SEARCH RESULTS FOR: stroke

Myocardial Infarction: Findings on History

Yu Yan - MI Findings on History - FINAL.pptx - Myocardial Infarction: Findings on HistoryLegend:Published January 30, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceTristan JonesNanette Alvarez** MD at time of publication Systolic function(necrotic myocardium cannot contract as well)Reflexive ? in sympathetic activity (to try to maintain CO)Clammy skin? stroke volume (SV), ? cardiac output (CO)Myocardial infarction (tissue necrosis)Note: Myocardial ischemic pain may differ between patients, but recurrences usually feel the same in any given patient.Generalized vasoconstrictionVasoconstriction of skin arteriolesCool skinLocal myocardial inflammationIrritation of T1-T4 sympathetic afferentsIrritation of cardiac branches of vagus nerveSignals enter spinal cord, mixes with T1-T4 dermatomesCrushing, Diffuse L).(Onset: often at rest; crescendo)Activation of reflexive vagal responses (listed below)Weakness, dizziness, nausea, vomitingInflammatory mediators irritates nerves innervating the heart (the cardiac plexus)Cytokines act on hypothalamic T0 regulatorMild fever? Sweating (diaphoresis)Inflammatory cytokines can spread systemicallyBrain perceives nerve irritation as pain coming from T1-T4 dermatomesBlood backs up from the LV, into the left atrium and eventually accumulates in the pulmonary vasculatureHigh pulmonary venous blood pressure forces fluid out of capillaries, into pulmonary interstitium & alveoliRespiratory muscles work harder to ventilate lungsSoggier lung interstitium ? lung complianceDyspnea(Shortness of breath)Fluid compresses airways, ? resistance to airflow 102 kB / 204 words" title="Yu Yan - MI Findings on History - FINAL.pptx - Myocardial Infarction: Findings on HistoryLegend:Published January 30, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceTristan JonesNanette Alvarez** MD at time of publication Systolic function(necrotic myocardium cannot contract as well)Reflexive ? in sympathetic activity (to try to maintain CO)Clammy skin? stroke volume (SV), ? cardiac output (CO)Myocardial infarction (tissue necrosis)Note: Myocardial ischemic pain may differ between patients, but recurrences usually feel the same in any given patient.Generalized vasoconstrictionVasoconstriction of skin arteriolesCool skinLocal myocardial inflammationIrritation of T1-T4 sympathetic afferentsIrritation of cardiac branches of vagus nerveSignals enter spinal cord, mixes with T1-T4 dermatomesCrushing, Diffuse "Pain" or "tightness": Often retrosternal, with radiation to shoulder, neck, and inner aspect of both arms (R > L).(Onset: often at rest; crescendo)Activation of reflexive vagal responses (listed below)Weakness, dizziness, nausea, vomitingInflammatory mediators irritates nerves innervating the heart (the cardiac plexus)Cytokines act on hypothalamic T0 regulatorMild fever? Sweating (diaphoresis)Inflammatory cytokines can spread systemicallyBrain perceives nerve irritation as pain coming from T1-T4 dermatomesBlood backs up from the LV, into the left atrium and eventually accumulates in the pulmonary vasculatureHigh pulmonary venous blood pressure forces fluid out of capillaries, into pulmonary interstitium & alveoliRespiratory muscles work harder to ventilate lungsSoggier lung interstitium ? lung complianceDyspnea(Shortness of breath)Fluid compresses airways, ? resistance to airflow 102 kB / 204 words" />

myocardial-infarction-findings-on-physical-exam

Yu Yan - MI Findings on Physical Exam - FINAL.pptx Myocardial Infarction: Findings on Physical Exam Author: Yan YuReviewers:Sean SpenceTristan JonesNanette Alvarez** MD at time of publication Systolic function(necrotic myocardium cannot contract as well) Diastolic compliance (necrotic myocardium does not relax as well to accommodate blood)Necrosis of papillary muscles:S4(4th heart sound)? Force of ventricular contractionsMitral valve regurgitationBlood

jvp-kussmals-sign-explained

Yu Yan - JVP explained - FINAL.pptx Myocardium of right ventricle becomes fibrotic and stifferKussmaul's sign: JVP increases with inspirationJugular Venous Pressure (JVP): Kussmal's Sign explainedExcessive pericardial fluid compresses heart walls on all sidesLegend:Published January 7, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceJason BasermanJason Waechter** MD at time of publication? Right ventricle wall complianceConstrictive pericarditisRight ventricle prevented from fully expanding ? ability of the right ventricle to accommodate higher venous returnBackup of venous blood into right atrium and preceding internal jugular veinsRestrictive cardiomyopathyInflamed, fibrotic pericardium restricts expansion of heartRight ventricle myocardial infarct Cardiac tamponade (rare)InspirationMore venous blood tries to enter the low-pressure thoracic cavity via the right ventricle? pressure in thoracic cavity JVP should return to normal within 3 respiration cyclesJugular Venous Pressure (JVP): Physical Exam FeaturesExerts less force against vesselsTilting the head of the bed:Low pressure, & the thinner walls of the internal jugular veins, are less able to keep lumen open when compressedLegend:Published January 7, 2013 on www.thecalgaryguide.comMechanismPathophysiologySign/Symptom/Lab FindingComplicationsAuthor: Yan YuReviewers:Sean SpenceJason BasermanJason Waechter** MD at time of publicationBlood in internal jugulars settles to bottom of the vein (analogy: half-full tube of water is turned vertically)Visible waves in the JVP correspond to stages of the cardiac cycleNon-palpableBiphasic waveform? JVP The Jugular Venous Pressure (JVP) Blood pressure in the internal jugular veinsV-waveA-waveRight atrial contractionBlood passively fills right atrium during ventricular systole? JVP? JVPIn: ? intrathoracic pressurePressing hard on abdomen (overlying the liver), or doing a valsalvaFacing lower afterload, Right heart more readily pumps blood into pulmonary circulation? abdominal pressure? venous blood forced up into right atriumVenous blood pressure is normally very lowOccludableNote: Since the internal jugular veins are continuous with the right atrium, the JVP is a reliable estimate of right atrial blood pressure (Central Venous Pressure). The JVP on the right side is a better

Pulsus Paradoxus

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

Non Neural Complications of Stroke

Stroke - Pathogenesis

Left Heart Failure: Pathophysiology (Neurohormonal Activation)

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

Benzodiazepine (BZD) withdrawal: clinical findings and complications

Benzodiazepine (BZD) withdrawal: clinical findings and complications Abrupt cessation of chronic ingestion of BZDs Administration of BZD antagonist (flumazenil) on patients who have developed -* tolerance/dependence to BZD Withdrawal Seizure Negative physiological reactions BZD intake inhibition a mygd to f, • of a la Withdrawal symptoms Benzodiazepine Withdrawal GABA receptor activity (less inhibition alleviated by ingesting BZD Tolerance GABA BZD intake Conformational changes in the GABA receptor 1, receptor's Withdrawal Insomnia Pro-excitatory 4— state of excitatory neurotransmitters) 4— to the agent activity affinity for the agent A Activation of ACC and OFC Feelings of fear Activation of PAG Behavioural response of fight or flight Legend: Pathophysiology Mechanism Activation of hypothalamus '1` Cortisol CAD, T2DM, Stroke Sign/Symptom/Lab Finding Activation of PBN V t RR, SOB, Asthma, or a sense of being smothered Activation of LC t Sympathetic Activity t BP, t HR variability, tremor, and diaphoresis Authors: Usama Malik Reviewers: Sina Marzoughi Aaron Mackie* * MD at time of publication Notes: • The onset of withdrawal can vary according to the half-life of the BZD involved. Symptoms may be delayed up to three weeks in BZDs with long half-lives, but may appear as early as 24 to 48 hours after cessation of BZDs with short half-lives. Abbreviations: • ACC: Anterior Cingulate Cortex • BP: Blood Pressure • CAD: Coronary Artery Disease • HR: Heart Rate • LC: Locus Coeruleus • MI: Myocardial Infarction • OFC: Orbitofrontal Cortex • PAG: Periaqueductal Gray • PBN: Parabrachial Nucleus • RR: Respiratory Rate • SOB: Shortness of Breath • T2DM: Type 2 Diabetes I` atherosclerosis, cardiac ischemia, MI, or sudden death

Arterial Insufficiency- Signs and symptoms

Arterial Insufficiency- Signs and symptoms Adderley gagnon Waechter atheroma thrombus artery vessel diameter hardening blockage artery embolism left atrium thrombus plaque rupture resistance to flow circulation to tissues distal to occlusion narrowing tissue perfusion positive Allen's test ABI absent pulses cool extremity pallor dependent robor O2 availability muscle cell metabolic needs exercise demand supply transient ischemia anaerobic metabolism lactic acid buildup muscles intermittent claudication reproducible cramp-like pain alleviated by rest blood velocity poiseuille's law turbulent flow bruits over time arterioles maximally vasodilator and desensitized to pro-vasodilatory stimuli loss ability compensate reduced vessel diameter chronic limb ischemia atrophic changes hair loss muscle atrophy thin shiny skin nail thickening fungus critical limb ischemia end stage chronic thrombo-embolic event stroke ischemic limb ischemic clotting cascade initiated tissue necrosis pain at rest ulcers big toe heel underside foot gangrene amputation nerve infarction hyporeflexia paraesthesia thromboembolic

Reactive Neutrophilia- Pathogenesis and Clinical Findings

reactive neutrophilic pathogenesis clinical findings infection inflammation malignancy drugs emotional stimuli stress smoking hyposplenism asplenia rheumatoid arthritis Crohn's epinephrine retinoic acid glucocorticoids anxiety exercise heat stroke surgery neutrophils neutrophil bone marrow demarginalization splenic sequestration neutrophilic ANC peripheral blood smear absolute neutrophil count left shift bands metamyelocytes myelocytes toxic granulations dohle bodies brenneis Siddique savoie ryznar

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

virchows-triad-and-deep-vein-thrombosis-dvt

Suspected Deep Vein Thrombosis (DVT): Authors: Dean Percy Yan Yu Reviewers: Tristan Jones Ryan Brenneis Man-Chiu Poon* Maitreyi Raman* * MD at time of publication Pregnancy, Oral Contraceptives (OCP) Pathogenesis and Complications Platelet Activation Increased clot formation Hypercoagulable State ↑ ability for the blood to coagulate upon stimulation Inherited Disorders Congenital defect in coagulation (ie. Factor V Leiden, Factor II mutation, Protein S/C deficiency) ↑ blood clotting ability Estrogen promotes hypercoagulability, especially in presence of other risk factors Notes: • Venous thrombus causes pulmonary embolism, arterial thrombus causes stroke • Previous DVT is risk factor for current DVT Trauma/Surgery Malignancy Abnormal release of coagulation-promoting cytokines Systemic injuryà activation of coagulation cascade Hypertension Bacteria Artificial Valve Physically damages blood vessel walls Adhere/invade vessel wall Abnormal surface Vessel Injury Exposes tissue factor on damaged cells and subendothelium for vWF binding Virchow’s Triad Venous Stasis Low blood flow rate over site of vessel injury, concentrating blood clotting factors at that site Fat contains more aromatase, converts more androgens to estrogen Sedentary lifestyle, poor venous return Obesity Clot formation typically occurs in leg veins Deep, large veins allow for blood pooling (stasis, hypercoagulability) Venous return from legs often against gravity (stasis) Valves in leg veins prone to backflow (stasis) ↓ muscle motion = ↓ venous blood flow Fracture, immobilization, bedrest, long vehicle/airplane ride Destruction of vein valve by clot Venous Insufficiency Clot prevents blood from returning to heart. Blood accumulating in the leg results in unilateral leg edema and venous inflammation (redness, warmth, tenderness) 1. 2. 3. Clot embolizes to the lungs Thromboembolus -*Pulmonary embolism (acute life threatening complication) -Chronic thromboembolic pulmonary hypertension Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published September 1, 2019 on thecalgaryguide.com

Aphasia

Aphasia (Wernicke’s and Broca’s): Pathogenesis and clinical findings Authors: Davis Maclean Reviewers: Heather Yong Tony Gu Yan Yu* Scott Jarvis* *MD at time of publication Ischemic stroke (common) Local Invasion (e.g. by a tumour, Head infection, or hemorrhage) Trauma Intracerebral Hemorrhage Dementia (e.g. Fronto- temporal Dementia) Episodic occurrences (e.g., migraine, epilepsy) Damage to language-dominant cerebral hemisphere (the left hemisphere, for the majority of humans): Damage affecting Broca’s Area in the Inferior frontal gyrus (area 44 & 45) Damage affecting Wernicke’s Area in the posterior part of the superior temporal gyrus (area 22) Localization: Inferior frontal gyrus, superior sylvian fissure Blood supply: superior division M2 branch middle cerebral artery Localization: Posterior perisylvian region, temporal lobe Blood supply: inferior division M2 middle cerebral artery Sensory speech areas still intact (posterior superior temporal lobe) Intact comprehension (intact hearing & reading) Impaired function of Broca’s Area ↓ output or generation of speech/ text If function of nearby motor areas is also impaired Contralateral hemiparesis (face, arm > leg) If function of other nearby areas is also impaired Impaired naming and repetition Motor speech areas still intact (inferior frontal lobe) Fluent (but non-sensical) speech output Impaired function of Wernicke’s Area Impaired compre- hension (i.e. cannot understand speech or text) Loss of sensory speech input to motor areas Errors in word usage, tense, structure If function of nearby sensory areas is impaired Contralateral sensory deficits Broca’s Aphasia Wernicke's Aphasia (Expressive language impairment: non-Fluent) Notes/Definitions: (Receptive language impairment/Fluent: the person can talk but their speech is nonsensical) • Dysarthria ≠ Aphasia (Dysarthria: disruption to neurons controlling the muscles that produce sounds, resulting in slurred/disjointed speech. Aphasia: acquired deficit in language comprehension or generation/output usually due to disruption of neurons in the cerebral cortex.) • “Global” aphasia affects both receptive and expressive language. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 1, 2020 on www.thecalgaryguide.com

vomiting-pathogenesis

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

Fecal-Incontinence

Fecal Incontinence: Pathogenesis and complications Note: The majority of fecal incontinence is multifactorial in cause Authors: Timothy Fu Reviewers: Chronic bowel straining Difficult vaginal delivery Direct internal anal sphincter impairment (controls ~70% of anal resting tone) ↓ anal resting tone Aging: Degene- ration of muscle fibers Movement disorders (e.g. arthritis, Parkinson’s); aging is a risk factorà ↓ mobility ↓ timely access to bathrooms Inflammation of colon (e.g., Ulcerative colitis, Radiation proctitis) ↓ capacity of rectal smooth muscle to stretch ↓ capacity to store stool ↑ urgency of defecation ↑ reflex relaxation of internal anal sphincter Chronic diarrhea, diarrhea- predominant irritable bowel syndrome, laxatives Yan Yu* Erika Dempsey* * MD at time of publication Stretch injury of Pelvic surgery Chronic constipation Build up of solid, immobile mass of stool in the rectum Loose stool is able to flow around impacted stool, exiting anal canal (overflow diarrhea) Sensory neuro- pathy (e.g. Diabetes) Altered mental conditions (e.g. stroke, dementia) pudendal nerve (innervating the pelvic muscles and external anal sphincter) Local neuronal damage Impaired pelvic muscle and external anal sphincter motor control Pelvic trauma Rectal prolapse Direct external anal sphincter impairment ↑ Stool volume ↑ Loose stools Rectal hyposensitivity (↓ perception of rectal distension) Patient fails to sense rectal fullness and voluntarily releases their external anal sphincter Voluntary external anal sphincter contraction is no longer sufficient in closing the anus Loose stool is more prone to escape through anal canal compared to solid stool Continence mechanisms are impaired Fecal Incontinence: The unintentional loss of solid or liquid stool Skin Skin Continence mechanisms are intact, but overwhelmed or ignored infection Skin erythema erosion Inability to control what is widely considered a basic, fundamental bodily process ↑ caretaker burden Social stigma ↑ skin contact with acidic irritant (stool) ↑ rate of institutionalization, (e.g., admission into long-term care) ↓ confidence, sense of agency ↑ stress, anxiety Skin inflammation ↓ social activity, work ↓ help-seeking ↓ treatment Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 2, 2020 on www.thecalgaryguide.com

Marfan-Syndrome

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

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu disease)

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

Anesthetic-Considerations-Aortic-Stenosis

Anesthetic Considerations: Hemodynamic Goals (“CRRAP Goals”) for Patients with Aortic Stenosis Undergoing Non-Cardiac Surgery CRRAP Goals: Contractility, Rate, Rhythm, Afterload, Preload Pathophysiology Driving Anesthetic Management Hemodynamic Anesthetic Intervention (CRRAP) Goals Author: Ryan Brenneis Reviewers: Stephen Chrusch Hannah Yaphe Yan Yu* Karl Darcus* * MD at time of publication Aortic stenosis = Narrow aortic valve opening Notes: -Cardiac Output = Heart Rate x Stroke Volume -Stroke volume has 3 determinates: 1. Contractility 2. Afterload 3. Preload If the patient’s heart cannot ↑ contractility to maintain cardiac output... ↑ resistance to forward blood flow àheart must ↑ its contractility (↑ the forcefulness of its contractions) to overcome this resistance Applying ↑ force over time causes left ventricle to undergo concentric hypertrophy Contractility deteriorates over time Heart rate must compensate for maintaining cardiac output Coronary Perfusion Pressure = Diastolic BP (DBP) – Left Ventricular End Diastolic Pressure (LVEDP) ↑ cardiac muscle massà↑ myocardial metabolism and oxygen demand ↑ left ventricular wall stiffnessà↓ LV filling while relaxed (diastolic dysfunction) Intraoperative ↓ in contractility compromises cardiac output Bradycardia ↓ cardiac output Tachycardia ↓ filling time of left ventricle (↓ preload) Coronary perfusion occurs during diastole Coronaries require a high DBP to maintain perfusion Tachycardia ↓ perfusion time Hypotension ↓ coronary perfusion pressure Possible myocardial ischemiaà ↓ blood pumped into vessels 40% of LV preload supplied from atrial kick Loss of atrial kick with arrhythmias à↓ cardiac output Note: Aortic stenosis severity (see slide on aortic stenosis) and the type/risk of surgery guide the hemodynamic consequences and need for intervention Adequate intravascular volume required to passively fill stiff ventricle Contractility ↓ use of negative inotropic Maintain drugs, e.g. calcium channel contractility blockers (“Inotrope”: drug that alters heart’s contractility) Rate Keep heart rate above 60 bpm Keep heart rate below 80 bpm Consider transcutaneous pacing, anticholinergics, & sympathetic agonists ↑ anesthetic depth, consider beta blocker (e.g. Esmolol) Afterload Maintain a Mean Arterial Pressure >70mmHg Consider sympathomimetic drugs to treat hypotension Monitor blood pressure closely via arterial line Consider increasing anesthetic depth for severe hypertension Rhythm Maintain Sinus Rhythm Consider presurgical placement of defibrillator pads & crash cart Amiodarone ready & available during operation, to terminate any arrhythmias Preload Maintain Euvolemia Possible use of transesophageal echo to monitor preload Ensure adequate venous access- consider central venous catheter and large bore IV’s Legend: Pathophysiology Mechanism Goal Anesthetic Intervention Published October 25, 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

acute-mca-territory-ischemic-stroke-findings-on-non-contrast-ct

Acute MCA-Territory Ischemic Stroke: Findings on Non-Contrast CT See Calgary Guide slide – Ischemic Stroke: Pathogenesis Middle cerebral artery (MCA) strokes are generally caused by emboli (blood clot that travelled from elsewhere in the body) and less commonly caused by thrombus (blood clot that has developed locally in the MCA) Embolism (or thrombus) occludes flow through the MCA Acute embolism (or thrombus) is more dense than surrounding tissue Acute embolism (or thrombus) material attenuates (absorbs more X-rays) more than surrounding tissue (results in area of brightness) Hyperdense MCA sign ↓ blood supply to MCA vascular territory (e.g. basal ganglia or insula) ↓ oxygen for aerobic metabolism (produces large amounts of ATP) ↓ ATP production in area of ischemia ↓ energy for ATP-dependent Na+/K+ pumps (that move Na+ out of cells) in affected neurons (grey matter) Neurons have a higher metabolic rate than other nervous system cells (e.g oligodendrocytes that make myelin) and thus are more vulnerable to hypoperfusion and ischemia As grey matter contains more neurons than white matter, grey matter is more vulnerable to hypoperfusion and ischemia Grey matter shows changes on CT earlier than does white matter Normal grey versus white matter on CT On CT, structures that are more dense (e.g. bone, tissues) absorb more X-raysà brighter. Less dense regions (e.g. water, fluids, fat) absorb less X-raysàdarker. Authors: Evan Allarie Davis Maclean Viesha Ciura* Yan Yu* Reviewers: Katie Lin* Aravind Ganesh* Gary Klein* *MD at time of publication ↓ extra-cellular Na+ concentration Na+ in extracellular space is replenished via capillaries Water follows the Na+ out of the capillaries ↑ intra-cellular Na+ concentration Change in osmotic gradientàwater moves from extracellular space into cells ↑ water content inside & around affected neurons (grey matter) Affected grey matter looks darker on CT (more similar to white matter) White matter contains more fatty myelin (lower density than grey matter)à appears darker on CT Normal insular ribbon (difficult to see here): grey matter usually seen lateral to red line shown here Grey matter, with more neurons, has a higher densityà appears brighter on CT Normal basal ganglia: Lentiform nucleus (putamen + globus pallidus) outlined here Loss of grey-white differentiation throughout MCA vascular territory Difficult to see on this window (adjustable brightness of image) but is present on this scan and easily seen at different window levels Areas with the least collateral circulation (e.g. basal ganglia or insula) show findings first Insular ribbon sign (loss of insular ribbon) Disappearing basal ganglia sign (loss of visible basal ganglia) Comparison to normal anatomy helps outline pathologic findings Comparison to normal anatomy helps outline pathologic findings Images presented here are multiple CT images from the same patient with a large MCA territory ischemic stroke (Image credit: Alberta Health Services Repository) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 7, 2021 on www.thecalgaryguide.com

VITT

Vaccine Induced Thrombosis and Thrombocytopenia (VITT): Pathogenesis and Clinical Findings Current leading theory: COVID-19 viral vector vaccines (Johnson and Johnson and AstraZeneca) contain an anionic molecule (currently unspecified), which binds to the cationic platelet factor 4 (PF4) molecule in the bloodstream, forming vaccine/PF4 complexes Authors: Brooke Fallis Reviewers: Yan Yu* Katie Lin* * MD at time of publication Spleen macrophages remove antibody/platelet complexes from circulation Fewer unbound platelets in circulation detected on complete blood count (CBC) Thrombocytopenia: Platelets <150x!

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

chronic-hypertension-complications

Chronic Hypertension: Complications Chronic Hypertension Long term Blood Pressure (BP) ≥ 135/85 (on ambulatory or home blood pressure measurement) in patients without diabetes, or BP ≥ 130/80 in patients with diabetes Authors: Samin Dolatabadi, Yan Yu* Reviewers: Meena Assad, Jessica Krahn Juliya Hemmett* * MD at time of publication ↑ Afterloadà ↑ Resistance to left ventricle ejection To overcome resistance and preserve cardiac output, the myocardium undergoes structural and functional changes Left ventricular hypertrophy and fibrosis Stiff ventricle ↓ Contractility of the left ventricle Impaired forward flow of blood from heart Chronic stress on the endothelium of systemic blood vessels ↑ Blood pressure in retinal circulation Hypertensive Retinopathy (See slide on Chronic Hypertensive Retinopathy: Pathogenesis and Clinic Findings) Smooth muscle of kidney’s afferent arterioles constricts to prevent transmission of ↑ blood pressure to glomerulus Overtime, smooth muscles of afferent arterioles hypertrophy from prolonged vasoconstriction Chronic stress and trauma on endothelial and smooth muscle cells of kidney Injury leads to excretion of cytokines and extracellular matrix such as fibrin and collagen into subendothelial layer Endothelial dysfunction (See slide on Atherosclerosis: Pathogenesis) Atherosclerosis Loss of normal arterial architecture in the brain due to stress of ↑ blood pressure Weakening of cerebral arteries Formation and rupture of microaneurysms Intracerebral Hemorrhage Accumulation of plaques in the walls of cerebral arteries ↓ Cerebral blood flow Ischemic Stroke Accumulation of plaques in the walls of coronary arteries ↓ Myocardial blood flow Oxygen supply- demand mismatch Coronary Artery Disease Thickening of arteriolar wall and narrowing of afferent arterioles ↓ Glomerular blood flow Glomerular and tubular ischemia Glomerular sclerosis and tubular atrophy Blood backs up into lungs ↓ perfusion of blood throughout the bodyà inability of the heart to meet metabolic demands Congestive Heart Failure Hypertensive Nephrosclerosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 4, 2021 on www.thecalgaryguide.com

SIADH

Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH): Pathogenesis and clinical Malignancy (e.g. Small cell lung cancer, head and neck cancer) Tumor originates from neuroendocrine cells Tumor acts as an ectopic site of ADH production ADH binds receptors on basolateral side (facing peritubular capillary) of principal cells in nephron ADH ↑ principal cells’ production of Aquaporin type II channels on their apical surface (side facing tubule lumen) ↑ Reabsorption of water from the collecting ducts back into circulation ↑ Blood Volume (↑ extracellular fluid volume) Blood Na+ levels diluted Hyponatremia (blood Na+ <135 mEq/L) Brain injury (e.g. Stroke, encephalitis hemorrhage, trauma) ↑ hypothalamic ADH production, storage in posterior pituitary, & pituitary secretion of ADH ↑ Uncontrolled ADH secretion SIADH (Syndrome of Inappropriate Anti-Diuretic Hormone) Drugs (e.g. Cyclophosphamide, SSRIs, vincristine) Break down into active metabolites Metabolites mimic ADH activity findings Authors: Krusang Patel Yan Yu* Reviewers: Davis Maclean Brooke Fallis Juliya Hemmett* * MD at time of publication Atria and Ventricles of the heart stretch Heart secretes ↑ atrial natriuretic and B-type natriuretic peptides (ANP/BNP) Peptides promotes natriuresis (excretion of Na+ into urine) Loss of Na+ in serumàalters charge balance across neuron membranesàImproper action potential firing: ↓ Renin secretion ↓ Release of Angiotensin II & Aldosterone ↓Reabsorption of Na+ into circulation in area postrema of medulla in hypothalamus in motor neurons Extracellular fluid volume becomes hypotonic relative to intracellular fluid volume Water moves from circulation into cells Extracellular fluid volume normalizes Euvolemia Nausea Headaches Muscle Cramps ↓ Urine volume Cells, particularly neurons, swell up Cerebral edema Neurons burst and die Severe Neurocognitive Effects (confusion, mood swings, hallucinations, seizure, coma) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 30, 2021 on www.thecalgaryguide.com

Renal Artery Stenosis

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

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

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

Status-Epilepticus

Status Epilepticus: Pathogenesis and clinical findings Authors: Katherine Liu Reviewers: Negar Tehrani Ephrem Zewdie Ran (Marissa) Zhang Carlos Camara-Lemarroy* * MD at time of publication Structural brain injury (stroke, trauma, hypoxia) Drugs that lower seizure threshold Antiseizure drug discontinuation Alcohol, barbiturate, benzodiazepine withdrawal Metabolic disturbance Infection See “Generalized Seizures” Altered excitability and communication between neuronal structures Isolated generalized seizures Ongoing seizure activity and repetitive neuronal firing Changes in receptor trafficking (seconds to minutes) Changes in neuromodulator expression in hippocampus (minutes to hours) Endocytosis of synaptic GABAA inhibitory receptors ↓ Number of inhibitory GABAA receptors Progressive resistance to benzodiazepines (drugs that upregulate GABA receptors) as seizure continues ↑ Expression of excitatory peptides (substance P, neurokinin B) Abbreviations: • GABA- γ-aminobutyric acid • NMDA- N-methyl-D-aspartic acid • AMPA- α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid NMDA and AMPA excitatory receptors mobilize to synaptic membrane ↑ Number of excitatory NMDA and AMPA receptors ↓ Expression of inhibitory peptide (dynorphin, galanin, somatostatin, neuropeptide Y) Seizure-induced failure of inhibitory mechanisms involved in seizure termination and increased neuronal excitability Status Epilepticus (SE) An abnormally prolonged seizure ≥ 5 minutes or 2+ sequential seizures without full recovery in between ↑↑ Glutamate release and activation of NMDA excitatory receptors ↑ Ca2+ entry into neurons Mitochondrial dysfunction ↑ Reactive oxygen species (nitric oxide) production Neuronal injury/death (↑ risk of developing chronic epilepsy) ↑ Autonomic activity Intense, sustained muscle contractions Persistent stimulus OR altered neuronal landscape (i.e., Immune mediated) Refractory SE: SE that does not respond to 1st or 2nd line therapy Prolonged seizures (≥30 mins) lead to failure of compensatory mechanisms Circulatory collapse ↓ Cerebral blood flow • Hypertension • Hyperglycemia • ↑ Cardiac output • ↑ Secretions • Hypotension • Hypoventilation Energy demands > ATP produced through oxidative phosphorylation Myocytes start utilizing anerobic glycolysis ↑ Lactic acid production ↑ Serum lactate Sustained muscle activity produces body heat Hyperpyrexia (axillary temperature ≥ 40° C) Myocyte injury Leakage of muscle contents into the circulation (Rhabdomyolysis) ↑ Serum creatine kinase Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 27, 2022 on www.thecalgaryguide.com

pheochromocytoma-pathogenesis-and-clinical-findings

Pheochromocytoma: Pathogenesis and clinical findings Author: Jaye Platnich Huneza Nadeem Reviewers: Mark Elliott Alexander Arnold Ran (Marissa) Zhang Hanan Bassyouni* * MD at time of publication ↑ Blood pressure results in the activation of neural pain receptors Sustained or paroxysmal 2o hypertension (↑ blood pressure) Pallor Tachycardia (↑ heart rate), palpitations Diaphoresis (excessive sweating) Hyperglycemia Weight loss, fatigue Familial Disorders (10%) E.g., Multiple Endocrine Neoplasm 2 Syndrome (MEN2) types A and B, Neurofibromatosis 1 (NF-1), Von Hippel Lindau Syndrome (VHL), familial pheochromocytoma Dysfunction of various tumor suppressor and/or oncogene proteins Uncontrolled proliferation of the chromaffin cells in the medulla of the adrenal gland(s) Adenoma formation (10% bilateral) Over-production of epinephrine and norepinephrine from the adrenal adenoma(s) or extra- adrenal tumour (10%) Detectable metanephrines (epinephrine/norepinephrine breakdown products) in both plasma and urine Sporadic DNA mutations arising from DNA damage from exposure to mutagens, malignancy (10%), or during DNA replication Detectable mutations on the Von Hippel Linda (VHL), (Rearranged During Transcription) RET, (Succinate Dehydrogenase) SDH, and/or other tumour suppressor or oncogenes Visible adrenal mass on CT scan Heart attack, stroke, or death (Note: These tumors can be fatal therefore screening is essential in patients with adrenal masses or 2o hypertension) Episodic hyper-activity of the sympathetic nervous system Hyper-stimulation of G protein-coupled receptors involved in catabolic metabolic processes Headaches ↑ Vasoconstriction of peripheral blood vessels Hyper-stimulation of adrenergic receptors on cardiac myocytes ↑ Secretion from the eccrine sweat glands Panic, tremor, anxiety ↑ Ability to mobilize glucose into the bloodstream through enhanced lipolysis, glycogenolysis and gluconeogenesis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 20, 2014, updated June 27, 2022 on www.thecalgaryguide.com

Epilepsy Pathogenesis

Epilepsy: Pathogenesis Genetic susceptibility Angelman syndrome, Fragile X syndrome, Tuberous sclerosis, neurofibromatosis Chromosomal abnormalities cause abnormal neural patterns Neural Cerebral palsy, focal cortical dysplasia Malformation of cortical development Cerebrovascular Intracranial hemorrhage, ischemic stroke Other Acquired Head trauma, cerebral infection (i.e., HSV1, VZV, cysticercosis) Neoplasm Metabolic Inborn errors of metabolism Inherited enzyme deficiencies Neurodegenerative Alzheimer’s Disease Protein-rich plaque build-up and brain atrophy Inflammation and formation of scar tissue irritates neural tissue Infiltration of mass, grey matter irritation Damage to the brain and subsequent alteration of neuronal circuitry Neurotransmitter imbalances (i.e. ↑ glutamate, ↓ GABA, ↓ serotonin, ↓ dopamine, ↓ noradrenaline) Abbreviations: • HSV1 – Herpes Simplex Virus 1 • VZV – Varicella Zoster Virus ↑ Inflammatory cytokines (e.g. interleukin-6, tumor necrosis factor-α) Altered neurogenesis and gliosis Ion channel and receptor dysfunction causes imbalance of ion channel charges Authors: Keerthana Pasumarthi Christopher Li Reviewers: Negar Tehrani, Ephrem Zewdie, Ran (Marissa) Zhang, Carlos R. Camara-Lemarroy* * MD at time of publication Neurons fire in burst activity (referred to as paroxysmal depolarization shift) and often in groups (hypersynchrony) Abnormal neural activities eventually create self-reinforcing circuits and transform neural network over time Injuries from falls, bumps, operating heavy machinery Involuntary contractions Loss of consciousness Post-ictal confusion Recurrent seizures Sudden Unexplained Death of Epilepsy Patient (SUDEP) Loss of airway reflexes Aspiration of saliva or food contents Aspiration Pneumonia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 5, 2022 on www.thecalgaryguide.com

burn-shock-pathogenesis-complications-and-clinical-findings

Burn Shock: Pathogenesis, Complications, and Clinical Findings Thermal burn injury > 20% Total Body Surface Area Authors: Shayan Hemmati Reviewers: Christy Chong Ben Campbell Donald McPhalen* * MD at time of publication ↑ Production of local inflammatory markers (ex. histamine, bradykinin, and prostaglandins) Endothelial cell lining in blood vessel walls is compromised ↑ Local vessel permeability Shift of plasma + proteins from vessel into interstitial space Direct vascular thermal injury (within burn wound) ↑ Production of circulating inflammatory mediators (ex. IL-1, IL-6, TNF-!) ↑ Systemic vessel permeability ↑ Circulating reactive oxygen species Damage to DNA, proteins, and lipids throughout body, including myocardium (muscle cells of the heart) ↑ Myocardial stress Myocardial dysfunction ↓ Cardiac contractility ↓ Stroke volume ↓ Cardiac output Cardiogenic Shock Refer to Cardiogenic Shock: Pathogenesis, Complications and Clinical Findings ↓ Protein concentration in vessels causes ↓ intravascular oncotic pressure Further shift of plasma from vessel into interstitial space (↑ interstitial proteins pull plasma into interstitium) ↓ Intravascular plasma ↑ RBCs per unit volume of plasma ↑ Systemic vasoconstriction to maintain blood pressure (↑ Afterload) ↓ Circulating blood volume leads to less venous return (↓ Preload) ↑ Hematocrit Pitting edema (burned & unburned tissue) ↓ Circulating blood volume Hypovolemic Shock Refer to Hypovolemic Shock: Pathogenesis, Complications and Clinical Findings Burn Shock: A complication of large burns causing end-organ hypoperfusion with resultant organ dysfunction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 15, 2022 on www.thecalgaryguide.com

Ischemic Stroke: Pathogenesis

Ischemic Stroke: Pathogenesis Small artery occlusion Acute injury (<20mm diameter) of basal or brainstem penetrating arteries Large artery atherosclerosis Cholesterol plaque ↓ diameter of intra- or extracranial vessel Cardiac embolism Blood clot in heart breaks free, travels to brain Other E.g. volume loss, severe infection Unknown E.g. 2 or more mechanisms Modest ↓ in O2 at penumbra (see figure) Authors: Mizuki Lopez Andrea Kuczynski Illustrator: Mizuki Lopez Reviewers: Sina Marzoughi Usama Malik Hannah Mathew Ran (Marissa) Zhang Andrew M Demchuk* Gary M. Klein* * MD at time of publication Significant ↓ in O2 at ischemic core (see figure) ↑ Anaerobic metabolism ↓ ATP Production Dysfunction of Na+/K+ ATPase pump (for 1 ATP molecule, 3 Na+ moved out of cell, 2 K+ moved into cell) H2O influx following Na+ Cerebral edema Compression of vessels and surrounding tissue damages blood-brain barrier ↑ Permeability of damaged blood-brain barrier Infiltration by peripheral immune cells Immune cells release inflammatory cytokines ↓ Cerebral Blood Flow Penumbra Ischemic core Metabolic demands are greater than supply of ATP Cell death Microglia (resident neural immune cells) activate to clean dead cell debris Microglia release inflammatory cytokines (TNFα, IFγ, IL-1β) Cytokines lead to astrocyte activation (support cells for neurons) Astrocytes release more inflammatory cytokines Inflammation of brain tissue ↑ Na+, Ca2+ influx, K+ outflux ↓ Glutamate (excitatory neurotransmitter) reuptake by astrocytes (support cells for neurons) ↑ Glutamate in extracellular fluid Spreading depolarization from core (unclear mechanism) Activate biochemical pathways including glutamate receptor activation ↑ Glutamate activity Activate glutamate receptors that conduct Ca2+ ↑ Ca2+ influx into neuron Activation of catabolic proteases, lipases, nucleases in neuron Dysfunction of neuronal protein synthesis and activity Neuronal cell death ↑ Volume of dead (infarcted) brain tissue Neurons depolarize and release glutamate Reversal of Na+ Dependent Glutamate Reuptake Transporters on astrocytes (normally 3 Na++ 1 H+ + 1 glutamate into cell, for 2 K+ out) ↑ Glutamate in extracellular fluid Stroke symptoms (e.g. weakness, slurred speech, visual field losses, autonomic dysfunction) (see Ischemic Stroke: Impairment by Localization stroke slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 14, 2017; updated November 6, 2022 on www.thecalgaryguide.com

Ischemic Stroke Impairment by Localization

Ischemic Stroke: Impairment by localization Contralateral weakness and sensory loss in the lower extremity Authors: Andrea Kuczynski Yvette Ysabel Yao Reviewers: Sina Marzoughi Usama Malik Mao Ding Andrew M Demchuk* * MD at time of publication Ischemia in the anterior cerebral artery Motor and sensory cortices of lower limb damage Hypertension, dyslipidemias, diabetes, smoking Atherosclerosis, thrombosis, or stenosis (narrowing) in respective blood vessels Ischemia: ↓ blood flow (See Ischemic Stroke: Pathogenesis slide) Left hemisphere damage Right hemisphere damage Motor and sensory cortices of upper limb and face damage Urinary incontinence Aphasia (inability to comprehend or produce Ischemia in the middle cerebral artery (MCA) MCA divides into segments language) (See Aphasia slide) Left sided agnosia (visual perceptual deficits) Contralateral hemiparesis (weakness on side of body opposite to injury) & sensory deficits, visual field deficits, aphasia, agnosia (inability to process sensory information), apraxia (motor planning deficits) & agraphia (inability to communicate by writing) M1-MCA (sphenoidal segment) M2-MCA (insular segment) Ischemia in the posterior cerebral artery Spares the lower extremity, affects the upper extremity and face Lesion to frontal lobe (Broca area) Infarction of occipital cortex Lesion to superior temporal gyrus of temporal lobe (Wernicke area) No homonymous hemianopsia (one-sided visual field loss) Expressive Broca’s/motor aphasia (inability to produce language) Contralateral homonymous hemianopsia (visual field loss on opposite side) Receptive Wernicke’s/sensory aphasia (inability to comprehend language) Sensory loss, memory loss, contralateral homonymous hemianopsia & alexia (reading difficulty) Ischemia of the occipital lobe, posteromedial temporal lobes, midbrain & thalamus Ischemia in the vertebral basilar artery Ischemia in the basilar artery Ischemia of brainstem & medulla Ischemia of midbrain, thalami, inferior temporal & occipital lobes Cranial nerve disorders: dysarthria (slurred/slowed speech) (IX, X), diplopia (double vision), facial numbness or paresthesia (VII), Foville’s syndrome (ipsilateral cerebellar ataxia), Horner's syndrome, (paresis of conjugate gaze and contralateral hemiparesis, facial palsy, pain & thermal hypoesthesia) Motor deficits: Millard-Gubler syndrome (pons lesion), Raymond’s syndrome (ipsilateral abducens impairment, contralateral central facial paresis & contralateral hemiparesis), Wallenburg syndrome (sensory deficits in the contralateral limb, ipsilateral face), ataxia (abnormal gait), unilateral or bilateral sensory loss of position & vibration Cranial nerve disorders: dysconjugate gaze (unpaired eye movements) (III, IV, VI), ipsilateral facial hypoalgesia (↓ pain sensitivity) (V), unilateral lower motor neuron face paralysis (VII), vertigo (spinning sensation), dysarthria (weak speech muscles) (IX, X) Motor deficits: contralateral hemiparesis, quadriplegia (paralysis of all 4 limbs), contralateral limb hypoalgesia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published February 3, 2018, updated February 28, 2023 on www.thecalgaryguide.com

Hemorrhagic Stroke

Hemorrhagic Stroke: Pathogenesis and clinical findings Authors: Andrea Kuczynski Oswald Chen Reviewers: Sina Marzoughi Usama Malik Anjali Arora Ran (Marissa) Zhang Mao Ding Michael D Hill* Gary Klein* * MD at time of publication Primary Intracerebral Hemorrhage (~75%) Secondary Intracerebral Hemorrhage (~25%) Amyloid Angiopathy Amyloid deposits in blood vessels and weakens vessel walls Hypertension Lipohyalinosis (lipid and protein aggregation in arterial walls) weakens blood vessels Unknown Aneurysm Dilation of a weakened blood vessel Drugs (e.g., cocaine, crystal meth, decongestants, anticoagulants) Vascular Malformations Note: the pathophysiology and exact mechanism is not well known Release of toxic blood plasma components (coagulation factors, immunoglobins) Red blood cell lysis Cytotoxic hemoglobin (heme, iron) release Fenton-type free radical generation (Fe(II) + H2O2 → Fe(III) + OH− + OH•) Oxidative damage to carbohydrates, lipids, nucleic acids, and proteins in brain Necrosis of hypoxic brain tissue Neurological signs: focal motor weakness, aphasia, vision loss, sensory loss, imbalance/incoordination, altered LOC Rupture of blood vessel(s) Accumulation of blood → hematoma formation ↓ Cerebral tissue perfusion (↓ O2 availability) ↓ Mitochondrial oxidative phosphorylation (final step in aerobic glucose metabolism) ↓ Adenosine triphosphate (ATP) production ↑ Anaerobic glucose metabolism → ↑ Cerebral lactate production Cerebral lactic acidosis Impaired cellular metabolism Death of neurons and glia Microglia clear debris and release inflammatory markers (TNFα, IFγ, IL-1β) ↑ Endothelial cell apoptosis and ↑ blood-brain barrier permeability Cerebral edema Increased intracranial pressure: papilledema, sudden headache, non-reactive pupils, ↓ level of consciousness (LOC), nausea/vomiting Astrocytes release glutamate (main excitatory neurotransmitter) Activation of neuronal metabotropic glutamate receptors ↑ Ca2+ influx into neurons Excitotoxicity (excess stimulation of glutamate receptors leading to neuronal death) Dysfunction of Na+/K+ ATPase pump (moves 3 Na+ out of cell and 2 K+ into cell) on neurons ↓ Na+ efflux and ↓ K+ influx Neuronal membrane potential becomes less negative (closer to threshold potential) Neurons depolarize → ↑ Glutamate release General findings: Seizures, lethargy Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published June 6, 2018, updated February 28, 2023 on www.thecalgaryguide.com

Coronary Artery Bypass Graft CABG Indications

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

Approach To Dementia

Approach to Dementia/Major Neurocognitive Disorder (NCD) Authors: Iqra Rahamatullah Mahrukh Kaimkhani Reviewers: Yvette Ysabel Yao Mao Ding Gary Michael Klein* *MD at time of publication 1) Changes noticed? Modest ↓cognitive performance from previous, DOES NOT interfere with daily independence MILD COGNITIVE IMPAIRMENT More pronounced ↓cognitive performance from previous, DOES interfere with daily independence MILD TO MODERATE DEMENTIA ↓Cognitive performance, difficulty with ≥1 basic activities of daily living (ADL) or ≥2 instrumental ADLs MODERATE TO SEVERE DEMENTIA DEMENTIA Fluctuating course, acute onset, inattention WITH either disorganized thinking or altered level of consciousness DELIRIUM 2) Is it dementia? Normal, age-related: ↓focus, ↓cognitive speed, ↓reaction time, ↓memory NORMAL COGNITIVE DECLINE 3) What is the cause of the dementia? (main causes discussed here) Loss of cognitive functioning, including memory, language, problem solving, and other thinking abilities, that interferes with independence in everyday activities Beta-secretase cleaves beta amyloid protein Atherosclerosis or thrombosis Misfolded alpha- synuclein Toxic beta amyloid plaque and tau tangle (sticky) formation Ischemia to areas of brain (strokes) Build ups and deposition within neurons (Lewy bodies) Disrupted signaling, inflammation, hippocampal and cerebral impairment Necrosis of brain tissue in areas impacted by strokes Neuronal impairment and atrophy (especially in substantia nigra) Neuronal atrophyàfrontal + temporal lobe atrophy Progressive atrophy of basal ganglia and dorsal striatum + lateral ventricles expanding Death of dopaminergic neurons in substantia nigra Alzheimer’s Dementia Vascular Dementia Lewy Body Dementia Frontotemporal Dementia Huntington’s Disease Parkinson’s Disease ↓Memory, ↓learning, ↓language skills, disorientation, inattention Total debilitation, fatal infections Findings vary depending on area Step-wise worsening impairment Parkinsonism, hallucinations, REM- sleep behavior disorder Total debilitation, dependence Personality and behavioral changes Mental status changes Chorea, ↓cognition, mood changes Aspiration, dementia, suicide Resting tremor, rigidity, anosmia Depression, dementia, falls Abnormal protein inclusions and tangles (usually tau) form in neurons Autosomal dominant disease (with anticipation) with ↑CAG repeats in Huntingtin gene Genetic mutations, environmental exposures, or idiopathic cause Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 17, 2023 on www.thecalgaryguide.com Approach to Dementia/Major Neurocognitive Disorder (NCD) Authors: Iqra Rahamatullah Mahrukh Kaimkhani Reviewers: Yvette Ysabel Yao Fluctuating course, acute onset, inattention WITH either disorganized thinking or altered level of consciousness (LOC)? DELIRIUM 1) Changes noticed? 2) Is it dementia? Normal, age-related: ↓focus, ↓cognitive speed, ↓reaction time, ↓memory NORMAL COGNITIVE DECLINE Modest ↓cognitive performance from previous, DOES NOT interfere with daily independence MILD COGNITIVE IMPAIRMENT More pronounced ↓cognitive performance from previous, DOES interfere with daily independence MILD TO MODERATE DEMENTIA ↓Cognitive performance, difficulty with ≥1 basic activities of daily living (ADL) or ≥2 instrumental ADLs MODERATE TO SEVERE DEMENTIA 3) What is the cause of the dementia? (main causes discussed here) Beta-secretase cleaves beta amyloid protein Atherosclerosis or thrombosis Misfolded alpha-synuclein Toxic beta amyloid plaque and tau tangle (sticky) formation Ischemia to areas of brain (strokes) Build ups and deposition within neurons (Lewy bodies) Disrupted signaling, inflammation, hippocampal and cerebral impairment Necrosis of brain tissue in areas impacted by strokes Neuronal impairment and atrophy (especially in substantia nigra) Neuronal atrophyàfrontal + temporal lobe atrophy Progressive atrophy of basal ganglia and dorsal striatum + lateral ventricles expanding Death of dopaminergic neurons in substantia nigra Alzheimer’s Dementia Vascular Dementia Lewy Body Dementia Frontotemporal Dementia Huntington’s Disease Parkinson’s Disease ↓Memory, ↓learning, ↓language skills, disorientation, inattention Total debilitation, fatal infections Findings vary depending on area Step-wise worsening impairment Parkinsonism, hallucinations, REM- sleep behavior disorder Total debilitation, dependence Personality and behavioral changes Mental status changes Chorea, ↓cognition, mood changes Aspiration, dementia, suicide Resting tremor, rigidity, anosmia Depression, dementia, falls DEMENTIA Loss of cognitive functioning, including memory, language, problem solving, and other thinking abilities, that interferes with independence in everyday activities Abnormal protein inclusions and tangles (usually tau) form in neurons Autosomal dominant disease (with anticipation) with ↑CAG repeats in Huntingtin gene Genetic mutations, environmental exposures, or idiopathic cause Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 17, 2023 on www.thecalgaryguide.com

Mitral Regurgitation Pathogenesis and clinical findings

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

Sustained Monomorphic Ventricular Tachycardia Clinical findings

Sustained Monomorphic Ventricular Tachycardia: Clinical findings Sustained Monomorphic Ventricular Tachycardia A wide QRS complex tachycardia originating from the ventricles lasting > 30 seconds. Common mechanisms include re-entry (e.g., scar-mediated) or a ventricular ectopic focus with increased automaticity. Refer to Sustained Monomorphic Ventricular Tachycardia: Pathogenesis slide for more details. Authors: Rahim Kanji Reviewers: Stephanie Happ, Raafi Ali, Derek Chew* * MD at time of publication The sinoatrial node continues to depolarize the atria while the ventricles depolarize independently and more rapidly Heart rate > 100 beats per minute The re-entrant circuit/ectopic focus uniformly and consistently depolarizes ventricular myocytes Occasionally, a sinoatrial impulse conducts to the ventricles Loss of coordination between the contractions of the atria and ventricles ECG Finding: AV Dissociation The impulse conducts normally through the His-Purkinje pathway and coincides with abnormal ventricular depolarization ECG Finding: Fusion beat Patient feels a forceful and rapid heart rate Palpitations Right atrium periodically contracts against a closed tricuspid valve Cannon A waves (intermittent irregular jugular venous pulsations with large amplitudes) ↓ Ventricular filling time ↓ Preload ↓ Stroke volume cardiac output Inadequate perfusion to organs ECG Finding: Uniform morphology of QRS complexes Direct myocyte-to- myocyte spread of the electrical impulse proceeds slower than an impulse conducted via the His-Purkinje pathway ECG Finding: Wide QRS complexes (≥ 120 milliseconds) The impulse conducts normally through the His-Purkinje pathway in between abnormal ventricular depolarizations ECG Finding: Capture beat Muscles and other organs General malaise Heart Chest pain Brain Presyncope/ syncope Inability to adequately respond to increased cardiac demand Shortness of breath Hemodynamic collapse Sudden cardiac arrest Death Hypotension Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 22, 2023 on www.thecalgaryguide.com

Statins Mechanisms and Side Effects

Statins: Mechanisms of action & side effects Authors: Rupali Manek, Julia Iftimie Reviewers: Gurreet Bhandal, Raafi Ali, Joshua Dian, Laura Byford-Richardson Samuel Fineblit*, Alexander Ah-Chi Leung* * MD at time of publication Competitive inhibitors of HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis) ↓ Coenzyme Q10 (ubiquinone) ↑ Mitochondrial superoxide ↓ Hepatic membrane stability ↓ Conversion of HMG-CoA to mevalonic acid ↑ Hepatic VLDL uptake ↓ Hepatic apolipoprotein B-100 secretion ↓ Oxidative phosphorylation Impaired mitochondrial function ↑ Liver enzyme leakage ↓ Mitochondrial ATP production ↑ Aminotransferases enzymes in liver ↑ Clearance of LDL cholesterol from bloodstream Myopathy/ myalgias (muscle aches) Hepatotoxicity ↓ Circulating LDL cholesterol ↓ LDL, ↑ HDL, ↓ TG ↓ Hepatic cholesterol synthesis ↓ VLDL synthesis ↑ Cell surface LDL receptor expression Statins First line therapy for treating hypercholesterolemia (↑ LDL cholesterol in blood) Common examples: rosuvastatin, atorvastatin, simvastatin, pravastatin, etc. ↑ Apolipoprotein AI production & ↑ hepatic HDL neogenesis ↓ TG ↑ HDL ↑ Vasodilation ↓ C-reactive protein ↓ Impacts of coagulation cascade ↓ Atherosclerosis (plaque along walls of blood vessels) ↓ Cardiovascular disease & mortality Pleotropic effects (i.e. non lipid related effects) Abbreviations: HMG-CoA – Hydroxymethylglutaryl-CoA LDL – Low-density lipoprotein VLDL – Very low density lipoprotein HDL – High density lipoprotein TG – Triglycerides Inhibition of synthesis of isoprenoid intermediates in the mevalonate pathway ↑ Nitric oxide activity ↓ Inflammation ↓ Tissue factor expression ↓ Macrophage proliferation ↓ Tissue factor (promotes macrophage mediated thrombus formation) ↑ Blood flow & endothelial function ↓ Thrombin generation ↓ Metalloproteinases expression ↑ Inhibition of metalloproteinase-1 ↓ Thrombogenicity (production of blood clot/thrombus) Plaque stabilization (↓ risk of atherosclerotic plaque rupture, myocardial infarction, and stroke) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Physiological Outcome Published July 9, 2017, updated Nov 6, 2023 on www.thecalgaryguide.com

Death Cardiovascular Respiratory and Neurologic Mechanisms

Death: Cardiovascular, Respiratory and Neurologic Mechanisms Mitochondria in tissues unable to utilize O2 Reduced hemoglobin in blood to carry O2 Low oxygen content in blood (CaO2) Hypoxemia (Type I Respiratory Failure): low dissolved oxygen in blood (PaO2) Lungs can’t oxygenate blood fast enough Lungs can’t rid blood of CO2 fast enough Hypercapnia / hypercarbia (Type II Respiratory Failure): elevated dissolved CO2 in blood (PaCO2) Cerebral vasodilation Toxins: e.g. cyanide, pesticides, arsenic Severe anemia Distributive problems: Systemic inflammation (sepsis, anaphylaxis, pancreatitis), adrenal insufficiency, vasodilatory drugs Obstructive problems: Cardiac tamponade*, tension pneumothorax* or massive pulmonary embolism* Hypovolemic* problems (low blood volume): Hemorrhage, dehydration, widespread skin disruption or burns Cardiac valve dysfunction Myocardial infarction* or cardiomyopathy Cardiac arrhythmia or heart block Disturbed electrical activity in cardiomyocytes Peripheral metabolic disturbances Hypokalemia*, Hyperkalemia* Acidosis* (including renal failure) Hypothermia* Toxins* (e.g. cocaine, beta blockers, tricyclics) Severe thyroid derangement Inappropriate systemic vasodilation Adjacent forces impair heart filling Low cardiac preload Low stroke volume (SV; depends on valves, contractility, preload) Decreased systemic vascular resistance (SVR) Low blood pressure (BP = CO x SVR) Decreased cardiac output (CO = SV x HR) Disseminated intravascular coagulationàwidespread thrombi that occlude blood flow (also causes hemorrhage, see relevant box at left) Methemoglobinemia: some hemoglobin gets stuck in a state that can’t carry O2 Hemoglobin has reduced capacity to carry or release O2 Drugs: e.g. dapsone, nitrates Carbon monoxide poisoning Circulatory collapse / shock: inadequate perfusion of tissue with blood Respiratory collapse: blood has insufficient useable O2 content Ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) Hypoxia*: inadequate O2 delivery or utilization in tissues Hypoxia creates metabolic disturbances that impair cardiac cells. Alternatively, any of the preceding conditions marked with (*) can directly trigger cardiac arrest first Pulseless Electrical Activity (PEA): organized activity on ECG with no cardiac output (can be preceded or mimicked by pseudo-PEA, in which there is still some output on ultrasound) Low atmospheric pressure or oxygen content Severe lung disease Asthma, COPD, interstitial lung disease, congestive heart failure, pulmonary hypertension, pulmonary embolism, lung collapse / atelectasis Acute respiratory distress syndrome Pneumonia, aspiration pneumonitis, inhalational injury, systemic inflammation, drowning Severe hypoventilation Respiratory fatigue, advanced COPD, chest wall disorders, neuromuscular disorders, upper airway obstruction, toxins (e.g. opioids, botulism) Can degenerate at any time Asystole: no cardiac electrical activity or output Death Respiratory arrest: cessation of breathing Inability to protect airway Decreased level of consciousness Note This is a broad overview of the many scenarios that can result in death. For detailed explanations of the various disease mechanisms, refer to the corresponding slides. * = reversible causes of cardiac arrest (Hs and Ts) Author: Ben Campbell Reviewers: Yan Yu* Huma Ali* * MD at time of publication Bradycardia (low heart rate, HR) Unopposed parasympathetic stimulation of heart (can also cause vasodilation, see Distributive problems) Disruption of spinal cord sympathetic control Injury to cervical or upper thoracic spinal cord Irreversible cessation of cardiac, respiratory, and brain function Prolonged seizure initially causes increased cardiovascular activity, until the system fatigues Disruption of respiratory control center in medulla Expanding skull contents squeeze brainstem (herniation) Increased intracranial pressure Edema from intracranial hemorrhage, trauma, brain mass Edema, inflammation, hypoxia and/or metabolic derangements cause diffuse neuron dysfunction Central nervous system infection Dementia, particularly with delirium Massive ischemic stroke Seizure activity prevents or alters breathing Metabolic disturbances that affect the central nervous system Hypoglycemia Hypocalcemia, hypercalcemia Hyponatremia, hypernatremia Uremia Acute liver failure (hyperNH4) Many drugs / toxins Withdrawal (e.g. EtOH) Status epilepticus Brainstem lesion (e.g. stroke, neoplasm, inflammatory) Nervous System Insult Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 11, 2023 on www.thecalgaryguide.com Respiratory System Insult Cardiovascular System Insult Cardiogenic problems

Complication of MI - Acute Mitral Regurgitation

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

Aspiration Pneumonia

Aspiration Pneumonia: Pathogenesis and clinical findings Intractable vomiting ↑ Likelihood of oropharyngeal and gastric contents exiting the esophagus, entering the trachea to the lung If the acidic gastric contents are sterile, then aspirating this results in inflammation and lung injury without development of infection Aspiration pneumonitis Alveolar macrophages recruit neutrophils to local site of infection. Subsequent cytokine release compromises the vascular endothelial cell wall barrier and ↑ alveolar-capillary permeability ↑ inflammation due to fluid and cellular debris build-up in alveoli overdose (e.g. opioids) (e.g. stroke) Altered level of consciousness and impaired cough/clearance Tube Poor Alcohol and Substance Medications Neurologic diseases Esophageal and gastric motility disorders Impaired swallowing Chronic obstructive pulmonary disorder feeding oral health Bacteria adhere to epithelial surfaces and ↑ risk of airway and lung bacterial colonization Aspirated oropharyngeal and gastric contents can also contain bacteria ↓ Elimination and clearance of foreign bacteria from airway and lung Macroaspiration (large volume aspiration) of oropharyngeal bacteria, during eating and drinking Bacteria and fluid fill bronchi and alveolar space Aspiration Pneumonia Alterations to lung microbial flora An infectious lung process caused by inhalation of foreign bacterial and oropharyngeal and gastric contents Aspiration of acidic fluid and pneumonia causative pathogen (typically anaerobes or bacteria in normal oral flora) with resultant inflammation Infiltrate develops in a gravity-dependent pattern in patches around bronchi segments. Produces proinflammatory cytokines, (e.g. tumor necrosis factor-alpha, and interleukin-1) Hypothalamic production of prostaglandin E2 results in thermogenesis Fever Authors: Luiza Radu Reviewers: Mao Ding, *Yan Yu, *Jonathan Liu *MD at time of publication Aspiration to the right lung more common due to large diameter and more vertical orientation of the right main bronchus Crackles and ↑ lung vibrations (fremitus) on auscultation Productive Cough Impaired alveolar gas exchange Chemoreceptor detection of ↓ pO2 triggers ↑ ventilation Hypoxemia Dyspnea Consolidation in lower lobes (particularly superior segments) and posterior segments of upper lobes If untreated, a pus-filled lung cavity develops (e.g. abscess) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Jan 11, 2024 on www.thecalgaryguide.com

Cranial Nerve IV Palsy

Cranial Nerve IV Palsy: Pathogenesis and clinical findings Congenital (e.g. Möbius Syndrome) Dysgenesis (defective development) of CN IV Microvascular Disease (e.g. Stroke) Damage or occlusion (complete or partial blockage) to the blood vessels supplying CN IV Trauma Temporary or permanent damage to the nerve fibers Neoplasm Metastasis (e.g. Leptomeningeal) Compression of the nerve fibers along the nerve tract Primary (e.g. Schwannoma) Tumor develops new blood vessels that redirect blood flow to the malignancy, away from the nerve Ischemia of CN IV Infection (a rare cause) (e.g. Ehrlichia chaffeensis, Tuberculosis meningitis) Infectious process in the subarachnoid space Damage to axons of CN IV Cranial Nerve (CN) IV Palsy Superior oblique musculature weakness due to CN IV dysfunction Lesion to the fascicle of CN IV (extending from midbrain to cavernous sinus) Impaired ability to conduct motor commands from nucleus to superior oblique muscle in the eye Weak superior oblique innervation Difficult abduction and intorsion of the eye Contralateral superior oblique weakness Lesion to the nucleus of CN IV (located in the midbrain) Disturbed signal production occurring prior to demarcation of fibers to contralateral side The pathophysiology above can cause damage to structures surrounding CN IV in the midbrain Impacting ipsilateral sympathetic chain descending from the hypothalamus prior to reaching the superior cervical ganglion Authors: Shahab Marzoughi Reviewers: Sunawer Aujla Yvette Ysabel Yao Yan Yu* Gary Michael Klein* * MD at time of publication Vertical/oblique Diplopia (double vision) Hypertropia (one eye is deviated upward compared to the other) Perinaud’s Syndrome (upgaze palsy, convergence retraction nystagmus, and pupillary hyporeflexia) See relevant Calgary Guide slide on Parinaud’s Syndrome Loss of eye muscle movement coordination and function of other structures relating to gait Ataxia Ipsilateral Primary Horner’s Syndrome (miosis, anhidrosis, ptosis) See relevant Calgary Guide slide on Horner Syndrome Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 16, 2024 on www.thecalgaryguide.com

Eisenmenger Syndrome

Eisenmenger Syndrome: Pathogenesis and clinical findings Ventricular septal defect Patent ductus arteriosus Authors: George S. Tadros Reviewers: Stephanie Happ Shahab Marzoughi Kim Myers* * MD at time of publication Atrial septal defect Blood shunted from systemic to pulmonary circulation Long-standing “left-to-right” shunt with too much pulmonary blood flow ↑ Flow of blood through the pulmonary circulation (from right ventricle to pulmonary arteries) ↑ Shear stress and circumferential stress on the pulmonary arteries and arterioles Atrioventricular septal defect Truncus arteriosus (Only one common artery arises from the heart rather aorta and pulmonary artery) Long-standing “right-to-left” shunt with too much pulmonary blood flow Structural changes occur in pulmonary arteries and arterioles to adapt to ↑ flow and pressure Hypertrophy of the smooth muscles (media) of pulmonary arteries and arterioles Thickening of the intima (innermost layer) of pulmonary arteries and arterioles ↑ Pulmonary vascular resistance (pressure in the pulmonary arteries) Pressure within the right ventricle gradually ↑ Right ventricular pressure is equal to, or exceeds left ventricular pressure Shunt changes from left-to-right to right-to-left “Right-to-Left” Shunt De-oxygenated blood originating from the right ventricle bypasses the lungs and goes into systemic circulation ↓ Oxygen delivery to tissue across the body Pulmonary hypertension (mean pulmonary artery pressure at rest ≥ 25mmHg) Right ventricular hypertrophy (enlarging) Hypertrophied right ventricle cannot contract effectively Right ventricle loses ability to pump blood efficiently Right heart failure Megakaryocytes (platelet precursors) are shunted away from the capillary beds of the lungs, where they usually get fragmented into platelets Chronic central cyanosis (generalized bluish discoloration) Induction of vascular endothelial growth factor (VEGF) in fingers Terminal digit clubbing (uniform swelling of the fingers and toes) Hypoxemia (<90% O2 saturation) Thrombocytopenia (↓ platelet count) Spontaneous bleeding events Body tries to compensate for ↓ O2 by ↑ oxygen-carrying capacity of the blood Polycythemia (↑ in red cell count) and ↑ hemoglobin concentration ↑ blood viscosity Hypercoagulable and prothrombotic state Not enough O2 to meet the body’s demands Fatigue Epistaxis (nose bleeds) Minor (non-life-threatening) Major (life-threatening) Pulmonary hemorrhage Dental bleeds Menorrhagia (heavy periods) Pulmonary Embolism (clot in pulmonary vessels) Stroke Deep vein thrombosis (clot in deep veins) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 5, 2024 on www.thecalgaryguide.com

Circle of Willis Anatomy and Physiology

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

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