Osler Notes 2019 PDF

Editor-in-Chief: Alfiya Mukharyamova Senior Editors: Owen Litwin and Corey Toye Illustrator: Danica Quickfall Acknowledgment: Bellal Jubran, Abrar AlJassim and Neil-Verma 1 Table of Contents Block A – Molecules to Global Health..................

Editor-in-Chief: Alfiya Mukharyamova Senior Editors: Owen Litwin and Corey Toye Illustrator: Danica Quickfall Acknowledgment: Bellal Jubran, Abrar AlJassim and Neil-Verma 1 Table of Contents Block A – Molecules to Global Health.................................................................................................................... 4 Part 1: Epidemiological Measures................................................................................................................................................ 5 Part 2: Key Points from the Ottawa Primer & Health Issues.............................................................................................. 6 Part 3: Introductory Medical Pharmacology & Genetics...................................................................................................... 9 Appendix.............................................................................................................................................................................................11 Block B - Respirology............................................................................................................................................. 12 Part 1: Key definitions....................................................................................................................................................................13 Part 2: Interpretation of Blood Gases.......................................................................................................................................13 Part 3: Obstructive Lung Disease...............................................................................................................................................14 Part 4: Restrictive Lung Disease.................................................................................................................................................18 Part 5: Pneumonia...........................................................................................................................................................................19 Part 6: Tuberculosis (see Block G for additional details)..................................................................................................20 Part 7: Lung Cancer.........................................................................................................................................................................21 Part 8: Miscellaneous pulmonary diseases.............................................................................................................................23 Block C - Cardiology.............................................................................................................................................. 25 Part 1: Physiology............................................................................................................................................................................26 Part 2: The Sequence of ECG Interpretation...........................................................................................................................27 Part 3: Arrhythmias.........................................................................................................................................................................28 Part 4: Acute Coronary Syndrome..............................................................................................................................................30 Part 5: Valvular Heart Disease and Heart Sounds................................................................................................................32 Part 6: Pericardial Diseases........................................................................................................................................................34 Part 7: Heart Failure.......................................................................................................................................................................35 Part 8: Acute Pulmonary Edema................................................................................................................................................37 Part 9: Peripheral Vascular Disease.........................................................................................................................................37 Block D: Renal......................................................................................................................................................... 38 Part 1: Basic Concepts in Renal Physiology............................................................................................................................39 Part 2: Water Homeostasis...........................................................................................................................................................40 Part 3: Electrolyte Imbalance......................................................................................................................................................40 Part 4: Acid Base Disorders..........................................................................................................................................................44 Part 5: Glomerular Disease...........................................................................................................................................................46 Part 6: Acute and Chronic Kidney Disease..............................................................................................................................47 Part 7: Hypertension.......................................................................................................................................................................51 Part 8: Nephrolithiasis...................................................................................................................................................................51 Part 9: Lower Urinary Tract Disorders....................................................................................................................................52 Block E: Digestion and Metabolism...................................................................................................................... 53 Part 1: Hernias..................................................................................................................................................................................54 Part 2: Esophageal Disorders......................................................................................................................................................55 Part 3: Gastric Disorders...............................................................................................................................................................59 Part 4: Intestinal Disorders..........................................................................................................................................................62 Part 5: Diseases of the Liver.........................................................................................................................................................67 Part 6: Biliary Disease....................................................................................................................................................................71 Part 7: Pancreatic Disorders........................................................................................................................................................74 Part 8: Anorectal Disorders..........................................................................................................................................................76 Part 9: Hypothyroidism vs. Hyperthyroidism.......................................................................................................................78 Part 10: Diabetes Mellitus.............................................................................................................................................................79 Part 11: Adrenal Gland Pathology..............................................................................................................................................80 Part 12: The basics of common vitamin and mineral deficiencies.................................................................................81 Block F: Defence..................................................................................................................................................... 83 Introduction: Innate Immune System vs Adaptive Immune System.............................................................................84 Part 1: Fever.......................................................................................................................................................................................84 Part 2: Innate Immune Deficiency.............................................................................................................................................85 2  Part 3: Hypersensitivity Reactions............................................................................................................................................86 Part 4: Vaccination..........................................................................................................................................................................87 Part 5: Emergency Conditions.....................................................................................................................................................88 Part 6: Anemia (note: this topic is covered in different blocks each year).................................................................90 Block G: Infection................................................................................................................................................... 94 Part 1: The Basics of Lab Diagnostics........................................................................................................................................95 Part 2: Antibiotics............................................................................................................................................................................96 Part 3: Virology.................................................................................................................................................................................98 Part 4: Mycology............................................................................................................................................................................ 100 Part 5: Parasitology...................................................................................................................................................................... 101 Part 6: Upper Respiratory Tract Infections......................................................................................................................... 102 Part 7: Tuberculosis (TB)........................................................................................................................................................... 104 Part 8: Fever of Unknown Origin (FUO)................................................................................................................................ 104 Part 9: Sepsis and Bacteremia.................................................................................................................................................. 105 Part 10: HIV..................................................................................................................................................................................... 106 Part 11: Meningitis....................................................................................................................................................................... 108 Part 12: Hepatitis.......................................................................................................................................................................... 110 Part 13: Diarrhea.......................................................................................................................................................................... 111 Part 14: Osteomyelitis................................................................................................................................................................. 112 Part 15: Infective Endocarditis................................................................................................................................................ 113 Part 16: Urinary Tract Infections (Basics) and STIs......................................................................................................... 114 Block H: Movement.............................................................................................................................................. 116 Part 1: Spinal and musculoskeletal injuries........................................................................................................................ 117 Part 2: Osteoarthritis and Rheumatoid Arthritis.............................................................................................................. 122 Part 3: Osteoporosis (reviewing canadian osteoporosis screening guidelines once is helpful)...................... 124 Part 4: Gout...................................................................................................................................................................................... 124 Part 5: Neuropathies.................................................................................................................................................................... 125 Part 6: Low Back Pain................................................................................................................................................................. 127 Block I: Reproduction and Sexuality.................................................................................................................. 128 Introduction: Physiology to Know.......................................................................................................................................... 129 Part 1: Disease Processes of the Male Reproductive System........................................................................................ 130 Part 2: Diseases of the Female Reproductive System...................................................................................................... 132 Part 3: Pregnancy and Delivery............................................................................................................................................... 138 Part 4: Neonatology and Pediatrics........................................................................................................................................ 141 Block J: Behaviour................................................................................................................................................ 145 Part 1: Neurology Introduction................................................................................................................................................ 146 Part 2: An Abbreviated Approach to the Neurologic Exam............................................................................................ 147 Part 3: Neurology Problems...................................................................................................................................................... 148 Part 4: Ophthalmology................................................................................................................................................................ 163 Part 5: Otolaryngology................................................................................................................................................................ 170 Part 6: Psychiatry.......................................................................................................................................................................... 178 Dermatology.......................................................................................................................................................... 184 Radiology............................................................................................................................................................... 191 Practice Questions................................................................................................................................................. 199 3 Block A – Molecules to Global Health Editors: Christelle Khadra and Sara Ismail Acknowledgement: Gabriel Souza 4 PART 1: EPIDEMIOLOGICAL MEASURES Epidemiological measures help us to interpret results from different clinical trials, so that we are able to choose the best therapeutic options for our patients. Moreover, they are also important in terms of public health, since they give us important information on the patterns of diseases among different populations. For additional information about basic calculation of incidence and prevalence please refer to your block notes. Table A1: Basic Statistics of Epidemiology Measure Definition Mathematical Formula Sensitivity Proportion of all people with disease who test positive, or the = TP/ (TP + FN) (true-positive probability that a test detects disease when it is present. = 1 – (false-negative rate) rate) Good for ruling out (think SNout = SENSITIVITY; rule OUT) disease (low prevalence disease especially). Not affected by prevalence of disease in population. Specificity Proportion of all people without disease who test negative, or = TN/(TN + FP) (true-negative the probability that a test indicates non-disease when disease = 1 – (false-positive rate) rate) is absent. Good for ruling in (think SPin = SPecificity; rule IN) disease (low prevalence disease especially). Not affected by prevalence of disease in population. Positive Proportion of positive test results that are true positive. = TP/(TP + FP) predictive Probability that person actually has the disease given a value (PPV) positive test result. PPV varies directly with prevalence or pretest probability: high pretest probability  high PPV. Therefore, if the prevalence cannot be calculated or 4x4 table is not available, the PPV cannot be determined. Negative Proportion of negative test results that are true negative. = TN/(FN + TN) predictive Probability that person actually is disease free given a value (NPV) negative test result. NPV varies inversely with prevalence or pretest probability: high pretest probability  low NPV. Therefore, if the prevalence cannot be calculated or 4x4 table is not available, the NPV cannot be calculated. Attributable The difference in risk between exposed and unexposed risk groups, or the proportion of disease occurrences that are attributable to exposure. (eg, if risk of lung cancer for Disease smokers is 21% and risk in nonsmokers is 1%, then 20% of the 21% risk of lung cancer in smokers is attributable to Risk Factor + - smoking) + a b Absolute risk Absolute reduction in risk associated with a treatment as - c d reduction compared to a control (eg, if 8% of people who receive a (ARR) placebo vaccine develop flu vs. 2% of people who receive a flu vaccine, then ARR = 8% - 2% = 6%). Number Number of patients who need to be treated for 1 patient to NNT = 1/ARR needed to treat benefit. 5 Table A1 (con’t): Basic Statistics of Epidemiology Measure Definition Mathematical Formula Rate ratio “The ratio of the probability of an event occurring (for Incidence rate in exposed / example, developing a disease, being injured) in an incidence rate in unexposed exposed group to the probability of the event occurring in a comparison, non-exposed group.” (Wikipedia) Hazard ratio “The ratio of the hazard rates corresponding to the Time to event in exposed / time to conditions described by two levels of an explanatory event in unexposed variable” Wikipedia Risk ratio “The ratio of the risk of an event in the two groups” Cumulative incidence in exposed / Handbook Cochrane cumulative incidence in unexposed Attributed “The attributable fraction measures the excess event rate (Incidence in exposed – incidence fraction or risk fraction in the exposed population that is in unexposed) / incidence in attributable to the exposure.” exposed Population = (Incidence in all – incidence in attributable risk unexposed) Population “PAF is the proportional reduction in population disease (Incidence in all – incidence in attributable or mortality that would occur if exposure to a risk factor unexposed ) / incidence in all fraction were reduced to an alternative ideal exposure scenario (eg. no tobacco use).” WHO Likelihood of a Tells us how much the probability of the disease LR+ = TPR / FPR positive test increases when a test is positive. LR+ = (Sensitivity)/(1-Specificity) (LR+) Likelihood of a Tells how much the probability of disease decreases in LR- = FNR / TNR negative test the presence of a negative test. LR- = (1-Sensitivity)/(Specificity) (LR-) PART 2: KEY POINTS FROM THE OTTAWA PRIMER & HEALTH ISSUES Determinant of health: “The range of social, economic and environmental factors which determine the health status of individuals or populations. Examples of social determinants of health: income and social status, social support networks, education and literacy, employment and working conditions, social environments, physical environments, personal health practices and coping skills, healthy child development, biology and genetic endowment, health services, gender, culture.” The continuum of strategies  Diagnosis, treatment and rehabilitation: very soon, we will have learned to be doctors and dentists!  Primary prevention: decreases incidence. Timing: before the person gets the disease.  Secondary prevention: decreases prevalence. Timing: detect the disease early to cure or slow down the progression with greater success than if diagnosed clinically.  Tertiary prevention: decreases impact. Timing: the person has symptomatic disease. The goal is to care for those with disease.  Ottawa charter: 5 action areas for health promotion > build healthy public policy, create supportive environments, strengthen community actions, develop personal skills, reorient health services. 6   Action on the social determinants of health: Intersectoral action, whole of government, health in all policies. Source: Lecture “A continuum of strategies” given by Dr. Andermann Health issues of immigrants and refugees  More than 6 M immigrants in Canada. Most live in the cities of Toronto, Vancouver and Montreal.  Considerations of issues in migrants/refugees include:  Infectious diseases (viral hepatitis (especially if coming from a high prevalence country, ex: China HBV, Egypt HCV), vaccine preventable diseases, TB, malaria, intestinal parasites, HIV, syphilis and other STDs).  Non-infectious diseases (chronic health issues, such as diabetes, malignancies, Fe deficiency anemia, dental, vision  Psychological/stress (depression – may be under reported)  Barriers to access health care.  Increased risk of hepatocellular carcinoma in refugees particularly.  Health determinants in immigrants/refugees:  Pre-immigration: increased risk of disease and poor access to health care: Level of poverty, education access to health care, environmental factors (urban versus rural living) and cultural influences are important pre-immigration determinants of health. But remember: Migrants are NOT a homogenous group and an individual’s risk profile depends on country of origin, socio-economic factors and whether they have lived in a rural or urban setting.  Post-immigration (patient, provider and system levels).  CIC medical exam (pre-screening, done prior to arrival in country of origin): its goal is to identify any potential danger to public health or security; identify/prevent excessive burden on the social or health care system in Canada. It includes:  History to rule out costly chronic diseases  Physical exam,  Chest X-ray (>11 years old),  VDRL (> 15 years old) for syphilis,  Urinalysis (> 5 years old),  HIV (began in 2002). 7  It does NOT include:  Vaccination status is not asked about  Hepatitis testing  Latent TB testing (the CXR only tests for active TB but cannot rule out latent TB)- PPD is not part of the CIC medical exam and thus latent TB can stay untreated. Work as a determinant of health – occupational health  Occupational health is the multidisciplinary approach to the recognition, diagnosis, treatment, and prevention and control of diseases, injuries and other adverse health conditions resulting from hazardous exposures in workplace. Hazards may be chemical, biological (infectious agents), physical (noises, vibration, radiation, extreme temperature, etc.), biomechanical (repetition, forceful exertion, awkward positions, duration, frequency, etc.), psychological / organizational (cognitive, emotional, temporal demands, etc.)  Common occupational disorders include: musculoskeletal disorders, accidental injuries / fatalities, mental health disorders, contact dermatitis, hearing loss, respiratory disorders (asthma, pneumoconiosis – asbestosis and silicosis), cardiovascular diseases, cancer, infectious diseases, reproductive hazards (breastfeeding), neurologic disorders, liver diseases, kidney diseases.  Important determinant of health inequalities: a strong relationship between health and SES --- one of the major determinants of these health inequalities is work exposure. Social determinants of Aboriginal Health: poverty, food security and housing, access to health care services, residential school experience, colonization.  In general, on virtually every measure of health status, Aboriginal peoples fare much worse than an average Canadian.  Health discrepancies: obesity, type 2 diabetes, injuries, tuberculosis, suicide, hypertension, iron deficiency (children) and dental caries (children).  Note: The prevalence of diabetes among First Nation adults is nearly 4 times as great as the general Canadian population: one in three First Nation adults aged 50-69 year-old have diabetes. First Nation females have a higher prevalence of diabetes compared to First Nation males across all age categories, and it is most prevalent among First Nation females. Homelessness / health issues  Main health issues include: alcoholism (22%), drug addiction (78%) as well as mental health problems.  In terms of mental health issues: 61% of homeless people have a psychological diagnosis, including psychotic (13%) as well as bipolar disorders (10%). Notifiable disease/ Maladies à déclaration obligatoire (MADO)- Quebec:  Physicians are required to report some diseases, poisonings, and infections to the Public Health department.  It includes 2 main categories: o “Maladies à surveillance extrême” (Extreme surveillance diseases): it includes 7 diseases that should be IMMEDIATELY and URGENTLY by telephone or fax simultaneously to the National Director of Public Health and the Director of Public Health in your area followed by a written confirmation within 48 hours. These include:  Botulism,  Cholera,  Yellow fever,  Hemorrhagic fever (Ebola, Crimee-congo, Marburg, Lassa),  Anthrax (maladie du charbon), 8   Plague (Peste),  Smallpox (variole). o “Maladies, infections et intoxications à déclaration obligatoire” (Diseases, infections and intoxications that should be mandatory reported): should be reported within 48 hours to the public health director in your area. The complete list of diseases can be in appendix.  Information that should be reported: name of the disease, detailed patient’s information (name, sex, occupation, date of birth, address including postal code, telephone number and RAMQ health insurance number) (note that in this case the physician is obliged to divulge the patient’s information to the public health officials NOT keep it anonymous). For the full information to report, please see the appendix.  Note that some diseases are also “à traitement obligatoire” (mandatory to treat as they present a public health risk, such as TB. PART 3: INTRODUCTORY MEDICAL PHARMACOLOGY & GENETICS Cancer and pharmacology  Cancer screening is not without risk: over-diagnosis, overtreatment and false positives. We should note that not all trials that assess cancer routinely quantify such harms.  Toxicity is the main problem with cancer therapy / drugs. Even if they may work very well, their side effects limit their efficacy in patients: they might ask to reduce the dose; patients do not comply.  The therapeutic index for cancer drugs is very low: we are using drugs with unacceptable levels of toxicity.  Kidney and liver function, bone marrow reserve, general health, and concurrent medical problems must all be considered in therapeutic plan. Compliance: It is the extent to which patients follow treatment. Non-compliance with the prescribed dosing schedule is a major reason for therapeutic failure, especially in the long-term treatment.  Treatment of chronic disease using anti-diabetic, antihypertensive, anti-retroviral, and anticonvulsant agents also represents a compliance problem.  Unless WE work at it, only 50% of patients follow the prescribed dosage regimen in a reasonably correct way, one-third comply only partly, and about one in six patients is essentially noncompliant.  Missed doses are more common than too many doses.  The number of drugs does not appear to be as important as the number of times a day doses must be remembered.  Reducing the number of required dosing occasions can improve compliance.  We must involve patients in the responsibility for their own health.  Note: diabetes is one of the worst diseases for compliance-related issues. Drug safety  Therapeutic Index (TI) = aka therapeutic ratio, comparison of the amount causing toxicity to the amount causing therapeutic effect. TI= LD50/ED50  Increased TI = increased margin of safety. Note that LD50 (Lethal dose 50%) is the dose that causes death in 50% of patients, and ED50 (effective dose 50%) is the dose that leads to therapeutic effect in 50% of patients.  Sources of interpatient variability in drug responses: age, gender, specific physiological states (pregnancy), concurrent drugs, concurrent diseases, adverse or allergic reactions to drugs, pharmacogenetic phenotype (polymorphisms), pharmacokinetics, pharmacodynamics, etc.  Potency = recognition/ affinity for the drug  Efficacy = transduction: how good it is at translating its effect of its binding into a biological response 9 Basic antidotes (for future reference; not R&E focused): Toxic agent Antidote Acetaminophen Acetylcysteine Acetylcholinesterase inhibitor, including insecticides Atropine + pralidoxime Digoxin Digoxin immune fac Ethylene glycol, methanol Ethanol or fomepizole Benzodiazepines, zolpidem, zaleplon Flumazenil Heroin, morphine, opioids Naloxone Carbon monoxide Oxygen Muscarinic blockers Physostigmine Oral poisoning (EXCEPT: iron, cyanide, lithium, solvents, acids, corrosives) Activated charcoal Source: Lecture “Basic Science Pharmacology/Toxicology“ given by Dr. Barbara Hales Genetics: Empiric risk calculations:  Calculating pedigree risks in autosomal recessive disorders: (His risk) x (her risk) x ¼  Risk of recurrence in the same couple for autosomal recessive disease is 1 in 4  Risk of recurrence in the same couple for an autosomal dominant disease is 1 in 2  Risk of a sibling of an affected individual should be considered 2/3 (we know that both parents are carriers but if he/she was affected we would have known)  Risk of a sibling of carrier:1/2 (may or may not have the mutation)  X-linked inheritance: Males > females, all daughters of affected males will be carriers but the condition NEVER transmitted from father to son. Type of Inheritance Parent % Unaffected % Carrier % Affected/Carrier Affected Autosomal Recessive Both parents are 25% 50% 25% Inheritance carriers 1 parent is a carrier 50% 50% 0% Autosomal Dominant 1 parent is a carrier 50% If you get the gene à auto 50% Inheritance affected X-linked Inheritance Mom is a carrier 50% daughter 50% daughter 50% son (usually recessive) 50% son Dad is affected 100% son 100% daughter 0% Y-linked Inheritance Always dad 100% If son gets the gene à auto 100% son daughter affected Source: Table by Gabrielle Rashkovan 10 APPENDIX 11 Block B - Respirology Editors: Alexander Ni and Amine Zoughlami Acknowledgement: Kelly Lau 12 PART 1: KEY DEFINITIONS Hypercapnia: high arterial CO2 pressure, generally due to hypoventilation, altered lung excretion. Eupnea: ventilation allows maintaining normal arterial CO 2 pressure (35 – 45 mm Hg). Hypocapnia: low arterial CO2 pressure, generally due to hyperventilation Hypoxemia: low arterial O2 pressure, can be due to hypoventilation, low FiO2, VQ mismatch, shunting Hypoxia: low oxygen delivery to tissue (low cardiac output, hypoxemia, anemia, CO poisoning) Spirometry tests: FEV1 (Forced Expiratory Volume) – air volume forcibly expelled from max inspiration in 1 st second FVC (Forced Vital Capacity) – air volume forcibly expelled from max inspiration to max expiration FEV1/FVC – normal ratio is 0.7-0.9 (declines with age) PEF (Peak Expiratory Flow) – max air flow (volume/time) expired Typical PFT Patterns Obstructive Restrictive FEV1 ↓↓ ↓ FVC ↓ ↓ FEV1/FVC ↓ Normal or ↑ TLC, FRC, RV ↑ ↓ PART 2: INTERPRETATION OF BLOOD GASES Key to determining the etiology of a hypoxic patient is determining whether the alveolar-arterial oxygen pressure gradient changed: 13 Approach to acidemia or alkalemia will be briefly covered here. Very high yield for RE. Part 3 of Block D (Renal) goes into greater detail as to etiology and evaluation Table 1B: Approach to acid-base disorders Disorder pH Primary problem Compensation Metabolic acidosis < 7.35 HCO3- < 24 mEq ↓ PaCO2 Metabolic alkalosis > 7.45 HCO3- > 26 mEq ↑ PaCO2 Respiratory acidosis (hypoventilation) < 7.35 PaCO2 > 45 mm Hg ↑ HCO3- Respiratory alkalosis (hyperventilation) > 7.45 PaCO 2 < 35 mm Hg ↓ HCO3- Trick to determine what is the primary problem: Respiratory origin: pH and HCO3- change in opposite direction Metabolic origin: pH and HCO3- change in same direction PART 3: OBSTRUCTIVE LUNG DISEASE 1. Chronic Obstructive Pulmonary Disease (COPD) A) Definition Clinical spectrum of diseases that all cause airflow obstruction, air trapping, and lung hyperinflation. Risk factors: o Cigarette smoking (#1 risk factor; close to 90% of COPD caused by smoking) o Exposure to smoke, occupational exposure, indoor/outdoor pollution o Genetics (eg: alpha-1-antitrypsin deficiency) B) Diagnosis: requires spirometry Obstructive pattern on lung dynamics ◦ FEV1/FVC ratio < 0.7 ◦ No reversibility of obstruction post-bronchodilator (main difference with asthma) Lung statics (plethysmography): ◦ Air trapping: Increased FRC and RV ◦ Hyperinflation: Increased TLC Hyperinflation on CXR: large airfields, diaphragmatic flattening, barrel chest (anterior-posterior diameter is greater than right-left diameter) Every individual disease has its own diagnostic criteria (not important for RE) Severity assessed by MRC grade and Gold stage (important prognostic markers and used to monitor response to treatment) 14  Table 3A: MRC Dyspnea Grading Table 3B: Gold Staging Grade Definition (FEV1/FVC < 0.70) 1 Breathlessness only when performing Stage Post-bronchodilator FEV1 strenuous exercise 2 Short of breath when hurry on the level or I: Mild ≥80% predicted walking slight hill 3 Walks slower than most people at level, II: 50-79% predicted stops after a mile or 15 minutes walk at own Moderate pace 4 Stops for breath after 100 meters walk or a III: Severe 30-49% predictor few minutes walk on level ground 5 Too breathless to leave the house or when IV: Very < 30% predictor or 3 highly suggestive consecutive months per year over the last 2 years Clinical features “Pink puffer” “Blue bloater” (Note: both Progressive dyspnea Productive cough (dyspnea occurs usually overlap) Increase work of breathing later) (pursed-lip, accessory muscle use) Wheezing, cyanosis Barrel chest Respiratory acidosis from CO2 retention Signs of right heart failure: peripheral edema, jugular venous distension, hepatic congestion Other diseases include: 1) Bronchiolitis (small airway disease) Goblet cell hyperplasia in response to inflammation causes mucus plugging of bronchioles Classically seen in infants with RSV infection. Also caused by cigarette smoke Clinical features (in infants): nasal flaring, intercostal retractions, grunting, apnea 2) Bronchiectasis Chronic infection and inflammation causes fibrosis and irreversible dilation of airways. Causes: o Infection: classically Pseudomonas + Impaired drainage (cystic fibrosis, primary ciliary dyskinesia, bronchial tumor) Symptoms include: chronic productive cough (purulent yellow/green sputum, hemoptysis), recurrent infections Physical examination: wheezes or rhonchi, clubbing of the fingers Treatment: Prophylactic antibiotics against infectious agents Bronchopulmonary drainage: clearance of airway secretions Chest physiotherapy Typical COPD treatment algorithm (see later) C) Treatment Non-pharmacological: ◦ Smoking cessation: improves survival ◦ Long-term oxygen (if hypoxemia): improves survival ◦ Pulmonary rehabilitation ◦ Vaccination against respiratory pathogens (influenza, Streptococcus pneumoniae) Pharmacological 16  ○ Step 1: short acting beta-2 agonists (SABA, eg: salbutamol) or short-actinc muscarinic antagonists (SAMA, eg: ipratropium) as needed ○ Step 2: Long-acting muscarinic antagonists (LAMA, eg: tiotropium) and/or Long-acting beta-2 agonists (LABA, eg: salmeterol) with SABA/SAMA as rescue medication ○ Step 3: Inhaled corticosteroids (ICS, eg: fluticasone). Often used as ICS/LABA combination because more effective D) COPD exacerbation Definition: sustained (> 48 h) worsening of dyspnea, cough or sputum production Etiology o Infections (80%), especially influenza or non-infectious (environmental, medications) Treatment: o Systemic corticosteroids (oral preferred over IV) with SABA/SAMA o Empiric antibiotics if bacterial pathogen is suspected  Caution: do NOT give 100% oxygen to improve hypoxemia. Acute hypercapnia can result, leading to confusion, lethargy, and eventual coma.  2 main reasons: 1) Adequate V/Q match is maintained by hypoxic vasoconstriction, which shunts blood away from poorly ventilated areas. With 100% oxygen, hypoxic vasoconstriction is reversed and poorly ventilated areas become perfused, which reduces CO2 elimination 2) Chronic COPD patients have a blunted ventilatory response to CO2 and instead rely on hypoxemia to drive their respiration. With 100% O2, this hypoxemic respiratory drive is eliminated, which leads to hypoventilation and CO2 retention. 2. Asthma A) Definition Hypersensitivity to inhaled allergens or pollutants leading to airway inflammation Causes airway hyper-responsiveness, smooth muscle hyperplasia/hypertrophy (bronchoconstriction), and increased mucus production (obstruction) B) Clinical features Recurrent episodes of cough, wheezing or chest tightness, especially at night Identifiable triggers: airborne allergens, pollutants, exercise or upper respiratory tract infection (URTI) Prolonged history of URTI Physical exam: wheezing, ronchi. In acute exacerbation, respiratory distress and pulsus paradoxus (drop in systolic BP >15 mmHg with inspiration) C) Diagnosis 1. Spirometry: FEV1/FVC < 0.70 with bronchodilator response (indicate airway hyper-responsiveness) a. ↑FEV1 by 12 % AND 200 mL in 30 minutes b. If on ICS, ↑FEV1 by 20 % AND 250 mL 2. Methacholine challenge test: PC20 (concentration of methacholine that↓ FEV1 by 20%) less than 4 mg/mL 3. PEF daily variability > 15% 4. Sputum analysis for eosinophils – GOLD STANDARD (but rarely performed) D) Treatment Step 1: Environmental control with SABA as needed Step 2: Add ICS (alternative: leukotriene receptor antagonist [LTRA, eg: montelukast]) 17  Step 3: Use ICS/LABA combination Step 4: Oral corticosteroids Step 5: Biologics: omalizumab (anti-IgE), dupilumab (anti-IL4 receptor, alpha subunit) Table 4B: Hints for bronchodilators and inhaled corticosteroids BRONCHODILATORS: blue/green CONTROLLERS: orange/red/purple Rescue: short-acting bronchodilator agents (SABA) Inhaled Corticosteroids (ICS) ‘ides’ and ‘ones’ beta agonists (salbutamol) Beclomethasone, fluticasone, budesonide, ciclesonide anticholinergics (ipratropium) ICS-LABA (combination therapy) Controller: long-acting beta-2 agonists (LABA) Fluticasone/salmeterol or budesonide/formoterol beta agonists (salmeterol) Critical points: NEVER give an asthmatic a LABA without an ICS: increased risk of mortality NEVER give an asthmatic (or patient with COPD) non-selective beta-blockers (eg: propanolol), since can result in bronchoconstriction Be cautious when giving NSAIDS or high-dose ASA to an asthmatic: blocking prostaglandin synthesis can shunt arachidonic acid metabolites to the leukotriene pathway and potentially worsen inflammation E) Acceptable asthma control in Canada: (1) Daytime symptoms < 4 days/week (5) FEV1 > 85% of predicted (2) Night-time symptoms < 1 night/week (6) Mild exacerbations (3) SABA use Men ; Blacks > Others. Classical exam presentation is that of an asymptomatic middle aged black woman showing hilar adenopathy. Imaging: bilateral hilar adenopathy. Other findings depending on stage of illness include parenchymal infiltrates and fibrosis with honeycombing. 18 b) Clinical features: multi-system disease process that can infiltrate any organ. Constitutional symptoms + others (examples in brackets): - Pulmonary (SOB, cough), cutaneous (erythema nodosum), ocular (uveitis), MSK (arthritis), heart (heart block, arrhythmia), nervous system (optic nerve dysfunction, peripheral neuropathy) c) Treatment: DO NOT treat if asymptomatic: watch and wait If symptomatic: systemic steroids, immunosuppressants. B. Interstitial lung diseases a) Definition: Inflammation with resulting fibrosis of lung parenchyma in response to a certain etiologic agent b) Etiological subtypes - Pneumoconioses: caused by inorganic/organic particles or gases. Silica: upper lobe fibrosis (“silica from ground [sand], affects the roof”). Asbestos: calcified pleural plaques and lower lobe fibrosis (“asbestos from the roof [insulation], affects the ground”). Increased risk of lung cancer and mesothelioma (synergistic risk with smoking) Coal: upper lobe fibrosis Beryllium: granulomas mimic sarcoidosis, therefore occupational history is crucial - Hypersensitivity Pneumonitis: immune reaction against organic antigens (eg: animal fur, bird proteins, Aspergillus...) resulting in granulomas and fibrosis. Clinical picture can be more acute here, and symptoms may resolve with cessation of exposure. - Drug-induced fibrosis: classically bleomycin, methotrexate, and amiodarone - Collagen vascular disorders: SLE, RA, scleroderma, ankylosing spondylitis, Goodpasture, GPA - Idiopathic: some form of immunological process (alveolar PMN infiltrates, but no granulomas) c) Treatment: No cure. Systemic corticosteroids to alleviate symptoms, but only 1/3 patients improve. Remove occupational exposure if possible F) Complications Progressive fibrosis leads to pulmonary hypertension and eventual right heart failure PART 5: PNEUMONIA A) Definition: Lung infection, typically involving alveolar space and parenchyma. B) Causes: Many infectious agents can cause pneumonia. Causes can be narrowed down with age, SES, prior Abx use, underlying conditions (ROH abuse, COPD, diabetes, CHF, immune system status, …). C) Clinical Features: o Signs and Symptoms: Fever, chills, Dyspnea, Cough (productive or not), Chest pain, Tachypnea o On exam, may find signs of consolidation (bronchial breath sounds, egophony, dullness to percussion, increased tactile fremitus (or decreased if accompanied by pleural effusion). whispered pectoriloquy and rackles Common Causes: 1. Streptococcus pneumoniae: Lobar pneumonia. Most common community-acquired pathogen. a. Most susceptible: elderly, smokers, ROH, young children b. Acute-onset, high grade fever with chills, pleuritic chest pain and dyspnea. c. Rusty-colored sputum. 19  d. Intra-alveolar exudate. e. Imaging: Lobar consolidation with air bronchograms. 2. Staphylococcus aureus: Bronchopneumonia. a. Most susceptible: children, inpatients, post-influenza pneumonia, elderly b. Presence of drug-resistant strains (MRSA, VRSA) c. Imaging: Patchy, diffuse lobar distribution, necrotizing cavitation. One or more lobes can be involved. No air bronchograms. Inflammation originates from bronchioles into adjacent alveoli. 3. Mycoplasma pneumoniae: Atypical “walking” pneumonia. Most common atypical. a. Most susceptible: young and healthy adults. b. Cough is non-productive, low-grade fever, sore throat, no significant loss of function. Bullous myringitis can be present. c. Imaging: interstitial pattern on CXR. Ground-glass opacities, nodules on CT. 4. Klebsiella pneumoniae: Aspiration pneumonia a. Most susceptible: elderly, patients with stroke, seizure, alcoholism b. More likely to be right-sided: right bronchus is larger, shorter and more vertical than the left. c. Abscess formation possible 5. Influenza pneumonia a. Flu-like illness (myalgia, lethargy, fever, sore throat) b. High mortality rate of some strains in elderly w/ chronic diseases, and children c. Imaging: reticulonodular d. Management is supportive, prevention is key with seasonal vaccination in at-risk populations 6. Pseudomonas aeruginosa: hospital-acquired in context of underlying disease a. Most susceptible: immunosuppressed, COPD, CF b. Purulent green sputum c. Important organism to diagnose and treat specifically. Not many antibiotics cover it. Table 5B: Analysis of Pleural Fluid via Thoracocentesis (KEY) Exudate Transudate Uncomplicated Complicated Empyema Free Flowing Free flowing +/- Loculated Loculated Serous Serosanguinous Pus pH > 7.2 pH > 7.2 pH < 7.2 Protein/LDH low Protein/LDH High Sterile Sterile +/- bacteria bacteria PART 6: TUBERCULOSIS (SEE BLOCK G FOR ADDITIONAL DETAILS) A) Microbiology Infection with obligate aerobic bacillus Mycobacterium tuberculosis – humans are the only known host; spread via respiratory droplets Stains with acid-fast stain (Ziehl-Neelson stain); NOT visualized on Gram stain B) Pathogenesis M. tuberculosis is taken up by alveolar macrophages  infected macrophages migrate to the hilar lymph nodes, where T cells induce macrophage differentiation into epithelioid histiocytes and formation of granulomas with central necrosis (caseating). 20  In most patients, this primary infection is healed, resulting in a fibrotic and calcified nodule (Ghon complex). This is termed latent TB. 90% of patients with latent TB remain symptomatic. The remaining 10% reactivate the bacillus, most often due to to a breakdown in cell-mediated immunity – progressive primary TB Reactivated TB has a predilection for the lung apices, since the oxygen tension is the highest there TB can spread within the lung (pulmonary TB) or hematogenously to any organ (miliary TB) C). Risk factors a) To contact TB: Travel to areas of high prevalence (eg: Middle East, South Asia, etc…), vulnerable populations (eg: Indigenous, prisons, healthcare workers etc), living with someone with active TB b) For TB reactivation HIV - most important risk factor States of immune compromise (eg: chemotherapy, anti-TNF agents), young, elderly, poor nutrition, etc. D). Clinical features a) Latent TB: asymptomatic b) Active pulmonary TB: nonspecific symptoms Chronic cough +/- hemoptysis + constitutional symptoms such as fever, chills, night sweats, weight loss. c) Miliary TB: reflect affected organ. e.g. spine (Pott’s disease), meningitis, etc. E). Screening and Diagnosis a) Latent TB: CXR: calcified nodules are suggestive. Sensitive, but not specific Tuberculin skin test (TST): purified protein derivative (PPD) of TB is implanted subcutaneously and tests for past exposure to TB (T-cell mediated Type 4 hypersensitivity reaction). There are different size cutoffs for different populations. Past BCG vaccination may cause a false positive. HIV may cause a false negative. Interferon gamma release assay (IGRA): alternative to TST b) Active TB: TST is NOT useful, because it only tests for exposure and cannot detect active disease CXR: cavitations, especially in the apices Sputum acid-fast stain or PCR Sputum culture: gold standard, but takes up to 6 weeks so impractical clinically F). Treatment a) Latent TB: many regiments exist. Most common is 9 months of isoniazid b) Active TB: 4-drug regimen – multiple drugs to avoid resistance PART 7: LUNG CANCER A). Risk factors: Cigarette smoke: # pack-years is directly proportional to risk and severity Chemical and radiation exposure, genetics (for adenocarcinoma: ALK, EGFR, KRAS mutations) B) Subtypes Hint: Cancers that start with “S” (ie: squamous and small cell) are: “S”entral (central) Associated with Smoking Can lead to paraneoplastic Syndrome 21 Table 6B: Subtypes of Lung Cancer Type Features Squamous Cell Carcinoma Risk factors: think irritation to the epithelium. o Smoking anything + Airborne Chemical/Particle/Pollutant exposure o GERD/Trachea-Esophageal Reflux o Alcohol abuse Grows from into the lumen of the proximal lobar airways, occluding them. May lead to hemoptysis (due to blood vessel destruction or necrosis of tumour) and/or distal obstructive pneumonitis (pneumonia-like inflammatory process) CXR: central bronchial mass with cavitation Histology: Keratin positive with intercellular bridges Small Cell Carcinoma: Very aggressive cancer (2-3 months of life after diagnosis), early metastases 100% of cancers associated with smoking Spreads from epithelium into the submucosa, hence no hemoptysis or obstructive pneumonitis CXR: Unilateral hilar mass (vs sarcoidosis: bilateral) Histology: small blue neuroendocrine cells Adenocarcinoma:  The most common form of cancer in non-smokers  Genetic predisposition: classically Asian female.  Located peripherally, therefore identified as peripheral nodule on CXR  Histology: glandular differentiation with identifiable fibrous tissue within the large airway folds  Bronchoalveolar subtype may grow along alveolar wall: carcinoma in situ Large Cell Carcinoma:  If you can't identify it was adeno/small cell/squamous cell carcinomas, then it is large cell; we use it as a garbage bin diagnosis  Generally seen as a peripheral large mass with necrosis  No specific differentiation Mesothelioma  Malignant proliferation of mesothelium. Usually seen in pleura, but may also involve pericardium and peritoneum – may present as bloody pleural effusion (hemothorax)  Associated with chronic asbestos exposure C). Clinical features A.Constitutional symptoms: weight loss, fatigue, chills, night sweats, fever, clubbing B.Local (pulmonary) symptoms: cough +/- hemoptysis, dyspnea, chest pain 22 C.Regional symptoms: due to involvement/compression of adjacent structures e.g. dysphagia, hoarseness, SVC obstruction (facial edema, discoloration) in apical tumour (Pancoast): ◦Brachial plexus involvement: arm pain, weakness, paresthesia ◦Superior cervical ganglion: Horner's syndrome (ptosis, miosis, anhidrosis) D.Paraneoplastic syndromes: due to tumour cells producing ectopic hormone/antibody e.g. Syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH (Cushing's syndrome), etc. E.Metastases: symptoms related to involved organ F) Diagnosis: requires biopsy Central tumours: bronchoscopy Peripheral tumours: trans-thoracic needle aspiration (+/- ultrasound guidance) G). Screening: screen all high-risk patients (ie: heavy smokers aged 55-74) with 3 annual low-dose CT scans. CXR is NOT effective for screening H). Treatment: Small cell: responds to chemotherapy, but usually recurs. Surgery is usually not an option because it has widely spread at the time of diagnosis Non-small cell: resistant to chemotherapy. Surgical resection can be curative. PART 8: MISCELLANEOUS PULMONARY DISEASES 1. Pulmonary embolism: A) Definition:  Caused by the lodging of a blood clot in the pulmonary vasculature. It is a consequence of the formation of a venous thrombus (DVT) that has dislodged and travelled to the lungs. B) Causes:  Similarly to DVT, causes are best thought of in relation to Virchow’s Triad (Hypercoagulability, Endothelial dysfunction, and Stasis). C) Risk Factors:  Hypercoagulable state (birth control pill, pregnancy)  Prolonged immobilization  Obesity  Major surgery (especially pelvic ortho surgery)  Trauma D) Clinical Features can include any of the following:  Signs: Tachypnea, Rales, Tachycardia, Increased P2 sound, Low-grade fever  Symptoms: Sudden dyspnea, Pleuritic chest pain, Cough, Hemoptysis, Calf tenderness, Syncope, Circulatory collapse (hypotension,...)  Note that the patient may also be entirely asymptomatic. E) Diagnostic modalities  Choice depends on clinical suspicion. Modified Wells Criteria to guide the degree of clinical suspicion: includes signs/symptoms of DVT, HR>100, immobilization, history of DVT/PE, hemoptysis, malignancy. 23   Gold standard imaging is CTPA, however can also use CXR mainly to rule out other diagnoses, VQ scan, pulmonary angiography, or D-Dimers in low-probability scenarios (highly sensitive)  Arterial blood gas may reveal respiratory alkalosis (due to hyperventilation) with low PaO2. F) Treatment:  Begin PRIOR to complete diagnostic workup if there is a significant clinical suspicion. Treatment algorithm is complex but mainly consists of heparin acutely with bridging to long-term warfarin or novel oral anticoagulants for 3-6mo, and supportive therapy to stabilize vital signs. 2. Pneumothorax A) Definition: Entry and accumulation of air in the pleural space B) Types (both can arise with any etiology) Non-tension: pneumothorax confined to one hemithorax, mediastinum not deviated Tension: pressure from growing pneumothorax shifts trachea and mediastinum to opposite side C) Etiology  Traumatic: with penetrating chest wall injuries (eg: stab wounds) Non-traumatic: ○ Spontaneous: classically seen in tall, thin males ○ Lung bullae: paraseptal emphysema D) Clinical features Sudden-onset pleuritic chest pain with dyspnea Hyperresonance to percussion Circulatory compromise with tension pneumothorax: hypotension, etc. E) Diagnosis CXR: hyperlucency of lung field with clear pleural line F) Treatment Respiratory support: O2 Aspiration of intra-pleural air with chest tube insertion 3. Obstructive sleep apnea A) Definition: repeated cessation of ventilation for >10 seconds during sleep B) Pathophysiology Laxity of neck muscles and soft tissues collapse with inspiration  airway obstruction Ventilatory effort increases due to obstruction, which causes further collapse  complete obstruction Resulting apnea/ventilation cycles leads to hypoxemia/reoxygenation cycles C) Risk factors Obesity #1 risk factor, craniofacial abnormalities, family history, smoking D) Clinical features Loud snoring relieved by sleeping on the side Daytime sleepiness and somnolence E) Complications Systemic and pulmonary hypertension, cardiac arrhythmias, especially atrial fibrillation, sudden cardiac death F) Treatment Weight loss, avoid alcohol and sedatives Continuous positive airway pressure (CPAP) 24 Block C - Cardiology Editors: Corey Toye and Karl Yared Acknowledgement: Abrar AlJassim and Bing-Yu Chen 25 PART 1: PHYSIOLOGY  Cardiac output is roughly 5-6 L/min (adjusted in terms of magnitude and distribution situationally)  Hagen-Poiseuille Equation: (η = viscosity)  CO = Heart Rate (HR) x Stroke volume (SV)  SV = volume ejected each beat = End diastolic volume (EDV) - End systolic volume (ESV) o SV increases with increased preload, decreased afterload and increased contractility  Ejection fraction = SV / EDV (Normal 55-70%)  Pulse pressure = Systolic BP - Diastolic BP  Mean Arterial Pressure (MAP) = Diastolic BP + ⅓ Pulse Pressure  since MAP >> PRa  Starling’s Law of the heart: Stroke volume increases in proportion to end-diastolic volume o Increased filling (and thus filling pressure) results in greater force of contraction  Jugular venous pulse: pressure pulsations in the RA are transmitted to the large veins  Arterioles are resistance vessels (regulate blood flow), veins and venules are capacitance vessels Source: Dr. Walker, The Heart Pump Lecture (2017) 26 PART 2: THE SEQUENCE OF ECG INTERPRETATION 1. Calibration: check the 1.0 mv vertical box inscription (normal standard – 10mm) a) vertical axis = voltage (mv): 1mm = 0.1mv b) horizontal axis = time (ms): 1mm = 0.04 sec, 5mm = 0.2 sec 2. Rhythm: normal = sinus rhythm a) each P wave is followed by a QRS complex/ each QRS is preceded by a P wave b) P wave is upright in leads i, ii and iii c) PR interval is >0.12 sec (3 small boxes) 3. Heart Rate: normal rate = 60-100bpm (bradycardia 100), use one of 3 methods: a) 1 500/ (number of mm between beats) b) count off method: 300-150-100-75-60-50 c) number of beats in 6 sec x 10 4. Intervals a) normal PR = 0.12-0.20 sec (3-5 small boxes) b) normal QRS < 0.10 sec (< 2.5 small boxes) c) normal QT < half the R-R interval, if heart rate normal 5. Mean QRS axis: normal if QRS is primarily upright in leads i and ii (+90 0 to -300) a) right axis deviation, if QRS is negative in lead i and positive in lead ii. (the r waves are “kissing”  it’s right to kiss) b) left axis deviation, if QRS is positive in lead i and negative in lead ii 6. P wave abnormalities: inspect P in lead ii and v1 for left atrial enlargement a) in RA enlargement, the initial component of the P wave is prominent (>2.5 mm tall) in lead ii. b) in LA enlargement, there is a large terminal downward deflection in lead v1 (>1 mm wide and >1 mm deep) 7. QRS wave abnormality: inspect for ventricular hypertrophy, bundle branch blocks, path Q waves a) RVH: R >S in lead v1 and right axis deviation b) LVH: S in v1 plus R in v5 or v6 ≥ 35 mm or R in avl > 11 mm or R in lead i > 15 mm c) right bundle branch block: widened QRS, RSR' in v1 (”rabbit ears”) and prominent s in v6 d) left bundle branch block: widened QRS, broad, notched R in v6, absent Rand prominent S in v1 e) pathological Q waves are more prominent with a width > 1 mm (1 small box) and depth >25% of the height of the QRS complex 8. ST segment or T wave abnormality: a) MI/STEMI: ST segment elevation b) NSTEMI: ST depressions or T wave inversions c) Pericarditis: diffuse ST elevation and PR depression 27 PART 3: ARRHYTHMIAS Table 1C: Arrhythmias: Etiology, ECG Findings and Treatments. Sinus Tachycardia. Sinus Bradycardia. Sick Sinus Syndrome HR > 100 bpm HR < 60 bpm Etiology Physiological: normal Physiological: normal Pathophysio: Sinus node adaptation process (e.g. adaptation process (e.g. in intermittently fails to fire, during exercise) trained athletes) causing “sinus pauses”. Pathological: caused by Pathological: caused by Sympathetic action usually disease or genetic disease or genetic prevents complete sinus arrest. abnormalities. abnormalities. Results in syncope, rarely sudden death. Often in elderly Treatment Tx if pathological: beta- Tx if pathological: Atropine, Pacemaker blocker, calcium channel reduction or withdrawal of blocker. causative drugs. Supraventricular Tachyarrhythmia (Narrow QRS) AVRT Atrial Flutter Atrial fibrillation ECG Tachycardia (150-250 Atrial rate 240-300 bpm, No P-waves Findings bpm) ventricular rate 75-150 bpm. Irregularly irregular, usually 150 Inverted P-waves right Rapid succession of P-waves bpm after QRS or absence of P- saw tooth appearance. waves Treatment Valsalva or carotid Rhythm control preferred Rate control (Beta-blockers, massage, adenosine, (ablation), rate control possible diltiazem, verapamil, digoxin, calcium channel (beta-blocker, diltiazem, amiodarone), cardioversion, antagonists (verapamil and verapamil, digoxin, amiodarone, CHADS2 (anticoagulation). diltiazem), beta-blockers, Na+ blocker), CHADS2 digioxin, digoxin, catheter (anticoagulation). ablation 28 Ventricular Tachyarrhythmias (wide QRS) Etiology ECG Findings Treatment Ventricular Enhanced automaticity, Wide QRS, usually no P- Electrical cardioversion, Tachycardia delayed after waves. Typically 150-180 bpm lidocaine, amiodarone, depolarizations, early Na+ blockers after depolarizations and reentry. Ventricular Ventricular tachycardia, Chaotic ventricular rhythm (no Emergency DC Fibrillation acute MI identifiable waves), no cardioversion, implantable effective cardiac pumping. defibrillator. Long QT Syndrome Bradycardia, K+ channel QT interval >1 2 of R-R Stop K+ channel blocker dysfunction (delayed interval. Prolonged action drugs, increase heart rate repolarization), drug potentials can lead to early induced after-depolarization arrhythmias. Torsades de Pointes Long QT syndrome Ventricular rate >100 bpm, Electrical cardioversion, usually 150-300 bpm, treat long QT syndrome Resembles ventricular tachycardia ECG. AV block Etiology ECG Findings Treatment 1st Slowing of AV conduction (long PR PR interval >0.20s No degree interval), no blocked beats. treatment Benign and asymptomatic required 2nd degree (Type 1) AV node dysfunction (progressive AV Progressive PR lengthening Usually no nodal fatigue 2° calcium channel on a beat-to-beat basis, until treatment dysfunction), increased vagal tone. conduction to the ventricles required Usually asymptomatic. fails (“blocked” P-wave), and the cycle begins again. 2nd degree (Type 2) Disease in the His-Purkinje system Constant PR interval with Pacemaker (resulting in longer QRS) intermittent absences of Common progression to 3rd degree QRS. block Blocked P-waves occur without gradual PR lengthening. 3rd degree Complete AV block. Irregular PR intervals Pacemaker No sinus impulses get to ventricles. Constant PP and RR Atria and ventricles activate intervals independently. His-Purkinje system sets the rate of ventricular contraction. 29 PART 4: ACUTE CORONARY SYNDROME Table 2C: Acute Coronary Syndrome: Symptoms, Diagnostic Testing and Treatment. Unstable Angina NSTEMI STEMI Pathophysiology Region of myocardial necrosis resulting from acute thrombosis of coronary artery. Partial occlusive thrombus Partially occlusive thrombus Occlusive thrombus with or occlusive thrombus with prolonged ischemia transient ischemia Symptoms Crescendo, episodes at Prolonged “crushing” chest pain, more severe and wider rest, or new onset severe radiation than usual angina, pain does not resolve with angina rest, more activation of sympathetic system (sweat, tachycardia, vasoconstriction) Physical Exam Severe: rales, S4, mitral regurg, dyskinetic apical impulse Serum Biomarkers No Yes Yes ECG Findings ST depression and/or T ST depression and/or T wave ST elevation (and Q wave inversion inversion waves later) Treatment Assess risk with TIMI score Time is Muscle! General Measures If score is 3, then PCI or CABG. Standard Post-discharge - NSTEMI and U/A patients do NOT benefit from Tx: Dual antiplatelet (ASA + clopidogrel) fibrinolytic therapy. Beta Blocker, Statin, - Similar post-discharge medications to STEMI. ACEi, Nitro puffer *If Dx at a non-PCI capable hospital, transfer patient for PCI if time from first medical contact to will be 70% stenosis, Plaque rupture, platelet aggregation, decreased O2 supply precursor to acute MI Treatment 1. Address risk factors (smoking, dyslipidemia, hypertension, DM) 2. Reduce O2 demand and increase perfusion: Nitrates, Beta-Blockers, Calcium Channel blockers 3. Prevent acute cardiac events: Antiplatelet (ASA, Clopidogrel) 4. Lipid lowering therapy (statins) 5. Ace-inhibitors 6. Revascularization if refractory to medications (PCI, CABG) Table 4C: Localization of Myocardial Infarct (exercise below) Anatomic Site Leads with Q waves Artery Inflicted Inferior II, III, aVF RCA Anteroseptal V1 - V2 LAD Anteroapical V3 – V4 LAD Anterolateral VS – V6, I, aVL CFX Posterior V1 – V2 (tall R wave, RCA not Q wave.) 31 PART 5: VALVULAR HEART DISEASE AND HEART SOUNDS Heart Sounds o S1 = closure of the AV valves (mitral and tricuspid o S2 = close of the semilunar valves (aortic and pulmonic), can split to A2/P2 on inspiration Extra heart sounds o S3 = early diastole during exaggerated early diastolic filling (volume overload), use bell o S4 = late diastole, atrial contraction into a non-compliant ventricle (pressure overload), use bell o Ejection click = systolic sound, opening of aortic or pulmonic valve o Opening snap = diastolic sound, opening of mitral or tricuspid valve (due to stenosis) Other murmurs (not as important as the ones in the tables) o Tricuspid valve regurgitation: Holosystolic, blowing murmur, best heard at left sternal border, radiates to the right sternum, intensity increases with inspiration o Ventricular septal defect: Holosystolic, blowing, 4th-6th ICS, does NOT radiate to axilla or change with inspiration o Mitral valve prolapse: Late systolic murmur, preceded by a midsystolic click o Continuous murmurs: heard throughout cardiac cycle. eg. patent ductus arteriosus o To-and-fro murmur: systolic and diastolic murmur (eg. aortic stenosis and aortic regurgitation) Systolic Findings Etiology Symptoms Treatment Mitral Holosystolic, uniform Mitral annulus Acute: Pulmonary Diuretics (edema) Regurgitation intensity, high-pitched (calcification, LV edema, acute HF blowing murmur, continues dilation) Surgery is indicated if beyond S2, has S3 (volume Chronic: patient is symptomatic overload) Mitral leaflets Fatigue (low CO), or EF becomes normal (MVP, infective L.HF (dyspnea, (60%). * EF is usually Physical: Heard at apex endocarditis, orthopnea), elevated due to volume radiating to left axilla, lateral rheumatic fever) Atrial fibrillation, overload. displaced apex R.HF (ascites, Chordae tendineae pedal edema) rupture (MI) Aortic Systolic ejection, crescendo- Congenital Syncope, angina, Surgical aortic valve Stenosis decrescendo, (bicuspid), dyspnea on replacement or TAVR- decreased/absent S2, exertion TAVI (transcatheter paradoxical S2 split (P2-A2), Calcific / valve replacement) if present S4 (pressure Degenerative Concentric LV symptomatic or EF overload) hypertrophy 250 mL to external pressure shaped LV cardiac biomarkers Echo: Quantify volume hindering RA CT/MRI: thick pericardium Echo: complications? of fluid, determine if emptying) Cardiac catheterization: Look for source: PPD, filling defect Prominent y descent CXR Treatment Post MI: Aspirin Observe if Pericardiocentesis Surgical removal of the Purulent: catheter asymptomatic pericardium drainage, intensive Pericardiocentesis if Abx signs of hemodynamic Idiopathic/Viral: self- compromise limited,pain relief 34 PART 7: HEART FAILURE A) Definition: When heart is unable to pump blood forward at a sufficient rate to meet the metabolic demands of the body or when it is able to do so only if the cardiac filling pressures are abnormally high Three categories based on EF: 1) Reduced EF, HFrEF (EF50%), 3) Mid-range EF, HFmrEF (EF 40-49%) B) Etiology: 1) Heart Failure with Reduced EF Impaired contractility: destruction of myocytes (MI), abnormal function ○ Ex. CAD (MI), chronic volume overload (MR, AR), dilated cardiomyopathy Pressure overload: high afterload (aortic stenosis, HTN) 2) Heart Failure with Preserved EF (Diastolic filling dysfunction) Abnormal LV diastolic function o Impaired early diastolic relaxation (ATP-dependent), increased stiffness of the ventricular wall o Ex. LVH, Restrictive cardiomyopathy, Myocardial fibrosis, Transient MI, cardiac tamponade Table 5C: Symptoms and Physical Findings in Left and Right Sided Heart Failure Symptoms Physical Findings Left Sided Dyspnea Tachypnea, Cheyne-Stokes breathing Orthopnea Tachycardia, Pulsus alternans (advanced) Paroxysmal nocturnal dyspnea Cachexia, diaphoresis Fatigue Pulmonary rales or crackles, pleural effusions Dulled mental status Cardiac apex: diffusely enlarged, +/- sustained (AS) Reduced urine output or lifting (MR) Nocturnal cough Loud P2 Rarely hemoptysis S3 gallop (in systolic dysfunction) S4 gallop (in diastolic dysfunction) Murmurs (depending on etiology) Right sided Peripheral edema Parasternal RV heave *The most Weight gain Jugular venous distention common cause of Right upper quadrant discomfort Hepatomegaly + abdominal tenderness right-sided heart (liver distension) Peripheral edema failure is left-sided Anorexia and nausea Murmurs (if tricuspid regurgitation) heart failure Right-sided S3 and S4 New York Heart Association Classifications of Chronic Heart Failure Class 1: No Limitation of physical activity Class 2: Slight limitation of activity. Dyspnea and fatigue with moderate exertion (e.g., walking upstairs quickly). Class 3: Marked limitation of activity. Dyspnea with minimal exertion (e.g., slowly walking upstairs). Class 4: Severe limitation of activity. Symptoms are present even at rest. C) Precipitating factors: Increased metabolic demands (fever, infection, anemia), Increased circulating volume (excessive sodium, fluids), Increased afterload (uncontrolled HTN, PE), Impaired contractility (medications, MI, ethanol), excessive bradycardia, non-compliance of HF medications D) Diagnostic Studies: 35  CXR (upper zone vascular redistribution, Kerley B lines, alveolar edema, cardiomegaly (>0.5 ratio), pleural effusions, enlargement of azygous vein silhouette) B-Type Natriuretic Peptide: secreted on cardiomyocyte stretch, shows LV dysfunction Echocardiography: best test to measure ejection fraction E) Treatment HF with reduced EF: ○ Treat underlying condition, Eliminate acute precipitating cause ○ Treat pulmonary/systemic congestion: sodium restriction, loop diuretics ○ Vasodilators: ACE Inhibitor, ARB, ARNI = reduced mortality ○ Beta blocker (for those without deterioration or volume overload) = reduced mortality ○ Aldosterone antagonist (symptomatic despite ACE or ARB + Beta-blocker) = reduced mortality ○ Ivabradine, digoxin ○ Device therapy: Implantable Cardioverter Defibrillator, Cardiac Resynchronization Therapy ○ Cardiac transplant: refractory cases, mechanical assist devices considered HF with preserved EF ○ Treat etiology, treat pulmonary/systemic congestion (loop diuretics) ○ Beta-blockers, ACEI/ARBs, ARNI (being studied) ○ Spironolactone has potential reduced mortality benefit F) Acute Heart Failure: Sudden onset, may be previously asymptomatic patient or complicated compensated HF Symptoms: dyspnea and anxiety + tachycardia, cold/clammy skin, high RR, frothy sputum, rales Table 4C: Acute Heart Failure Profiles and Treatment Volume overload (wet) - elevated LV filling pressures No Yes (rales, JVP increase, lower extremity edema) No Profile A “Warm and Dry” Profile B “Warm and Wet” Reduced cardiac output and Normal hemodynamics Wet” lungs but preserved tissue Cardiopulmonary symptoms due to factor perfusion (“warm extremities”) vasoconstriction other than HF Tx: Diuretic and/or vasodilator Tx: Look for alternate explanations for Treat pulmonary edema with symptoms LMNOP Yes Profile L “Cold and Dry” Profile C “Cold and Wet” (reduced May arise in volume depleted pts or in pts Congestive findings + impaired tissue with very limited cardiac reserve in the forward cardiac output perfusion, absence of volume overload Marked systemic vasoconstriction cold Tx: Volume expansion Tx: Diuretic and/or vasodilator + extremities) Inotrope. Treat pulmonary edema with LMNOP *LMNOP: Lasix, Morphine, Nitrates, Oxygen, Positioning G) General Treatment: ○ Seat patient upright, supplemental oxygen, IV nitrates (reduce preload), rapid acting diuretic (furosemide IV), vasodilator (ACE-Inhibitor), IV inotropes if low CO, morphine 36 PART 8: ACUTE PULMONARY EDEMA Etiology: acute left-sided heart failure (e.g., typical of Profiles B and C), chronic compensated congestive heart failure, valvular heart disease, myocardial infarct, idiopathic. Pathophysiology: elevated capillary hydrostatic pressure causes rapid accumulation of fluid within the interstitium and alveolar spaces of the lung. Symptoms: severe dyspnea and anxiety Signs: tachycardia, cold/clammy skin (peripheral vasoconstriction), high respiratory rate, coughing of “frothy sputum,” rales +/- wheezing Treatment: L-M-N-O-P (Lasix, Morphine, Nitrates, Oxygen, Positioning) Life-threatening emergency that requires immediate improvement of systemic oxygenation and elimination of the underlying cause. PART 9: PERIPHERAL VASCULAR DISEASE 1) Aortic Aneurysms  Focal increase in vessel size by 50% compared with normal, dilation > 3cm  True aneurysm involves dilation of all 3 layers of aorta  Etiology: o Cystic medial degeneration (Marfan’s, Loeys-Dietz, Ehlers-Danlos) o Atherosclerosis/degenerative, Infections of arterial wall, Vasculitis (Takayasu, GCA)  Risk factors: smoking, HTN, dyslipidemia  Presentation: Asymptomatic pulsatile mass, compression of adjacent structures (cough, dyspnea, dysphagia, hoarseness), CHF (aortic regurg), back pain, GI symptoms  Investigations: Echo, CXR, CT, Angiogram  Management o Optimize risk factors, Medications (Beta-blockers or ACE-Inhibitors (mainly for Marfan’s), surgical repair, percutaneous endovascular repair 2) Aortic Dissection  Blood from the lumen passes through a tear in the intima and spreads along the medial layer  Most occur in ascending aorta (65%), descending (20%)  Risk Factors: elastic/muscular degeneration, HTN, age, cystic medial degeneration, trauma  Complications: rupture, occlusion of branch vessels (stroke, MI), distortion of aortic annulus  Presentation: tearing, ripping in the chest, pain travels with dissection  Investigations: BP in both arms (detect difference), CT contrast, TEE, MR angiography  Treatment: Reduce BP and cardiac contraction (Beta-blockers), surgery 3) Peripheral artery disease  Risk factors: atherosclerosis, smoking, DM2, dyslipidemia, HTN  Signs: Claudication, bruit at stenosis, diminished distal pulses, foot ulcers/infections, muscle atrophy, pallor, cyanosis, hair loss, gangrene  Treatment: RF modification, antiplatelets/anticoagulation, exercise, revascularization (Stent, surgery), amputation (if severe) 37 Block D: Renal Editors: Brian Dang and Owen Litwin Acknowledgement: Giuseppe Frenda and Bellal Jubran 38 PART 1: BASIC CONCEPTS IN RENAL PHYSIOLOGY Table D1: Hormones affecting the kidney Hormone Site of Release Trigger Effect Renin (enzyme) Juxtaglomerular cells Drop in BP, low distal tubule Conversion of angiotensinogen into Na, SNS AT1 Angiotensin I Precursor made by liver, converted into Renin None (AT1) AT1 by renin in plasma Angiotensin II Converted from AT1 to AT2 in lungs Angiotensin converting Constricts efferent arteriole, (AT2) enzyme (ACE) systemic vasoconstriction, Na resorption at proximal tubule, aldosterone and ADH secretion Aldosterone Adrenal cortex, zona glomerulosa AT2, high K, ACTH Increased resorption of Na (via ENaC channel) at cortical collecting duct, secretion of K and H ANP/BNP Atria and ventricles, respectively Increased volume Constricts efferent arteriole, dilates afferent arteriole, inhibits sodium resorption via ENaC ADH/vasopressin Posterior pituitary gland Decreased serum osmolality, Increased resorption of water and or severe volume depletion, urea in collecting duct AT2 Parathyroid Parathyroid glands low Ca, high PO4, low 1,25- Increased Ca resorption at distal hormone (OH)2 D3 tubule, less PO4 resorption at proximal tubule, stimulates 1,25- (OH)2 D3 production Table D2: Common diuretics and their sites of action Type Site of Action % Na Excreted Loop Diuretics (Furosemide) Thick Ascending Limb; Na-K-2Cl Transporter 35-50% Thiazide Distal Tubule; Na-Cl Transporter 5-8% K-Sparing Diuretics Collecting Tubules; block ENaC Channel 2-3% Key Terms: Effective Circulating Volume: The amount of fluid within the arterial system. Remember that only this fluid can contribute to tissue perfusion and trigger body homeostasis mechanisms (such as RAAS, SNS). Edema, ascites, or internal hemorrhage for example, are not included. Glomerular Filtration Rate (GFR): The volume of fluid that passes through all the glomeruli of a person over time. It is typically estimated using serum creatinine, a substance which entirely passes through glomeruli. One possible measurement of renal function. Secretion: Certain substances are moved into the renal tubules directly through the tubular cells (not the glomerulus). Important examples are potassium, acid, and certain drugs. If the tubular cells are damaged or not working well, these substances can build up in the body. Reabsorption: Certain substances are taken back into the blood by the renal tubular cells after passing through the glomerulus. Important examples are glucose, amino acids, phosphate. If the proximal tubules do not work properly, these may be lost in the urine. 39 PART 2: WATER HOMEOSTASIS Figure D3: Distribution of total body water Table D4: The distribution of common IV fluids with 1 L infusion Fluid D5W Normal Saline (NS) 3% Saline Concentration 300 mOsm dextrose 308 mOsm, 0.9% saline 3%, 513 mmol/L Na Compartments All Extracellular only Extracellular only Distribution (1L - 1/12 intravascular = 83 ml - ¼ intravascular = 250 ml - ¼ intravascular = 250 ml fluid) - 3/12 interstitial = 250 ml - ¾ interstitial = 750 ml - ¾ interstitial = 750 ml - 8/12 intracellular = 667 ml PART 3: ELECTROLYTE IMBALANCE [A] Hyponatremia: Definition An excess of water relative to sodium in the extracellular compartment. [Na+] 100) indicates a compensatory process for hypotension JVP might be elevated in patients with hypervolemic hyponatremia Edema might be present in hypervolemic patients. Causes: Important to assess volume status, which can determine etiology: i. Hypovolemic: Causes of hypovolemic hyponatremia include: Loss of isotonic fluid: Diarrhea, GI bleeding, Vomiting Adrenal insufficiency Thiazide diuretics ii. Euvolemic: The causes include: SIADH: There are four criteria that we use to establish that a patient has SIADH (*KEY) 40  a. Hyponatremia ( 100mOsm with normal kidney function Note: must rule out other causes before finalizing a Dx of SIADH Primary polydipsia Extremely low sodium diet Hypothyroidism iii. Hypervolemic: The edematous states. Congestive heart failure Liver disease Renal failure Treatment: The treatment depends on the volume status of the patient: a. Hypovolemic hyponatremia: administer isotonic saline (0.9%) to replace isotonic fluid loss. b. Euvolemic hyponatremia: In the case of SIADH, administer hypertonic salin