SEARCH RESULTS FOR: 2023

Approach to Arterial Blood Gases ABGs

Approach to Arterial Blood Gases (ABGs) Normal pO2 should be FiO2 x 4-5 (FiO2 in room air= 21%) pH >7.40 = Alkalemia 1. Adequate oxygenation? 2. Define the acid-base disturbance Diarrhea (Loss of electrolytes not reabsorbed through bowel) Normal ABG on Room Air = 7.40 / 40 / 90 / 24 pO2 ↓ than expected Possible hypoxemia See slide on Hypoxemia: Pathogenesis and Clinical Findings (pH) (Loss of acidic fluids from stomach) (HCO3-) (pCO2) (pO2) Renal Tubular Acidosis (RTA) pH <7.40 = Acidemia Metabolic derangement (Due to poisons, infection, or ketones) Gain of acid (H+) Brain unable to promote respiratory drive (ex. drugs, trauma) Inability for chest wall to expand (ex. obesity, neuromuscular weakness, pleural or chest wall abnormalities) Vomiting or nasogastric suction Impaired tubular transport of H+ (Due to loop/thiazide diuretics, hypomagnesemia, congenital abnormalities) 1o Hyperaldosteronism = ↑ H+ ion secretion at distal tubule (Due to tumours, congenital abnormalities , malignant hypertension, etc) Type II RTA = HCO3- not reabsorbed Type I or IV RTA = H+ not secreted GI or renal loss of HCO3- Hypoventilation ↑ CO2 from ↓ exhalation Respiratory Acidosis Acute= ↑10:↑1, Chronic= ↑10:↑3 GI or renal loss of acid (H+) ↑ HCO3- from ↓ H+ to bind with Metabolic Alkalosis ↑7:↑10 ↑ Ventilation from stress, trauma, infection ↓ CO2 from ↑ exhalation Respiratory Alkalosis Acute= ↓10:↓2, Chronic= ↓10:↓4 3. Identify the primary (1o) process 4. Compensatory mechanisms in lungs and kidneys attempt to lose/retain CO2 or HCO3- to maintain normal pH. Determine if compensation is appropriate (approximate normal ratio of change in pCO2 : HCO3- is shown in green boxes). If inappropriate, there is a secondary (2o) process occurring HCO3- binds with extra H+ ↓ HCO3- Metabolic Acidosis ↓12 :↓10 Less CO2 than expected, due to ↑ exhalation = Less acid in serum 2o Respiratory alkalosis More CO2 than expected, due to ↓ exhalation = More acid in serum 2o Respiratory acidosis Less HCO3- than expected, due to 2o gain of H+ or loss of HCO3- 2o Metabolic acidosis More HCO3- than expected, due to 2o loss of H+ 2o Metabolic alkalosis Less CO2 than expected, due to ↑ exhalation = Less acid in serum 2o Respiratory alkalosis ↑ CO2 than expected, due to ↓ exhalation = More acid in serum 2o Respiratory acidosis Less HCO3- than expected, due to 2o gain of H+ or loss of HCO3- 2o Metabolic acidosis More HCO3- than expected, due to 2o loss of H+ 2o Metabolic alkalosis 5. Calculate anion gap (AG) to determine the presence and type of metabolic acidosis. This is done regardlessofthe1o or2oprocess, as there may also be a hidden metabolic acidosis 6. HAGMA only: In normal blood buffer system, acid gain should match bicarbonate lost. If not, identify if another process is causing an inappropriate loss or gain of HCO3- Gain of acid (∆AG) = AG-12 LossofHCO3- (∆HCO3-)=24-HCO3- 7. Calculate Osmolar Gap (for HAGMA) or Urine net charge (for NAGMA) to narrow the etiology Authors: Sravya Kakumanu Reviewers: Huneza Nadeem, Ben Campbell *Adam Bass, *Yan Yu * MD at time of publication (normal is ~12) Calculate AG = Na+- Cl- - HCO3- If a metabolic acidosis is present, ↓ HCO3- is compensatedby↑otherserumanionstomaintain neutral charge If no metabolic acidosis was identified in steps 2-4: No Metabolic acidosis present Classically, the compensating anion is Cl-,maintaininganormalAG AG ≤ 12 If a 1o or 2o metabolic acidosis was identified in steps 2-4: Normal Anion Gap Metabolic Acidosis (NAGMA) In this scenario, a normal distal nephron should be excreting excess acid Excess acid is normally excreted as ammonium (NH +) with Cl- 4 The more Cl- in the urine relative to cations, the more acid is being excreted Calculate urine (U) net charge to determine cause of NAGMA = UNa+ + UK+ - UCl- When the cause is addition of an abnormal acid, HCO3- is used up asabuffer,andthecompensatinganionistheabnormalacid's conjugate base – which is not measured in the AG calculation ↓ HCO3- is compensated by unmeasured anionsà the AG ↑ AG>12 High Anion Gap Metabolic Acidosis (HAGMA) Calculate ∆AG = AG-12 Calculate ∆HCO3- = 24-HCO3- ∆HCO3- > ∆AG Loss of HCO3- > Gain of acid Additional process causing further loss of HCO3- HAGMA + NAGMA ∆HCO3- = ∆AG Loss of HCO3- = Gain of acid Only acid gain from HAGMA causing HCO3- loss HAGMA only ∆HCO3- < ∆AG Loss of HCO3- < Gain of acid Additional process causing gain of HCO3- despite losses due to HAGMA HAGMA + Metabolic alkalosis See slide on Metabolic Alkalosis: Pathogenesis -ve U net charge Appropriately large Cl- excretionà Toxic alcohol ingestion ↑ serum osmolality (and H+) from metabolites produced, so osmolality helps identify etiology Calculate osmolar gap to determine cause of HAGMA = (measured serum osm) – (expected serum osm) = (measured serum osm) – (2(Na+) + urea + serum glucose) +ve U net charge Inappropriately small Cl- excretionà impaired acid excretion is the issue Type IV or Type I RTA See slide on Normal Anion Gap Metabolic Acidosis: Pathogenesis and Laboratory Findings HCO3 GI losses or Type II RTA - loss is the issue Osmolar gap > 10 (extra osmoles present) Toxic alcohol poisoning Osmolar gap ≤10 (normal) Test for other causes See slide on High Anion Gap Metabolic Acidosis: Pathogenesis and Laboratory Findings Legend: Disease State Mechanism Lab Finding/Calculation Published January 29, 2023 on www.thecalgaryguide.com

Hidradenitis Suppurativa

Genetic mutations causing impaired function of gamma-secretase (NCSTN, PSEN1 or PSENEN genes) Defective notch signaling pathway (a regulator of many cell processes) Hormones (excess androgen activity) Smoking (nicotine exposure) Skin to skin friction Systemic inflammation Hidradenitis Suppurativa: Pathogenesis and Clinical Findings Other unknown genetic factors Follicular occlusion HS nodule Epidermal layer Dermal- Epidermal Junction Dermal layer Inflammatory cytokine- mediated activation of nociceptors Inflammatory cytokines Sebaceous gland Apocrine sweat gland Hair follicle Pilosebaceous- apocrine unit Changes in gene expression of hair follicle and apocrine gland anti-microbial peptides Accumulation of corneocytes (dead keratinocytes) and sebum àfollicular occlusion and rupture ↑ Interleukin-36 (IL-36, a cytokine) Altered keratinocyte differentiation Hair follicle hyperkeratinization Abnormal structure and function of the pilosebaceous- apocrine unit Infiltration of normal skin flora microbes, macrophages, dendritic cells, and Th17 cells Increased density of nicotinic acetylcholine receptors in pilosebaceous-apocrine unit (see figure) Mechanism not fully understood Hyperhidrosis Pain Innate immune cells produce inflammatory cytokines: tumour necrosis factor alpha (TNF-α) and various interleukins (IL-1, IL-6, IL-12, IL-17, IL-22 and IL-23) IL-17 promotes neutrophil migration into the skin Formation of neutrophil extracellular traps (NETs) B-cell activation and IgG autoantibody formation against skin tissue antigens Scarring Ongoing inflammation impairs wound healing Granulocyte infiltration and activation, release of granulocyte colony-stimulating factor Accumulation of keratin, purulent and/or serosanguinous fluid in dermis Inflammatory papules, nodules, and abscesses Pro-inflammatory cytokine-mediated response, leading to epithelial hyperplasia with increased fibrosis and collagen remodelling in the dermis Formation of epithelial tissue tunnels in the dermis with two cavities on either end that open to the skin surface and fill with fluid or keratin Hidradenitis Suppurativa Chronic Inflammatory skin disease that occurs in areas with a high density of apocrine sweat glands, including the axilla, underneath the breasts, groin, and buttocks Sinus tracts (dermal connections between lesions) Double-ended comedones Authors: Leah Johnston Reviewers: Mehul Gupta Lauren Lee Stephen Williams Ben Campbell Laurie Parsons* * MD at time of publication Wound drainage and odour Psychological distress Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 30, 2023 on www.thecalgaryguide.com

Pityriasis Rosea

Pityriasis Rosea: Pathogenesis and clinical findings Authors: Leah Johnston Reviewers: Lauren Lee Stephen Williams Ben Campbell Laurie Parsons* * MD at time of publication Pityriasis Rosea Epidermal layer Dermal-Epidermal Junction Dermal layer Psoriasiform hyperplasia, parakeratosis, spongiosis and Preceding viral infection, reactivation of latent Human Herpesvirus (HHV-6 or HHV-7) Female sex (2:1 female to male ratio) Risk factors Recent vaccinations: Bacillus Calmette-Guerin (BCG), influenza, H1N1, diphtheria, smallpox, hepatitis B, and Pneumococcus Red blood cell lymphocytes extravasation Perivascular dermal infiltrates: lymphocytes, monocytes, and eosinophils Spongiosis (intercellular fluid accumulation in epidermis) Erythematous, pink-salmon or brown coloured lesions Altered production of melanin by epidermal melanocytes Post-inflammatory hyperpigmentation or hypopigmentation Prodromal symptoms: fatigue, nausea, headaches, joint pain, enlarged lymph nodes, fever, and/or sore throat Age 10 to 35 Exact mechanism unknown Activation of T-cell mediated host immune response ↑ Signal proteins in serum including interleukin 17 (IL-17), interferon gamma (IFN-γ), vascular endothelial growth factor (VEGF), and induced protein 10 (IP-10), leading to increased capillary permeability Spring and fall seasons Fluid extravasation from blood vessels Red blood cell extravasation Often asymptomatic, can be pruritic Cell infiltration isn’t as intense or doesn’t produce as dramatic an inflammatory response as other skin conditions ↑ CD4 lymphocytes, monocytes, eosinophils and Langerhans cell infiltration into the dermis and epidermis Pityriasis Rosea Activation of B cells and production of anti- keratinocyte IgM antibodies Parakeratosis (incomplete keratinocyte maturation) and proliferation of epidermal cells (known as psoriasiform hyperplasia) Thickened epidermal layer Scale A self-limited, papulosquamous eruption that is characterized by round or oval-shaped, erythematous to brown patches or plaques with scaling borders that typically occur on the trunk and proximal extremities and tend to follow Langer’s lines. Often initially presents with a larger herald patch as the first sign. Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published January 30, 2023 on www.thecalgaryguide.com

Inhalational Injury

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

Large Bowel Obstruction: Findings on Abdominal X-ray

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

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

Myelodysplastic Syndrome Pathogenesis and clinical findings

Myelodysplastic Syndrome (MDS): Pathogenesis and clinical findings Authors: Mao Ding Reviewers: Ashar Memon Man-Chiu Poon Yan Yu* * MD at time of publication Stem cells differentiateà accumulation of bone marrow cells with aberrant morphology & maturation Idiopathic (unknown cause) Treatment related: exposure to ionizing radiation, chemotherapeutic agents (e.g., alkylating agents, anti- metabolite, topoisomerase II inhibitors) Environmental toxins (e.g., tobacco, benzene & other organic solvents) Familial predisposition to MDS Acquired somatic (non- reproductive) gene mutations (DNA alterations) Inherited germline (reproductive cells) gene mutations Recurrent mutations cause alteration(s) in one or more protein functions with/without chromosomal abnormalities in hematopoietic stem cell (earliest cell of blood cell differentiation): Mutation in the transcription factor gene RUNX1 impairs regulation of normal hematopoietic (blood cell) development Mutation(s) in epigenetic regulator genes (DNMT3A, TET2) impairs regulation of DNA methylation Mutation in splicing regulator genes (SF3B1) causes mistakes in splicing mRNA moleculesàaberrant translation (production) of proteins Chromosomal abnormalities: deletions (chromosome 5, 7, and/or 20), duplications (chromosome 8), structural abnormalities (inversion of a gene segment) Myelodysplastic Syndrome Mutation-associated clonal disorders of hematopoietic stem cells, causing dysplasia (abnormal development) of one or more myeloid cell lineages (granulocytes, monocytes, red blood cells & platelets) in the bone marrow Genetic mutations or chromosomal abnormalities occur in hematopoietic stem cellsàclonal expansion of abnormal cells in bone marrow Apoptosis (programed cell death) of clonal cells, inhibiting development of granulocytes, monocytes, red blood cells & platelets in the bone marrow Neoplastic myeloid precursor cells (blasts) accumulate in the bone marrow Acute Myeloid Leukemia (AML) > 20% Blasts in the bone marrow Excessive blasts displace other precursor cells & inhibit differentiation Pancytopenia (↓ number of cells of ALL 3 cell lines: platelets, white blood cells & red blood cells) (see Acute Myeloid Leukemia for signs/symptoms/complications) ↓ Number of mature functional blood cells leave the bone marrow to go to peripheral bloodà↓ number of cells of one or more cell lines Bone marrow’s inability to make sufficient blood cells cause extramedullary hematopoiesis (formation/activation of blood cells outside the medulla of bone) at sites such as liver and/or spleen Hematopoietic stem cells migrate to the spleen/liver & differentiate into blood cells Expanding bone marrow physically pushes on bone’s cortex from within, activating nociceptors Multifactorial causes mostly with unclear mechanisms Intracellular granules precipitate inside blasts & the precipitate spills into the blood ↑Division & death of cancerous cells → ↑ cell lysis & release of intracellular contents into plasma Bone pain B symptoms: Weight loss, fever, night sweats Auer Rods (needle- like crystals) seen on blood smear ↑ Serum levels of uric acid, K+, LDH ↓ Red blood cells Anemia fatigue, pallor ↓ White blood cells Leukopenia Recurrent infections ↓ Platelets Thrombo- cytopenia Bruising, bleeding Accumulation of cells within the spleen/liver increase the size of the organ Splenomegaly Hepatomegaly Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 4, 2023 on www.thecalgaryguide.com

Central Retinal Vein Occlusion

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

Skin Grafts Transplant physiology and clinical findings

Skin Grafts: Transplant physiology and clinical findings Authors: Ruchika Sharma Shyla Bharadia Reviewers: Mao Ding Ryan T. Lewinson A. Rob Harrop* *MD at time of publication STSGs may be meshed for greater coverage of surface area Split thickness donor sites may be re- harvested 6. Graft maturation (months-years) Skin anatomy Sebaceous gland alongside hair follicle Hair Follicle Sweat gland Blood vessels Full thickness donor sites cannot be re-harvested Epidermis Dermis Subcutaneous tissue Full thickness skin graft (FTSG) including the epidermis and entire dermis The full thickness donor site is closed by primary intention (sutured) Skin grafts Indicated when healing by secondary intention (natural closure) is not possible. The graft consists of avascular skin harvested from an uninjured donor site Split thickness skin graft (STSG) including the epidermis and a portion of the dermis The split thickness donor site heals by re- epithelialization Donor grafts are applied to the injured area 1. Initial adherence (8 hrs) A fibrin network fastens the graft to the wound bed Fibroblasts, leukocytes & phagocytes from the wound bed enter the fibrin network, building a fibrous connection between the graft & wound bed 2. Plasmatic imbibition (24-48 hrs) The graft absorbs nutrients and dissolved oxygen from plasma in the recipient wound bed The graft appears white in color 3. Inosculation and capillary ingrowth (2-4 days) Capillary buds from the recipient wound bed anastomose with vessels on underside of graft Physiology of graft take 4. Revascularization (5-7 days) 5. Graft contraction (6-18 months) Actin in myofibroblasts contract & approximate the wound edges Angiogenic factors enable revascularization allowing rapid, high-volume flow through large vessels Lymphatic drainage established Dermal structures such as hair follicles, sweat & sebaceous glands may be partially restored Grafts are pruritic (itchy), discoloured, and do not function or look like normal skin Grafts are reinnervated from periphery to center STSGs are reinnervated faster than FTSGs, though incompletely Graft fails (does not adhere) with a poorly vascularized and unclean wound bed Restoration of vasculature returns color to the graft Successfully adhered grafts are pink (STSG) or marginally paler (FTSGs) and immobile The deep dermal layer in FTSGs better inhibits myofibroblast action STSGs heal with significant contracture, limiting function & mobility Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications First published February 6, 2017, updated March 12, 2023 on www.thecalgaryguide.com

Primary Hemostasis

Primary Hemostasis: Normal physiology, disorders, and clinical findings Authors: Mina Mina Reviewers: Parker Lieb Mao Ding Kareem Jamani* *MD at time of publication Normal physiology: Injury to blood vessels from trauma (blunt or penetrating injury) Disorders of primary hemostasis: Collagen and microfibrils (subendothelial elements that are normally protected) are exposed to circulating blood due to vessel injury Storage granules in endothelial cells release large multimers of clotting factor von Willebrand (vWF) when damaged Acquired or inherited reduction in vWF quantity or quality (see vWF deficiency slide) von Willebrand Disease Defect in expression of GpIb interferes with platelet ability to bind to vWF Bernard-Soulier syndrome Defect in platelet membrane glycoproteins IIb and IIIa Glanzmann’s Thrombasthenia Insufficient platelets to form a platelet plug Thrombocytopenia (low platelet count) Disorders of primary hemostasis: problems with formation of a platelet plug Platelet adhesion: vWF binds to collagen and interacts with the platelet surface receptor glycoprotein Ib (GpIb) allowing platelet adhesion Platelet activation: mediated by agonists like ADP, thrombin and collagen Mucocutaneous bleeding (bleeding of the skin and mucous membrane) ↑ Closure time, ↑ bleeding time Platelets change shape and release substances from their granules Conformational changes in platelet cell surface glycoprotein IIb/IIIa ↑Affinity for fibrinogen through GpIIb/IIIa ADP Fibrinogen, vWF, and other substances Thromboxane A2 (see note) Induces aggregation Epistaxis Menorrhagia Note: Petechiae Platelet aggregation: fibrinogen forms bridges between adjacent platelets by binding to activated glycoprotein IIb/IIIa Interaction with coagulation factors: platelets provide a scaffold that allows the activation of phospholipid-dependent coagulation factors Primary hemostasis (formation of a platelet plug) Secondary hemostasis (see slide for normal physiology) Drugs like Aspirin and NSAIDs inhibit Thromboxane A2 synthesis (by inhibiting cyclooxygenase) and thereby inhibit platelet aggregation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 30, 2023 on www.thecalgaryguide.com

Concussion

Concussion: Acute pathophysiology and findings Authors: Calvin Howard Cormac Southam Yvette Ysabel Yao Reviewers: Emily Ryznar Mao Ding, Gary Klein* * MD at time of publication Activation of inhibitory cholinergic system of dorsal pontine tegmentum (structure with role in sleep- wake regulation) Disruption of reticular activating system (brain area that regulates arousal) Altered level of consciousness Direct blow to the head or the body that causes an impulsive force to the head (i.e., falls, motor vehicle accidents, sports, assaults) Skull acceleration / deceleration Coup (brain strikes skull on side of impact) Brain tissue swelling Cerebral edema (fluid build up around brain) ↑ Intracranial pressure Cerebral herniation (shifting of brain tissue into adjacent space) Contrecoup (brain strikes skull on opposite side of impact) Anatomical damage Skull fracture Broken bone fragments ruptures blood vessels Intracranial hemorrhage (bleeding into brain tissue) Papilledema (swelling around optic disk, where optic nerve enters eyeball) Disruption of messages from eye to brain Vision problems (i.e., blurred or double vision) Cellular damage Indiscriminate, rapid neurotransmitter release ↑Extracellular K+ and glutamate, accumulation of intracellular calcium Ionic disequilibrium across neuronal membrane Energy consumed by Na+/K+ ATPase pumps to re-establish ionic homeostasis ↑ Cerebral glucose metabolism ↑ Energy demand Brain injury Axonal stretch due to biomechanical forces Microtubule disruption Structural (cytoskeletal) disturbance Axonal degeneration Impaired neural communication Broken bone fragments Ruptures blood vessels Compresses blood vessels ↓ Cerebral blood flow ↓ Cerebral glucose supply ↓ Energy supply ↓ Oxygenated blood to brain Brain cell death Chronic brain atrophy Persistent impaired cognition Cellular energy crisis (mismatch between energy supply and demand due to effort in restoring homeostasis) Nausea, vomiting ↓ Participation in daily Confusion, disorientation, unsteadiness, headache activities and work Death Anxiety, depression Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 12, 2019, updated March 27, 2023 on www.thecalgaryguide.com

Pyogenic Brain Abscess on MRI

Pyogenic Brain Abscess on MRI: Findings and Pathogenesis Common pathogens such as staphylococcus and streptococcus bacteria exist in the outside environment or on the skin Hematogenous Spread Direct Spread Pathogen travels to brain by bloodstream Pathogen travels to brain by ears or sinus Pathogen enters the brain parenchyma by crossing the blood brain barrier (BBB) transcellularly, paracellularly or by a Trojan Horse mechanism Authors: Omer Mansoor, Aly Valji, Nameerah Wajahat Reviewers: Mao Ding, Reshma Sirajee, James Scott* *MD at time of publication R Transcellular Pathogen invades BBB cell directly to enter Paracellular Pathogen goes between BBB cells by disrupting tight junctions Trojan Horse Pathogen bypasses BBB by hiding inside a macrophage cell Ring Enhancing Lesion Sensitive, but not specific for a Brain Abscess Pathogen causes parenchymal inflammation and progresses through four stages of infection Axial T1 + Gadolinium MRI Head. Pyogenic Brain Abscess showing infection at Stage 3 or 4. T1 highlights fat, whereas T2 highlights fat and water*. R Stage 1: Early Cerebritis Focal infection (2-3 days) with no pus formation Stage 2: Late Cerebritis Progressive (1 week) infection of abscess Stage 3: Early Encapsulation In 1-2 weeks, pus is formed from the pathogen Stage 4: Late Encapsulation After 2 weeks, abscess shrinks in size as it necroses Pathogen causes acute inflammatory changes of swelling (edema) and vascular congestion No fibrous capsule is formed yet and infection is not well localized on a T1 MRI Increased edema could be seen on T2 MRI Poor Demarcation and Vasogenic Edema Abscess is not well-defined with minimal enhancement on T1 but can have increased signal on T2 Fibrous capsule is formed by surrounding healthy brain tissue that walls off abscess Capsule is made of granulation tissue and fat, which lights up non-specifically on a T1 MRI Use Diffusion Weighted Imaging (DWI) to distinguish abscess from other brain lesions DWI measures water diffusion in different directions, specifically diseased areas where water movement is restricted Restricted Diffusion Edema and inflammation allow water to move freely (hyperintense signal) *Imaging Source: Feraco et al., 2020: https://jptcp.com/index.php/jptcp/article/download/688/685?inline=1 DWI Sequence Axial MRI Head. Same Pyogenic Brain Abscess as above. DWI is the mainstay imaging sequence for diagnosing a pyogenic brain abscess*. Legend: Pathophysiology Mechanism Radiographic Findings Complications Published Mar 25, 2023 on www.thecalgaryguide.com

Carpal Tunnel Syndrome

Carpal Tunnel Syndrome: Pathogenesis and clinical findings Diabetes Mellitus (See Pathogenesis Slide) ↑ Blood sugar: deposition of advanced glycation end (AGE) products (proteins or lipids glycated when exposed to sugar) AGE attaches to and prevents tendons from moving properly Authors: Amanda Eslinger Yvette Ysabel Yao Reviewers: Matthew Harding Owen Stechishin Mao Ding, Cory Toth* * MD at time of publication Wrist trauma (distal radius fractures, carpal/metacarpal fractures, tendon ruptures) Repetitive Strain Injury (repetitive hand & wrist movements) Irritation, swelling & thickening of tendons in carpal tunnel Calcium deposits Calcifica tion Deposition Amyloidosis Amyloid (protein aggregates) deposition Gout (See Gout Slide) Uric acid crystal deposition Pregnancy ↑ Concentration of hormones & uterine pressure on inferior vena cava Backup of blood into systemic circulation Autoimmune (i.e. Rheumatoid arthritis, scleroderma, lupus, Sjogren’s syndrome) ↑ Inflammatory cytokines causing inflammation Hypo- thyroidism Myxedema (swelling of skin and underlying tissues) in carpal tunnel Idiopathic or Congenital Edema Narrowed carpal tunnel leads to ↑ internal pressure Carpal Tunnel Syndrome Vascular: median artery thrombosis in carpal tunnel Median nerve compression inside the carpal tunnel Mechanical disruption of median nerve Compression exacerbated with flexed wrists (i.e. sleep, driving, holding phone/cup) Disruption of daily activities and sleep Ischemia (↓ blood supply) to median nerve Hypoxia (↓ oxygenated blood flow) Metabolic conduction block (impaired axonal transport due to ischemia) Nerve conduction study (show sensory nerve impulses slowing across the wrist, followed by mild / moderate / severe loss of sensory nerve amplitude Damage to the myelin sheath ↓ Saltatory conduction (action potential propagation along myelinated axons) Neuropraxia (nerve compression blocks conduction) Interruption in axonal continuity Axonotmesis (endoneural tube stays intact but myelin & distal axon degenerates) Recovery possible Full disruption of myelin, axon & nerve sheath Neurotmesis (axons no longer have an endoneural tube to guide regrowth) Recovery impossible ↓ Ability to contract and use abductor pollicis brevis muscle ↓ Signals through median nerve Interference with signals to the brain causes unusual sensations Hypoalgesia (↓ pain Dysesthesia (tingling, burning, or sensitivity at 1st 3 1⁄2 digits) painful sensation at 1st 3 1⁄2 digits) Thenar muscle wasting Reduced hand dexterity Weak thumb abduction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published December 2nd, 2013, updated March 22, 2023 on www.thecalgaryguide.com

Complications of Prematurity

Prematurity: Overview of complications Premature babies born <37 weeks of pregnancy Author: Elizabeth de Klerk Simran Sandhu Reviewers: Yan Yu, Mao Ding Nick Baldwin* *MD at time of publication Immature immune system Prematurity Structurally immature lungs Immature retinal vessels are more sensitive to O2 Supplemental O2 makes retinal environment hyperoxic (excessive supply of O2) Hyperoxia vasoconstricts retinal blood vessels leading to retinal ischemia Ischemic retina produces vascular endothelial growth factor (VEGF) to generate new blood vessels + improve retinal perfusion Excess VEGF causes abnormal blood vessel proliferation Abnormal vessels are fragile + prone to hemorrhage which can lead to retinal distortion Retinopathy of Prematurity (ROP) (See relevant slide) Poor structural support to blood vessels of the germinal matrix (the tissue surrounding the lateral ventricles of the brain) Vessels are vulnerable to hemodynamic instability Abrupt changes to cerebral blood flow damage blood vessels Vessels bleed into germinal matrix and lateral ventricles Intraventricular Hemorrhage (IVH) (See relevant slide) Note: Pre-term complications not discussed here include hypothermia, hypoglycemia, apnea, patent ductus arteriosus Low quantity: ↓ surfactant production Low quality: ↓ surfactant activity (different lipid + protein composition compared to full-term infants) ↑ Infections ↓ Number of white blood cells and complement protein ↑ Bacterial colonization of GI tract + penetration of intestinal wall Abnormally high surface tension of alveoli Alveoli spontaneously collapse (diffuse alveolar atelectasis) Ineffective ventilation of alveoli (V)ànot supplying pulmonary blood (Q) with oxygen (V-Q mismatch) Respiratory Distress Syndrome (RDS) (See relevant slide) Positive pressure ventilation (PPV) used therapeutically PPV disrupts lung development & damages lung tissue Bronchopulmonary Dysplasia (BPD) (See relevant slide) Intestinal ischemia, or Formula Feeds (unclear mechanisms) Activation of inflammatory cascade releases cytokines (peptides that help activate immune response) Cytokines cause bowel necrosis (tissue death) Necrotizing Enterocolitis (NEC) (See relevant slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 31, 2013, updated March 25, 2023 on www.thecalgaryguide.com

Acute Pulmonary Embolism on CTPA

Acute Pulmonary Embolism: Computed Tomography Pulmonary Angiogram (CTPA/CTPE) Virchow’s Triad: Hypercoagulability, venous stasis, vascular endothelial injury Image Source: European Society of Radiology Image: Polo mint sign on axial CTPA. Image Source: Journal of The Indian Academy of Echocardiography Image: Railway sign on axial CTPA. Image Source: Moore et al. 2018 Image: Pleural effusion and pulmonary infarction on axial CTPA. Authors: Aly Valji, Nameerah Wajahat, Omer Mansoor Reviewers: Reshma Sirajee, Sravya Kakumanu, Victória Silva, Mao Ding Vincent Dinculescu* *MD at time of publication Deep Vein Thrombosis (DVT): Majority of pulmonary embolism (PE) arise from DVT: Clot travels via inferior vena cava → right atrium → right ventricle → pulmonary arteries/arterioles See “Virchow’s Triad and Deep Vein Thrombosis” for full pathogenesis Polo Mint Sign Clot visualized in short axis, Filling defect entirely surrounded by IV contrast creating a circle (polo mint) Railway Sign Clot visualized in long axis, Filling defect surrounded by IV contrast on two sides creating the appearance of a railway track Type I or II Ventilation/Perfusion respiratory failure (V/Q) mismatch Reverse Halo Sign Pulmonary infarction leads to wedge shaped opacity with a rim of consolidation (black arrows) surrounding “ground glass” (red arrows) Pulmonary Embolism: Clot in pulmonary arteries See “Signs and Symptoms of Pulmonary Embolism” for full presentation Saddle Embolus: Large clot over the pulmonary trunk bifurcation Lobar/Segmental/Subsegmental Embolus: Clot within the pulmonary arteries of the lungs Blockage of pulmonary arteries = ↓ Blood flow, ↑ Right heart pressure ↓ Gas exchange b/w lungs and blood Ischemia of lung tissue → infarction → inflammation of dead tissue ↑ Right heart filling and expansion Left heart filling impaired ↓ Cardiac output due to ↓ Left heart filling “Massive PE” = sustained systemic hypotension or bradycardia (SBP < 90 mmhg, HR < 40 bpm) Saddle Embolus Filling defect due to blockage of bifurcation. IV contrast appears white, and embolus appears grey Pleural Effusion Exudative Pleural Effusion Tissue inflammation → ↑ blood vessel permeability = Leakage of fluid into pleural space Transudative Pleural Effusion ↑ Hydrostatic pressure from right heart congestion = Pushes fluid into pleural space Image Source: Samra et al. 2017 Image: Saddle embolus on axial CTPA. Legend: Pathophysiology Mechanism Radiographic Findings Complications Published March 28, 2023 on www.thecalgaryguide.com

Sarcoidosis pathogenesis and CXR findings

Sarcoidosis: Pathogenesis and chest X-Ray findings Authors: Harshil Shah Reviewers: Mao Ding Tara Shannon Vincent Dinculescu* * MD at time of publication Genetic predisposition Unknown sarcoid antigens Sarcoid antigens interact with pattern recognition receptors on macrophages in the lungs Macrophages become activated Helper T cells and macrophages release cytokines (proteins made by immune cells that modulate cell growth and division) such as tumor necrosis factor to neighboring cells Tumor necrosis factor is a pro- inflammatory cytokine promoting cell survival and proliferation, predominantly in the upper/middle lung for unknown causes More macrophages and helper T cells are activated and accumulate in the mediastinum, peritracheal region, and the upper/middle lung Macrophages and helper T cells promote fibroblasts (cells that produce collagen) in the upper and middle lungs Macrophages in the lungs present the antigen to the helper T cells in lymph nodes Helper T cells become activated and accumulate in the lungs Image Credit: Radiopaedia The right peritracheal and bilateral hilar lymph nodes becomes swollen Inflammatory signals stimulate macrophages to form granulomas (clusters of white blood cells) in the lungs, peritracheal and bilateral hilar lymph nodes X-ray images show visible white opacities in areas of increased densities, such as areas of macrophage and helper T cell concentration Enlarged peritracheal lymph node Stage 1 and 2 Enlarged bilateral hilar lymph node Stage 1 and 2 Interstitial Opacities Stage 2 and 3 Bilateral and symmetric lacey lung markings in upper/middle lungs Decreased lung volume on either sides (higher than normal diaphragm) Collagen accumulate which causes fibrotic tissue (scarred and thickened), replacing healthy tissue Pulmonary fibrosis of upper and middle lung Stage 4 The fibrotic tissue is stiffer, reduces amount of air held in lungs, and has a higher density (appearing white) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 7, 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

Benzodiazepine Mechanism of Action

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

Subdural Hematoma on CT

Acute and Chronic Subdural Hematoma on CT: Pathogenesis and findings Brain shrinkage with age or alcohol misuse Head trauma Congenital or acquired coagulopathy (i.e. anticoagulant use) Other (i.e. brain mass) Stretching & tearing of bridging cortical veins that cross from the cortex to dural sinuses Crescent shape Blood accumulation in the potential space between the dura mater & the arachnoid mater As the blood clots over time, its appearance varies on CT and is measured as different radiodensities (MRI may be needed to detect subtle bleeds) Acute < 3 days Subacute 3 days to 3 weeks Chronic > 3 weeks Acute on Chronic Acute blood (50-60 HU) is hyperdense to the surrounding cortex As blood clot ages and protein degradation occurs, the density drops to 35-40 HU The collection of blood becomes hypodense (~0 HU) to adjacent cortex Both hypodense & hyperdense collections visible forming a hematocrit level Hounsfield units (HU) are a measure of radiodensity (Air -1000 HU appears black, CSF is 0 HU appears dark, and cortical bone is >1000 HU appears white) Hypodense collection A pre-existing chronic hematoma Hematocrit level Fluid-fluid level in the case of an acute bleed into a pre-existing chronic subdural collection. This can also be seen in patients with coagulopathy as blood clots improperly, allowing for dependent blood layering Hyperdense collection Acute blood sinks inferiorly (as CT is taken with patient supine) Authors: Nameerah Wajahat, Aly Valji, Omer Mansoor Reviewers: Reshma Sirajee, Tara Shannon, Mao Ding, Petra Cimflova* *MD at time of publication Subdural hemorrhages spread past suture lines to take on a crescent shape (seen bilaterally on this CT), but limited by dural reflections (falx cerebri, tentorium) R Intracranial pressure ↑ Mass effect on the brain tissue Midline shift Shift of brain tissue across the center line of the brain (dashed line shows ideal midline) Ventricular effacement (partial) Ventricles appear smaller as some cerebrospinal fluid (CSF) is pushed out Sulcal effacement CSF filled sulci become less apparent as CSF is squeezed out and gyri are lying on each other Herniation Protrusion of brain through rigid membranes or foramina of skull Axial CT Head: Acute on Chronic Bilateral Subdural Hematoma showing features of both acute and chronic bleeding. Image Source: Radiopaedia.org Legend: Pathophysiology Mechanism Radiographic Findings Complications Published May 10, 2023 on www.thecalgaryguide.com

Telogen Effluvium

Authors: Ayaa Alkhaleefa Telogen effluvium (TE): Causes, pathophysiology, and clinical findings Reviewers: Elise Hansen, Sunawer Aujla, Dr. Jori Hardin* *MD at time of publication Telogen effluvium: non-scarring alopecia characterized by diffuse shedding of telogen-phase hair due to a reactive process Hypothyroidism ↓ Thyroid hormones (T3,T4) ↓ Binding of thyroid hormone to receptors in the skin and hair Cell division ceases in keratinocytes The catagen phase of the hair cycle is triggered (involuting phase where hair enters apoptosis) Delayed re-entry of telogen (resting) hair into the anagen (growing) phase Post-partum hair loss (telogen gravidarum) ↑ Circulating placental estrogen Prolonged anagen phase ↑ Hair growth during pregnancy Baby is delivered ↓ Estrogen and other trophic hormones postpartum The increased amount of anagen hairs from pregnancy all enter catagen phase simultaneously Nutritional deficiencies i.e. iron deficiency Critical illness Fever triggers various pro- inflammatory cytokines (tumor necrosis factor, interleukin 1b, interleukin 6, and interferon types 1 and 2) Premature entry into catagen phase (the body induces cell-cycle arrest in all non-essential structures) Hair follicle keratinocytes undergo apoptosis in response to inflammation Ribonucleotide reductase (an enzyme involved in DNA synthesis) cannot utilize iron as a co-factor ↓Iron stores ↓ Expression of iron- dependent genes (CDC2, NDRG1, ALAD, and RRM2) ↓ Expression of matrix genes of a healthy hair follicle (Decorin and DCT) ↓ Production of matrix keratinocytes (cells that form the hair shaft of growing hair) Arrest of matrix proliferation Hair shedding commonly occurs in the bitemporal areas 2-3 months after triggering event Hair shaft Hair follicle Telogen phase Skin Epidermis Dermal- Anagen phase Epidermal Junction Dermis Catagen phase Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 10, 2023 on www.thecalgaryguide.com

Diabetic Retinopathy

Diabetic Retinopathy: Pathogenesis and clinical findings Authors: Graeme Prosperi-Porta Lucy Yang Reviewers: Stephanie Cote Usama Malik Mao Ding Johnathan Wong* * MD at time of publication Family history of T1DM Genetics: (DR3, DR4, DQ non-asp genes) Ethnicity: White youth, African American, Hispanic, Asian-Pacific Islanders, and American Indigenous Type 1 Diabetes Mellitus (T1DM) (see Diabetes Mellitus, Type I for pathogenesis) Type 2 Diabetes Mellitus (T2DM) (see Diabetes Mellitus, Type II for pathogenesis) Polycystic Ovarian Syndrome Family history of T2DM History of Gestational Diabetes ↑ Body Mass Index ↑ Age Ethnicity: Indigenous Americans, African American, Hispanic Poor glycemic control Chronic high blood sugaràinflammatory response ↑ cytokines and growth factors including vascular endothelial growth factor (VEGF) Vascular permeability Retinal neovascularization Vascular endothelial dysfunction: basement membrane thickening, vascular cell death, vascular occlusion from platelet aggregation Retinal hypoxia Outpouchings of the weakened capillary walls or endothelial buds attempting to re-vascularize the ischemic retina Weakened blood-retinal barrier (BRB) allows for rupture into the deeper retinal layers Lipid deposits with sharp margins due to lipoproteins & other proteins leaking through the damaged blood-retinal barrier Nerve fiber layer infarcts from occlusions of the precapillary arterioles Retinal hemorrhages occur in the more superficial nerve layer Focal areas of saccular venous bulges due to significant retinal ischemia & endothelial wall weakening and damage Diabetic Retinopathy (DR) A complication of diabetes due to chronic hyperglycemia resulting in abnormal permeability and ischemia of retinal vessels Micro-aneurysms Dot/blot hemorrhages Hard exudates (yellow opaque solids on retina) Cotton-wool spots (cloudy translucent patches on retina) Flame hemorrhages (multiple opaque red patches) Venous beading (veins with areas of narrowing forming bead-like segments) Traction retinal detachment Bleeding into the vitreous humor Pericyte death, breakdown of endothelial tight junctions & basement membrane thickening damages blood-retinal barrier Damaged blood- retinal border leaks fluid into the retinal tissues Macular edema (swelling of macula) Mild Non-proliferative DR Moderate Non-proliferative DR Severe Non-proliferative DR Proliferative DR Presence of neovascularization Localized retinal ischemia causes upregulation of vascular endothelial growth factor causing fine, irregular & easily friable neovascularization in the disc, macula, and/or retina Neovascularization (fine loop networks of new blood vessels) Neovascular membranes in vitreous gel form vitreoretinal adhesions and contract Fragile vessels extending into the vitreous humor Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 28, 2017, updated May 18, 2023 on www.thecalgaryguide.com

OA Clinical findings

Osteoarthritis: Pathogenesis and clinical findings Ehlers-Danlos Syndromes (connective tissue disorders, e.g., Familial Hypermobility Syndromes) Damage of normal cartilage under abnormal loading Authors: Sean Spence Modhawi Alqanaie Reviewers: Yan Yu Jennifer Au Mao Ding Gary Morris* * MD at time of publication Single large traumatic event or repeated microtrauma Damage to normal articular cartilage under normal loading (force put on a joint) Genetic anomalies in cartilage production and inborn errors of cartilage metabolism Damage of abnormal cartilage under normal joint loading Destruction/attrition of articular cartilage Osteoarthritis A degenerative joint disease that can affect both load bearing joints (knee, hip) as well as in smaller joints (proximal inter-phalangeal, carpometacarpal joints in hand) Repeated physical joint trauma Aberrant bone deposition secondary to wear on subchondral bone Formation of osteophytes (bony projections) and subchondral sclerosis (bone thickening) Lack of cartilage Direct contact between bony processes with movement of the joint Inflammation alters the chemical milieu of joint tissue Synovial fluid forced into bone Damage to subchondral (under cartilage) blood vessels Subchondral fractures cytokines regulate hyaluronic acid synthase Synovium makes lower molecular weight hyaluronic acids (a potent proinflammatory molecule) ↓ synovial fluid viscosity ↑ risk of infection Increased secretion of proteolytic enzymes ↑ joint fluid production Joint effusion Disruption of normal joint architecture Palpable bony hypertrophy (ex. Bouchard’s nodes (bony bumps on the middle joints of the finger)) Impaction of osteophyte with normal joint structures during movement Physical disability Crepitus (grating sound in a joint) Joint movement with reduced lubrication stimulates joint nociceptors Stimulation of joint nociceptors (sensory receptors that detect damaging stimuli) in subchondral bone Pain with use of joint Pain with motion ↓ Range of motion Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 1, 2012, updated May 18, 2023 on www.thecalgaryguide.com

Digestion and Absorption of Macromolecules

Digestion and Absorption of Macromolecules Authors: Krisha Patel Reviewers: Parker Lieb, Sunawer Aujla Ran (Marissa) Zhang, Shyla Bharadia, Mao Ding Sylvain Coderre* *MD at time of publication Lipids (triglycerides) Gastric lipase breaks down triglycerides into diglycerides and fatty acids (little digestion of triglycerides occur in stomach) Bile, produced by the liver, and pancreatic lipase enter the small intestine through the common bile duct The hydrophobic and hydrophilic properties of bile allow it to effectively bind hydrophobic fats with hydrophilic pancreatic lipases Pancreatic lipases break down triglycerides into monoglycerides, fatty acids, and glycerol as a result of emulsification by bile Monoglycerides and fatty acids are absorbed through bile-stabilized chylomicrons (lipid molecules arranged in spherical form) Triglyceride-rich chylomicrons are transported through the lymphatic system and require the activity of tissue lipoprotein lipase when they arrive at the tissue Triglycerides enter systemic circulation for metabolism, energy source, and fat storage Ingestion of nutrition sources containing macromolecules Carbohydrates (oligosaccharide) Salivary amylases in the mouth break down oligosaccharides and starch into shorter polysaccharides Pancreatic amylases break down polysaccharides into monosaccharides, disaccharides, and oligosaccharides in the stomach Brush border enzymes in small intestinal villi break down disaccharides into Proteins (peptides) Pepsinogen is secreted by the stomach wall Hydrochloric acid activates pepsinogen to pepsin in the stomach Pepsin breaks down protein peptides into oligopeptides and amino acid chains The pancreas generates trypsinogen and other enzymes to be released into the duodenum Trypsinogen undergoes cleavage in the duodenum through the action of duodenal enteropeptidases to form trypsin Intravenous proton pump inhibitors used in upper gastrointestinal bleeds stabilize pepsinogen, and prevent pepsin from breaking down clotting factors (proteins) enabling clotting Maltose Maltase monosaccharides: Sucrose Sucrase Glucose + fructose Lactose Lactase Glucose + galactose Glucose + glucose Conditions affecting the duodenum (e.g., Celiac disease) can lead to lower enteropeptidase levels, resulting in impaired protein digestion Activation of trypsinogen to trypsin within the pancreas, rather than in the duodenum, contributes to autodigestion observed in acute pancreatitis Absorption of glucose and galactose through active transport via SGLT-1 carrier protein in the Jejunum and Ileum Absorption of fructose through facilitative diffusion via transporter GLUT5 in the Jejunum and Ileum Pancreatic enzymes (trypsin, chymotrypsin, carboxypeptidase) break down oligopeptides and amino acid chains into amino acids, dipeptides, and tripeptides in the duodenum Monosaccharides enter systemic circulation for energy use and storage Active Na+ cotransporters facilitate amino acid absorption in the jejunum and ileum PEPT1 enzymes facilitate absorption of dipeptides and tripeptides, which are then immediately cleaved into amino acids in the jejunum and ileum Amino acids enter systemic circulation for building & repairing muscles Legend: Pathophysiology Mechanism Treatment Effect Complications Published May 18, 2023 on www.thecalgaryguide.com

Physiology of Anti-diuretic hormone

Physiology of Anti-diuretic Hormone (ADH)/Arginine Vasopressin (AVP) Authors: Manaswi Yerrabattini Reviewers: Parker Lieb Mao Ding Shyla Bharadia Laura Hinz* * MD at time of publication Limbic activation (e.g., pain, nausea) Placental production of vasopressinase during pregnancy catalyzes the breakdown of ADH, leading to a temporary Diabetes Insipidus state (see Diabetes Insipidus: Pathogenesis and Clinical Findings slide) Systemic arteriole vasoconstriction Hypovolemia/Hypotension Hyperosmolar state (i.e., extracellular fluid osmolarity above a certain threshold, most commonly due to hypernatremia) Sensed by osmoreceptors in hypothalamus Angiotensin II synthesized through activation of Renin- Angiotensin-Aldosterone System (RAAS) (see Physiology of RAAS slide) Binds to receptors located in the hypothalamus ↓ pressure sensed by baroreceptors in the heart (left atrium and large veins) Receptors transmit signals to brain via the vagus nerve ↓ Arterial baroreceptor firing ↑ Sympathetic activity of nerves innervating afferent arterioles ↑ Hypothalamic secretion of ADH (peptide hormone), transportation to posterior pituitary, and release from posterior pituitary into blood circulation Blood Vessels (Minor role) Kidneys (Main role) ADH binds to to Vasopressin-2 receptors on basolateral side of principal cells in kidneys ↑ Insertion of aquaporin II channels onto apical membrane of late distal tubule and collecting ducts ↑ Water reabsorption ↓ Urine Output and Maintains narrow range of serum osmolarity ↑ Urine Osmolarity and preserves sodium homeostasis ADH binds to Vasopressin-1 receptors on smooth muscle of blood vessels ADH activates calcium signaling pathway ↑ Blood Pressure Maintains overall fluid volume status Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 20, 2023 on www.thecalgaryguide.com

Acute Laryngitis

Acute Laryngitis: Pathogenesis and clinical findings Infectious Author: Charmaine Szalay-Anderson Reviewers: Shayan Hemmati, Sunawer Aujla, Derrick Randall*, Viral (most common) Malaise Fever Fungal Atopy (asthma, allergy) Non-infectious Gastroesophageal Reflux Trauma or damage to larynx Smoking Yan Yu* * MD at time of publication Environmental Pollution/Inhalants Bacterial (S. pneumoniae, H. influenzae, M. catarrhalis) Systemic immune response Spread of infection to larynx through upper respiratory tract Infection of the vocal folds and surrounding tissue Mechanical (vocal misuse/ trauma) (Area in the neck that contains the structures for voice production, anatomically anterior to the esophagus, inferior to the pharynx and superior to the trachea) Irritation of the vocal folds and surrounding tissue Inflammatory cascade triggered Acute Laryngitis Symptoms for <3 weeks Acute injury to vocal folds Vocal fold lesions (i.e., vocal polyps) Laryngeal inflammation Neutrophils and macrophages release inflammatory cytokines Local laryngeal inflammationà↑ vascular permeability ↑ Secretion of mucous leading to airway congestion Cough reflex initiated to clear airway congestion Cough Edema of vocal folds and surrounding tissue Dysphagia (difficulty swallowing) Dysphonia (difficulty speaking) Odynophagia (painful swallowing) Swelling impairs vocal cord vibration Frank aphonia (loss of voice) Progressive worsening of edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 24, 2023 on www.thecalgaryguide.com

Neonatal Sepsis

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

Menopause

Menopause: Pathogenesis and Clinical Findings Perimenopause/Menopausal Transition: Phase preceding last menstrual period in which the first symptoms may occur. Many clinical findings of menopause can occur in perimenopause. 1-2 million primordial follicles first appear in fetal ovaries in the end of the first trimester of the mother’s pregnancy Typically beginning in adolescence, puberty triggers physiological and anatomical changes Menarche (commencement of menstrual cycles) See relevant slide: Menstrual Cycle Physiology: Ovarian Cycle – Brief Overview Each cycle involves ovulation, during which an oocyte is released from the ovary’s dominant follicle into the Fallopian tube Some non-dominant follicles degenerate in a process known as atresia Menstrual cycle stops Menopause marks 1 year since last menstrual cycle ↓ Fluid transudatio n from blood vessels of vaginal wall ↓ Vaginal lubrication Vaginal tissue becomes thinner and more easily irritated Over time, fewer follicles remain in the ovary Some cycles become anovulatory (no oocyte is released from ovary) ↓ Ovulation causes prevents thickening of the endometrial lining ↓ regularity and frequency of periods Ovaries eventually stop releasing oocytes ↑ Oxidative stress- induced apoptosis of dermal fibroblasts Remaining non-dominant follicles become less sensitive to LH and FSH Since follicular cells are responsible for estrogen production, less follicles result in reduced estrogen production ↓ Expression of serotonin receptors in the CNS ↓ LDL receptor expression and ↑HMG- CoA reductase activity ↓ Regulation of the production and clearance of LDL ↑ LDL Cholesterol levels Author: Sunawer Aujla Reviewers: Ashar Memon Yan Yu* * MD at time of publication ↓ Serotonin activity ↓ Density of ↓ Healthy vaginal flora ↑ pH of vaginal fluid ↑ Spread of bacteria otherwise unable to survive in low pH environment Recurrent urinary tract infections ↓ Calcitonin ↑ Sensitivity of bone mass to Parathyroid Hormone ↑ Activation of osteoclasts Mechanism is likely multifactorial and the subjective symptoms of menopause may contribute Depression 5HT receptors in thermoregulatory region of hypothalamus ↑ Inhibition of sexual responses initiated in prefrontal cortex ↓ Libido 2A ↓ Collagen, elastin, and hyaluronic acid ↓ Proliferation of smooth muscle fibers ↓ Inhibition of osteoclasts Narrower thermoregulatory zone Injury to epithelial tissue in multiple areas of the body Atrophy of bladder and urethra epithelium Urinary incontinence More bone resorption than formation Osteoporosis See relevant slide: Osteoporosis: Pathogenesis and risk factors Sometimes, for unknown reasons, core body temperature increases above upper threshold of narrowed thermoregulatory zone Hot Flashes Sudden, temporary onset of body warmth, flushing, and sweating Sometimes, for unknown reasons, core body temperature decreases below lower threshold of narrowed thermoregulatory zone Chills Sudden, temporary onset of shivering, tingling, cold feeling Atrophy of vaginal epithelium Dyspareunia Pain during sexual intercourse ↓ Integrity of of blood vessels Atherosclerosis ↑ Risk for cardiovascular disease Genitourinary Syndrome of Menopause Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 7, 2023 on www.thecalgaryguide.com

Burns - Full Thickness - Pathogenesis and Clinical Findings 2023

Full Thickness Burns: Pathogenesis and clinical findings Radiation Sunlight, x-ray, nuclear Emission/explosion can cause damage to keratinocytes (see Calgary Guide Slide: Superficial Thickness Burns: Pathogenesis and Clinical Findings) Author and Illustrator: Amanda Eslinger Tracey Rice Reviewers: Sunawer Aujla Alexander Arnold Duncan Nickerson* Jori Hardin* * MD at time of publication Epidermis Dermis Sub-cutaneous tissue Fire Contact Scald Chemical Electrical Transfer of heat energy causes direct injury to keratinocytes Hypoxic injury (lack of oxygen) causes ischemia-related cell death leading to necrosis Full thickness burn Non-uniform damage to the epidermal, dermal & subcutaneous layers at varying widths & depths due to unpredictable injury pattern Degraded epidermal & dermal layers cover granulated tissue Ulceration covered by eschar: a thick, dried, black (necrotic) layer Long-term risk of ulcers & infections ↑ Vascular permeability in subcutaneous layers ↑ Intravascular fluid leaves capillaries, ↓ uptake by lymph vessels Edema Compression of surrounding muscles, nerves & vessels Ischemia and/or necrosis ↓ Immunologic response due to impaired epidermal barrier function ↑ Microbial growth creating biofilm & secretion of chemicals that inhibit natural protective process Irritated, inflamed wound bed +/- exudate ↑ Risk of infection & septic shock Destruction of somatosensory structures Hypoesthesia (↓ sensation to stimuli) ↑ Risk of repeated injury due to ↓ response to noxious stimuli Destruction of cutaneous capillary beds ↓ Healing due to ↓ dermal structures throughout wound White or leathery appearance Chronic wounds require surgical interventions ↑ Risk of contractures & skin barrier weakness Legend: Mechanism of Injury Pathophysiology Sign/Symptom Complication Published December 2, 2013, updated June 26, 2023 on www.thecalgaryguide.com

Burns - Full Thickness - Pathogenesis and Clinical Findings

Full Thickness Burns: Pathogenesis and clinical findings Radiation Sunlight, x-ray, nuclear Emission/explosion can cause damage to keratinocytes (see Calgary Guide Slide: Superficial Thickness Burns: Pathogenesis and Clinical Findings) Author and Illustrator: Amanda Eslinger Tracey Rice Reviewers: Sunawer Aujla Alexander Arnold Duncan Nickerson* Jori Hardin* * MD at time of publication Epidermis Dermis Sub-cutaneous tissue Fire Contact Scald Chemical Electrical Transfer of heat energy causes direct injury to keratinocytes Hypoxic injury (lack of oxygen) causes ischemia-related cell death leading to necrosis Full thickness burn Non-uniform damage to the epidermal, dermal & subcutaneous layers at varying widths & depths due to unpredictable injury pattern Degraded epidermal & dermal layers cover granulated tissue Ulceration covered by eschar: a thick, dried, black (necrotic) layer Long-term risk of ulcers & infections ↑ Vascular permeability in subcutaneous layers ↑ Intravascular fluid leaves capillaries, ↓ uptake by lymph vessels Edema Compression of surrounding muscles, nerves & vessels Ischemia and/or necrosis ↓ Immunologic response due to impaired epidermal barrier function ↑ Microbial growth creating biofilm & secretion of chemicals that inhibit natural protective process Irritated, inflamed wound bed +/- exudate ↑ Risk of infection & septic shock Destruction of somatosensory structures Hypoesthesia (↓ sensation to stimuli) ↑ Risk of repeated injury due to ↓ response to noxious stimuli Destruction of cutaneous capillary beds ↓ Healing due to ↓ dermal structures throughout wound White or leathery appearance Chronic wounds require surgical interventions ↑ Risk of contractures & skin barrier weakness Legend: Mechanism of Injury Pathophysiology Sign/Symptom Complication Published December 2, 2013, updated June 26, 2023 on www.thecalgaryguide.com

diverticulosis-vs-diverticulitis-distinguishing-features

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

Knee Osteoarthritis

Authors: Jared Topham Knee Osteoarthritis: Pathogenesis and clinical findings Reviewers: Liam Thompson, Raafi Ali Yan Yu*, Kelley DeSouza* * MD at time of publication Primary Causes Secondary Causes Aging ↓ Synovial fluid in joint Gender Females > males Genetics Family history of osteoarthritis Race Black > Caucasian Joint malposition (e.g. valgus or varus) Articular trauma Inflammatory disease or infection (e.g. Rheumatoid or septic arthritis) Obesity and ↑leptin ↑ Chondrocytes, inflammatory mediators, and metalloproteinases Extracellular matrix degradation ↑ Knee joint loading forces Metabolic syndromes (e.g. diabetes mellitus) ↑ Oxidative stress and insulin resistance Low-grade systemic inflammation ↓ Elasticity and ↑ degradation of cartilage ↑ Friction in knee joint with movement ↓ Cartilage along femoral groove and posterior surface of patella Pain, catching, and crepitus (crackling/clicking sound) in the patellofemoral joint Inability/difficulty with kneeling or climbing stairs Abnormal distribution of forces accumulate and stress articular surface ↑ Damage/laxity to soft tissue structures stabilizing knee joint Knee Osteoarthritis (Multifactorial entity characterized by cartilage breakdown, deterioration of connective tissue, and bone deformities) ↓ Cartilage between distal femur and proximal tibia ↓ Joint spaceàto articular dysfunction Radiographic changes See Osteoarthritis (OA): X-Ray Features slide Repeated attempts to repair cartilage and joint disruption Subchondral bone thickening (sclerosis) under joint cartilage and bone spur (osteophyte) formation around joint line Rotational/antero-posterior instability and ↑ external adduction moments during walking Alterations in proteoglycans, fiber arrangement, and collagen composition in soft tissue structures within/around knee joint ↑ Shear forces and medial compartment narrowing erode and pinch soft tissue structures within the knee joint Cruciate ligament degeneration Weakened passive stabilizers of the knee joint Knee giving way and instability (falls) Meniscal tears, if large àprevents knee extension/flexion Locking of the knee Joint line tenderness: Patient points to area of tenderness/pain reproducible upon palpation Anatomical axis of hip, knee, and ankle joints ↑ loading medially Medial > lateral joint line tenderness ↑ Joint friction activating nociceptors in the surrounding anatomical tissues Injury and inflammation ↑ nociceptive responses in soft tissue structures and subchondral bone within knee joint Nociceptive feedback to brain inhibits activity of motor cortex neurons controlling muscles around the knee ↓ Motor output and muscle activation over time ↓ Muscle strength/endurance, lower limb muscle use, functional ability (walking, stairs, etc.) Joint inflammationà accumulation of fluid within joint Stiffness, swelling, redness, and pain Limited joint space reduces range of motion for femur to roll/slide on tibia ↓ Knee flexion and extension Flexion contracture and antalgic gait Reduced weight acceptance of the joint and surrounding muscles/tendons ↓ Mobility and physical dysfunction Muscular atrophy Reduced function of active stabilizers of the knee joint (quadriceps, adductors, hamstrings) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 30, 2023 on www.thecalgaryguide.com

Rotator Cuff Disease

Rotator Cuff Disease: Pathogenesis and clinical findings Authors: Jared Topham Reviewers: Raafi Ali, Yan Yu*, Kelley DeSouza* * MD at time of publication Aging Collagen fiber disorientation and myxoid degeneration Tendons, ligaments, and connective tissue are replaced by gelatinous and/or mucoid substance Obesity ↑ Loading on shoulder structures ↓ Static stability (from glenoid labrum and ligamentous components) of glenohumeral joint Tensile forces Repeated eccentric tension from overhead activities Trauma, sports, and occupation ↑ Torque, compression, and translational stresses Metabolic syndromes Reactive oxygen species interact with ↑ glucose forming advanced glycation end-products (AGEs) which accumulate in soft tissues Smoking Impingement syndromes Vessel damage, ischemia, tenocyte apoptosis Macro-trauma causing an acute, complete tear in the rotator cuff muscle(s) ↓Dynamic stability (from rotator cuff and periscapular muscles) and range of motion of the shoulder at the glenohumeral joint ↑ Bone on bone contact of proximal humeral head and boney structures of the scapula Subacromial bursa degeneration ↓ Protection of underlying supraspinatus muscle from attrition between humeral head and acromion Rotator Cuff Syndrome (Inflammation, impingement, or tearing of one or more of the four muscles/tendons of the rotator cuff: supraspinatus, subscapularis, infraspinatus, teres minor) Repetitive loading and micro-tearing of tendon/muscle fibers ↑ Oxidative stressors and inflammatory cascades ↓ Vascularity of rotator cuff structures Radiographic changes: See Rotator Cuff Disease: X-ray and ultrasound features slide, in addition to: calcific tendonitis, calcification of in the coracohumeral ligament, and hooked acromion (calcification from tendon pulling) In some cases, soft tissues enclose/surround shoulder joint capsule thicken (fibrose) and tighten Degenerative joint disease and rotator cuff arthropathy Proximal humeral head migration and ↓ subacromial space Inflammation and insufficient healing of rotator cuff structures, which may lead to: Supraspinatus (shoulder abduction) degeneration Pain, shoulder stiffness, ↓ active AND passive range of motion Adhesive Capsulitis (frozen shoulder) Infraspinatus and teres minor (external rotation) degeneration Rotator cuff tendons become inflamed and irritated as they rub against acromion Subacromial impingement Subscapularis (internal rotation) degeneration +Lift-off test: Inability to hold dorsum of the hand off lumbar spine while internally rotating shoulder ↓ Shoulder strength and muscular atrophy Pain with passive shoulder flexion beyond 90° Winging of the scapula during arm adduction +Empty-can test: Weakness and/or arm depression with resisted abduction with arm internally rotated in 90° +Drop-arm test: Inability to maintain shoulder in abducted position at 90° and/or adduct the arm in a controlled manner (resulting in ”dropping”) Weakness to resisted external rotation with elbow in 90° flexion, inability to keep arm externally rotated (infraspinatus) +Hornblower’s sign: decreased external rotation strength in arm abduction (suggests additional teres minor tear) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 30, 2023 on www.thecalgaryguide.com

Keratosis pilaris

Keratosis Pilaris (KP): Risk factors, pathophysiology, and clinical findings Authors: Ayaa Alkhaleefa Reviewers: Tracey Rice Sunawer Aujla Jori Hardin* MD at time of publication* Loss-of-function mutation in filaggrin (a multifunctional structural protein expressed in the epidermis) Inhibits the release of specific amino acids that maintain Keratin (a protein critical to the integrity of the skin barrier) cannot aggregate to align intermediate filaments within corneocytes (cells that comprise the stratum corneum) the natural moisture of the skin ↑ Skin pH (normal pH is 5.5) Distention of the follicular opening ↑ Surface area for hair to sprout Growth of multiple hairs from the distended follicle Development of thick, coiled hairs Rupture of follicular epithelium by the circular hair shaft Skin Epidermal layer Dermal-Epidermal Junction Dermal layer Mutation in filaggrin Keratin accumulation in corneocytes with hair Grouped keratotic follicular papules Excessive keratin accumulates in the follicular spaces ↑ Keratinization of the follicular epithelium forms a keratinous plug in the infundibulum (funnel-shaped epithelial segment of the hair follicle) Irritation of the hair follicle Excess irritation triggers release of inflammatory cytokines FLG FLG Inflammatory cascade creates edematous environment Symmetrical keratotic papules are commonly grouped along extensor surfaces of the upper arms, thighs, and buttocks Perifollicular edema Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Published 27, JUNE, 2023 on www.thecalgaryguide.com

Dermatitis herpetiformis

Dermatitis Herpetiformis: Pathogenesis and clinical findings Genetic predisposition, HLA-DQ2 and HLA-DQ8 Long term exposure to gliadin, a component of gluten, via dietary gluten ingestion Tissue transglutaminase (TTG) in gut lumen is cross linked to gliadin HLA-DQ2 on antigen presenting cells recognizes gliadin antigen Gliadin antigen is presented to sensitized T helper cells and epitope spreading occurs Authors: Elise Hansen Reviewers: Sunawer Aujla Jori Hardin* * MD at time of publication Type 1 T helper cells and plasma cells produce IgA antibody with gliadin antigen Type 1 T helper cells and plasma cells produce IgA antibody with gliadin crosslinked to TTG Type 1 T helper cells and plasma cells produce IgA antibody with gliadin crosslinked to epidermal transglutaminase 3 (TG3) IgA anti-TTG and IgA anti-TG3 circulate in bloodstream IgA anti-TG3 antibodies reach dermis TG3-IgA complex forms and deposits in papillary dermis TG3-IgA complex and Interleukin 8 stimulate neutrophil chemotaxis Neutrophils infiltrate papillary dermis Neutrophils produce proteases Proteases destroy the basement membrane of the dermis Epidermis no longer adheres to dermis Epidermal transglutaminase 3 (TG3) is released from superficial keratinocytes Vesicles filled with IgA deposits and neutrophils Epidermal layer Destruction of dermal papillae/ basement membrane Dermal layer Y Grouped vesicles on extensor surfaces Pruritus TG3-IgA complex Grouped excoriations on extensor surfaces Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published August 25, 2023 on www.thecalgaryguide.com

Superficial thickness burns

Superficial Thickness Burns: Pathogenesis and clinical findings Author: Amanda Eslinger Elise Hansen Illustrator: Amanda Eslinger Reviewers: Alexander Arnold Sunawer Aujla Yan Yu* Duncan Nickerson* * MD at time of publication Epidermis (Penetrated by superficial burns) Dermis Sub-cutaneous tissue Erythema Radiation Sunlight (most common), x-ray, nuclear emission/explosion Specific to sunlight radiation, UV rays reach keratinocytes in the epidermis p53 tumor suppressor protein is induced in keratinocytes Transient cell cycle arrest Apoptotic pathway is Fire Contact Scald Chemical Electrical Direct damage to keratinocytes Skin erosion and sloughing of skin cells Direct stimulation of nociceptive nerve endings in the epidermis DNA repair mechanisms are activated Mistakes in repair process Malignancy (See ‘Basal Cell Carcinoma’ Slide & ‘Squamous Cell Carcinoma’ Slide) Fluid leaves vasculature and enters interstitial tissues of the skin, causing it to swell Edema Triggers release of endothelin A proalgesic protein Selective excitement of nociceptive nerve ending in epidermis Pain initiated in keratinocytes Keratinocytes apoptose Prostaglandins, arachidonic acid metabolites, substance P & proinflammatory cytokines are released into surrounding tissue ↑ Vascular permeability ↑ bloodflow carries warmth to body area Irritation of endothelial cells in the dermal vascular plexus Release of endothelium derived vasodilators such as nitric oxide Vasodilation, ↑ blood flow through vessels ↑ blood under skin leads to skin appearing red Warmth Pressing on skin occludes blood vessels temporarily, making skin Blanchable underneath appear white immediately after pressure is lifted Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 2, 2013, updated Aug 25, 2023 on www.thecalgaryguide.com

Rotator Cuff Disease Xray and Ultrasound Features

Rotator Cuff Disease: X-ray and ultrasound features Rotator cuff tears can affect each of the muscles making up the rotator cuff individually, or in combination Authors: Jared Topham Reviewers: Raafi Ali, Kelley DeSouza* * MD at time of publication Supraspinatus tear (most common) Chronic (>3 months) tear with degenerative-type changes Rotator cuff insufficiency, loss of supporting structures holding humeral head inferiorly Displacement of the humeral head anterosuperiorly and instability of joint Microtrauma affecting superior aspect of glenohumeral joint “Acetabularization” or coracoacromial arch: concave acromial erosion and increased sclerosis (hardening) Subscapularis tear (second most common) Teres minor tear Infraspinatus tear Rotator Cuff Syndrome (Inflammation, impingement, or tearing of one or more of the four muscles/tendons of the rotator cuff: supraspinatus, subscapularis, infraspinatus, teres minor) Acute (partial or full thickness) tear of rotator cuff tendons Humeral subluxation (partial displacement of humeral head relative to glenoid) High riding humerus: decreased acromial humeral distance Decreased acromial humeral interval/space (impinging tendons of rotator cuff) Full: Defect extends from the subacromial bursa (fluid filled sack beneath the acromion and above the rotator cuff tendons) to the articular surface of the glenohumeral joint Tendon/muscle fibers completely separated from bone and/or muscle fiber connections severed Partial: Focal defect affecting a portion of the tendon which may involve the bursa or glenohumeral articular surface Non-visualization of the tendon Acetabularization of glenoid Fluid replaces empty space of tendon tear Overlying fat around the sub acromial bursa falls into tendon gap Sagging peribursal fat sign on ultrasound “Femoralization” of the humerus: bone erosion (destruction) and rounding of greater tuberosity Osteoarthritis of glenohumeral joint: See Osteoarthritis (OA): X-ray features slide Hyperechoic (brightened) line between articular cartilage of humeral head and muscle tendon on ultrasound Cartilage interface sign on ultrasound Hypoechoic (darkened) tendon outline discontinuity on ultrasound imaging Femoralization (rounding) of greater tuberosity Subluxation of the humeral head relative to the glenoid Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 6, 2023 on www.thecalgaryguide.com

5HT3 Antagonists

5-HT3 Antagonists: Mechanism of action and adverse side effects A class of medications that are used for the prevention and treatment of nausea and vomiting caused by chemotherapy, radiation, or postoperatively. Authors: Arzina Jaffer Madison Amyotte Reviewers: Jasleen Brar Mao Ding Karl Darcus* * MD at time of publication ↓ Postoperative nausea & vomiting Central Actions Binds to 5-HT3 (serotonin) receptors in the area postrema within the brainstem containing the chemoreceptor trigger zone ↓ Binding of serotonin which is released from the raphe nucleus in the brainstem ↓ Stimulation of vomiting center (medulla) supressing the vomiting reflex ↓ Stimulation of vagus nerve resulting in ↓ signals to chemoreceptor trigger zone ↓ Abdominal pain signals to the brain ↓ Levels of serotonin uptake in gastrointestinal tract ↓ Stimulation of gastrointestinal tract, diaphragm, and abdominal muscles Peripheral Actions Binds to 5-HT3 (serotonin) receptors on the vagus nerve terminals Other Actions Unknown mechanism for patients with significant cardiac history (e.g., congenital long QT syndrome, bradycardia, electrolyte abnormalities) Unknown mechanism Unknown mechanism ↓ Binding of serotonin which is released from enterochromaffin cells in the gastrointestinal tract Potential blockage of K+ channels in the heart ↓ Visceral sensation associated with irritable bowel syndrome ↓ Colonic motility slowing the rate of digestion ↓ Diarrhea Constipation Alters depolarization and repolarization of the heart Prolongation of QT interval Headache Drowsiness Torsades de Pointes arrhythmia Cardiac arrest Death Rare complications Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 6, 2023 on www.thecalgaryguide.com

Strabismus

Strabismus: Pathogenesis and clinical findings Microvascular dysfunction, trauma, or compression of oculomotor nerve Oculomotor nerve palsy: Dysfunction of the nerve innervating the superior rectus (elevation), inferior rectus (depression), medial rectus (adduction), and inferior oblique muscles (excyclotorsion) Thyroid eye disease (see Thyroid Eye Disease slide for pathogenesis) Inflammatory processes Thickening & fibrosis of extraocular muscles, most commonly the inferior rectus muscle (functions to rotate the eye and depress the gaze) Brown syndrome (congenital) Anomalous interaction between the trochlea and superior oblique muscle tendon Restriction of normal movement of the superior oblique tendon through the trochlea Trochlear palsy (Dysfunction of the trochlear nerve (CN IV)) Weakness of the superior oblique muscle innervated by CN IV (responsible for depression of the gaze and incyclotorsion & rotation of the eye) Near reflex: convergence (eyes adduct), accommodati on (thickening of the lens) & miosis (constriction of the pupil) Excessive accommodation in hyperopic (farsighted) eyes Over-activation of near reflex Accommodative esotropia Aneurysm, infection, iatrogenic injury to cranial nerve (CN) VI Abducens palsy: ocular motor paralysis Failure of CN VI to develop normally in utero Duane syndrome: congenital malformation of CN VI Congenital fibrosis of the extraocular muscles (CFEOM) Restrictive global paralysis of the extraocular muscles that control the movements of the eye Phenotype CFEOM2 Phenotype CFEOM1 & 3 Dysfunction of the abducens nerve (CN VI: innervates the ipsilateral lateral rectus muscle which abducts the eye [turns it laterally]) Orbital fracture (fracture of the orbital floor) Intraorbital contents (inferior rectus muscle and/or surrounding tissue) herniate through the fractured site & are entrapped Idiopathic infantile esotropia Intermittent exotropia Unclear process Exotropia: affected eye is rotated laterally Esotropia: affected eye is rotated medially Hypotropia: affected eye is rotated downward compared to non-affected eye Hypertropia: affected eye is rotated upward compared to non-affected eye Horizontal Strabismus Two different images are received by the eye that cannot be fused together Visual cortex suppresses the input from one eye in order to avoid having diplopia Amblyopia/lazy eye: visual cortex diminishes neural inputs from the corresponding cortical areas of affected eye ↓ Spatial awareness Vertical Strabismus Binocular diplopia: double vision when both eyes are open, and absent when either eye is closed Atypical alignment of the eye Psychosocial consequences: negative impact to mental health due to social bias or abuse, social anxiety, and difficulties with self-image Authors: Mina Mina Lucy Yang Reviewers: Mao Ding William Stell* * MD at time of publication ↓ Visual acuity ↓ Oculomotor control Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 6, 2023 on www.thecalgaryguide.com

normal neonatal changes pathogenesis and clinical findings

Normal Neonatal Changes: Physiology and Clinical Findings The neonatal period is between infants’ time of birth and 4 weeks gestational age. This slide focuses only on changes that are part of the normal growth and development of neonates born at full term (38-42 weeks). Authors: Erin Auld, Dasha Mori Reviewers: Kayla Feragen Mao Ding Danielle Nelson* *MD at time of publication Birth weight: Loss of birth weight up to 10%; should be re-gained within 10-14 days (30 g/day) Stool: transitions from meconium (first stool of neonate that is black, tarry and sticky) to normal (green/brown or yellow mustard) within 2-3 days Meconium passage: within 24 hours of birth Growth • Height: 2.5 cm/month • Head Circumference: Average 1 cm/month in the first year with greatest growth in the first month • Weight: 20-30 g/day for the first 3 months Urination: within the first 24 hours Mother receives intravenous fluids during delivery Colostrum (first milk secretion that contains antibodies) produced in first 2-3 days of lactation post-partum (Lactogenesis I) GI tract maturation Adequate dietary intake Maturation of urinary tract Adequate fluid intake ↑ maternal blood volume Fluid moves between fetus and mother through placenta Fetus’s fluid volume ↑ Infant’s urine output ↑ in first 24 hours post-partum Low breast milk intake in first 2-3 days ↓ progesterone, ↑ prolactin in mother at birth Infant ingests colostrum Mostly water loss, some fat loss ↑ Breast Milk Production (Lactogenesis II) Stomach stretches ↑ in gastrointestinal tract motility (gastrocolic reflex) Ingestion of milk post-partum further stimulates GI maturation 110-120 kilocalories/kg/day Gastrointestinal tract formation begins when the fetus is 4 weeks old. Maturation continues into infancy. Normal gestational age (38-42 weeks) Fetus ingests amniotic fluid in utero Stimulates structural changes, enzymatic activity, and metabolic activity of GI tract Mature detrusor sphincter complex, appropriate bladder capacity, proper renal perfusion, and regular arousal of the neonate Breast milk: Feeding when infant demands it, approximately every 2-3 hours Formula: Feeding when infant demands it, approximately every 4 hours Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 24, 2015, updated Sept 28, 2023 on www.thecalgaryguide.com

Obstructive Hydrocephalus on CT MRI Pathogenesis and findings

Obstructive Hydrocephalus on CT/MRI: Pathogenesis and findings Authors: Nathan Archibald Reviewers: Matthew Hobart, Mao Ding James Scott* * MD at time of publication Congenital Causes: Arnold-Chiari malformation, Dandy-Walker malformation, intrauterine infections, aqueductal stenosis Acquired Causes: Tumor, trauma, hemorrhage, infection Flow in cerebrospinal fluid pathway is obstructed (most commonly at the foramina Monro, aqueduct of Sylvius, fourth ventricle, and foramen magnum) Acute: Lateral walls and inferior surface of the third ventricle bulge out Temporal horns Temporal horns of the lateral of the lateral ventricles dilate ventricles dilate Cerebrospinal fluid accumulates upstream ↑ Ventricular pressure Ventricles dilate (ventriculomegaly) ↑ Intracranial Pressure (See Increased Intracranial Pressure: Clinical Findings Slide) Headache Papilledema Impaired consciousness Nausea and vomiting Image Credit: Radiopaedia Image Credit: radRounds Ventricular ependymal lining is disrupted Cerebrospinal fluid migrates into the surrounding brain parenchyma Transependymal edema Fourth ventricle may Fourth ventricle may Chronic: Septum pellucidum becomes fenestrated Pronounced dilation of the ventricles, especially the lateral and third ventricles Fornices become depressed Corpus callosum thins and elevates dilate, although the dilate, although the posterior fossa often posterior fossa often Distended ventricles compress overlying cortex prevents it from prevents it from getting too large getting too large High T2 or FLAIR High T2 or FLAIR signal around the signal around the lateral ventricles on lateral ventricles on MRI MRI Image Credit: Cumming School of Medicine Image Credit: Radiology Key Third ventricle, pineal, infundibular and supra- optic recesses balloon out Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Oct 10, 2023 on www.thecalgaryguide.com

Acute Respiratory Distress Syndrome

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

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

Guillain-Barre Syndrome

Guillain-Barré Syndrome: Pathogenesis and clinical findings Author: Nissi Wei Mao Ding Reviewers: Owen Stechishin Matthew Harding Cory Toth* * MD at time of publication ↑ Protein in cerebrospinal fluid (CSF) Minor triggers surgery, trauma, bone marrow transplant Initiate immune response (unknown mechanism) GI/respiratory infection (1-3 weeks prior) Campylobacter jejuni, cytomegalovirus, HIV, Epstein-Barr Virus Molecular mimicry: shared ganglioside antigens between peripheral nerve and pathogen coat proteins IgG antibodies to ganglioside antibodies in serum Nerve Conduction Study : ↓ conduction velocity, conduction block Triggered immune response cross-reacts with peripheral nerves, beginning at nerve roots ↑ permeability of blood- nerve barrier at level of proximal nerve roots Demyelination: antibodies attack Schwann cells secondary damage Axonal damage: antibodies attack nodes of Ranvier Nerve Conduction Study: ↓ CMAP (compound muscle action potential) amplitude, normal conduction velocity Acute inflammatory demyelinating polyneuropathy (AIDP) (80-90%) Acute motor axonal neuropathy (AMAN) Acute motor sensory axonal neuropathy (AMSAN) Acute immune-mediated polyneuropathy Tachycardia & Dysrhythmias (Needs cardiac monitoring) Sudden Death Dysautonomia: disruption of the autonomic nervous system responsible for involuntary functions Sensory deficits Motor deficits Universal Areflexia (loss of deep tendon reflexes) Phrenic nerve involvement Diaphragm paralysis Cranial Nerve (CN) involvement Bulbar palsy (CN IX, X, XI,XII) Oculomotor weakness (CN III, IV, VI) Eye Movement Abnormalities (Miller Fisher Syndrome – rare form of regionally- restricted AIDP) BP Fluctuation/ Orthostatic Hypotension (drop of blood pressure from seated/lying to standing) Urinary Retention (transient, late-course) Limb Weakness (legs usually affected first) Impaired swallowing àaspiration pneumonia ↓ ability to clear airway secretions Pain & Paresthesia (in back and extremities) Respiratory Failure (Life threatening: needs ventilatory observation and possibly support) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 1, 2013, updated Oct 15, 2023 on www.thecalgaryguide.com Guillain-Barré Syndrome Minor triggers (surgery, trauma, GI/respiratory infection Campylobacter jejuni, CMV, HIV , EBV (1-3 weeks prior) Molecular mimicry: shared ganglioside antigens between peripheral nerve and pathogen coat proteins Author: Nissi Wei Reviewers: Owen Stechishin Matthew Harding Cory Toth* * MD at time of publication ↑ Protein in CSF bone marrow transplant) Initiate immune response (unknown mechanism) IgG antibodies to ganglioside antibodies in serum NCS: ↓ conduction velocity, conduction block Triggered immune response cross-reacts with peripheral nerves, beginning at nerve roots ↑ permeability of blood- nerve barrier at level of proximal nerve roots NCS: ↓ CMAP amplitude, normal conduction velocity Demyelination: antibodies attack Schwann cells secondary damage Axonal damage: antibodies attack nodes of Ranvier Acute inflammatory demyelinating polyneuropathy (AIDP) (80-90%) Acute motor axonal neuropathy (AMAN) Cranial nerve involvement Dysautonomia Acute motor sensory axonal neuropathy (AMSAN) Eye Movement Abnormalities (Miller Fisher Syndrome – rare form of regionally-restricted AIDP) Acute immune-mediated polyneuropathy Oculomotor weakness (CN III, IV, VI) Bulbar palsy (CN IX, X, XI,XII) Phrenic nerve involvement ↓ ability to clear airway secretions Impaired swallowingà aspiration pneumonia Diaphragm paralysis Respiratory Failure (Life threatening: needs ventilatory observation and possibly support) Motor deficits Sensory deficits Pain & Paresthesias in back and extremities Limb Weakness (legs usually affected first) Universal Areflexia Urinary Retention (transient, late-course) Sudden Death BP Fluctuation, Orthostatic Hypotension Tachycardia, Dysrhythmias (Needs cardiac monitoring) Abbreviations: • NCS - nerve conduction study • CMAP - compound muscle action potential • EBV - Epstein-Barr Virus • CMV - cytomegalovirus • CN - cranial nerve Note: Aα, Aβ peripheral nerve fibres (large, fast-conducting, heavily myelinated axons for muscle stretch, light touch & proprioception) are more affected than Aδ and C fibres (small, less myelinated, slowly-conducting fibres for pain and temperature) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 1, 2013 on www.thecalgaryguide.com

Pulmonary Embolism Pathogenesis and Clinical Findings

Pulmonary Embolism: Pathogenesis and Clinical Findings Virchow’s Triad Body attempts to break down clot Fibrinogen breakdown products in blood Lab: Positive D-Dimer D-Dimer only performed if clinical suspicion of PE low (Well’s Criteria) Authors: Mackenzie Gault Mao Ding Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson* *MD at time of publication Hypercoagulable State Blood clot develops (commonly in deep veins of legs) Venous stasis = Deep Vein Thrombus (95% of PE) Vessel injury Ultrasound: Presence of Clot in Deep Vein of Leg Clot dislodges & migrates to inferior vena cava (IVC)àright atrium of heartàright ventricleàlodges in pulmonary arteries/arterioles Pulmonary Embolism (PE) Thromboembolic blockage of pulmonary vasculature ↓ perfusion to lung parenchyma Clot occludes pulmonary arteries/ arterioles ↑ dead space ventilation and V/Q mismatching Blood pumped from RV to pulmonary arteries cannot pass clot ↑ pulmonary and right ventricle (RV) pressure RV Strain ↑ RV workload, ↓ right coronary artery perfusion Computed Tomography- Pulmonary Angiogram (CTPA): Filling Defect (*see Radiology slide for CTPA findings) Echo: ↑ RV size + ↓ RV function ECG: S1Q3T3 Pattern (McGinn-White Sign: a large S wave in lead I, a Q wave in lead III and an inverted T wave in lead III together indicate acute right heart strain Lab: ↑ Brain natriuretic peptide (BNP) Chest Pain Tachycardia Dyspnea (shortness of breath) Pleuritic chest pain (worsens during breathing) Ischemia of lung tissue distal to clot X-Ray: usually normal, except Hampton’s Hump (↑ opacity in pleural based area), a rare but specific sign of PE) Air flow/ventilation to lungs unaffected VQ Scan (performed when CT contrast is contraindicated): Ventilation- perfusion ratio (V/Q) mismatch Chemoreceptors detect ↑ CO2 and ↓ O2 Signal brain to ↑ breathing rate Tachypnea (rapid breathing) ↓ Arterial O2 Lab: ↑Troponin BP: Hypotension Lab: ↑ Lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Feb 7, 2018, updated Oct 15, 2023 on www.thecalgaryguide.com Pulmonary Embolism: Pathogenesis and Laboratory Findings Virchow’s Triad Authors: Mackenzie Gault Reviewers: Midas (Kening) Kang Usama Malik Kevin Solverson * * MD at time of publication Body attempts to break down clot Fibrinogen breakdown products in blood Positive D-Dimer ↓ perfusion to lung parenchyma Vessel injury = Deep Vein Thrombus (95% of PE) Ultrasound: Presence of Clot in Deep Vein of Leg Notes: Hypercoagulable State Venous stasis Blood clot develops (commonly in deep veins of legs) Clot dislodges, migrates to IVCàright atrium of heartà right ventricleàlodges in pulmonary artery Pulmonary Embolism (PE): Thromboembolic blockage of pulmonary vasculature Clot occludes pulmonary artery/ arterioles • D-Dimer is only performed if clinical suspicion of PE low (Well’s Criteria) • CT-PA is the current diagnostic test for PE • V/Q Scan is performed when CT contrast is contraindicated • X-Ray is usually normal in PE (Except Hampton’s Hump, a rare but specific sign of PE) Ischemia of lung tissue distal to clot X-Ray: Hampton’s Hump pleural based area of ↑ opacity Air flow/ ventilation to lungs unaffected Pleuritic Chest Pain + Dyspnea VQ Scan: V/Q Mismatch ↑ dead space ventilation and V/Q mismatching Chemoreceptors detect ↑ CO2 and ↓ O2 Signal brain to ↑ breathing rate Tachypnea ↓ Arterial O2 Blood pumped from RV to pulmonary arteries cannot pass clot ↑ pulmonary and RV pressure RV Strain CT-PA: Filling Defect Echo: ↑ RV size + ↓ RV Function ECG: S1Q3T3 Pattern Lab:↑ BNP Chest Pain Tachycardia ↑ RV work load, ↓ right coronary artery perfusion Abbreviations: • BNP – Brain Natriuretic Peptide • CT-PA – Computed Tomography-Pulmonary Angiogram • ECG – Electrocardiogram • IVC – Inferior Vena Cava • RV – Right Ventricle • V/Q – Ventilation-Perfusion ratio ↑ Troponin Hypotension ↑ Lactate Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 07, 2018 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

Alcohol Withdrawal Syndrome

Alcohol Withdrawal Syndrome (AWS): Pathophysiology & clinical findings Authors: Rupali Manek Gurreet Bhandal Erika Russell Reviewers: Harjot Atwal Yvette Ysabel Yao Mao Ding Nureen Pirbhai* * MD at time of publication Chronic alcohol use ↓Autonomic adrenergic systems ↓ Dopamine in the nucleus accumbens ↑ EtOH depressant effects on brain ↓ Glutamate- induced excitation ↑ GABA-induced inhibition ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) Long-term physical dependence Abrupt alcohol cessation àabrupt ↓ in blood EtOH concentration Alcohol withdrawal Syndrome Symptoms that occur when patients stop drinking or significantly decrease their alcohol intake after long-term dependence ↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown ↓ Phosphate available to make ATP ↓ ATP ↓ Magnesium (common in patients with DT) Impaired Na-K ATPase function Dysrhythmias ↑ Glutamate-activated depolarization in the brain ↑ Neuronal excitability Seizures Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Apr 15, 2017, updated Oct 18, 2023 on www.thecalgaryguide.com Alcohol Withdrawal Syndrome (AWS): Pathophysiology & clinical findings Authors: Rupali Manek Gurreet Bhandal Erika Russell Reviewers: Harjot Atwal Yvette Ysabel Yao Mao Ding Nureen Pirbhai* * MD at time of publication Chronic alcohol use ↓Autonomic adrenergic systems ↓ Dopamine in the nucleus accumbens ↑ EtOH depressant effects on brain ↓ Glutamate- induced excitation ↑ GABA-induced inhibition ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) Long-term physical dependence Abrupt alcohol cessation àabrupt ↓ in blood EtOH concentration Alcohol withdrawal Syndrome Symptoms that occur when patients stop drinking or significantly decrease their alcohol intake after long-term dependence ↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) ↓ Phosphate available to make ATP ↓ ATP Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Pathophysiology & clinical findings Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication ↓Autonomic adrenergic systems ↓ Glutamate-induced excitation Chronic alcohol use ↑ EtOH depressant effects on brain ↓ Dopamine in the nucleus accumbens ↑ GABA-induced inhibition ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) ↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Physical dependence due to chronic alcohol use Abrupt alcohol cessation Abrupt ↓ in blood EtOH concentration Alcohol withdrawal ↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) ↓ Phosphate available to make ATP ↓ ATP Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: ↓Autonomic adrenergic systems ↓ Dopamine in the nucleus accumbens Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication Alcohol Withdrawal: Pathophysiology & clinical findings Chronic alcohol use ↑ EtOH depressant effects on brain ↓ Glutamate-induced excitation ↑ GABA-induced inhibition ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) ↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Physical dependence due to chronic alcohol use Abrupt alcohol cessation Abrupt ↓ in blood EtOH concentration Alcohol withdrawal ↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Pathophysiology & clinical findings Chronic alcohol use ↓ Dopamine in the nucleus accumbens ↓Autonomic adrenergic systems Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal ↑ GABA-induced inhibition Nureen Pirbhai* * MD at time of publication ↑ EtOH depressant effects on brain ↓ Glutamate-induced excitation ↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) ↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating) Physical dependence due to chronic alcohol use Abrupt alcohol cessation Abrupt ↓ in blood EtOH concentration Alcohol withdrawal ↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Pathophysiology & clinical findings Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication ↑ EtOH depressant effects on brain ↓ Glutamate-induced excitation ↑ Glutamate receptors in attempt to maintain normal arousal state Chronic alcohol use ↑ GABA-induced inhibition GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) ↓ Dopamine in the nucleus accumbens ↓Autonomic adrenergic systems Abrupt alcohol cessation Physical dependence due to chronic alcohol use Alcohol withdrawal ↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use Central nervous system overactivity Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation ↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems) ↑ Sympathetic activity: ↑HR, ↑RR ↑BP, tremor & diaphoresis (↑sweating) Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation ↑ Dopamine in nucleus accumbens Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (predominately visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Fluid and electrolyte abnormalities Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑ RR & ↓ oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Magnesium (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Pathophysiology & clinical findings Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication ↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use CNS overactivity Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (predominately visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days Alcohol cessation ↓ Dopamine Alcohol withdrawal Chronic alcohol use ↑ EtOH depressant effects on brain in the NAc ↓Autonomic adrenergic systems ↑ Dopamine in nucleus accumbens (NAc) relative to chronic alcohol use Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours ↑ Autonomic adrenergic systems relative to chronic alcohol use ↑ Sympathetic activity: ↑HR, ↑RR ↑BP, tremor & diaphoresis (↑sweating) ↓ Glutamate- induced excitation ↑ Glutamate receptors in attempt to maintain normal arousal state ↑ GABA-induced inhibition GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone) Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation Withdrawal seizures: Generalized tonic- clonic convulsions 24-48 hours after alcohol cessation Fluid and electrolyte abnormalities Abbreviations: CNS – Central nervous system K – Potassium DT – Delirium tremens Mg – Magnesium NAc – Nucleus accumbens NMDA – N-methyl-D-aspartate EtOH – Alcohol NT – Neurotransmitter Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑ RR & ↓ oral intake) Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins) ↓ K (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane) ↓ Mg (common in patients with DT) Dysrhythmias, seizures ↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis or muscle breakdown Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 28th, 2014 on www.thecalgaryguide.com Alcohol Withdrawal: Clinical Findings and Complications Authors: Erika Russell Reviewers: Harjot Atwal Nureen Pirbhai* * MD at time of publication Note: *The onset of alcohol withdrawal generally begins 6-24 hours after the last drink with symptoms peaking between 24-36 hours after and gradually lessening. Symptoms typically progress from early symptoms and increased sympathetic activityà hallucinationsàseizures àpotentially Delirium Tremens. Alcohol withdrawal is mild-moderate in severity for 90% of patients. Those who progressively worsen however can enter Delirium Tremens (DT) which has a mortality rate of up to 20%. More likely to have DT if had DT before, age >30 years, concurrent illness, >2 days after EtOH cessation before seeking help, and history of sustained drinking. Long term, heavy alcohol use that leads to physical dependence Abrupt ↓ in blood EtOH concentration Negative physiological reactions to ↓ alcohol intake Adaptive suppression of GABA activity from chronic alcohol enhancement Alcohol Withdrawal* Withdrawal symptoms alleviated by ingesting alcohol Alcohol taken to relieve withdrawal AND/OR Social and internal relapse cues trigger urge to use alcohol Blood EtOH levels >600 mg% can lead to lethal respiratory depression by suppressing the respiratory centers in the brainstem Upregulated autonomic adrenergic systems from chronic alcohol inhibition Discontinuation of alcohol leads to rebound over- activity of the brain and noradrenergic systems Increased Sympathetic Activity Tachycardia, hypertension, tremor and diaphoresis Generalized Tonic-Clonic Seizures Usually begin within 8-24 hours of alcohol cessation and peak after 24 hours. Risk of having seizures ↑ with repeated withdrawals. 1/3 of people can progress to DT if seizures left untreated. Discontinuation of alcohol causes a sudden relative deficiency in inhibitory GABA activity Reduction in dopamine in the nucleus accumbens (NAc) from chronic alcohol exposure Discontinuation of alcohol causes a increase in dopamine levels in NAc Hallucinations Commonly visual (but can be auditory or tactile), develop 12-24 hours after alcohol cessation. Early Symptoms Anxiety, insomnia, vivid dreams, anorexia, nausea, headache and psychomotor agitation Delirium Tremens (DT) Life-threatening state of greatly exaggerated withdrawal symptoms (severe tachycardia, diaphoresis etc.) with confusion/disorientation and hallucinations that generally appears 72-96 hours after the last drink and lasts 2-3 days. Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications

Sustained Monomorphic Ventricular Tachycardia Pathogenesis

Sustained Monomorphic Ventricular Tachycardia: Pathogenesis Structural Heart Disease: (90% of cases) A ventricular scar forms (in the setting of coronary artery disease or cardiomyopathy) that cannot conduct electrical activity The scar is surrounded by a circular conduction pathway consisting of an ⍺- limb (slow conduction with a fast refractory period) and a β-limb (fast conduction but a slow refractory period) A correctly timed depolarization impulse arrives during the refractory period of the β-limb so it can only propagate through the ⍺-limb The β-limb’s refractory period ends just before the impulse leaves the ⍺-limb of the circular pathway Retrograde depolarization occurs into the ⍺ -limb, creating a self-sustaining closed- loop circuit within the ventricle “Re-entry” cause of tachyarrhythmia Idiopathic Causes: (10% of cases) Structurally normal heart on imaging Trigger(s) such as catecholamines ↑ cyclic adenosine monophosphate Intracellular calcium overload occurs in some ventricular myocytes ↑ Intracellular calcium activates sodium- calcium exchangers Sodium influx into the myocytes During normal myocyte repolarization, the net calcium-mediated depolarization reaches the myocyte threshold for an action potential A triggered action potential (termed a “delayed afterdepolarization”) repeatedly occurs within the ventricle “Triggered activity” cause of tachyarrhythmia Authors: Rahim Kanji Reviewers: Stephanie Happ, Raafi Ali, Derek Chew* * MD at time of publication 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: Clinical findings for details Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 22, 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

Pharmacotherapy for Dyslipidemia Overview

Pharmacotherapy for Dyslipidemia: General overview Dyslipidemia Authors: Rupali Manek Reviewers: Gurreet Bhandal, Raafi Ali, Yan Yu*, Samuel Fineblit* *MD at time of publication Hypolipidemia (↓ HDL or ↓ apoB containing lipoproteins like LDL) Bile-acid sequestrants Bind bile acids in intestinal lumen to prevent reabsorption by enterohepatic (gut-liver) circulation ↑ Excretion of bile acids and cholesterol in stool ↓ LDL in blood Side effects: GI disturbances, commonly interact with other drugs by interfering with absorption See Calgary guide slide on “Bile-acid sequestrants: Mechanisms of action & side effects” for complete description of mechanism and side effects (clinical imbalance of lipids) Hypertriglyceridemia (if VLDL mediated & in need of treatment for pancreatitis prevention) Hypercholesteremia (↑ LDL in blood) Ezetimibe Inhibits cholesterol absorption via NPC1L1 transporter ↑ Hepatic (liver) LDL receptor expression ↑ LDL clearance from blood ↓ LDL in blood Avoid in pregnancy See Calgary guide slide on “Ezetimibe: Mechanisms of action & side effects” for complete description of mechanism and side effects Combined hyperlipidemia (↑ Triglycerides and ↑ cholesterol) Statins (ex. rosuvastatin, atorvastatin, simvastatin, pravastatin) Competitive inhibitors of HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis) Fibrates (ex. fenofibrate, gemfibrozil) Activate PPAR! (nuclear receptor) ↑ Lipolysis (breakdown of lipids) and free fatty acid oxidation ↓ Triglycerides in blood Side effects: GI discomfort, rash, pruritis Contraindicated in pregnancy, renal failure, liver & gallbladder disease See Calgary guide slide on “Fibrates: Mechanisms of action & side effects” for complete description of mechanism and side effects PCSK9 inhibitors (ex. evolocumab and alirocumab which are monoclonal antibodies) Inhibit PCSK9 (holds the LDL:LDL receptor complex together as it is internalized into the cell for destruction of LDL) LDL receptor returns to surface without being destroyed ↑ LDL receptor expression ↑ LDL clearance from blood ↓ LDL in blood See Calgary guide slide on “PCSK9 Inhibitors: Mechanisms of action & side effects” for complete description of mechanism and side effects ↓ Cholesterol synthesis in liver ↑ LDL receptor expression in liver LDL receptor recognizes apoB100 (structural protein on LDL) and apoE (structural protein found on chylomicron, VLDL, IDL) ↑ Clearance of LDL cholesterol from bloodstream ↓ LDL cholesterol in blood ↑ HDL in blood ↓ Triglycerides in blood ↓ Atherosclerosis (plaque along walls of blood vessels) Abbreviations: HDL – High density lipoprotein; HMG-CoA – Hydroxymethylglutaryl- CoA; LDL – Low-density lipoprotein; PCSK9 – Proprotein convertase subtilisin/kexin type 9; PPAR! – Peroxisome proliferator-activated receptor alpha; NPC1L1 – Niemann-Pick C1-Like 1; VLDL – Very low-density lipoprotein Side effects: Myalgias (muscular aches), rhabdomyolysis (muscle breakdown), transaminitis (liver inflammation), liver failure, ↑ risk of diabetes mellitus Contraindicated in pregnancy See Calgary guide slide on “Statins: Mechanisms of action & side effects” for complete description of mechanism and side effects Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 6, 2023 on www.thecalgaryguide.com

Anesthetic Considerations for Obese Patients

Anesthetic Considerations In Patients With Obesity Pathophysiology Driving Anesthetic Management Goal Anesthetic Intervention Excess body fat in mouth and pharynx ↑ Total body fat & fat-free mass ↑ Mallampati score ↑ Neck circumference Loss of muscle tone in pharynx & tongue following neuromuscular blocking drugs Airway access difficulty & ↑ Intubation time ↑ Respiratory rate ↓ Time to desaturation Hypoventilation while supine ↓ Functional residual capacity ↑ Gastric aspiration risk ↑ Dosage requirements of lipophilic drugs ↑ Drug metabolism & clearance ↑ Energy cost of weight-bearing activity ↑ Basal metabolic rate ↓ Total respiratory compliance Excess weight compresses lungs Airway obstruction ↑ Oxygen required ↓ Functional residual capacity ↑ Work of breathing Secure a patent airway & avoid hypoxemia Optimize positioning Maintain oxygenation & lung protection Aspiration prophylaxis Achieve optimal anesthetic dosing for altered distribution Optimize anesthetic dosing for altered metabolism & clearance Intubate via endotracheal tube, avoid supraglottic airway device Consider video laryngoscopy Use head-elevated laryngoscopy positioning (“sniffing” position) Pre-oxygenate to ↑ oxygen reserve during intubation Avoid supine positioning, in place of alternate positioning (i.e., reverse trendelenburg) Lung-protective ventilation (↓ tidal volume, optimize oxygen levels, positive end expiratory pressure & recruitment maneuvers) Pre-operative fasting, gastric ultrasound to assess volume Rapid sequence induction to reduce aspiration risk Adjust drug dosages based on individual recommendations to account for altered distribution, metabolism & clearance Excess body fat on chest wall Excess intra- abdominal fat ↑ Gastric volume Excess body fat ↑ Circulating blood volume Obesity- related restrictive lung disease ↑ Load compressing chest wall BMI ≥30 kg/m2 Note: effects vary with the severity of obesity ↑ Pressure on diaphragm and lungs ↓ Outward chest wall force ↑ Abdominal pressure ↑ Fat acts as a reservoir for lipophilic drugs ↑ Fat storage in hepatocytes ↑ Cardiac output ↑ Pressure on gastric contents ↑ Distribution half-life of lipophilic drugs ↑ Volume of distribution for lipophilic drugs ↑ Hepatic cytochrome transcription ↑ Glomerular filtration rate and hepatic blood flow Authors: Brianna Rosgen Reviewers: Kayleigh Yang Ran Marissa Zhang Karl Darcus* * MD at time of publication Legend: Pathophysiology Mechanism Goal Anesthetic Intervention Published Nov 8, 2023 on www.thecalgaryguide.com

Overview of burns

Overview of Burns: Pathogenesis and Types Authors: Haley Shade, Amanda Eslinger* Reviewers: Christy Chong, Parker Lieb, Sunawer Aujla, Alexander Arnold*, Yan Yu*,Duncan Nickerson*, Donald McPhalen* Illustrator: Devjyoti Dutta* * MD at time of publication Contact Electrical Chemical Radiation (excluding sunburn) Less common Burns from any source can result in 3 damage zones Common Fire Scald Zone of coagulation: innermost zone; maximum damage through necrosis and irreversible tissue loss Zone of stasis: middle zone; decreased tissue perfusion, potentially salvageable Zone of hyperemia: outermost zone; tissue perfusion is increased, damage is reversible Epidermis, dermis, and subcutaneous tissue Full Thickness (3rd degree burn) Normal Skin Epidermis only Superficial Thickness (1st degree burn) Epidermis and superficial (papillary) dermis Superficial Partial Thickness (2nd degree burn) Epidermis and deep (reticular) dermis Deep Partial Thickness (2nd degree burn) Skin and deep tissues, muscle, fascia, nerves, blood vessels, bone Composite tissue injury (4th degree burn) Compartment syndrome Epidermal layer Dermal-Epidermal Junction Superficial (Papillary) Dermis Deep (Reticular) Dermis Note: The total burn surface area (TBSA) can be estimated using the rule of nines (1st degree burns are not included): Head and Neck: 9% total, Chest and Upper Back: 9% each, Arm: 9% each, Leg: 18% each (front and back), Abdomen and Lower Back: 9% each, Genital Area: 1% Refer to Complications of Burns Burn Shock Refer to Burn Shock: Pathogenesis, Complications, and Clinical Findings Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 8, 2023 on www.thecalgaryguide.com

Death Cardiovascular Respiratory and Neurologic Mechanisms

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

Turner Syndrome Pathogenesis and Clinical Findings

Turner Syndrome: Pathogenesis and clinical findings Author: Simran Pherwani Ashar Memon, Christy Chong Reviewers: Tara Shannon Simran Sandhu, Mao Ding Danielle Nelson* * MD at time of publication Non-disjunction in phenotypically female gametes (i.e. homologous X-chromosomes or sister chromatids fail to separate) Partial or complete absence of second sex chromosome, leaving only one normal X-chromosome Possible Chromosomal Profiles Other meiotic error → deletion or misdivision of X-chromosomal material Complete loss of one X- chromosome in all cells (45,X) (45%) Skeletal Abnormalities ↓ Expression of SHOX gene (present on X- and Y-chromosomes) ↓ Cellular proliferation in growth plates of bones in extremities during embryonic development Short stature High-arched palate Genu valgum (knock knees) Micrognathia (smaller lower jaw) Broad chest Cubitus valgus (forearm angled outward) Mosaicism (complete loss of one X-chromosome in some cells (e.g., 45,X/46,XXX, etc)) (50%) Congenital Heart Defects (most serious) Single copy of TIMP1 gene and presence of risk TIMP3 allele, and differential expression of KDM6A gene Bicuspid aortic valve Aortic coarctation Aortic dilation (worsened by hypertension) One X-chromosome and presence of Y-chromosomal material in some or all cells (e.g., 45,X/46,XY) Presence of an X- isochromosome (most commonly i(Xq)) Other structural abnormalities of X-chromsome (e.g., Ring Chromosome X, partial deletion of X, X or Y marker chromosome) Endocrine Disorders Turner Syndrome The most common sex chromosomal abnormality in females (affects 1/2000-3000) Results in deletion or non- functioning of one X chromosome Clinical presentations vary depending on chromosome profile Aortic dissection Renal disease Neurocognitive Deficits Mechanism unknown Deficit in social skills Specific (non-verbal) learning disorder (otherwise normal intelligence) ↓ Executive function skills ↓ Visuospatial skills ↓ Attention Accelerated follicular apoptosis (i.e., loss of oocytes from ovaries) → streak gonads Ovaries are unable to respond to high gonadotropins (FSH, LH) Hypergonadotropic hypogonadism Premature ovarian insufficiency ↓ Expression of immune- associated genes on X- chromosome ↑ Autoimmunity Autoimmune diseases (celiac, thyroiditis, IBD, metabolic abnormalities) ↓ Estrogen levels Lack of breast development ↑ Liver enzymes (Additional mechanisms likely) ↓ Bone mineral density Other Dysmorphic Features Lymphedema Webbed (buildup of lymph neck fluidàswelling) Primary amenorrhea Infertility Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com

Non-Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease: Pathogenesis and clinical findings Diagnosis of Metabolic Syndrome when ≥ 3 out of the 5 preceding risk factors are present Authors: Stephanie Happ Reviewers: Obesity Hypertension Diabetes Hypertriglyceridemia Hypercholesterolemia Iffat Naeem Sunawer Aujla Edwin Cheng* * MD at time of publication Insulin resistance develops in adipose tissue and hepatocytes ↓ Ability of insulin to suppress lipolysis of adipose tissue ↑ Delivery of free fatty acids from adipocytes to the liver ↑ De-novo lipogenesis in the liver Hepatic Steatosis: accumulation of fat in the liver (in the absence of alcohol consumption, termed Non-Alcoholic Fatty Liver (NAFL)) Steatohepatitis: chronic inflammatory and apoptotic climate in the hepatocytes (in the absence of alcohol consumption, termed Non-Alcoholic Steatohepatitis (NASH)) Fibrosis of the Liver: excessive scarring of liver tissue resulting from chronic inflammation, although liver architecture is largely intact Fat droplets form and grow in the hepatocytes Hepatic mitochondria increase their workload in attempt to break down the excess free fatty acids through beta-oxidation ↑ in cellular workload creates more reactive oxygen speciesà Inflammation and apoptosis of hepatocytes On-going inflammation damages hepatic stellate cells (the primary extracellular matrix–producing cells of the liver) causing the release of fibrinogenic cytokines Cirrhosis of the liver: normal lobular structure distorts and is replaced by regenerating nodules and bridging septa, disrupting normal liver blood flow Deposition of fibrotic material and collagen within the perisinusoidal spaces of the liver Decompensated Cirrhosis Hepatocellular carcinoma Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com

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

RICE mechanism of action

Rest, Ice, Compression, Elevation (RICE): Mechanism of action Healing of an injury requires pain and inflammatory control to encourage activity. The goal of Rest, Ice, Compression, Elevation (RICE) is to decrease inflammation. Though activity itself will contribute to pain and inflammation, it is integral to the rehabilitation process. Authors: Matthew Roberts Emma Windfeld Reviewers: Alexander Arnold Amanda Eslinger Shyla Bharadia Mao Ding Bradley Jacobs* * MD at time of publication Rest: (weight bearing or stressful motion discontinued) Further damage to affected tissues from mechanical stress is prevented Ice: (applied to injury) Compression: (wrap applied to injured area) Mechanical force applied to tissue Excess fluid is pushed back into capillaries and lymph network Elevation: (limb raised above heart) Blood flow to tissue is constricted Mechanism not well understood ↓ delivery of inflammatory mediators such as polymorphonuclear neutrophils and macrophages to injured site ↓ production of inflammatory cytokines (pro-inflammatory substances) such as Tumor Necrosis Factor-α, Platelet Derived Growth Factor, Epidermal Growth Factor, and Transforming Growth Factor-β ↓ Inflammation Gravity ↑ venous blood return to systemic circulation ↓ edema (accumulation of fluid in interstitium) Early initiation of injury-specific rehabilitative exercises improves range of motion, strength, and proprioception Stress to targeted area induces inflammation that, when tightly regulated, is integral to repair Injured muscle, tendon, bone, or ligament is strengthened ↓ Pain ↑Range of motion and therefore function Early recovery from injury Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 9, 2013, updated Oct 15, 2023 on www.thecalgaryguide.com Rest, Ice, Compression, Elevation (RICE): Mechanism of action Healing of an injury requires pain and inflammatory control to encourage activity. The goal of Rest, Ice, Compression, Elevation (RICE) is to decrease inflammation. Though activity itself will contribute to pain and inflammation, it is integral to the rehabilitation process. Authors: Matthew Roberts Emma Windfeld Reviewers: Alexander Arnold Amanda Eslinger Shyla Bharadia Bradley Jacobs* * MD at time of publication Rest: (weight bearing or stressful motion discontinued) Further damage to affected tissues from mechanical stress is prevented Ice: (applied to injury) Compression: (wrap applied to injured area) Mechanical force applied to tissue Excess fluid is pushed back into capillaries and lymph network Elevation: (limb raised above heart) Gravity ↑ venous blood return to systemic circulation Blood flow to tissue is constricted ↓ delivery of inflammatory mediators such as polymorphonuclear neutrophils and macrophages to injured site Mechanism not well understood ↓ production of inflammatory cytokines (pro- inflammatory substances) such as Tumor Necorsis Factor-α, Platelet Derived Growth Factor, Epidermal Growth Factor, and Transforming Growth Factor-β ↓ Inflammation ↓ Pain ↓ edema (accumulation of fluid in interstitium) ↑Range of motion and therefore function Early initiation of injury- specific rehabilitative exercises improves range of motion, strength, and proprioception Stress to targeted area induces inflammation that, when tightly regulated, is integral to repair Injured muscle, tendon, bone, or ligament is strengthened Early recovery from injury Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications RICE: Mechanism of action Authors: Matthew Roberts Emma Windfeld Reviewers: Alexander Arnold Amanda Eslinger Shyla Bharadia Bradley Jacobs* * MD at time of publication Rest (weight bearing or stressful motion discontinued) Ice (applied to injury) Compression (wrap applied to injured area) Elevation (limb raised above heart) Constricts blood flow to tissue Mechanism not well understood Mechanical force applied to tissue ↓ Delivery of polymorphonuclear neutrophils and macrophages to injured site Excess fluid pushed back into capillaries and lymph network Gravity ↑ venous blood return to systemic circulation Prevents further damage to affected tissues from mechanical stress ↓ Production of inflammatory cytokines ↓ Edema (accumulation of fluid in interstitium) ↓ Inflammation ↓ Pain ↑Range of motion and therefore function Early initiation of injury-specific rehabilitative exercises to improve range of motion, strength, and proprioception Stress to targeted area induces inflammation that, when tightly regulated, is integral to repair Injured muscle, tendon, bone, or ligament is strengthened Early recovery from injury Legend: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications

Mechanical Ventilation mechanisms of action and complications

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

Acute Respiratory Distress Syndrome ARDS CXR findings

Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Author: Iffat Naeem Direct or indirect lung injury causing acute respiratory distress syndrome (see Acute Respiratory Distress Syndrome slide for pathogenesis and clinical findings) Activation of dysregulated inflammatory cascade Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Bilateral infiltrate that can present in all regions of lung Air bronchograms Silhouette sign Reviewers: Victória Silva, Mao Ding Tara Lohmann* *MD at the time of publication Edema not due to a cardiogenic cause Damage to alveolar epithelium Necrosis of epithelial cells Erosion of alveolar basement membrane ↑ Alveolar epithelium permeability Damage to lung capillary endothelium Release of inflammatory cytokines Neutrophils migrate into alveoli Fluid-filled alveoli show as white/grey opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and widespread damage to alveoli and interstitium that show as white/grey opacities ↑ Capillary endothelium permeability Alveolar edema Degradation of alveolar- capillary barrier Proliferative phase Alveolar epithelium attempts to recover Chronic phase Can either resolve or progress to fibrotic thickening and scaring of alveoli ↑ Leakage of fluid from capillaries into alveoli and lung interstitium Pulmonary fibrosis (scarring) ‘White lung’ appearance Image credit: Radiopaedia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 25, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Direct or indirect lung injury causing acute Author: Iffat Naeem Reviewers: Victória Silva respiratory distress syndrome* Activation of dysregulated inflammatory cascade Bilateral infiltrate that show as white/grey can present in Damage to alveolar epithelium Necrosis of epithelial cells Erosion of alveolar basement membrane ↑ Alveolar epithelium permeability Damage to lung capillary endothelium Fluid-filled alveoli opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and all regions of lung Release of inflammatory cytokines Neutrophils migrate into alveoli Alveolar edema Air bronchograms ↑ Capillary endothelium permeability Degradation of alveolar-capillary barrier Proliferative phase Alveolar epithelium attempts to recover Chronic phase Can either resolve or progress to fibrotic thickening and scaring of alveoli ↑ Leakage of fluid from capillaries into alveoli and lung interstitium Silhouette Sign widespread Pulmonary damage to alveoli ‘White lung’ appearance fibrosis (scarring) and interstitium that show as white/grey opacities *See corresponding Calgary Guide slides for more details Image credit: Radiopaedia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Direct or indirect lung injury causing acute respiratory Author: Iffat Naeem Reviewers: Victória Silva distress syndrome* Activation of dysregulated inflammatory cascade Bilateral infiltrate that show as white/grey can present in Damage to alveolar epithelium Necrosis of epithelial cells Denudation of alveolar basement membrane ↑ epithelium permeability Degradation of alveolar-capillary barrier Alveolar epithelium attempts to recover through (proliferative phase) Damage to lung capillary endothelium Fluid-filled alveoli opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli results in lack of differentiation of heart borders Diffuse and all regions of lung Air bronchograms Release of proinflamm atory cytokines Neutrophil migration into airspace Alveolar Edema ↑ capillary endothelium permeability ↑ leakage of fluid from vasculature into airspace and lung interstitium Can either resolve or progress to fibrotic Silhouette Sign widespread Pulmonary damage to alveoli ‘White lung’ appearance thickening and scaring of Fibrosis alveoli (chronic phase) and interstitium that show as white/grey opacities Image credit: Radiopaedia *See corresponding Calgary Guide slides for more details Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Author: Iffat Naeem Reviewers: Victória Silva Acute Lung Injury (see ‘ARDS: Pathogenesis and Clinical findings’ slide) causing impaired oxygenation Lung injury not due to cardiogenic cause (see ‘ARDS: Pathogenesis and Clinical findings’ slide) Alveolar endothelium damage promotes inflammatory marker release Exudative phase (1-6 days): neutrophils adhere to damaged endothelium and release pro- inflammatory mediators Accumulation of intra-alveolar fluid that is rich in neutrophils, macrophages, and red blood cells Proliferative phase (7-14 days): proliferation of alveolar epithelial Fibroblasts deposit collagen tissue in alveolar walls and spaces Can either resolve or progress to fibrotic thickening and scaring Alveolar Edema Fluid-filled alveoli show as white/grey opacities Air-filled bronchi appear dark when surrounded by grey/white opacification of fluid-filled alveoli Increased opacification from fluid-filled alveoli Bilateral infiltrate present in all regions Air bronchograms results in lack of Silhouette Sign differentiation of heart borders Diffuse alveolar damage ‘White lung’ appearance Image credit: Radiopaedia *See corresponding Calgary Guide slides for more details Legend: (chronic phase) Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published X, 2023 on www.thecalgaryguide.com Lung injury not due to a cardiogenic cause Absent pleural effusion Normal heart size Absent Kerly B lines No perihilar infiltrate pattern Acute Respiratory Distress Syndrome (ARDS): Chest X-Ray Findings

Anesthetic Considerations One Lung Ventilation

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

Zenkers Diverticulum Pathogenesis and Clinical Findings

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

vWF Deficiency

von Willebrand Factor (vWF) Deficiency: Authors: Tristan Jones, Nimaya De Silva Reviewers: Sean Spence, Yan Yu, Paige Shelemey, Tony Gu, Raafi Ali, Man-Chiu Poon*, Lynn Savoie* * MD at time of publication Pathogenesis and clinical findings Inherited Acquired Autosomal dominant inheritance Recessive inheritance Type III: Complete quantitative vWF deficiency Presence of antibodies to vWF (a blood clotting protein involved with platelet adhesion), often in setting of autoimmune disease Antibodies bind and inactivate existing vWF Clonal lympho-proliferative disease (uncontrolled production of lymphocytes, a type of immune cell) Adsorption of vWF multimers on to tumor cells ↑ Plasma clearance of vWF ↓ vWF to stabilize/carry plasma Factor VIII (blood clotting protein) ↓ Plasma Factor VIII Impaired intrinsic pathway of coagulation cascade (see Calgary Guide slide on coagulation cascade) Type I: Partial quantitative vWF deficiency Type II: Impaired vWF function (qualitative deficiency) ↓ Binding to vWF-specific antibody on immunoassay ↓ vWF antigen assay (diagnostic test for quantitative vWF deficiency) ↑ Bleeding/closure time (bleeding time measures the length of time required to form a platelet plug) Spontaneous hematomas (large collection of blood outside the blood vessels) Menorrhagia (heavy menstrual bleeds) vWF Deficiency ↓ vWF quantity and/or function ↓ vWF available to bind to damaged blood vessel collagen to anchor platelets Impaired platelet plug formation Bleeding from mucosal surfaces Easy bruising Gum bleeding ↑ Time for blood clot to form Risk of severe hemorrhage ↑ Partial Thromboplastin Time (PTT) (measures the integrity of the intrinsic pathway) Epistaxis (nose bleed) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-published December 5, 2023 on www.thecalgaryguide.com

Operative Vaginal Delivery Indications

Operative Vaginal Delivery (forceps/vacuum): Indications Authors: Taylor Pigott Akaya Blair Reviewers: Michelle J. Chen Sylvie Bowden* Stephanie Cooper* Sarah Glaze* * MD at time of publication Abnormal fetal heart rate/fetal distress ↓ Risk of maternal and fetal morbidity/ morality Rupture of membranes without fetal head adequately applied to maternal pelvis Small pelvic outlet Narrow vaginal canal Cardiovascular disease Diabetes Hypertension Abdominal trauma Short umbilical cord Large for gestational age (LGA) fetus Neurological/ muscular disease ↑ Pain during labor Maternal contraindication to Valsalva maneuver (e.g., cardiac disease, cystic lung) Rush of fluid past the fetal head out through cervix Umbilical cord prolapse Umbilical vasoconstriction Umbilical cord compression ↓ Blood flow through umbilical cord Fetal presenting part applies pressure on umbilical cord Impaired vascular function and narrowed vessels ↓ blood flow around the body ↓ Oxygen transfer across the placenta Fetal oxygen deprivation and hypoxia Operative vaginal delivery with forceps or vacuum expedites delivery Placenta partially or completely separates from uterine wall (abruption) Increased tension of umbilical cord on placenta Fetal shoulder is lodged behind maternal pubic symphysis Delivery of the body is delayed Inability to adequately bear down to push Myometrium runs out of energy from repeated contractions and becomes less able to contract (↓ uterine tone) Uterine spiral arteries dependent on contractions for vasoconstriction remain dilated, allowing blood flow Postpartum hemorrhage Uterine rupture ↑ Risk of future pelvic organ prolapse ↑ Risk of future incontinence Prolonged labour Repeated contraction/ relaxation of the uterus without progress tears and damages uterine muscles ↓ Maternal endurance Inadequate fluid and food intake prior to/ during labor Multiples ↑ Sympathetic nervous system activation during labor Maternal exhaustion Uterine muscles stretch to accommodate multiple growing fetuses ↑ Pushing against pelvic floor and perineum Pushing force damages pelvic floor muscles and nerves ↓ Myometrial contractility ↑ Need for vaginal exams to check on labour progress Bacterial overgrowth in vagina and/or uterus Maternal infection Fetal infection ↓ Strength of contractions Epidural anesthetic Inability to ambulate to urinate ↑ Urinary catheterizations ↑ Epinephrine secretion from adrenal cortex Blood is shunted away from uterus/internal organs and towards heart and skeletal muscle Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published 03, ##, 2023 on www.thecalgaryguide.com

Low Ankle Sprain

Low Ankle Sprain: Pathomechanics and Clinical Findings Authors: Parker Lieb, Joseph Kendal Illustrator: Erica Lindquist Reviewers: Liam Thompson, Tara Shannon, Sunawer Aujla, Stephanie de Waal, Amanda Eslinger, Dave Nicholl, Maninder Longowal Gerhard Kiefer* *MD at time of publication Ankle eversion beyond normal range (less common) Excessive stress to medial ankle deltoid ligament Ankle plantar flexion and inversion beyond normal range (most common) Excessive stress to lateral ankle ligament(s) Associated fracture of malleolus or subtalar joint Bone pain, inability to weight bear Recruitment of inflammatory cells to damaged area ↑ Local pro- inflammatory cytokines ↑ Capillary permeability & vasodilation to damaged area Collagen fibers in ligament(s) rupture Low Ankle Sprain (medial or lateral) Local blood vessels tear Blood leaks into surrounding tissue Grade I Mild injury Grade II Moderate injury Grade III Severe injury Minimal ligament disruption Incomplete ligament tear Complete ligament tear No joint laxity Joint laxity Gross joint laxity Mechanical and functional instability Decreased ankle joint space Ankle Impingement (compression of soft and/or bony structures in joint) Chronic ankle instability Talus subluxation with anterior force on heel + Anterior drawer test Recurrent sprains Synovial inflammation & hypertrophy Remodeling of collagen and bone Degenerative changes (e.g., osteophytes, subchondral sclerosis) Damage to mechanoreceptors in muscles surrounding ankle joint Bruising Swelling Focal tenderness over torn ligament(s) Pain on injury and with weight bearing Impaired proprioception & neuromuscular control Nociceptors activated by trauma and inflammatory factors Falls Antalgic gait Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 9, 2014; updated Aug 15, 2023 on www.thecalgaryguide.com