christopher Doig* *MD at time of publication Sepsis Pathogen (Bacteria, Fungi, Virus, or Parasite) Comorbidities Immunosuppression or ↑ susceptibility (e.g. splenectomy) Pathogen virulence Invasion and host immune avoidance Vulnerable infection site ↑ likelihood of spread of infection & mortality Genetics ↑ Sensitivity of innate immune response Community acquired Hospital acquired Infection of host Innate immune response Fever, Leukocytosis/ Leukopenia, Left Shift/ Bandemia Compensatory response Tachypnea, Altered Level of Consciousness, Hypotension ↓ perfusion and oxygen delivery to organs Dysregulated Host Response Pro- and anti-inflammatory response Life-threatening organ dysfunction caused by a dysregulated host response to infection The Sequential Organ Failure Assessment (SOFA) or quick SOFA (qSOFA) Scores may be used to assess mortality risk Respiratory ↓ PaO2 / FiO2 (mmHg) Nervous ↓ Level of consciousness Septic Shock Cardiovascular ↓ Mean Arterial Pressure Organ Dysfunction Liver ↑ Bilirubin Kidney ↑ Creatinine, Acute oliguria Coagulation Thrombocytopenia, ↑ INR or aPTT Require vasopressors to ↑ mean arterial pressure Persistent hypotension despite adequate fluid resuscitation ↓ Mean Arterial Pressure (< 65 mmHg), ↑ Lactate (> 2 mmol/L) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 12, 2019 on www.thecalgaryguide.com

adrenergic-agonists-for-treating-hypotensionlow-blood-pressure

Side effects Authors: Arsalan Ahmad, Lance Bartel, Yan Yu* Reviewers: Billy Sun, Mackenzie Gault, Melinda Davis* *MD at time of publication Legend: Published February 19, 2019 on www.Pathophysiology Mechanism Sign/Symptom/Lab Finding thecalgaryguide.com Epinephrine Norepinephrine High Dose Low Dose Adrenergic Agonists for Treating Hypotension/Low Blood Pressure (BP) β1-receptor activation on cardiac myocytes ↑ contractility α1-receptor activation on the smooth muscle of blood vessel walls ↑ intra-cellular Ca2+ in these cells, ↑ their contraction Ephedrine Direct effect Indirect effect ↑ release of endogenous norepinephrine from the adrenal medulla (see above) Mimics epinephrine (see above) Primary Indications: anaphylaxis, cardiac arrest Primary Indications: Hypovolemic states (e.g. blood loss), Low systemic vascular resistance states (e.g. sepsis, Anesthesia-induced hypotension) Primary Indications: mainly used in Anesthesiainduced hypotension ↑ intracellular Ca2+ ↑ rate of myocyte contraction Phenylephrine ↑ Cardiac Output ↑ heart rate ↑ strength of myocyte contraction ↑ arterial wall tone ↑ stroke volume Pushes more blood to flow back to heart (↑ preload) ↑ systemic vascular resistance (SVR) More blood in ventricles stretch myocytes more optimally for ↑ contractility (Frank Starling Law) ↑ venous wall tone ↑ Blood Pressure Nonspecific activation of α and β receptors on other areas of the body (e.g. on the autonomic nervous system) as well as on cardiac myocytes Hypertension Cardiac Dysrythmias: e.g. palpitations, ventricular fibrillation Tremors Cardiac arrest All four drugs

Endometritis

Endometritis: Pathogenesis and clinical findings Prolonged rupture of membranes > 24 hours between amnion rupture and delivery ↑Time for vaginal flora to ascend into the uterus Assisted vaginal delivery Use of forceps or vacuum Multiple digital vaginal exams Manual examination of the vagina to assess cervical dilation Internal monitoring Intrauterine device to monitor the fetus or contractions Group B Streptococcus colonization Opportunistic bacteria present in the normal vaginal flora of up to 30% of women Bacterial Vaginosis Overgrowth of anaerobic bacteria with associated decrease in protective Lactobacillus species Foreign bacterial ascension into the uterus Sepsis Cesarean delivery ↑ Exposure of vaginal flora to the uterus Introduction of bacteria directly into the uterus Spread of infection to myometrial and parametrial layers of uterus Authors: Gabrielle Wagner Reviewers: Danielle Chang Crystal Liu Aysah Amath* * MD at time of publication ↑ Susceptibility to bacterial invasion of the uterine lining Endometritis Postpartum infection of the uterine endometrial lining Activation of innate Fever, immune response Inflammation of uterus Leukocytosis Accumulation of WBCs within vaginal discharge Purulent or foul-smelling lochia (vaginal discharge) Uterine tenderness Pelvic and/or abdominal pain Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 26, 2019 on www.thecalgaryguide.com

C5-C9-deficiency

C5-C9 deficiency: pathophysiology and clinical findings Authors: Heather Yong Reviewers: Jessica Tjong, Crystal Liu, Yan Yu*, Nicola Wright* * MD at time of publication Normal complement response The complement pathway is a non- specific response to bacterial pathogens Bacterial infection Classical, alternative, or lectin pathway activation Complement cascade MAC formation on bacterial surface C5b, C6, C7, C8, C9 Complement proteins create trans- membrane channels within bacterial cell walls/cell membranes Critical bacterial proteins leak out of the cell, breakdown of entire cell Primary (hereditary) causes Secondary (acquired) causes All are autosomal recessive Biologic therapy ex. eculizumab Absence or suboptimal functioning of Abbreviations: • MAC: Membrane Attack Complex • CH50: Classic Hemolytic Complement Test • AH50: Alternative Hemolytic Complement Test • CNS: Central Nervous System • CSF: Cerebrospinal Fluid ≥1 terminal complement proteins C5-C9 deficiency Inability to form MAC ↑ susceptibility to systemic Neisseria infection Commonly N. meningitidis Rarely N. monorrhoeae Nasopharyngeal colonization of N. meningitidis, ↑ susceptibility to bacteremia CH50 ± AH50 assay No lysis Note: Total complement activity assay <10% activity C5, C6, C7, C9 <50% activity C8 Varied bactericidal action via other complement proteins • Risk of invasive meningococcal disease is 1000-10000X higher in C5-C9 deficiency than in the general population • Reason is unknown • C5-C9 deficient patients are not at greater risk for contracting other gram (-) infections • Clinical meningitis in C5-C9 deficiency is less severe and fatality is rare Bacterial lysis Especially gram (-)ve bacteria like Neisseria Bacteria cross the blood-brain barrier, causing swelling and damaging brain tissue Fatigue, fever, headache, altered mental status, etc. Inflammation of CSF and meninges Activation of dura and pia mater fibres Headache, neck stiffness Bacteria release toxins Damage to surface blood vessels Maculopapular rash Exact mechanism unknown Recurrent meningitis CNS damage due Sepsis to recurrent meningitis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 16, 2019 on www.thecalgaryguide.com

Cellulitis

Cellulitis: Pathogenesis, clinical findings and complications Authors: Tegan Evans, Spencer Yakaback Reviewers: Brian Rankin, Timothy Fu, Laurie Parsons*, Yan Yu* * MD at time of publication Cracked skin Surgery Normal Skin Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous fat Resident skin flora: Coagulase-negative Staphylococci* Transient skin flora: Staphylococcus aureus* Streptococcus pyogenes Gram negative bacteria Fungi Pathogen in deep dermis and subcutaneous fat *most common pathogens Break in skin barrier (may not be obvious) and entry of pathogen Risk Factors: Immunocompromised Host: -Diabetes mellitus+ -Lymphedema -Malnourishment -Older patient+ -Obesity+ -Peripheral vascular disease General Infection Risk: -History of cellulitis+ +highest risk factors Risk Factors for MRSA Cellulitis: Increased exposure to MRSA: -Contact sports -Crowded living conditions -Health care workers -Indigenous descent -Sharing towels, equipment Increased susceptibility: -Immunodeficiency -Young age Direct inoculation (e.g. trauma) Organism virulence overwhelms host defense mechanisms (related to risk factors) Cellulitis: A bacterial infection in which pathogens penetrate deep dermis and/or subcutaneous fat Cytokines activate immune response Accumulation of pus (bacteria, white blood cells, dead skin) Abscess formation Infection spreads to nearby lymph nodes Lymphadenitis Infection spreads through lymph vessels Ascending lymphangitis Local inflammatory response in skin Pain Warmth Edema Erythema (redness) with indistinct margins Vesicles and bullae Organisms penetrate blood vessels Bacteremia (presence of bacteria in blood) Systemic inflammation Distant spread to bone Osteomyelitis Distant spread to endocardium (inner lining of heart chambers and valves) Endocarditis Fever Malaise Chills Sepsis (rarely) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 27, 2020 on www.thecalgaryguide.com

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

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

disseminated-intravascular-coagulation

Disseminated Intravascular Coagulation (DIC): Pathogenesis and clinical findings Authors: Emily Wildman Mehul Gupta Sean Spence Yan Yu* Reviewers: Kiera Pajunen Wendy Yao Tristan Jones Man-Chiu Poon* Lynn Savoie* * MD at time of publication Sepsis Microorganisms express pathogen- associated molecular patterns (PAMPs) Severe Trauma Damaged endothelial cells release damage- associated molecular patterns (DAMPs) Solid and Hematologic Malignancies Cancer cells express tissue factor and release procoagulants Immune cells recognize DAMPs and PAMPs and begin expressing tissue factor and releasing procoagulants Systemic activation of coagulation cascade Activation of coagulation cascade results in the factor X mediated conversion of large quantities of prothrombin (factor II) to its active form, thrombin (factor IIa) Thrombin cleaves fibrinogen (factor I) circulating in blood to an activate form known as fibrin (factor 1a) ↓ Serum fibrinogen Diffuse coagulation causes imbalances between coagulation and anticoagulation pathways Consumption of coagulation factors (including platelets, fibrinogen, prothrombin, factor V, factor VIII) exceeds rate of production Fibrin, in conjunction with platelets, form widespread thrombi within vasculature Fibrin thrombi accumulate in the microvasculature and shear transiting red blood cells Microangiopathic hemolytic anemia (MAHA) ↑ thrombi formation ↑ fibrinolysis, a parallel process that naturally degrades fibrin thrombi Relative deficiency of coagulation factors leads to a bleeding diathesis (tendency to bleed) despite widespread clots ↑ Prothrombin time (PT) ↑ Partial thromboplastin time (PTT) ↑ D-dimer Fibrin thrombi ↑ Fibrin degradation products Platelets are used up forming thrombià less free platelets in circulation ↓ Platelets on Complete Blood Count accumulate in microvasculature of major organs Deposition of thrombi occlude blood flow resulting in ischemia of organ parenchyma Lack of coagulation factors can predispose spontaneous hemorrhage in various organs Multiple organ dysfunction syndrome (MODS) - (renal failure, hepatic dysfunction, stroke, pulmonary disease) Clinical manifestations of bleeding, including petechiae (pinpoint red spots on skin), ecchymoses (bruising), weeping wound sites, bleeding mucous membranes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published Aug 7, 2012, updated July 27, 2019 & Aug 29, 2021 on www.thecalgaryguide.com

Pneumonie: Pathogenese und klinische Befunde

Pneumonie: Pathogenese und klinische Befunde Autoren: Laura Byford-Richardson Rezensenten: *Yan Yu, Sadie Kutz, Natalie Morgunov, *Kerri Johannson Übersetzung: Sarah Schwarz Übersetungsprüfung: Gesche Tallen* *MD zum Zeitpunkt der Veröffentlichung Anmerkungen: • Pathogene können Bakterien, Viren, Pilze oder Parasiten sein • Die Pneumonie ist eine Entzündung der unteren Atemwege (im Gegensatz zur Entzündung der oberen Atemwege z.B. die Bronchitis) und kann unterteilt werden in: Ambulant erworbene, nosokomial (im Krankenhaus) erworbene Pneumonie Die Immunantwort variiert je nach eingedrungenem Erreger (z.B. Pneumokokken verursachen ein lobär betontes, H. influenzae ein interstitiell betontes Entzündungsbild) Rauchen unterdrückt die Funktionsfähigkeit der neutrophilen Granulozyten und schädigt das Lungenepithel Chronische Lungenerkrankungen z.B. COPD, Asthma oder Lungenkrebs zerstören das Lungengewebe und bieten Krankheitserregern mehr Angriffsfläche für Infektionen Durch Immunsuppression z.B. bei HIV, Sepsis, Glucocorticoid- oder Chemotherapie wird die Immunantwort eingeschränkt Systemisch kommt es zu einer inflammatorischen Immunantwort Durch systemische Zytokinfreisetzung wird die hypothalamische Thermoregulation beeinträchtigt Erregersexposition durch Inhalation, Aspiration, Kontakt- oder hämatologische Übertragung Anfällige Person und/oder virulenter Erreger Proliferation des Erregers in unteren Atemwegen und Alveolen Lokal reagiert das Alveolarepithel mit einer Chemokinausschüttung um neutrophile Granulozyten an den Entzündungsort zu mobilisieren LOBÄR betont: Lokal begrenzte Akkumulation von neutrophilen Granulozyten und Plasmaexudat in Alveolen INTERSTITIELL betont: Zelluläre Infiltrate (Immunzellen und Immunzellfragmente) in den Alveolarwänden (zwischen Alveolen und Kapillaren) Fieber Anmerkungen: Schüttelfrost Irritation der Atemwege mit Hustenreiz Flüssige Infiltrate in Alveolen führen zur Schleimbildung Produktiver Husten Das Exudat vermindert die Röntgenstrahlendur chlässigkeit, entzündete Areale erscheinen im Röntgenbild heller/weiß. Verschattung im Röntgen Alveolen sind durch Flüssigkeitsansamml ungen blockiert Verdickung der Alveolarwände, Diffusionsstrecke ↑ Irritation der Alveolarwände mit Hustenreiz Bei ausschließlich interstitieller Infiltration -> Husten ohne Schleimproduktion Trockener Husten • Andere Symptome der Pneumonie sind: Brustschmerzen, Nutzung der Atemhilfsmuskulatur, auskultatorisch Rasselgeräusche, Müdigkeit • Diese Symptome sind jedoch unspezifisch O2 und CO2- Austausch vermindert Hypoxie Periphere & zentrale Chemorezeptoren werden aktiviert, Atemfrequenz ↑ Luftnot Legende: Pathophysiologie Mechanismen Symptome/Klinische Befunde Komplikationen Veröffentlicht: 26. September 2016 auf www.thecalgaryguide.com

Celulitis

Celulitis: Patogénesis, hallazgos clínicos y complicaciones Autores: Tegan Evans, Spencer Yakaback Revisores: Brian Rankin, Timothy Fu, Laurie Parsons*, Yan Yu* * MD en el momento de la publicación Traducción: Anagabriela Duarte María Rosario Talavera* Piel agrietada Cirugía Inoculación directa (e.j., trauma) Organismos penetran los vasos sanguíneos Bacteremia (presencia de bacterias en sangre) Piel normal Capa epidérmica Unión dérmica- epidérmica Capa dérmica Grasa subcutánea Flora cutánea residente: Staphylococcus coagulasa negativos* Flora cutánea transitoria: Staphylococcus aureus* Streptococcus pyogenes Bacterias gram negativas Hongos Patógeno en dermis profunda y grasa subcutánea *patógenos más comunes Rotura de la barrera cutánea (puede que no sea evidente) y entrada de patógenos Virulencia del organismo supera los mecanismos de defensa del huésped (asociado a los factores de riesgo) Celulitis: Una infección bacteriana en la que los patógenos penetran la dermis profunda y/o la grasa subcutánea Citocinas activan la respuesta inmune Acumulación de pus (bacterias, glóbulos blancos, piel muerta) Formación de abscesos Factores de riesgo: Huésped inmunodeprimido: -Diabetes mellitus+ -Linfedema -Desnutrición -Paciente adulto mayor+ -Obesidad+ -Enfermedad vascular periférica Riesgo de infección general: -Historia de celulitis+ +factores de riesgo mayores Factores de riesgo para celulitis por SARM: Mayor exposición a SARM: -Deportes de contacto -Hacinamiento -Trabajadores de la salud -Ascendencia indígena -Compartir toallas, equipos Mayor susceptibilidad: -Inmunodeficiencia -Edad temprana Infección se propaga a los ganglios linfáticos cercanos Linfadenitis infección se propaga a través de los vasos linfáticos Linfangitis ascendente Respuesta inflamatoria local en la piel Diseminación a distancia en endocardio (revestimiento interno de las cámaras y válvulas del corazón) Endocarditis SARM: Staphylococcus aureus resistente a meticilina Dolor Calor Fiebre Malestar Diseminación a distancia en el hueso Osteomielitis Escalofríos Inflamación sistémica Edema Eritema (enrojecimiento) con márgenes indefinidos Vesículas y ampollas (poco frecuente) Sepsis Abreviaturas: Leyenda: Patofisiología Mecanismo Signos/Síntomas/Hallazgos de Laboratorio Complicaciones Publicado el 27 Septiembre, 2020 en 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

necrotizing fasciitis

Necrotizing Fasciitis: Pathogenesis and Clinical Findings Authors: Alyssa Federico, Amanda Eslinger, Matthew Harding, Mehul Gupta Reviewers: Heena Singh, Yan Yu*, Donald Graham*, Duncan Nickerson* * MD at time of publication Diabetes Loss of protective sensation in lower extremities Peripheral vascular disease Poor arterial perfusion causes necrosis of tissue Immune compromised host Increased susceptibility to infection Bacteria introduced to tissue Pharyngitis Blood carries bacteria from throat to other tissue (hematogenous spread) Laceration Recent surgery Injection Burn Blunt force trauma Childbirth Lower extremity wounds Bacteria enters tissue through open wound Infection of muscle fascia Local immune response Production of exotoxins by bacteria Disruptions of protective skin barrier Bacteria introduced into tissue during injury Necrotizing Fasciitis Type I infection: mixed aerobic and anaerobic bacteria Type II infection: group A streptococcus Type III infection: marine organisms, clostridial infections Type IV infection: fungal organisms Poor blood supply of muscle fascia allows for progressive spread of infection Systemic immune response Pyrogens produced by immune system Pyrogens travel through the bloodstream to the hypothalamus and alters the body’s thermal setpoint Transmission of bacteria from infected tissue to blood Sepsis Streptolysin (exotoxin) causes blood clot formation Blood clots in vessels Tissue ischemia in epidermis, dermis, subcutaneous fat, muscle fascia, and/or muscle Stimulation of programmed cell death Tissue destruction Pain more severe than clinical findings ↓ blood flow fails to meet tissue’s needs Tissue death Build up of gas in subcutaneous tissue from bacteria metabolism Crepitus ↑ serum creatinine kinase from protein breakdown ↑ blood flow to infected tissue Warmth Erythema Immune cells release vasoactive cytokines into the blood Capillary vasodilation Fluid and proteins shift from cells and capillaries to interstitial space Blood vessel dilation ↓ perfusion of vital organs Organ failure Hypotension ↑ heart rate to perfuse vital organs Tachycardia Bacteria releases toxins which are taken up into the bloodstream Immune cells produce inflammatory cytokines Circulating toxins activate T cells, over- activating the systemic immune response Toxic Shock syndrome Infection ↑ white blood cell production in bone marrow ↑ white blood cells Destructionof peripheral nerve endings Insensitivity to pain Tissue hypoxia à anaerobic metabolism Poor perfusion of lungs impairs gas exchange Tachypnea Cytokines affect dopamine production in the basal ganglia Acute malaise Production of non-specific acute phase reactants ↑ C reactive protein and erythrocyte sedimentation rate Fluid-filled blisters Edema Fever Compartment syndrome (see relevant Calgary Guide slide) Amputation ↑ serum lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published Nov 20, 2013, updated Dec 19, 2021 on www.thecalgaryguide.com

sepsis-y-shock-septico-patogenesis-y-hallazgos-clinicos

sepsis-y-shock-septico-patogenesis-y-hallazgos-clinicos

adult-pneumonia-pathogenesis-and-clinical-findings

Adult Pneumonia: Pathogenesis and clinical findings Author: Laura Byford-Richardson Reviewers: Tara Shannon, *Yan Yu, Sadie Kutz , Natalie Morgunov, *Kerri Johannson, *Julie Carson *MD at time of publication Smoking à suppressed neutrophil function and damaged lung epithelium Chronic lung conditions e.g. COPD, asthma, lung canceràdestroys lung tissue and offers pathogen more niduses for infection Immune suppression e.g. HIV, sepsis, glucocorticoids, chemotherapyà suppression of immune response Systemic inflammatory response towards invading microbe Systemic cytokine release leads to a disruption in hypothalamic thermoregulation Exposure to a pathogen via inhalation, aspiration, contiguous Notes: or hematological mechanism Susceptible host and/or virulent pathogen Proliferation of microbe in lower airways and alveoli Local response by alveolar epithelial cells release chemokines into surrounding tissue to recruit neutrophils to the site of inflammation • Pathogens can be bacteria, viruses, fungi and parasites • Pneumonia is a lower respiratory tract infection (in contrast to upper respiratory tract infections such as bronchitis) and can be further classified by location of exposure: community, health- care, hospital acquired Inflammatory response varies depending on type of invading pathogen (i.e. S. Pneumonia causes a lobar pattern and Influenza A & B cause an interstitial pattern) LOBAR: Accumulation of neutrophils and plasma exudate from capillaries into alveoli specific to a lung area/lobe INTERSTITIAL: Accumulation of infiltrates (i.e. inflamed cellular debris) in the alveolar walls (i.e. space between the alveolar spaces and bloodstream) Fever Notes: • Other signs and symptoms of pneumonia exist such as chest pain, accessory muscle use, crackles on auscultation and fatigue • These signs and symptoms are less specific to the ones outlined on this slide Irritation and attempted clearance of airways Fluid infiltrates are inside alveoli, airway clearance leads to phlegm production Productive Cough Fluid build up does not allow X-rays to pass through à white opacity on plain film at site of fluid buildup Consolidation on CXR Alveolar sacs blocked by fluid accumulation Thickening of alveolar walls ↑ diffusion distance between alveoli & capillaries Irritated alveolar walls trigger cough reflex Since fluid infiltrates are NOT in the alveoli, attempts to empty the alveoli through coughing doesn’t lead to production of fluid Dry Cough Chills/Rigors ↓ Exchange of CO2 and O2 Hypoxemia Triggers peripheral and central chemoreceptors to ↑ respiratory drive Dyspnea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 26 2016, updated Feb 9, 2022 on www.thecalgaryguide.com

etomidate

Etomidate Ultrashort-acting carboxylated imidazole anesthetic administered intravenously to induce unconsciousness, usual dose 0.3 mg/kg IV Directly inhibits adrenal 11-beta- hydroxylase (enzyme responsible for cortisol biosynthesis) ↓ Adrenal cortisol production ↓ Serum cortisol available for stress response Transient adrenal steroid insufficiency ↑ Morbidity & mortality in trauma/critically ill patients (Contraindicated in sepsis) Inhibits nitric oxide signaling Transient cerebral vasoconstriction ↓ Cerebral blood flow ↓ Oxygen delivery to brain ↓ Cerebral metabolic rate Suppression of electrical activity in brain Flat electroencephalogram Binds to GABAA (inhibitory CNS neurotransmitter) receptor Authors: Cindy Chang Ran (Marissa) Zhang Reviewers: Melissa King Brooke Fallis Julia Haber* * MD at time of publication Abbreviations: • CNS - Central Nervous System • GABAA- Gamma- aminobutyric acid type A • TRPA1- Transient receptor potential type A1 Higher selectivity for specific GABAA receptor subtypes compared to other induction agents Positively modulates GABAA receptor (GABAA receptor activated at lower concentrations of GABA ) ↓ Cerebral blood volume Activation of fewer GABAA receptor subtypes in neurons and cardiovascular structures compared to other induction agents ↓ Intracranial pressure ↑ Hemodynamic stability (minimal changes in blood pressure or heart rate) Myoclonus (brief, involuntary, irregular muscle twitch) ↑ Spontaneous CNS neuron firing to skeletal muscle Prolonged opening of GABAA receptors (acts as ion channel for chloride) Inhibits activity of nerve cells in the reticular activating system Activation of peripheral nociceptor receptors ↑ Involuntary muscle contractions Influx of chlorideàHyperpolarization of nerve membranes in reticular activating system (brainstem neuronal network that regulates arousal and sleep- wake transitions) Depression of arousal & loss of consciousness Induction of general anesthesia (no analgesic effect) Direct activation of TRPA1 cation channels (key receptor in pain pathway) Stinging pain with injection (Treat with co-administration of local anesthetic) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 9, 2022 on www.thecalgaryguide.com

ventilator-associated-pneumonia-pathogenesis-and-clinical-findings

Ventilator-Associated Pneumonia: Pathogenesis and Clinical Findings Respiratory failure or inability Risk factors: e.g. immunocompromised, poor swallowing to maintain airway ability, weakened respiratory muscles, chronic disease Insertion of endotracheal tube (ETT) for invasive mechanical ventilation to maintain respiration Paralytics and sedatives lead to inhibition of cough reflex Damage to cilia on epithelial cells of trachea during insertion of ETT ↓ Mucociliary clearance Insertion of nasogastric (NG) tube for feeding Constant opening by NG tube ↓ esophageal sphincter function Introduction of oropharyngeal microbes during intubation Severe acute illness impairs phagocytosis and dysregulates T- cells (mechanism unclear) Medications, chronic disease, or severe acute illness can weaken immune system Desensitization of pharyngoglottal adduction reflex (PAR) (PAR normally induces closure of epiglottis to protect the airway when swallowing) ↑ Reflux of gastric contents Accumulation of subglottic secretions containing microbes Microbial colonization on inside of ETT Development of biofilm on inside of ETT Dislodgement of biofilm into lower airway ↑ Age or chronic disease can weaken respiratory function Micro aspirations of subglottic and gastric contents Impaired mechanisms to remove microbes from airway Positive pressure pushes microbes down Fever/rigors ↑ White blood cell count Introduction of pathogenic microbes to airway Susceptible patient (not required for infection) Septic shock See Distributive Shock slide Sepsis Microbes descend airway and infect lungs Ventilator-Associated Pneumonia (VAP) Occurs > 48-72 hours after intubation ↑ Inflammatory response at infection site promoting immune cell extravasation and cytokine release Cytokine signalling ↑ permeability of capillaries leading to ↑ fluid leakage into interstitium and alveoli Authors: Sravya Kakumanu Reviewers: Ben Campbell *Tara Lohmann *Bryan Yipp * MD at time of publication Acute respiratory distress syndrome See ARDS pathogenesis slide Pleural effusion Lung consolidation on chest x-ray (CXR) ↑ Sputum production to clear fluid on CXR (Note: In patients with Acute Respiratory Distress Syndrome (ARDS), look for VAP consolidation in non- within alveoli/airways (may be Positive microbial culture from sputum dependent/upper regions of the lung where ARDS consolidation would be unexpected to extend to) purulent in worse infections) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 2, 2022 on www.thecalgaryguide.com

Neonatal Sepsis

Neonatal Sepsis: Pathogenesis and overview of clinical findings Maternal Risk Factors Author: Nick Baldwin, Daria Mori Reviewers: Elizabeth de Klerk, Jody Platt, Mao Ding, Yan Yu Naminder Sandhu* *MD at time of publication Neonate Risk Factors Prolonged rupture of membranes > 18 hours prior to delivery Untreated bacteria in urine during pregnancy Poor prenatal care (mechanism unclear; multifactorial) Group B Strep vaginal colonization Intra- amniotic infection Prematurity (< 37 weeks) or low birth weight (< 2500 gm) Under- developed immune system Predisposed to infection Congenital anomaly that disrupts skin Birth asphyxia (lack of oxygen and blood flow to brain) Male gender (mechanism unclear) Invasive Procedures Direct introduction of bacteria to neonate’s blood ↑ likelihood of introducing bacteria to the fetus Vertical transmission of maternal bacteria from lower genital tract to uterus Contamination of amniotic fluid Fetal bacteremia (presence of bacteria in bloodstream Direct transmission of bacteria from maternal birth canal to fetal blood during delivery Disruption in neonatal host defenses Neonatal Sepsis An invasive infection, usually bacterial, occurring during the neonatal period (<4 weeks of age for term infants, or <4 weeks after the due date for preterm infants) Note: *APGAR = appearance, pulse, grimace, activity and respirations at 1-, 5-, and 10-min post birth Gastrointestinal Poor feeding Vomiting Diarrhea, constipation, or bloody stool Urological ↓ Urine output Note: See relevant slide(s) for mechanisms of how each sign and symptom comes about. CVS/RESP Apnea/tachypnea Labored breathing Pallor or cyanosis Brady-/tachycardia Hypotension Metabolic Jaundice Hypo- or hyper-glycemia Metabolic acidosis CNS Lethargy Irritability Focal neurological signs Seizure General Low APGAR* Temperature instability Bulging or sunken fontanels Rash Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 3, 2013, updated June 7, 2023 on www.thecalgaryguide.com

Acute Respiratory Distress Syndrome

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

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

Onychomycosis

Dermatophyte Onychomycosis: Pathogenesis and clinical findings Authors: Holly Zahary Loreman Reviewers: Mina Youakim Elise Hansen Shahab Marzoughi Jodi Hardin* * MD at time of publication Host Risk Factors Environmental Risk Factors Immuno- compromised ↓ Immune response to infection Older age Peripheral vascular disease Reduced blood circulation Diabetes Pre-existing nail dystrophy Previous nail trauma Integrity of nail unit is compromised Micro- traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit High blood sugar favoring infection Dermatophytes invade corneocytes on stratum corneum, the uppermost non- living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Proximal Subungual White Superficial Tinea infection (e.g. Tinea Pedis, Corporis, Capitis) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue General Symptoms (All Subtypes) Spongiosis (Intercellular edema) Acanthosis (Thickening of stratum spinosum layer of epidermis) Hyperkeratosis (Thickening of stratum corneum In effort to rid infection) Papillomatosis (Projections of dermal papillae) Secondary damage to nail matrix Loss of nail Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis Dermatophytic infection of the nail bed Inflammation promotes ↑ fluid to tissues for ↑ immune cell delivery Widespread inflammation thickens parts of the epidermis in efforts to shed the infection Inflammation and epidermal hyperplasia (↑ growth of cells) influence local dermal papillae (group of cells just beneath the hair follicle) to proliferate and project above the skin Distal Subungual Superinfecting bacteria or other fungi proliferate beneath the compromised nail imparting a yellowish appearance Distal Subungual Subtype (Thick yellow nails, keratin and debris accumulate distally underneath nail plate) Dermatophytes invade the proximal end of the nail plate Dermatophytes penetrate through the cuticle to the newly forming nail plate moving distally Proximal Subungual Subtype (Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression) Fungi predominantly invade various areas of the superficial nail plate layers eventually joining together White Superficial Subtype (Chalky white scale that spreads slowly beneath nail plate, well-defined “white islands” that coalesce as disease progresses) The entirety of the nail plate is infected by the dermatophytes Widespread inflammation thickens the nail plate as well as beneath the nail (subungual hyperkeratosis) in efforts to shed the infection Total Dystrophic Subtype (End-stage nail disease, entire nail becomes thick and dystrophic) Local spread of infection Dermatophytes spread causing cracks in the skin deeper into toe Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Fissure (splits in the skin) Bacteria enters lymphatics and bloodstream Cellulitis Sepsis Onycholysis (nail plate separates from nail bed) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 13, 2024 on www.thecalgaryguide.com Dermatophyte Onychomycosis: Pathogenesis and clinical findings Authors: Holly Zahary Loreman Reviewers: Mina Youakim Elise Hansen Shahab Marzoughi Jodi Hardin* * MD at time of publication Host Risk Factors Environmental Risk Factors Immuno- compromised ↓ Immune response to infection Older age Peripheral vascular disease Reduced blood circulation Diabetes Pre-existing nail dystrophy Previous nail trauma Integrity of nail unit is compromised Micro- traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit High blood sugar favoring infection Dermatophytes invade corneocytes on stratum corneum, the uppermost non-living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Proximal Subungual White Superficial Distal Subungual Superinfecting bacteria or other fungi proliferate beneath the compromised nail imparting a yellowish appearance Distal Subungual Subtype (Thick yellow nails, keratin and debris accumulate distally underneath nail plate) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis Dermatophytic infection of the nail bed Inflammation promotes ↑ fluid to tissues for ↑ immune cell delivery Widespread inflammation thickens parts of the epidermis in efforts to shed the infection Inflammation and epidermal hyperplasia (↑ growth of cells) influence local dermal papillae (group of cells just beneath the hair follicle) to proliferate and project above the skin General Symptoms (All Subtypes) Spongiosis (Intercellular edema) Acanthosis (Thickening of stratum spinosum layer of epidermis) Hyperkeratosis (Thickening of stratum corneum In effort to rid infection) Papillomatosis (Projections of dermal papillae) Secondary damage to nail matrix Loss of nail Tinea infection (e.g. Tinea Pedis, Corporis, Capitis) Dermatophytes invade the proximal end of the nail plate Dermatophytes penetrate through the cuticle to the newly forming nail plate moving distally Proximal Subungual Subtype (Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression) Fungi predominantly invade various areas of the superficial nail plate layers eventually joining together White Superficial Subtype (Chalky white scale that spreads slowly beneath nail plate, well-defined “white islands” that coalesce as disease progresses) The entirety of the nail plate is infected by the dermatophytes Widespread inflammation thickens the nail plate as well as beneath the nail (subungual hyperkeratosis) in efforts to shed the infection Total Dystrophic Subtype (End-stage nail disease, entire nail becomes thick and dystrophic) Dermatophytes spread deeper into toe Bacteria enters lymphatics and bloodstream Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Local spread of infection causing cracks in the skin Fissure (splits in the skin) Cellulitis Sepsis Onycholysis (nail plate separates from nail bed) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published MONTH, DAY, YEAR on www.thecalgaryguide.com Dermatophyte Onychomycosis: Pathogenesis and clinical findings Authors: Holly Zahary Loreman Reviewers: Mina Youakim Elise Hansen Shahab Marzoughi Jodi Hardin* * MD at time of publication Host Risk Factors Environmental Risk Factors Immuno- Older compromised age ↓ Immune response to infection Peripheral vascular disease Reduced blood circulation Diabetes Pre-existing nail dystrophy Previous nail trauma Integrity of nail unit is compromised Micro- traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit High blood sugar favoring infection Dermatophytes invade corneocytes on stratum corneum, the uppermost non-living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Tinea infection (e.g. Tinea Pedis, Corporis, Capitis) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis Dermatophytic infection of the nail bed General Symptoms (All Subtypes) Spongiosis (Intercellular edema) Acanthosis (Thickening of stratum spinosum layer of epidermis) Papillomatosis (Projections of dermal papillae) Hyperkeratosis (Thickening of stratum corneum In effort to rid infection) Secondary damage to nail matrix Loss of nail Proximal Subungual White Superficial Distal Subungual Distal Subungual Subtype (Thick yellow nails, keratin and debris accumulate distally underneath nail plate) Proximal Subungual Subtype (Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression) White Superficial Subtype (Chalky white scale that spreads slowly beneath nail plate, well-defined “white islands” that coalesce as disease progresses) Total Dystrophic Subtype (End-stage nail disease, entire nail becomes thick and dystrophic) Local spread of infection causing cracks in the skin Dermatophytes spread deeper into toe Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Onycholysis (nail plate separates from nail bed) Fissure (splits in the skin) Bacteria enters lymphatics and bloodstream Cellulitis Sepsis Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Dermatophyte Onychomycosis: Pathogenesis and clinical findings Authors: Holly Zahary Loreman Reviewers: Mina Youakim Elise Hansen Shahab Marzoughi Jodi Hardin* * MD at time of publication Host Risk Factors Environmental Risk Factors Immuno- Older compromised age ↓ Immune response to infection Peripheral vascular disease Reduced blood circulation Diabetes Pre-existing nail dystrophy Previous nail trauma Integrity of nail unit is compromised Micro- traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit High blood sugar favoring infection Dermatophytes invade corneocytes on stratum corneum, the uppermost non-living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Tinea infection (e.g. Tinea Pedis, Corporis, Capitis) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis Dermatophytic infection of the nail bed Proximal Subungual White Superficial General Symptoms (All Subtypes) Spongiosis (Intercellular edema) Acanthosis (Thickening of stratum spinosum layer of epidermis) Papillomatosis (Projections of dermal papillae) Hyperkeratosis (Thickening of stratum corneum In effort to rid infection) Secondary damage to nail matrix Loss of nail Distal Subungual Distal Subungual Subtype (Thick yellow nails, keratin and debris accumulate distally underneath nail plate) Proximal Subungual Subtype (Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression) White Superficial Subtype (Chalky white scale that spreads slowly beneath nail plate, well- defined “white islands” that coalesce as disease progresses) Total Dystrophic Subtype (End-stage nail disease, entire nail becomes thick and dystrophic) Local spread of infection causing cracks in the skin Dermatophytes spread deeper into toe Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Onycholysis (nail plate separates from nail bed) Bacteria enters lymphatics and bloodstream Fissure (splits in the skin) Cellulitis Sepsis Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Dermatophyte Onychomycosis (Tinea Unguium): Pathogenesis, clinical findings, Authors: Holly Zahary Loreman Reviewers: Elise Hansen Name Name* * MD at time of publication and complications Host Risk Factors Environmental Risk Factors Immuno- compromised ↓ immune response to infection Older age Peripheral vascular disease Diabetes Pre-existing nail dystrophy Previous Nail Trauma Integrity of nail unit is compromised Micro-traumatic pressure on nail Dark, warm shoe environment Optimal conditions for fugal growth Exposure to tinea pedis or onychomycosis Direct spread of infection to nail unit Reduced blood circulation High blood sugar, favoring infection Tinea pedis infection (see ‘Tinea Capitis, Tinea Corporis, and Tinea Pedis’) Infection spreads to distal hyponychial space Dermatophytes colonize local tissue in nail plate and nail bed Dermatophytes feed on keratinized tissue Proximal Subungual White Superficial Dermatophytes invade corneocytes on stratum corneum, the uppermost non-living layer of keratinized skin Compromise/breaking of hyponychial seal or cuticle (connection between hyponychium and nail plate) Keratinocytes produce an acute, low-grade inflammatory cytokine response Onychomycosis (Tinea Unguium) (dermatophytic infection of the nail bed) Distal Subungual General Symptoms (All Subtypes) Spongiosis Intercellular edema Acanthosis Thickening of stratum spinosum layer of epidermis Papillomatosis Projections of dermal papillae Hyperkeratosis Thickening of stratum corneum In effort to rid infection Secondary damage to nail matrix Loss of nail Distal Subungual Subtype Thick yellow nails, keratin and debris accumulate distally underneath nail plate Proximal Subungual Subtype Whitish discolouration of nail plate that begins proximally and moves distally, indicative of immunosuppression White Superficial Subtype Chalky white scale that spreads slowly beneath nail plate, well-defined “white islands” that coalesce as disease progresses Total Dystrophic Subtype End-stage nail disease, entire nail becomes thick and dystrophic Local spread of infection causing cracks in the skin Dermatophytes spread deeper into toe Abnormal keratinization in hyponychium Keratin accumulates between nail plate and hyponychium Onycholysis (nail plate separates from nail bed) Tissue Damage Cellulitis Sepsis Bacteria enters lymphatics and bloodstream Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com

Neonatal Necrotising Enterocolitis in Premature Neonates

Neonatal Necrotising Enterocolitis (NEC) in Premature Neonates: Pathogenesis and clinical findings Prematurity risk factors ↓ Intestinal motility ↑ Intestinal stasis allows bacteria more time to proliferate Bacterial overgrowth in gut ↓ Goblet cells in intestinal epithelium ↓ Intestinal mucus layer production leads to impaired mechanical defense against pathogenic bacteria Immature tight junctions in intestinal epithelium ↑ Permeability of intestinal epithelial barrier ↑ Toll-like receptor 4 (TLR4) expression on intestinal epithelial cells Aberrant bacterial colonization of gut Impaired gut barrier allows for ↑ bacterial translocation across intestinal epithelium TLR4 on intestinal mesentery endothelial cells bind lipopolysaccharides (LPS) on Gram-negative gut bacteria Immune cells release proinflammatory mediators (TNF, IL-12, IL-18) Cytokines mediate ↑ enterocyte apoptosis (including enteric stem cells) and ↓ enterocyte proliferation Intestinal mucosa healing is impaired, leading to local inflammation & injury TLR4 on intestinal epithelial cells binds LPS from Gram-negative gut bacteria Authors: Rachel Bethune Naima Riaz Reviewers: Nicola Adderley Michelle J. Chen Kamran Yusuf* Jean Mah* * MD at time of publication Endothelial nitric oxide synthase expression is reduced Vasoconstriction from ↓ NO reduces blood flow to intestines Prolonged ↓ in O2 perfusion results in irreversible intestinal mucosal cell death (necrosis) Gas escapes into abdominal cavity Leakage of intestinal contents irritates parietal peritoneum Bacteria enter bloodstream Pneumo- peritoneum Abdominal distention Peritonitis Sepsis Blood from tissue damage mixes with intestinal contents Bloody stool Intestinal sensory neurons detect damage and send signals to medullary vomiting centre Bilious vomiting Damaged intestinal cells are unable to absorb nutrients Short gut syndrome Persistent intestinal mucosal injury creates penetrating lesions through intestinal wall Intestinal perforation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 6, 2019; updated Mar 21, 2024 on www.thecalgaryguide.com

Febrile Neutropenia Pathogenesis and clinical findings

Febrile Neutropenia (Neutropenic Fever): Pathogenesis and clinical findings Administration of cytotoxic chemotherapy for cancer treatment Acquired aplastic anemia Autoreactive T cells destroy bone marrow stem cells Congenital mutations in ELA2 gene (encodes neutrophil elastase) ↑ Neutrophil apoptosis Chemotherapy eliminates beneficial bacterial species from gut microbiota New microbiota composition allows for growth of colonizing bacteria Indwelling catheters inserted to deliver chemotherapy Skin-colonizing bacteria access tissues through catheters Bacteria penetrate tissue barriers Chemotherapy injures gastrointestinal mucosa Broken mucosal barrier increases susceptibility to infections Chemotherapy destroys circulating neutrophils Chemotherapy impairs bone marrow stem cells ↓ Production of neutrophils Neutropenia (Absolute Neutrophil Count (ANC) < 0.5x109 cells/L ↓ Immune cell ↓ Production of engulfment of microbes inflammatory mediators Fewer circulating neutrophils blunts the innate immune response Pathogens enter bloodstream from tissues Systemic infection Authors: Max Lazar Braxton Phillips Reviewers: Naman Siddique Michelle J. Chen Lynn Savoie* * MD at time of publication Dormant viral infections reactivate (e.g. cytomegalovirus, herpes simplex virus) ↑ Susceptibility to common bacterial infections Positive blood bacterial cultures Fever (T ≥ 38.3 oC or sustained T ≥ 38 oC for 1 hour) Immune system mounts an excessive inflammatory response that damages tissues and organs Sepsis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 5, 2018; updated Mar 30, 2024 on www.thecalgaryguide.com

Acute Otitis Media Complications

Acute Otitis Media: Complications Prolonged mucus buildup or swelling in Eustachian tube due to colds/allergies obstructs the Eustachian tube Fluid unable to drain through tube and accumulates in middle ear Acute Otitis Media Infection and inflammation of the middle ear Mastoid air cells are in physical contact with distal middle ear Pathogens move into mastoid air spaces Inflammation & infection in air spaces Mastoiditis Bacterial and immune cell debris (pus) accumulates in mastoid air spaces Untreated middle ear infection allows further bacterial proliferation Persistent effusion causes ion channel changes in inner ear Composition of endolymph and perilymph in inner ear changes Vestibular/Labyrinth dysfunction Feelings of Vertigo imbalance Purulent discharge from middle ear through perforation Otorrhea (ear discharge) ↑ Pressure in middle ear Pressure stretches tympanic membrane Cytokines reach hypothalamus through the bloodstream Hypothalamus responds to stimulation and ↑ thermoregulatory set-point High-grade fever Infection spreads into bloodstream Sepsis Cytokines alter metabolism pathways of neurotransmitters in the brain Cerebral cortex dysfunction Infection spreads to cranium Intracranial complications (e.g., meningitis, brain abscess, thrombus) 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 Helper T cells and macrophages release inflammatory cytokines into the bloodstream Perforation of tympanic membrane ↓ Conduction of sound waves Conductive hearing loss Pressure in middle ear diffuses out of perforation ↓ Tympanic membrane stretching Otalgia (ear pain) fades Accumulated debris compresses cranial nerve VII Facial nerve palsy Mastoid abscess Febrile seizures Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 28, 2013, updated Apr 29, 2024 on www.thecalgaryguide.com

Sickle Cell Disease Pathogenesis Clinical Findings and Complications

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

Neonatal Hypoglycemia Pathogenesis

Neonatal Hypoglycemia: Pathogenesis Normal physiology Placenta supplies fetal circulation with glucose Clamping of the umbilical cord stops the source of glucose Blood glucose level declines rapidly in the first 2-3 hours of life Low glucose causes an ↓ in insulin and an ↑ in epinephrine, cortisol and glucagon Glucagon and epinephrine act on receptors in the liver and skeletal muscle to promote gluconeogenesis (glucose production from non- carbohydrate sources), glycogenolysis (breakdown of glycogen into glucose), and fatty acid oxidation (conversation of fatty acids to ATP) Low glucose levels stimulate the neonate’s appetite, allowing them to adapt to intermittent feeds Infant feeding regularly on a diet with sufficient carbohydrates creates a consistent plasma glucose concentration Pregnant Parent Causes Impaired Glucose Production Inadequate Glucose Supply Pregnant parent using β-blockers β-blockers prevent epinephrine from binding to adrenergic receptors in skeletal muscle and liver Blocked sympathetic signaling in these organs prevents glycogenolysis ↓ Breakdown of glycogen into glucose Infant of a parent with diabetes Parent has a high level of glucose in their blood The fetus receives a glucose-rich blood supply Fetal pancreatic β cells ↑ insulin production Post-birth, glucose levels in the infant’s circulation ↓ but insulin levels remain high Excessive glucose uptake into cells Fetus born with a metabolism disorder (e.g. organic amino acid disorder, disorder of glycogen metabolism, disorder of gluconeogenesis) Genes that make proteins or hormones responsible for production, breakdown and regulation of glycogen are mutated Fetus born with an endocrine disorder (e.g. congenital adrenal hyperplasia, hypopituitarism, Turner Syndrome) Pituitary and/or adrenal gland dysfunction ↓ release of hormones that regulate glucose balance Fetal growth is restricted, fetus is small for gestational age, or is premature (<37 weeks gestation) Glycogen is deposited during the 3rd trimester of pregnancy. Infants born early have fewer stores; smaller infants born at term have ↓ stores, ↑ insulin sensitivity, & poorly coordinated counter- regulatory hormones ↑ Glucose demand for the transition to life out of the womb Glycogen stores used up quickly Perinatal stress (e.g. sepsis, asphyxia) Stress stimulates fetal adrenal glands to ↑ epinephrine secretion Fetal pancreatic ⍺- cells ↑ glucagon secretion ↑ Breakdown of muscles and fat for glucose- building blocks Glycogen stores used up quickly ↑ Glucose usage as fetal metabolic demands ↑ to manage stress Fetal β-cells secrete inappropriately high levels of insulin despite hypoglycemic state; this hyperinsulinism state can last for months & resolve spontaneously ↓ Serum glucose Neonatal hypoglycemia Authors: Dasha Mori Reviewers: Michelle J. Chen *Dr. Danielle Nelson *MD at time of publication Blood glucose < 2.6 mmol/L in term & preterm infants within 72 hours of birth or < 3.3 mmol/L after 72 hours of birth Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 19, 2024 on www.thecalgaryguide.com

Underfill Edema Pathogenesis

Underfill Edema: Pathogenesis Acute respiratory Sepsis, burns, distress syndrome, trauma anaphylaxis ↑ Inflammatory mediators Gaps form between epithelial cells lining blood vessels ↑ Capillary permeability Fluid extravasation into interstitial space Blood backing up in vena cava ↑ capillary hydrostatic pressure in venous system Pressure creates net fluid movement from vascular space into interstitial space Authors: Matthew Hobart Richard Chan Nojan Mannani Michelle J. Chen Reviewers: Raafi Ali Varun Suresh Saif Zahir Andrew Wade* Adam Bass* * MD at time of publication Nephrotic syndrome ↑ Renal albumin loss Scarring of liver tissue (cirrhosis) Vasodilatory medications Various mechanisms Right-sided heart failure Compromised right heart function ↓ forward flow ↓ Hepatic albumin synthesis Blood is unable to pass through hepatic vessels disrupted by cirrhosis and backs up in portal vein ↑ Blood pressure in portal vein (portal hypertension) Less blood volume in hepatic veins and vena cava (underfilling) Pregnancy ↑ Estrogen, progesterone and relaxin Vasodilation Gravity causes fluid accumulation in peripheral veins ↑ Capillary hydrostatic pressure ↑ Net fluid movement into interstitial space ↓ Serum albumin ↓ Capillary oncotic pressure Fluid extravasation into interstitial space More blood in portal vein ↑ capillary hydrostatic pressure in venous system Pressure creates net fluid movement from vascular space into interstitial space Less blood volume in arteries (underfilling) ↓ Effective arterial blood volume (EABV) ↓ Renal blood flow activates the renin-angiotensin-aldosterone system (RAAS) Angiotensin and aldosterone ↑ Anti-diuretic hormone released by tubular Na+ and H2O resorption posterior pituitary ↑ H2O resorption ↑ Fluid in circulation, worsening existing venous congestion ↑ Hydrostatic capillary pressure and fluid extravasation into interstitial space Underfill edema (edema worsened by activation of RAAS) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 19, 2015; updated Aug 5, 2024 on www.thecalgaryguide.com

Pediatric Pneumonia Pathogenesis and Clinical Findings

Pediatric Pneumonia: Pathogenesis and clinical findings Authors: Jasmine Nguyen Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Annie Pham Eric Leung* Jean Mah* * MD at time of publication Immunological: unvaccinated, primary immunocompromise, pre-existing illness (e.g. HIV, measles), malnutrition Environmental: smoke, air pollution, mold, crowded housing Recent hospitalization or antibiotic-use Physiological: neonates, low-birth weight, underlying lung disease These factors make the host more susceptible to infection Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to infection/proliferation of microbial pathogens at the alveolar level Exposure to pathogen via inhalation, hematogenous, direct exposure, or aspiration Epithelial cells in respiratory tract release cytokines that recruit neutrophils & plasma proteins to infection site, initiating a local inflammatory response Cytokines released into the bloodstream (e.g. TNF, IL-1) initiate a systemic inflammatory response ↑ Vascular permeability Accumulation of exudate, cellular debris, serous fluid, fibrin, or bacteria in the airway spaces ↑ Respiratory drive Tachypnea ↑ Excitability of the peripheral somatosensory system Circulating cytokines induce prostaglandin synthesis Airway irritation as cilia are unable to efficiently clear fluid buildup Crackles, ↓ breath sounds Fluid, protein, or inflammatory cells leak into pleural space Pleural effusion Pulmonary edema Fluid buildup in interstitial spaces ↑ gas diffusion distance Bacteria enter the bloodstream (if bacterial pneumonia) Sepsis Fluid buildup in the alveoli ↓ available surface area for gas diffusion ↓ Efficiency of gas exchange Intra- and extracranial arteries dilate Headache ↑ Thermo-regulatory set-point of the hypothalamus Fever Myalgia Hypoxemia Malaise Cough Fluid accumulation in the pleural space prevents full lung expansion ↑ Work of breathing (tracheal tug, paradoxical abdominal breathing, subcostal/suprasternal indrawing) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 28, 2018; updated Aug 25, 2024 on www.thecalgaryguide.com Pediatric Pneumonia: Pathogenesis and clinical findings Authors: Jasmine Nguyen Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Annie Pham Eric Leung* * MD at time of publication Immunological: unvaccinated, primary immunocompromise, pre-existing illness (e.g. HIV, measles), malnutrition Environmental: smoke, air pollution, mold, crowded housing Recent Hospitalization: length of stay, recent antibiotics, mechanical ventilation Physiological: neonates, low-birth weight, underlying lung disease (ciliary dysfunction, asthma, cystic fibrosis, bronchiectasis) Host is more susceptible to infection Exposure to pathogen: inhalation, hematogenous, direct, aspiration Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to infection/proliferation of microbial pathogens at the alveolar level Notes: • Additional findings in pediatric pneumonia may include increased irritability, nausea/vomiting, diarrhea, otitis, and headache • Viral pathogens most common in children <2yrs; bacterial pathogens most common in children >2yrs Local inflammatory response: epithelial cells release cytokines in response to infection, which recruit neutrophils and plasma proteins to site of infection ↑ Vascular permeability causes accumulation of plasma exudate, cellular debris, serous fluid, fibrin, or bacteria in the airway spaces Systemic inflammatory response: Cytokine release (eg. TNF, IL-1) ↑ respiratory drive Airway irritation as cilia are unable to efficiently clear fluid buildup Crackles, ↓ breath sounds Fluid, protein, or inflammatory cells leak into pleural space Pleural effusion Pulmonary edema Fluid buildup in interstitial spaces increases gas diffusion distance Fluid buildup in the alveoli decreases available surface area for gas diffusion ↓ efficiency of gas exchange Bacteria invade into the bloodstream (if bacterial pneumonia) Sepsis Hypoxemia Circulating cytokines induce prostaglandin synthesis, which raise the thermoregulatory set-point of the hypothalamus paradoxical abdominal breathing, subcostal/suprasternal indrawing) Fever Cough Fluid accumulation in the pleural space prevents full lung expansion, resulting in ↓ lung volumes Tachypnea ↑ Work of breathing (tracheal tug, Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Month Day, Year on www.thecalgaryguide.com Pediatric Pneumonia: Pathogenesis and clinical findings Immunological: immunization status, immune compromise Environmental: second-hand smoke, air pollution Hospitalization: length of stay, recent antibiotics, mechanical ventilation Neonates, immunocompromise, underlying lung disease (ciliary dysfunction, Cystic Fibrosis, bronchiectasis) Authors: Nicola Adderley Reviewers: Midas (Kening) Kang Usama Malik Eric Leung* * MD at time of publication Additional findings in pediatric pneumonia may include nausea, otitis, headache Viral pathogens most common in children <2yrs; bacterial pathogens most common in children >2yrs Interstitial pattern: suspect Mycoplasma pneumoniae, Influenza A + B, Parainfluenza Lobar pattern: suspect S. pneumonia, H. influenzae, Moraxella, S. aureus Systemic inflammatory response: Cytokine release (eg. TNF, IL-1) Exposure to pathogen: inhalation, hematogenous, direct, aspiration Susceptible host and/or virulent pathogen Infection and proliferation of pathogen in lower respiratory tract/parenchyma Pediatric pneumonia: Inflammatory response to proliferation of microbial pathogens at the alveolar level Notes: • • • • Local inflammatory response: neutrophils recruited to site of infection (LOBAR or INTERSTITIAL PATTERN, depending on pathogen) by epithelial cytokine release Irritation of contiguous structures and/or referred pain (mechanism unclear) Acute abdominal pain Cough Accumulation of plasma exudate (from capillary leakage at sites of inflammation), cell-debris, serous fluid, bacteria, fibrin ↑ respiratory drive Disruption of hypothalamic thermoregulation Fever/chills Irritation of airways and failure of ciliary clearance to keep up with fluid buildup Crackles, ↓ breath sounds Fluid buildup in spaces between alveoli (INTERSTITIAL PATTERN) Interstitial opacity on CXR Fluid buildup in alveoli (LOBAR PATTERN) ↓ efficiency of gas exchange (↑ diffusion distance in INTERSTITIAL, ↓ surface area in LOBAR) Hypoxemia Tachypnea Lobar consolidation on CXR Respiratory accessory muscle use (chest indrawing, paradoxical breathing, muscle retractions) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 28, 2018 on www.thecalgaryguide.com gin

Neonatal Hypoglycemia Clinical Presentation

Neonatal Hypoglycemia: Clinical Presentation Normal physiology Glucose is produced from endogenous lactate, glycerol, and amino acids until glucose supply is established through feeds Hepatic glycogen is broken down to produce glucose in the first 8-12 hours of life Glucose is absorbed in the small intestine and transported into the bloodstream The pancreas responds to ↑ glucose blood concentration by releasing insulin Insulin acts on glucose transporters that line the cell membrane to bring glucose into the cell Glucose is broken down into ATP, which is used by cells for energy Authors: Dasha Mori Reviewers: Michelle J. Chen Dr. Ian Mitchell* *MD at time of publication Neonates with predisposing factors that Neonates that are unable to feed for > 60-120 Infant is large for gestational age (> 90th percentile) or was born to pregnant person with diabetes Fetus was exposed to high levels of glucose through placental circulation Fetus adapted to high blood glucose by producing high amounts of insulin After birth, placental glucose supply is stopped but insulin remains high ↑ Insulin promotes inappropriately ↑ uptake of glucose into cells put them at high risk for hypoglycemia Cells cannot produce enough ATP from glucose to power physiological functions Immature nervous system, use of fatty acids or proteins as an alternate ATP source, or adaptation to low glucose in utero can mask symptoms of hypoglycemia Asymptomatic hypoglycemia Neonates with low blood glucose often don’t show any symptoms and are detected by screening infants who are at a high risk for hypoglycemia min are at risk for hypoglycemia Infant is small for gestational age or experienced fetal growth restriction Smaller neonates have smaller glycogen stores Preterm infants born < 37 weeks Glycogen is stored during the 3rd trimester; preterm infants did not have opportunity to build up stores Loss of glucose source from placental circulation after birth puts preterm neonate at risk for low blood sugar Body’s sympathetic system detects low glucose and triggers physical symptoms (neurogenic symptoms) Symptomatic hypoglycemia Neurons in brain are unable to produce enough ATP and thus function properly, triggering symptoms related to low sugar in the CNS (neuroglycopenic symptoms) Non-specific symptoms are not exclusive to hypoglycemia and warrant further investigation to exclude other differential diagnosis (sepsis, inborn errors of metabolism, neonatal abstinence syndrome, neonatal encephalopathy, perinatal asphyxiation) Jitteriness or tremors Sweating Irritability Tachypnea Pallor Pathologic poor feeding Weak or a high- pitched cry Change in level of consciousness (lethargy or coma) Seizures Pathologic hypotonia for gestational age Apnea Bradycardia Cyanosis Hypothermia Neonates with perinatal stress (e.g. birth asphyxia, meconium aspiration) Body uses more glucose to produce ATP to manage condition causing physiological stress Glucose stores are used up more quickly Born to pregnant person with beta-blocker use Body in stress releases epinephrine to promote sympathetic responses including glycogen breakdown into glucose Beta blockers from placental circulation prevent epinephrine from binding to its receptor in infant’s body Neonatal Hypoglycemia: Asymptomatic and symptomatic hypoglycemia satisfy the criteria of blood glucose < 2.6 mmol/L in both term and preterm infants within 72 hours of birth, and after 72 hours of age glucose < 3.3 mmol/L Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 4, 2024 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

Meckels Diverticulum

Meckel’s Diverticulum: Pathogenesis and Clinical Findings No clear predisposition Stercolith (hard fecal mass) forms & is trapped in diverticulum Foreign body enters diverticulum & becomes trapped inside Incomplete vitelline duct obliteration (~5-7 weeks gestation) Diverticulum sags into Intussusception (section bowel lumen & acts as lead of intestine slides into Meckel’s Diverticulum point for intussusception adjacent region) Persistent remnant of vitelline duct containing all 3 layers of ileal mucosa (asymptomatic in 96-98% of cases) Diverticulum remains attached to umbilicus by persistent fibrous band Volvulus (loop of ileum twists around diverticulum) Ectopic tissue present within diverticulum Diverticulum goes through abdominal wall defect Littre’s Hernia (diverticulum in hernial sac) Diverticulum becomes incarcerated Ectopic gastric mucosa produces acid secretions Ectopic pancreatic tissue secretes digestive enzymes Ileal mucosa adjacent to diverticulum become ulcerated Inflammatory mediators disrupt hypothalamic regulation Small bowel becomes obstructed Perforation of diverticulum Brisk painless bleeding from small bowel Chronic inflammation & ulceration Fever Nausea/ vomiting Small bowel necrosis Hematochezia (bright red blood per rectum) ↓ Effective arterial blood volume Mucosa undergoes dysplastic & neoplastic transformation Complete erosion through ileal mucosa Small bowel perforation Hypotension Neuroendocrine tumour or other cancer Diverticulum becomes blocked & triggers local inflammatory response Meckel’s Diverticulitis Inflammation of Meckel’s Diverticulum Diverticulum is distended due to inflammation Visceral afferent nerves are stimulated by intestinal stretch Abdominal pain Chronic painless bleeding from small bowel Melena (partially digested blood in stool) Iron-deficiency anemia Authors: Taylor Krawec, Merry Faye Graff Reviewers: Emily J. Doucette, Sylvain Coderre* * Indicates MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Intestinal contents leak into peritoneum Peritonitis Systemic inflammatory response to peritonitis Published May 31, 2025 on www.thecalgaryguide.com Sepsis

Unconjugated Hyperbilirubinemia

Pre-hepatic causes of ↑ bilirubin production Pathologic Unconjugated Neonatal Hyperbilirubinemia: Pathogenesis and clinical findings Hemolytic disease of the newborn** Isoimmune- mediated hemolysis Rhesus (Rh) factor incompatibility Maternal sensitization against Rh-positive fetal cells Maternal antibodies against Rh factor attack fetal RBCs ABO incompatibility Native maternal antibodies against non- native blood types attack fetal RBCs Sepsis** Widespread systemic inflammation Cytokines & complement factors damage RBC membranes Disseminated intravascular coagulation** (clotting proteins become overactive) Clots form in systemic circulation Small clots shear & damage RBCs in circulation Red blood cell (RBC) enzyme defects Glucose-6 phosphatase dehydrogenase (G6PD) deficiency** G6PD protects RBCs against oxidative damage ↑ RBC sensitivity to oxidative stress (during acute stressors) Pyruvate kinase deficiency (PKD) Abnormal glycolysis & cellular energy production ↓ RBCs life spans RBC membrane defects Hereditary spherocytosis RBCs are abnormally round (spherocytes) RBC membranes easily damaged in circulation Bilverdin reductase Hereditary elliptocytosis RBCs are abnormally elongated or oval converts bilverdin to Sickle cell Abnormal hemoglobin (HbS) RBCs become abnormally unconjugated bilirubin disease** polymerizes under ↓ O2 sickle shaped Hemoglobinopathies Thalassemia's** Defective hemoglobin chains in RBCs Irregularly shaped RBCs trapped in spleen RBC sequestration ↑ Production of RBCs (Polycythemia**) Accumulation of blood (i.e. Cephalohematoma, hemorrhage) ↑ RBC load & turnover Causes of ↓ hepatocellular bilirubin clearance Genetic defects in uridine diphosphate glucuronosyltransfe rase (UGT) enzyme (conjugates bilirubin in liver) Gilbert syndrome Unconjugated bilirubin ↓ UGT production remains insoluble & cannot Crigler–Najjar be excreted in bile syndrome Type II Crigler–Najjar syndrome Type I No UGT production Breast milk jaundice Breast milk contains β-glucuronidase Causes of ↑ entero-hepatic bilirubin circulation Intestinal obstruction Obstruction blocks bile flow from liver to intestines Breastfeeding jaundice Inadequate milk intake (volume depletion/dehydration) ↑ Reabsorption of bilirubin in the intestines **See corresponding Calgary Guide slide Legend: Macrophages engulf old or damaged RBCs in spleen & liver ↑ Hemolysis (RBC breakdown) RBCs release cellular contents including heme (from hemoglobin) Heme oxygenase converts heme to bilverdin ↑ Unconjugated (indirect) bilirubin accumulation in blood ↑ Total serum bilirubin levels Excess bilirubin deposition into elastin- rich tissues (eg. skin, sclera) due to ↑ affinity for elastin Pathologic neonatal jaundice (yellow discoloration of skin within first 24 hours of life) Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 13, 2025 on www.thecalgaryguide.com Authors: Merry Faye Graff Khushi Arora Reviewers: Annie Pham Emily J. Doucette Danielle Nelson* * MD at time of publication Hemolytic anemia** ↓ Bilirubin conjugation β-glucuronidase deconjugates bilirubin Bilirubin builds up in hepatic system Unconjugated bilirubin crosses blood-brain barrier Bilirubin-induced neurologic dysfunction (BIND) Kernicterus (bilirubin- induced neurological damage) Scleral icterus (yellowing of sclera in eyes)

Retropharyngeal Abscess

Retropharyngeal Abscess: Pathogenesis and clinical findings Viral upper respiratory tract infection (URTI) Secondary bacterial infection Bacterial URTI Dental infection Spinal discitis or osteomyelitis Retropharyngeal lymph nodes drain bacteria & debris from nasopharynx, adenoids, posterior paranasal sinuses & middle ear (these lymph nodes involute before puberty) Direct expansion into retropharyngeal space Microorganisms (classically polymicrobial), leukocytes & tissue debris secondary to infection accumulate in retropharyngeal space Retropharyngeal Abscess Collection of pus that develops in the retropharyngeal space between the buccopharyngeal fascia (anterior) & alar fascia (posterior) Inflammatory response Local tissue edema Worsening of mass effect Mass effect of abscess results in displacement or compression of trachea, esophagus or larynx Anterior & posterior cervical lymph nodes become inflamed Cervical lymphadenopathy Narrowing of airway lumen Compression of larynx &/or laryngeal nerves Neck swelling Neck extensor muscles become inflamed Partial Complete Pain with neck obstruction obstruction extension Dysphonia (hoarseness) Systemic cytokine release disrupts hypothalamic thermoregulation Asphyxiation Fever Narrowing of esophageal lumen Turbulent airflow through narrowed upper respiratory tract Insufficient tissue perfusion promotes compensatory ↑ respiratory rate ↓ Intrathoracic pressure Dysphagia (difficulty swallowing) Odynophagia (pain with swallowing) Difficulty swallowing oral secretions Stridor Tachypnea Intercostal retractions Drooling Legend: Oropharyngeal trauma Retropharyngeal space is inoculated with bacteria during traumatic injury Author: Stephanie de Waal* Reviewers: Annie Pham Taylor Krawec Michelle J. Chen Emily J. Doucette Danielle Nelson* *MD at time of publication Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Disruption of abscess results in rupture Mass effect partially relieved positionally Bacteria enters bloodstream Abscess contents drain into lower respiratory tract Sniffing position Sepsis (leaning forwards Aspiration pneumonia with slight neck extension) Spread of infection through alar fascia into “danger space” (region posterior to retropharyngeal space connecting to mediastinum) Spread of infection into mediastinum Descending necrotizing mediastinitis Published Aug 4, 2025 on www.thecalgaryguide.com

Hypocalcemia Physiology

Hypocalcemia: Physiology Hypomagnesemia** Pseudohypoparathyroidism (genetic resistance to PTH) Sepsis** or severe illness Authors: Serra Thai, Ryan Dion Reviewers: Jessica Hammal, Michelle J. Chen, Emily J. Doucette, Hanan Bassyouni* * MD at time of publication Parathyroid gland hypofunction from surgical removal, autoimmune disease, or congenital disease (e.g. DiGeorge Syndrome) Impaired Mg-dependent generation of cyclic adenosine monophosphate ↑ Systemic inflammation ↑ Calcium sequestration into cells (mechanism of action unknown) ↓ Liver function & albumin synthesis ↓ Or inappropriately normal parathyroid hormone (PTH) in circulation ↓ PTH receptor (PTHR) sensitivity ↓ Albumin-bound calcium in blood ↓ PTHR signaling in kidneys ↓ PTHR signaling in osteoblastic lineage Vitamin D deficiency** (e.g. cells within bones ↓ intake, malabsorption) False hypocalcemia (↓ total serum calcium with normal Ca2+ levels) Acute pancreatitis** ↓ Sodium-hydrogen exchanger 3 (NHE3) activity & expression in proximal tubule Chronic kidney disease (CKD)** ↓ 1-⍺ hydroxylase enzyme (converts inactive vitamin D to active form) activity in kidneys ↑ Claudin14 (tight junction membrane proteins) expression in thick ascending limb (TAL) of the loop of Henle ↓ Transcription of calcium transporter genes (TRPV5, calbindin D28K, NCX) in distal convoluted tubule ↓ Nuclear factor kappa B ligand (RANKL) expression & binding to receptors on osteoclast precursor cells Pancreatic enzymes are prematurely activated ↓ Sodium reabsorption triggers electrochemical gradient changes ↓ Glomerular filtration due to ↓ kidney function ↓ Activated vitamin D (calcitriol) synthesis Claudin14 binds cation channels composed of Claudin16 & 19 in TAL tight junctions Lipase released from pancreatic autodigestion breaks down peripancreatic fat ↓ Renal phosphate filtration from blood ↓ Binding of vitamin D regulated calcium transporters in duodenum & jejunum Binding blocks paracellular Ca & Mg transport from tubule into vasculature through tight junctions ↓ Probability of calcium transport channels opening ↓ Osteoclast differentiation (responsible for breaking down bone) Free fatty acids bind ionized Ca2+ to form insoluble calcium soaps (saponification) ↓ Circulating ionized calcium in blood ↑ Phosphate-calcium crystal formation ↓ Gastrointestinal ↓ Renal reabsorption ↓ Bone resorption of calcium of calcium reabsorption of calcium Hypocalcemia** (serum [Ca2+] <2.1mmol/L+) **See corresponding Calgary Guide slide Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 23, 2025 on www.thecalgaryguide.com Hypocalcemia: Physiology Authors: Serra Thai Ryan Dion Reviewers: Jessica Hammal Michelle J. Chen Emily J. Doucette Hanan Bassyouni* * MD at time of publication Parathyroid gland dysfunction from surgical removal, autoimmune disease, or congenital disease (e.g. DiGeorge) ↓ Parathyroid hormone (PTH) in circulation ↓ PTHR signaling in kidneys Chronic kidney disease (CKD) ↓ Renal blood flow ↓ Glomerular filtration ↓ Sodium-hydrogen exchanger 3 (NHE3) activity & expression in proximal tubule ↓ Sodium reabsorption Electrochemical gradient changes ↓ Phosphate excretion ↑ Phosphate-calcium complex formation **See corresponding Calgary Guide slide Legend: Pathophysiology Mechanism Hypomagnesemia** Pseudohypoparathyroidism (genetic resistance to PTH) Sepsis** or severe illness Impaired Mg-dependent generation of cyclic adenosine monophosphate ↑ Inflammation ↓ PTH receptor (PTHR) sensitivity ↑ Calcium sequestration into cells (unknown mechanism of action) ↓ Liver function Vitamin D deficiency (e.g. ↓ intake, malabsorption) ↓ 1-⍺ hydroxylase enzyme (converts inactive vitamin D to active form) activity in kidneys ↑ Claudin14 (tight junction membrane protein) proteins are expressed in the thick ascending loop of Henle ↓ Transcription of calcium transporter genes (TRPV5, calbindin D28K, NCX) in the distal convoluted tubule ↓ Synthesis of activated vitamin D (calcitriol) Claudin14 binds to cation channels composed of Claudin16 & 19 found ↓ Binding of vitamin D in TAL tight junctions regulated calcium transporters (TRPV6, calbindin9k, PMCa2B, NCX2) in the duodenum & jejunum Binding blocks paracellular Ca & Mg transport from tubule into vasculature through tight junctions between cells ↓ Probability of calcium transport channels opening ↓ Gastrointestinal reabsorption of Ca ↓ Renal reabsorption of calcium ↓ Synthesis of albumin ↓ PTHR signaling in osteoblastic lineage cells in bones ↓ Nuclear factor kappa B ligand (RANKL) expression & binding to receptors on osteoclast precursor cells ↓ Osteoclast differentiation (responsible for breaking down bone) ↓ Bone resorption ↓ Albumin- bound calcium with normal free (biologically active) Ca levels False hypocalcemia Acute pancreatitis ↓ Lipase secretion from pancreas ↑ Undigested fats in small intestine Free fatty acids percipitate calcium Hypocalcemia** (serum [Ca2+] <2.1mmol/L+) Published MONTH, DAY, YEAR on www.thecalgaryguide.com Sign/Symptom/Lab Finding Complications Hypomagnesemia* Impaired magnesium- dependent generation of cyclic adenosine monophosphate ↓ PTH receptor (PTHR) sensitivity Hypocalcemia: Physiology Authors: Serra Thai Ryan Dion Reviewers: Jessica Hammal Michelle J. Chen * MD at time of publication Parathyroid gland dysfunction from surgical removal, autoimmune disease, or congenital disease (e.g. DiGeorge) Pseudohypoparathyroidism (genetic resistance to PTH) Sepsis or severe illness ↓ Parathyroid hormone (PTH) in circulation ↓ PTHR signaling in kidneys Vitamin D deficiency (e.g. ↓ intake, malabsorption) ↓ Sodium-hydrogen exchanger 3 (NHE3) activity & expression in proximal tubule ↓ 1-⍺ hydroxylase enzyme (converts inactive vitamin D to its active form) activity in the kidneys ↑ Claudin14 (tight junction membrane protein) proteins are expressed in the thick ascending loop of Henle ↓ Transcription of calcium transporter genes (TRPV5, calbindin D28K, NCX) in the distal convoluted tubule Chronic kidney disease ↓ Sodium reabsorption ↓ Synthesis of activated vitamin D (calcitriol) ↓ Renal blood flow Electrochemical gradient changes Claudin14 binds to cation channels composed of Claudin16 & 19 found in TAL tight junctions ↓ Glomerular filtration ↓ Phosphate excretion ↓ Binding of vitamin D regulated calcium transporters (TRPV6, calbindin9k, PMCa2B, NCX2) in the duodenum & jejunum Binding blocks paracellular Ca (and Mg) transport from the tubule into vasculature through tight junctions between cells ↓ Probability of calcium transport channels opening ↑ Phosphate-calcium complex formation ↓ Gastrointestinal reabsorption of Ca ↓ Renal reabsorption of calcium *See corresponding Calgary Guide slide: “Hypomagnesemia: Physiology” ** See corresponding Calgary Guide slide: “Hypoca;cemia: Clinical Findings” Legend: ↑ Inflammation ↑ Ca sequestration into cells (unknown mechanism of action) ↓ Liver function ↓ Synthesis of albumin ↓ PTHR signaling in osteoblastic lineage cells in bones ↓ Nuclear factor kappa B ligand (RANKL) expression and binding to its receptors on osteoclast precursor cells ↓ Differentiation of osteoclasts which are responsible for breaking down (resorbing) bone ↓ Bone resorption ↓ Albumin- bound calcium with normal free (biologically active) Ca levels False hypocalcemia Acute pancreatitis ↓ Lipase secretion from pancreas ↑ Undigested fats in small intestine Free fatty acids percipitate calcium Hypocalcemia** (serum [Ca2+] <2.1mmol/L+) Complications Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Hypocalcemia: Physiology Authors: Serra Thai Reviewers: Jessica Hammal Michelle J. Chen * MD at time of publication Parathyroid gland dysfunction from surgical removal, autoimmune disease, or congenital disease (e.g. DiGeorge) Hypomagnesemia** Pseudohypoparathyroidism (genetic resistance to PTH) Sepsis or severe illness Impaired magnesium- dependent generation of cyclic adenosine monophosphate ↑ Inflammation ↓ Parathyroid hormone (PTH) in circulation ↓ PTH receptor (PTHR) sensitivity ↑ Ca sequestration into cells (unknown mechanism of action) ↓ Liver function ↓ Synthesis of albumin ↓ PTHR signaling in kidneys Vitamin D deficiency (e.g. ↓ intake, malabsorption) ↓ Sodium-hydrogen exchanger 3 (NHE3) activity & expression in proximal tubule ↓ 1-⍺ hydroxylase enzyme (converts inactive vitamin D to its active form) activity in the kidneys ↑ Claudin14 (tight junction membrane protein) proteins are expressed in the thick ascending loop of Henle ↓ Transcription of calcium transporter genes (TRPV5, calbindin D28K, NCX) in the distal convoluted tubule Chronic kidney disease ↓ Sodium reabsorption ↓ Synthesis of activated vitamin D (calcitriol) ↓ Renal blood flow Electrochemical gradient changes Claudin14 binds to cation channels composed of Claudin16 & 19 found in TAL tight junctions ↓ Glomerular filtration ↓ Phosphate excretion ↓ Binding of vitamin D regulated calcium transporters (TRPV6, calbindin9k, PMCa2B, NCX2) in the duodenum & jejunum Binding blocks paracellular Ca (and Mg) transport from the tubule into vasculature through tight junctions between cells ↓ Probability of calcium transport channels opening ↑ Phosphate-calcium complex formation ↓ Gastrointestinal reabsorption of Ca ↓ Renal reabsorption of calcium ↓ PTHR signaling in osteoblastic lineage cells in bones ↓ Nuclear factor kappa B ligand (RANKL) expression and binding to its receptors on osteoclast precursor cells ↓ Differentiation of osteoclasts which are responsible for breaking down (resorbing) bone ↓ Bone resorption ↓ Albumin- bound calcium with normal free Ca levels due to homeostatic mechanisms False hypocalcemia Acute pancreatitis ↓ Lipase secretion from pancreas ↑ Undigested fats in small intestine Free fatty acids percipitate calcium Hypocalcemia** (serum [Ca2+] <2.1mmol/L+) Published MONTH, DAY, YEAR on www.thecalgaryguide.com **See corresponding Calgary Guide slide: “Hypomagnesemia: Physiology” Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Hypocalcemia: Physiology Hypomagnesemia** Authors: Serra Thai Reviewers: Jessica Hammal * MD at time of publication Parathyroid gland dysfunction: removal, autoimmune, congenital (DiGeorge) Vitamin D deficiency: ↓intake, malabsorption Pseudohypoparathyroidism Sepsis/severe illness ↓PTHR activation in kidneys CKD ↓ Renal blood flow ↓ Glomerular filtration ↓ Sodium- hydrogen exchanger 3 (NHE3) activity & expression in proximal tubule ↓ Sodium reabsorption Electrochemical gradient changes ↓ Phosphate excretion ↑ Phosphate calcium complex formation **See corresponding Calgary Guide slide(s) Legend: ↓ 1-alpha hydroxylase enzyme activity ↓ Synthesis of activated vitamin D (calcitriol) ↓ Binding of vitamin D regulated calcium transporters (TRPV6, calbindin9k, PMCa2B, NCX2) in the duodenum & jejunum ↓ Gastrointestinal reabsorption of calcium Pathophysiology Mechanism Sign/Symptom/Lab Finding Impaired magnesium dependent generation of cyclic adenosine monophosphate ↑ Inflammation ↓ Parathyroid hormone (PTH) ↑ Claudin14 (tight junction membrane protein) activity in the thick ascending loop of Henle ↑ Binding of claudin14 to claudin16 Inhibition of claudin 16 & 19 from forming cation permeable pores in the tight junctions ↑ Calcium sequestration ↓ Liver function into cells (mechanism of action ↓ Synthesis of albumin ↓ PTH receptor remains (PTHR) sensitivity ↓ Albumin- unknown) bound calcium with normal ↓ PTHR activation in bones free Ca levels due to homeostatic mechanisms ↓ Transcription of calcium transporter genes (TRPV5, calbindin D28K, NCX) in the distal convoluted tubule ↓ Probability of calcium transport channels opening ↓ Renal reabsorption of calcium ↓ Osteoblast stimulation ↓ Nuclear factor kappa b ligand (RANKL) secretion ↓ Nuclear factor kappa b receptor (RANK) binding on osteoclast precursors cells ↓Osteoclast production ↓ Bone resorption False Hypocalcemia Acute pancreatitis ↓ Lipase secretion from pancreas ↑ Undigested fats in small intestine Free fatty acids percipitate calcium Hypocalcemia** (serum [Ca2 <2.1mmol/L+]) Published MONTH, DAY, YEAR on www.thecalgaryguide.com Complications Hypocalcemia: Physiology Hypomagnesemia** Authors: Serra Thai Pseudohypoparathyroidism Reviewers: Jessica Hammal * MD at time of publication Vitamin D deficiency: ↓ intake, malabsorption ↓ 1-alpha hydroxylase enzyme activity ↓ Synthesis of activated vitamin D (calcitriol) ↓ Binding of vitamin D regulated calcium transporters (TRPV6, calbindin9k, PMCa2B, NCX2) in the duodenum & jejunum ↓ Gastrointestinal reabsorption of calcium Parathyroid gland dysfunction: removal, autoimmune, congenital (DiGeorge) CKD ↓ Renal blood flow ↓ Glomerular filtration **See corresponding Calgary Guide slide(s) Legend: Sepsis/severe illness Impaired magnesium dependent generation of cyclic adenosine monophosphate ↑ Inflammation ↓ Signaling proteins ↓ Parathyroid hormone (PTH) ↓ PTH receptor (PTHR) sensitivity ↑ Calcium sequestration into cells (mechanism of action remains unknown) Pathophysiology Mechanism ↓PTHR1 activation in kidneys ↓ Activation of G- coupled protein signaling pathways ↑ Expression of sodium-phosphate co-transporters (NaPiIIa & NaPIIc) in proximal tubule ↓ Expression & phosphorylation of transient receptor potential vanilloid (TRPV5, calcium transporter channel) in distal convoluted tubule ↓ PTHR1 activation in bones ↓ Osteoblast ↑ Claudin14 (tight stimulation junction membrane protein) activity in the thick ascending loop of Henle ↓ Nuclear factor kappa b ligand (RANKL) secretion ↑ Binding of claudin14 to claudin16 ↓ Nuclear factor kappa b receptor Inhibition of (RANK) binding on osteoclast ↓ Phosphate excretion Electrochemical ↓ Amount of claudin 16 & 19 gradient TRPV5 & ↓ from forming precursors cells changes probability of cation-permeable channels pores in the tight ↑ Phosphate opening junctions calcium ↓Osteoclast production complex formation ↓ Paracellular transport of calcium ↓ Renal reabsorption of calcium ↓ Bone resorption Published MONTH, DAY, YEAR on www.thecalgaryguide.com ↓ Liver function ↓ Synthesis of albumin ↓ Albumin- bound calcium with normal free calcium levels due to homeostatic mechanisms False Hypocalcemia Acute pancreatitis ↓ Lipase secretion from pancreas ↑ Undigested fats in small intestine Free fatty acids percipitate calcium Hypocalcemia** (serum [Ca2 <2.1mmol/L+]) Sign/Symptom/Lab Finding Complications Hypocalcemia: Physiology Parathyroid gland dysfunction: removal, autoimmune, congenital (DiGeorge) Hypomagnesemia** Impaired magnesium dependent generation of cyclic adenosine monophosphate ↓ Parathyroid hormone (PTH) ↓ PTH sensitivity Vitamin D deficiency: ↓intake, malabsorption ↓ Enzyme 1-alpha hydroxylase activity ↓ Synthesis of activated vitamin D (calcitriol) ↓ Binding of vitamin D regulated calcium transporters in the duodenum & jejunum ↓ Gastrointestinal reabsorption of calcium Legend: ↓PTH receptor activation in kidneys ↑ Claudin14 activity in the thick ascending loop of Henle Inhibition of claudin 16 & 19 from forming cation permeable pores in the tight junctions ↓ Transcription of calcium transporter genes in the distal convoluted tubule ↓ Probability of calcium transport channels opening ↓ Renal reabsorption of calcium ↓ Sodium-hydrogen exchanger 3 (NHE3) activity & expression in proximal tubule ↓ Sodium reabsorption Electrochemical gradient changes ↓ Phosphate excretion ↑ Phosphate calcium complex formation Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications ↑ Inflammation Authors: Serra Thai Reviewers: Jessica Hammal * MD at time of publication Sepsis/severe illness ↑ Calcium sequestration into cells ↓ Liver synthesis of albumin ↓ Albumin- calcium binding False Hypocalcemia Acute pancreatitis ↓ Lipase secretion from pancreas ↑ Levels of undigested fats in small intestine Free fatty acids percipitate calcium ↓ PTH receptor activation in bones ↓ Osteoblast stimulation ↓ RANKL ligand secretion ↓ RAANK receptor binding ↓Osteoclast production ↓ Bone resorption Hypocalcemia (serum [Ca2+] <2.1mmol/L) Published MONTH, DAY, YEAR on www.thecalgaryguide.com Hypocalcemia: Physiology Vitamin D deficiency: ↓intake, malabsorption Parathyroid gland dysfunction: removal, autoimmune, congenital (DiGeorge) Hypomagnesemia** Impaired magnesium dependent generation of cyclic adenosine monophosphate ↓ Parathyroid hormone (PTH) ↓ PTH sensitivity ↓ Enzyme 1-alpha hydroxylase activity ↓ Synthesis of activated vitamin D (calcitriol) ↓ Binding of vitamin D regulated calcium transporters in the duodenum & jejunum ↓ Gastrointestinal reabsorption of calcium Legend: ↓PTH receptor activation in kidneys ↑ Claudin14 activity in the thick ascending loop of Henle Inhibition of claudin 16 & 19 from forming cation permeable pores in the tight junctions ↓ Transcription of calcium transporter genes in the distal convoluted tubule ↓ Probability of calcium transport channels opening ↓ Renal reabsorption of calcium ↓ Sodium-hydrogen exchanger 3 (NHE3) activity & expression in proximal tubule ↓ Sodium reabsorption Electrochemical gradient changes ↓ Phosphate excretion ↑ Phosphate calcium complex formation Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications ↑ Inflammation Sepsis/severe illness ↑ Calcium sequestration into cells ↓ Liver synthesis of albumin ↓ Albumin- calcium binding False Hypocalcemia Acute pancreatitis ↓ Lipase secretion from pancreas ↑ Levels of undigested fats in small intestine Free fatty acids percipitate calcium ↓ PTH receptor activation in bones ↓ Osteoblast stimulation ↓ RANKL ligand secretion ↓ RAANK receptor binding ↓Osteoclast production ↓ Bone resorption Hypocalcemia (serum [Ca2+] <2.1mmol/L) Authors: Name Name Name Name* Reviewers: Name Name Name Name* * MD at time of publication Published MONTH, DAY, YEAR on www.thecalgaryguide.com Hypocalcemia: Physiology Chronic kidney disease ↓ Renal blood flow ↓ Glomerular filtration Parathyroid gland dysfunction: removal, autoimmune, congenital (DiGeorge) Vitamin D deficiency: ↓intake, malabsorption Sepsis/severe illness ↓ NHE3 activity and expression in proximal tubule ↓PTH receptor activation in kidneys ↑ Claudin14 activity in the thick ascending loop of Henle ↓ Parathyroid hormone (PTH) ↓ Transcription of calcium transporter genes (TRPV5, calbindin D28K, NCX) in the distal convoluted tubule ↓ Enzyme 1-alpha hydroxylase activity ↓ PTH receptor activation in bones ↓ osteoblast stimulation ↓ RANKL ligand secretion ↑ Inflammation ↓ PTH sensitivity ↓ Glomerular filtration ↓ Liver synthesis of serum albumin False Hypocalcemia ↑ Calcium sequestration into cells** ↓ Lipase secretion from pancreas Acute pancreatitis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding ↓ Albumin- bound calcium Current mechanism is unknown ↑ levels of undigested fats in small intestine Complications Hypomagnesemia Multiple blood transfusions ↓ Sodium reabsorption Electrochemical gradient changes ↓ Phosphate excretion ↑ Phosphate calcium complex formation Inhibits claudin16 and 19 from forming cation permeable pores in the tight junctions ↓Probability of calcium transport channels opening ↓ Synthesis of activated vitamin D (calcitriol) ↓ RAANK receptor binding ↓ Calcium reabsorption ↓ Binding of vitamin D regulated calcium transporters (TRPV6, calbindin9K, PMCa2B, NCX2) in the duodenum and jejunum ↓osteoclast production ↓ Bone resorption ↓ Serum calcium Hypocalcemia <2.1 mmol/L ↑ Precipitation of calcium by free fatty acids Authors: Name Name Name Name* Reviewers: Name Name Name Name* * MD at time of publication Published MONTH, DAY, YEAR on www.thecalgaryguide.com https://journals.physiology.org/doi/full/10.1152/physrev.00003.2004?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88- 2003&rfr_id=ori%3Arid%3Acrossref.org – Calcium Absoprtion across Epithelia https://academic.oup.com/endo/article-abstract/137/1/13/2498579 - PTH and Calcium Signaling Pathways https://www.pnas.org/doi/10.1073/pnas.1616733114 - Information on Claudin 14 https://onlinelibrary-wiley-com.ezproxy.lib.ucalgary.ca/doi/full/10.1111/apha.13959 - effects of PTH on renal calcium and phosphate handling https://www.ncbi.nlm.nih.gov/books/NBK430912/ - Hypocalcemia overview + causes + pathophys https://www.orthobullets.com/basic-science/9010/bone-signaling-and-rankl - information about bone signaling https://www.sciencedirect.com/science/article/abs/pii/S0889852921000682?via%3Dihub – Calcium homeostasis article https://pubmed.ncbi.nlm.nih.gov/3012979/#:~:text=Abstract,intestine%2C%20require%20the%20parathyroid%20hormone. vitamin D metabolism and function – https://pmc.ncbi.nlm.nih.gov/articles/PMC2669834/#:~:text=Calcium%20is%20actively%20absorbed%20from,for%20proper %20mineralization%20of%20bone. – more vitamin D metabolism and specific receptors https://jidc.org/index.php/journal/article/view/32903236/2331 - sepsis + hypocalcemia

Pyelonephritis

Acute Pyelonephritis: Pathogenesis and clinical findings Female sex Indwelling Diabetes (especially post- urinary catheter mellitus menopausal due to loss of protective Lactobacillus species) Obstruction of bladder outlet (congenital/acquired) High blood glucose damages nerves controlling the bladder, as well as blood vessels supplying bladder nerves Glycosuria (elevated levels of glucose in urine) create nutritive environment for bacterial growth Excessive urine buildup increases pressure exerted against the bladder, pushing urine from bladder up to ureters Authors: Sergio F. Sharif Reviewers: Michelle J. Chen Jessica Revington Yan Yu* Juliya Hemmett* Brandon Christensen* * MD at time of publication Shorter urethra allows for fecal microbes to more readily enter the urinary tract Catheter inoculates deep urinary tract with bacteria & facilitates organisms to enter bladder Neurogenic bladder (decreased bladder control due to nerve damage) is unable to appropriately release urine, leading to urinary retention & failure to clear residing bacteria Bacteremia (bacterial infection in bloodstream) Bacteria initially colonize the lower urinary tract, then migrate up the tract towards one or both kidneys (most commonly Gram-negative rods, e.g., Escherichia coli) Bacteria, such as Staphylococcus species, spread from another site of infection to kidneys via bloodstream Acute Pyelonephritis Inflammation of the kidney interstitium due to upper urinary tract infection, usually bacterial Collective contribution of mechanisms stated below, if severe Sepsis** Concurrent cystitis irritates urinary tract (see lower UTI slide)** Bacteria expressing virulence factors (e.g., P fimbriae in Escherichia coli) exploit host susceptibility & infect upper urinary tract (ureters & kidneys) Positive urine culture Dysuria (pain & burning while urinating) Bacteria trigger IL-8 release by local immune cells in the upper urinary tract, triggering recruitment of neutrophils to renal tubules & interstitium Neutrophils degranulate in the infected tissue, phagocytose bacteria & form sacrificial neutrophil extracellular traps (resulting in neutrophil death) in attempt to clear infection Neutrophil-mediated immune response damages surrounding kidney tissue (tubular injury) Acute kidney injury** Immune cells at the site of infection release cytokines (e.g., IL-1, TNF), which disseminate systemically Cytokines act in the brain in concert with unclear mechanisms relating to tissue injury & inflammation triggered by infection (see Neurotransmitters & Pharmacology behind Nausea and Vomiting slide**) Cytokines bind receptors in the anterior hypothalamus, triggering pathways ultimately leading to heat-generating responses (e.g., shivering) Cytokines promote the growth & release of white blood cells from bone marrow into bloodstream Dead neutrophils collect in renal tubules near infection & attach to assemblies of mucoprotein (a renal tubular epithelium protein secreted into tubules) Pyuria (WBCs in urine) Nausea/vomiting Fever Leukocytosis (↑ WBCs) Urine white blood cell (WBC) casts (cylindrical particles with WBCs seen on microscopy) Costovertebral Flank pain CT KUB - angle tenderness findings may include focal or diffuse involvement, fat stranding, gas formation, &/or other complications including renal scarring **See corresponding and abscesses Calgary Guide slide(s) Complications Published November 23, 2025 on www.thecalgaryguide.com Unclear mechanism involving systemic inflammation worsens mental status in susceptible individuals Altered level of consciousness (especially in elderly) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding

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