Table of Contents


Index Abbreviations

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33.

Ethical, Legal and Organizational Aspects of Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Anesthesia and Peri operative Medicine Cardiology & Cardiovascular Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Clinical Pharmacology Dermatology Diagnostic Medical Imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Emergency Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Endocrinology Family Medicine Gastroenterology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. General Surgery Geriatric Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Gynecology Hematology Infectious Diseases Nephrology Neurology Neurosurgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Obstetrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Ophthalmology Orthopaedics Otolaryngology Pediatrics Plastic Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Population and Community Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Psychiatry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Respirology Rheumatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..




Urology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . .. Common Unit Conversions Commonly Measured Laboratory Values List of Abbreviations Index

Toronto Notes 2008


How to Use This Book

This book has been designed to remain as one book or to be taken apart into smaller booklets. Identify the beginning and end of a particular section; then carefully bend the pages along the perforated line next to the spine of the book. Then tear the pages out along the perforation. The layout of Toronto Notes 2008 allows easy identification of important information. These items are indicated by icons interspersed throughout the text:


The 'key' icon, found next to headings in the text, identifies key objectives and causal conditions as defined by the Medical Council of Canada or the National Board of Medical Examiners USA. If J appears beside a 'black-bar' title, all subsequent subheadings should be considered key topics. The 'pearl' icon, found in the sidebar, identifies concise, important information which will aid in the diagnosis and/or management of conditions discussed in the accompanying text. The 'light bulb' icon indicates helpful mnemonic devices and other memory aids. The 'flags' icon indicates information or findings that require urgent management or specialist referral. The 'camera' icon indicates topics that correspond with images found in the Colour Photo Atlas available on online. The 'X-ray' icon indicates topics that correspond to information or images contained within the Radiology Atlas located online. The 'PON icon indicates topics that corresponds with entries found in the POA Program­ "Clinical Information Set". The program can be downloaded from the website. The 'computer' icon indicates topics that correspond with electronic resources such as Functional NeuroanatomyTM or ECG Made Simple™ located online.

Chapter Divisions
To aid in studying and finding relevant material quickly, each chapter is organized in the following general frame­ work: Basic Anatomy/Physiology Review • features the high-yield, salient background information students are often assumed to have remembered from their early medical school education Common Differential Diagnoses • aims to outline a clinically useful framework to tackle the common presentations and problems faced in the area of
Diagnoses • the bulk of the book • etiology, epidemiology, pathophysiology, clinical features, investigations, management, complications, and prognosis Common Medications • a quick reference section for review of medications commonly prescribed Summary Key Questions • helps focus studying and re-iterate key concepts


Toronto Notes 2008

Common Unit Conversions
To convert from the conventional unit to the SI unit, multiply by conversion factor To convert from the SI unit to the conventional unit, divide by conversion factor

Conventional Unit
ACTH Albumin Bilirubin Calcium Cholesterol Cortisol Creatinine Creatinine clearance Ethanol Ferritin Glucose HbA1C Hemaglobin HDL cholesterol Iron, total Lactate (lactic acid) LDL cholesterol Leukocytes Magnesium MCV Platelets Reticu locytes Salicylate Testosterone Thyroxine (T4) Total Iron Binding Capacity Triiodothyronine (T3) Triglycerides Urea nitrogen Uric acid pg/mL g/dL mg/dL mg/dL mg/dL 1J9/dL mg/dL mLlmon mg/dL ng/mL mg/dL

Conversion Factor
0.22 10 17.1 0.25 0.0259 27.59 88.4 0.0167 0.217 2.247 0.0555 0.01 10 0.0259 0.179 0.111 0.0259 1 0.411

51 Unit
pmol/L gIL )..Imol/L mmol/L mmol/L nmol.L )..Imol/L mLls mmol/L pmol/L mmol/L proportion of 1.0 gIL mmollL )..Imol/L mmol/L mmol/L x 109 cells/L mmol/L fL x 109 cells/L

g/dL mg/dL )..Ig/dL mg/dL mg/dL x 1O~ cells/mm 3

mg/dL )..1m 3 x 103 cells/m m 3

% of RBCs
mg/L ng/dL ng/dL )..Ig/dL pg/dL mg/dL mg/dL mg/dL

0.01 0.00724 0.0347 12.87 0.179 0.0154 0.0113 0.357 59.48

proportion of 1.0 mmol/L nmol/L pmol/L IJmollL pmol/L mmol/L mmol/L )..Imol/L





F = (C x 1.8) +32 C = (F - 32) x 0.5555 1 kg = 2.2 Ibs 11b=160z 1 oz

Fahrenheit Kilograms Pounds Ounces Inches





=28.3 9 1 in =2.54 cm

Toronto Notes 2008

Common Unit Conversions 1

Commonly Measured Laboratory Values

Arterial Blood Gases pH
Serum Electrolytes Bicarbonate
Serum Nonelectrolytes Albumin ALP ALT Amylase AST Bilirubin (direct) Bilirubin (total) BUN Cholesterol Creatinine (female) Creatinine (male) Creatine Kinase - MB fraction Ferritin (female) Ferritin (male) Glucose (fasting) HbA1C LDH Osmolality Serum Hormones ACTH (0800h)
Cortisol (0800h)
Testosterone (male,free)
Thyroxine (T4)
Triiodothyronine (T3)
Hematologic Values ESR (female)
ESR (male)
Hemoglobin (female)
Hemog(obin (male)
Hematocrit (female)
Hematocrit (maJ)

Conventional Units

51 Units

7.35-7.45 35-45 mm Hg 80-105 mm Hg

7.35-7.45 4.7-6.0 kPa 10.6-14 kPa

22-28 mEq/L 8.4-10.2 mg/dL 95-106 mEq/L 1.3-2.1 mEq/L 2.7-4.5 mg/dL 3.5-5.0 mEq/L 136-145 mEq/L

22-28 mmol/L 2.1-2.5 mmol/L 95-106 mmol/L 0.65-1.05 mmol/L 0.87-1.45 mmol/L 3.5-5.0 mmol/L 136-145 mmol/L

3.5-5.0 g/dL 35-100 U/L 8-20 U/L 25-125 U/L 8-20 U/L 0-0.3 mg/dL 0.1-1.0 mg/dL 7-18 mg/dL <200 mg/dL 10-70 U/L 25-90 U/L 0-12 U/L 12-150 ng/mL 15-200 ng/mL 70-110 mg/dL <6% 100-250 U/L 275-300 mOsm/kg

35-50 gIL 35-100 U/L 8-20 U/L 25-125 U/L 8-20 U/L 0-5 IJmol/L 2-17 IJmol/L 1.2-3.0 mmol/L < 5.2 mmol/L 10-70 U/L 25-90 U/L 0-12 U/L 12-150 IJg/L 15-200 IJg/L 3.8-6.1 m mol/L <0.06 100-250 UlL 275-300 mOsm/kg

<60 pg/mL 5-23 IJg/dL <20 ng/mL 9-30 ng/dL 5-12 (g/dL 115-190 ng/dL 0.5-5IJ U/mL

<13.2 pmol/L 138-635 nmol/L < 20 ng/mL 0.31-1 pmol/L 64-155 nmol/L 1.8-2.9 nmol/L 0.5-5 IJU/mL

0-20 mm/h 0-15 mm/h 12.3-15.7 g/dL 13.5-17.5 g/dL 36-46% 41-53% 1.0-1.1 4.5-11 x 103 cells/mm 3 88-100 IJm1 150-400 x 103/m m 3 11-15 s 25-35 s 0.5-1.5% of RBC

0-20 mm/h 0-15 mm/h 123-157 gIL 140-174 gIL 36-46% 41-53% 1.0-1.1 4.5-11 x 109 cells/L 88-100 fL 150-400 x 109 /L 11-15 s 25-35 s 20-84 x 109 /L

2 Commonly Measured Laboratory Values

Toronto Notes 2008

limol IiE3 1,25(OH)2-vit D lll-ln DTPA 17-KS 17-0H prog 18FDG 2-PAM 5-HT micromoles unconjugated estriol 1,25-dihydroxy-vitamin D lll-in diethylene triamine penta acetic acid 17-ketosteroids 17-hydroxyprogesterone 18-fluorodeoxyglucose pralidoxime serotonin AFP AFV AG Ag AGA AGE AGUS AHA AHI AHTR AICA AIDP AIDS AIHA All AIN AIN AIN AION AION AIS AJR AK ALL ALND ALP ALS ALT AM AMAN AMI AMI AML AMM AMP AMSAN AN AN ANA ANC ANCA alpha-fetoprotein amniotic fluid volume anion gap antigen appropriate for gestational age advanced glycosylated end-products atypical glandular cells of undetermined significance American Heart Association apnea hypopnea index acute hemolytic transfusion reactions anterior internal carotid artery acute inflammatory demyelinating polyneuropathy acquired immune deficiency syndrome autoimmune hemolytic anemia angiotensin II acute interstitial nephritis allergic interstitial nephritis anterior interosseous nerve acute ischemic optic neuropathy anterior ischemic optic neuropathy androgen insensitivity syndrome abdominal jugular reflux actinic keratosis acute lymphoblastic leukemia axillary lymph node dissection alkaline phosphatase amyotrophic lateral sclerosis alanine aminotransferase morning acute motor axonal neuropathy acute myocardial infarction acute myocardial ischemia acute myeloid leukemia agnogenic myeloid metaplasia adenosine monophosphate acute motor-sensory axonal neurophathy acoustic neuroma anorexia nervosa antinuclear antibodies absolute neutrophil count anti-neutrophil cytoplasmic antibody analysis of variance autonomic nervous system anti-glomerular basement membrane anti-liver kidney microsome anti-Smith antibodies aortic root acute otitis media aortic valve antero-posterior atrial premature beat abductor pollicis brevis activated protein C adult polycystic kidney disease antepartum hemorrhage abductor pollicis longus anti phospholipid antibody anti phospholipid antibody syndrome acute promyelocytic leukemia apolipoprotein apolipoprotein B abdominal perineal resection antiphospholipid antibody syndrome activated partial thromboplastin time amine precursor uptake and decarboxylation aortic regurgitation autosomal recessive angiotensin II receptor blocker anti-ribonuclear protein comples acute respiratory distress syndrome acute renal failure absolute risk increase age-related macular degeneration ARR ART


A Fib



atrial fibrillation air entry Alcoholics Anonymous alveolar arterial abdominal aortic aneurysm arterial-alveolar oxygen diffusion gradient activity as tolerated antibody airway, breathing, and circulation arterial blood gases ankle-brachial index acceptable blood loss arterial blood pressure auditory brainstem response adriamycin, bleomycin, vincristine, decarbazine antibiotics before meals acromioclavicular abdominal circumference activated charcoal air conduction anterior chamber anterior cerebral artery asymptomatic cartic atherosclerosis study American College of Cardiology angiotensin converting enzyme angiotensin converting enzyme inhibitors acetylcholine acetylcholinesterase autologous chondrocyte implantation anterior cruciate ligament anticardiolipin antibody advanced cardiac life support active core rewarming albumin to creatinine ratio asymptomatic carotid surgery trial activated clotting time actinomycin D adrenocorticotropic hormone Alzheimer's disease atopic dermatitis autosomal dominant right ear antidiuretic hormone attention-deficit/hyperactivity disorder activities of daily living abductor digiti minimi attention deficit hyperactive disorder absorption, distribution, metabolism and elimination abductor pollicis adenosine diphosphate adverse drug reaction adverse event active external rewarming amniotic fluid acid-fast bacillus atrial fibrillation acute fatty liver of pregnancy




absolute risk reduction advanced reproductive technologies anti-retroviral aortic stenosis ankylosing spondylitis left ear above sternal angle acetylsalicylic acid American Society of Anesthesiology atypical squamous cell of undetermined significance atypical squamous cells of undetermined significance atrial septal defect anal souamous intraepitheliallesion anterior superior iliac spine antistreptolysin 0 antistreptolysin 0 titre antisocial personality disorder aspartate transaminase angiotensin advanced trauma life support acute tubular necrosis adenosine triphosphate all-trans-retinoic acid each ear abnormal uterine bleeding atrioventricular arteriovenous aortic valve area arteriovenous malformation avascular necrosis atrioventricular nodal reentrant tachycardia alert, verbal, pain, unresponsive atrioventricular reentrant tachycardia abdominal x-ray azidothymidine

ANS Anti-GBM Anti-LKM Anti-Sm AO AOM




vitamin B12 bronchioalvelolar cancer bipolar affective disorder brainstem auditory evoked potentials bronchoalveolar lavage bundle branch block blood brain barrier bone conduction basai cell carcinom3 bacille Ca1matte-Guerin birth control pill breast conserving surgerv barium enema blood glucose beta-human chorionic gunadotropin bilateral hilar lymphadenopathy two times a day biphasic positive airway pressure below knee basement membrane bowel movement Becker muscular dystrophy bone mineral density body mass index basal metabolic rate bone marrow transplant bulimia nervosa bronchiolitis obliterans with organizing pneumonia blood pressure biparietal diameter bronchopulmonary dvsplasia borderline personality disorder benign prostatic hyperplasia Abbreviations


Toronto Notes 2008


4 Abbreviations




Toronto Notes 2008


benign prostatic hypertrophy biophysical profile benign paroxysmal positional vertigo benign positional vertigo branch retinal artery occulsion bright red blood per rectum branch retinal vein occlusion blood sugar body surface area bovine spongiform encephalopathy bilateral salpingo-oophorectomy balanced salt solution bleeding time behind the ear blood urea nitrogen break-up time bacterial vaginosis body weight benzodiazepine





culture and sensitivity Caesarean section cardiothoracic ratio coracoacromialligament calcium cancer cancer antigen 125 coronary artery bypass graft coronary artery disease congenital adrenal hyperplasia complementary alternative medicine cyclic adenosine monophosphate cytoplasmic antineutrophil cytoplasmic antibody combined arterial 02 arterial 02 content Canada Assistance Plan community acquired pneumonia Children's Aid Society continuous arterial-venous hemodialysis complete blood count common bile duct cerebral blood flow cortical basal ganglionic degeneration cognitive behavioural therapy with meals carotid-cavernous coracoclavicular ligament chief complaint calcium channel blocker Consent and Capacity Board congenital cyanotic heart disease cholecystokinin chronic pelvic pain Canadian Cardiovascular Society centrai corneal thickness coronary care unit conduct disorder Crohn's disease Center for Disease Control congenital dislocation of the hip congenital dysplasia of the hip carcinoembryonic antigen conjugated equine estrogen control group event rate counting fingers cystic fibrosis chronic fatigue syndrome chronic granulocytic leukemia cyclic guanine monophosphate Canada Health Act



congenital heart disease congestive heart failure conductive hearing loss carbohydrate contraindications cardiac index confidence interval clean intermittent catheterization chronic inflammatory demyelinating polyneuropathy cervical intra-epithelial neoplasia carcinoma in-situ Creutzfeldt-Jakob disease creatine kinase creatine kinase-MB chloride confidence interval corpus luteum chronic lymphocytic leukemia cardiomyopathy Canadian Medical Association carpo-metacarpal joint cyclophosphamide, methotrexate and 5-fluorouracil cystometrogram chronic myelogenous leukemia Canadian Medical Protective Association Charcot Marie Tooth Disease cytomegalovirus cranial nerve cyanide central neurogenic hyperventilation central nervous system carbon monoxide cardiac output carbon dioxide catechol-O-methyl transferase chronic obstructive pulmonary disease cyclo oxygenase cyclo oxygenase-2 cerebral palsy chest pain cerebellar pontine angle continuous positive airway pressure cephalo-pelvic disproportion creatine phosphokinase central pontine myelinolysis continous passive motion chest pain on exertion cerebral perfusion pressure chronic pelvic pain calcium pyrophosphate dihydrate cardiopulmonary resuscitation College of Physicians &Surgeons of Ontario creatinine central retinal artery occlusion colorectal cancer creatinine clearance cardiac risk factor chronic renal failure corticotropin releasing hormone contralateral routing of signals C-reactive protein complex regional pain syndrome central retinal vein occlusion completed stroke central sleep apnea cerebrospinal fluid central steady and maintained cervical spine Cheyne-Stokes respiration cognitive therapy computed tomography CT angiogram connective tissue disease congenital talipes equinovarus (fetal) cardiotocography




cytotoxic T-Iymphocyte associated protein 4 community treatment order carpal tunnel syndrome central venous pressure cardiovascular cerebrovascular accident costovertebral angle cardiovascular disease cerebrovascular disease collagen vascular disease central venous pressure chorionic villus sampling cardiovascular system continuous venous venous hemodialysis coal worker's pneumoconiosis chest x-ray cytochrome p-450


diopter dilatation and curettage due to 5% dextrose in water dopamine disability adjusted life year dietary approaches to stop hypertension decibel diastolic blood pressure dilation and curettage discontinue direct current ductal carcinoma in situ dilated cardiomyopathy diffusing capacity for carbon monoxide dacryocystorhinostomy distal convoluted tubule 1-desamino-8-d-arginine vasopressin developmental dysplasia of hip dichloradiphenyl trichloroethane differential diagnosis diethylstilbestrol diffuse esophageal spasm dual x-ray absorptiometry dissociative fugue direct fluorescent antibody dermatitis herpetiformis dihydroergotamine dihydroepiandrosterone dihydroepiandrosterone sulfate dihydropyridine dihydropyridine calcium channel blocker dihydrotestosterone diabetes insipidus disseminated intravascular coagulation dissociative identity disorder deep inferior epigastric perforator distal interphalangeal joint diabetic ketoacidosis dermatomyositis diabetes mellitus disease modifying anti-rheumatic drugs dilated cardiomyopathy Duchenne muscular dystrophy dimercaptosuccinic acid dimethylsulfamethoxazole dermatomyositis deoxyribonucleic acid dinitrochlorobenzene


Toronto :-.iotes 2008





Abbreviations 5


dsyembryoplastic neuroeptheral tumour do not resuscitate deep neck space infections distalphalangeal depth diphosphoglycerate diagnostic peritoneal lavage diabetic retinopathy digital rectal exam distal radioulnar joint double strength Down syndrome digital subtraction angiography Diagnostic and Statistical Manual of Mental Disorders dexamethasone suppression test delirium tremens diphtheria, tetanus, pertussis diethylene triaminepentacetic acid deep tendon reflexes duodenal ulcer dysfunctional uterine bleeding deep vein thrombosis diagnosis dexamethasone dizygotic



estrogen extra-articular features evidence based medicine Epstein-Barr virus estimated blood volume estimated birth weight effective concentration of a drug endocervical curettage endocardial cushion defect extracorporeal drug removal extracellular fluid extracellular fluid volume effective circulating fluid volume electrocardiogram echocardiogram erythema chronicum migrans extracorporeal membrane oxygenation extensor carpi radialis brevis extensor carpi radialis longus electroconvulsive therapy extensor carpi ulnaris emergency department erectile dysfunction effective dose-50% estimated date of confinement extensor digitorum communis electron dense deposits extensor digiti minimi electrodiagnostic studies electroencephalogram experimental group event rate ejection fraction estimated fetal weight example esophageal gastroduodenoscopy enterohemorrhagic E. coli extensor hallucis longus enzyme immunoassay extensive in-situ component entero invasive E. coli extensor indicis proprius enzyme-linked immunosorbent assay electron microscopy erytherma multiforme emergency medical attendant etoposide, MTX, ACT-D, cyclophosphamide, vincristine maximal response that a drug can elicit electromechanical dissociation


electromyography eutectic mixture of local anesthetic esophageal motility study electronystagmography ear, nose, throat extraocular muscle or extraocular movement extensor pollicis brevis emergency postcoital contraception Established Programs Financing extensor pollicis longus erythropoietin electrophysiological study expressed prostatic secretions extrapyramidal side effects emergency room estrogen receptor endoscopic retrograde cholangiopancreatography expiratory reserve volume erythrocyte sedimentation rate end-stage renal disease extracorporeal shock wave lithotripsy essential thrombocythemia end-tidal carbon dioxide enterotoxigenic E. coli ethanol endotracheal tube examination under anesthesia endoscopic variceal ligation endovenous laser therapy


flexor pollicis longus functional residual capacity Fellow of the Royal College of Physicians of Canada Fellow of the Royal College of Surgeons of Canada focal segmental glomerular sclerosis follicular stimulating hormone free thyroxine index fluorescent treponemal antibodyabsorption full thickness skin graft failure to thrive fluorouracil fever of unknown origin forced vital capacity


female follow-up folinic acid fluorescein angiography fragment antigen binding French-American-British fetal alcohol effects familial adenomatous polyposis fetal alcohol syndrome fetal alcohol spectrum disorder focused abdominal sonogram in trauma foreign body fasting blood glucose fasting blood sugar flexor carpi radialis flexor carpi ulnaris flexor digiti minimi fibrinogen degradation product flexor digitorum profundus flexor digitorum superficialis forced expiratory flow rate forced expiratory flow at 25-75% of maximum flow rate fractional excretion of sodium free erythrocyte protoporphyrin functional endoscopic sinus surgery forced expired time forced expiratory volume in 1 second filtration fraction free fatty acid fresh frozen plasma fetal heart rate family history fraction of oxygen in inspired air fluorescence in situ hybridization femur length fast-fluid-attenuated inversion recover fine needle aspiration febrile non hemolytic transfusion reactions fecill occult blood test fall on outstretched hand false positive flexor pollicis brevis fasting plasma glucose



gram(s) genitourinary glucose-6-phosphate dehydrogenase general anesthetic gestational age gamma aminobutyric acid group A B-hemolytic streptococcus generalized anxiety disorder global assessment of functioning Group A Bhemolytic streptococcus goldmann applanation tonometry gallbladder glioblastoma multiforme glomerular basement membrane group B streptococcus Guillain-Barre syndrome Neisseria gonorrheal gonococcus giant cell arteritis Glasgow coma scale glucose challenge test gestational diabetes mellitus gross democratic product gastroesophageal gastroesophageal reflux disease glomerular filtration rate gamma-glutamyltranspeptidase growth hormone gamma hydroxybutyrate growth hormone-releasing hormone gastrointestinal gamete intra fallopian transfer gamete-immediate transfer gestational trophoblastic neoplasia gastrointestinal stromal tumour general medical condition glomerulonephritis genetically modified organism glomerulonephritis Gram negative Gram negative bacilli gluconeogenesis gross national product gonadotropin-releasing hormone giant papillary conjunctivitis globus pallidus pars externa globus pallidus pars interna gunshot wound glucose tolerance gestational trophoblastic neoplasm gravidity, term infants, parity, abortions, living children drops genitourinary graft versus host disease


6 Abbreviations




Toronto Notes 2008


hour hydrogen headache hemolytic anemia hepatitis A virus hemoglobin glycosylated hemoglobin Hep B immune globulin hepatitis Bimmune globulin hepatitis Bsurface antigen hepatitis Bvirus head circumference hepatocellular carcinoma Health Care Consent Act human chorionic gonadotropin hydrochloric acid hypertrophic cardiomyopathy bicarbonate hydrocephalus hematocrit hydrochlorothiazide hepatitis Cvirus Huntington's disease high density lipoprotein hepatitis 0 virus hypaque enema hemolysis, elevated liver enzymes, and low platelets Isyndrome) heart failure hereditary hemorrhagic telangiectasia human herpes virus head injury Haemophilus influenzae b hepatobiliary iminodiacetic acid scan Hosphallnsurance and Diagnostic Services Act hypoxic ischemic encephalopathy high intensity focused ultrasound heparin induced thrombocytopenia human immunodeficiency virus hepatojugular reflex hearing loss human leukocyte antigen hypoplastic left heart syndrome hand motion hyaline membrane disease hydroxymethylglutamyl coenzyme A Health Maintenance Organization hexamethylpropene aminooxime hereditary motor-sensory neuropathy hereditary non-polyposis color ectal cancer heterotopic ossification hypertrophic obstructive cardiomyopathy hyperglycemic hyperosmolar non-ketotic coma hypothalamic pituitary adrenal histrionic personality disorder high power field history of present illness human placenta lactogen high frequency oscillation human papilloma virus neart rate high resolution CT scan hormone replacement therapy hysterosalpingography high grade squamous intraephheliallesion Henoch-Sch6nlein Purpura herpes simplex virus height human T-cell leukemia/lymphoma virus hypertension hemolytic uremic syndrome homovanillic acid



history herpes zoster herpes zoster virus


iodide irrigation and debridement or incision and drainage intra-arterial intra-aortic balloon pump instrumental activities of daily living inflammatory bowel disease inclusion body myositis intermenstrual bleeding irritable bowel syndrome ideal body weight ileocecal immune complex inspiratory capacity implantable cardioverter defibrillator intracellular fluid intracerebral hemorrhage intracranial pressure intracytoplasmic sperm injection intensive care unit identifying data internal diameter intermediate density lipoprotein infant of diabetic mother infective endocarditis immunofluorescence internal fixation intrinsic factor immunofluorescence assay impaired fasting glucose immunoglobulin immunoglobulin A insulin-like growth factor immunoglobulin G immunoglobulin M impaired glucose tolerance ischemic heart disease interleukins interleukin-l interleukin-6 interstitial lung disease implantable loop recorder intramedullary intramuscular inferior mesenteric artery intermenstrual bleeding idiopathic myelofibrosis intermaxillary fixation infant mortality rate intermittent mandatory ventilation interferon isoniazid internuclear ophthalmoplegia international normalized ratio intraosseous intra-operative cholangiography intraocular lens intraocular pressure interphalangeal intraperitoneal ileal pouch-anal anastomosis interphalangeal depth intraductal papillary mucinous neoplasm injected polio vaccine intelligence quotient immediate release intra retinal microvascular abnormalities intrinsic sympathomimetic action in the ear immune thrombocytopenic purpura international units intrauterine death


intrauterine device intrauterine fetal demise intrauterine growth restriction intrauterine insemination intra venous inferior vena cava intravenous drug use in vitro fertilization intraventricular hemorrhage intravenous immunoglobulin in vitro maturation intravenous pyelogram intravenous urogram


jaeger juvenile arthritis Jakob-Creutzfeldt juxtaglomerular apparatus juvenile idiopathic arthritis juvenile nasopharyngeal angiofibroma juvenile rheumatoid arthritis jugular venous pressure



potassium postassium chloride kilogram potassium hydroxide Kolmer Reiter Protein kidney, ureter, bladder



litre live births lecithin/sphingomyelin ratio left atrium local anesthetic long-acting lupus anticoagulant left anterior descending left axis deviation left atrial enlargement left anterior fascicular block left atrial pressure leukocyte alkaline phosphatase lower abdominal resection laser-assisted in-situ keratomileusis left bundle branch left bundle branch block Lewy body disease large bowel obstruction low birth weight left circumflex artery left coronary lecithin-cholesterol acyltransferase light chain cast nephropathy liquor carbonis detergens Laboratory Center for Disease Control lobular carcinoma in situ lateral collateral ligament left circumflex artery loading dose lethal dose - 50% levodopa lactate dehydrogenase low density lipoprotein lower extremities loop electrosurgical excision procedure Lambert-Eaton myasthenic syndrome


Toronto Notes 2008








lower esophageal sphincter liver function test large for gestational age lower gastrointestinal luteinizing hormone left heart failure luteinizing hormone releasing hormone lithium left intercostal space left internal mammary artery left internal thoracic artery left lateral decubitus left lateral deubitis position left lower lobe left lower quadrant left lower sternal border light microscope laryngeal mask airway Licentiate of the MCC lower motor neuron lower motor neuron lesion last menstrual period low molecular weight low molecular weight heparin lymph node last normal menstrual period level of conciousness light perception lumbar puncture left posterior fascicular block lipoprotein lipase lipopolysaccharide likelihood ratio leukotriene receptor antagonist lower respiratory tract infection left sternal border lichen simplex chronicus lysergic acid diethylamide low grade squamous intraepitheliallesion L·thyroxine, levothyroxine laryngotracheoplasty leukotriene receptor antagonist left uterine displacement left upper lobe left upper quadrant lower urinary tract symptoms left ventricular left ventricular assist device left ventricular end diastolic left ventricular end diastolic pressure left ventricular ejection fraction left ventricular end systolic left ventricular failure left ventricular function left ventricle filling pressure left ventricular hypertrophy Iymphovascular space invasion left ventricular outflow tract left ventricular pressure



male Muscarinic mean arterial blood pressure minimum alveolar concentration Mycobacterium avium complex microangiopathic hemolytic anemia mycobacterium avium·intracellulare mucosal associated lymphomatous tissue lymphoma monoamine oxidase monoamine oxidase inhibitors mean arterial pressure meconium aspiration syndrome military anti·shock trousers multifocal atrial tachycardia


metacarpal middle cerebral artery Medical Council of Canada mean corpuscular hemoglobin mild cognitive impairment medial collateral ligament mucinous cystic neoplasm metacarpal phalangeal joint medium chain triglycerides mixed connective tissue disease mean corpuscular volume molluscum contagiosum virus maintenance dose muscular dystrophy multidose activated charcoal major depressive disorder major depressive episode metered dose inhaler multiple daily injections 3,4·methlenedioxy· methamphetamine (ecstacy) myelodysplastic syndrome microwave endometrial ablation middle ear effusion middle ear inflammation mitochondrial myopathy, encephalopathy, lactic·acidosis and stroke like episodes model for end stage liver disease multiple endocrine neoplasia milligram magnesium myasthenia gravis monoclonal gammopathy of undetermined significance malignant hyperthermia Mental Health Act microhemoglutination test for Ab to T. pallidium major histocompatibility complex myocardial infarction meta·iodo·benzoguanide monoclonallg depostion disease minutes medial longitudinal fasciculus malignant melanoma millimeters multiple myeloma maximal mid-expiratory flow rate mid maximal flow rate methimazole mini·mental status exam maternal mortality rate measles/mumps/rubella mini mental status examination mechanism of action multiple organ dysfunction syndrome maturity·onset diabetes of the young multi·organ system failure mercaptopurine medroxyprogesterone acetate membranous proliferative glomerulonephritis myocardial perfusion imaging methylpheyl tetra hydropindine mean platelet volume mitral regurgitation magnetic resonance mental retardation mitral regurgitation magnetic resonance angiography Medical Research Council magnetic resonance cholangiopancreatography magnetic resonance imaging modified radical mastectomy methicillin·resistant S. aureus mitral stenosis multiple sclerosis


mixed sleep apnea multisystem atrophy maternal serum alphafetoprotein material safety data sheets mental status examination monsodium glutamate melanocyte·stimulating hormone musculoskeletal maternal serum screen methicillin sensitive S. aureus mid-stream urine metatarsal medullary thyroid cancer metatarso phalangeal joint methotrexate methotrexate·folinic acid manipulation under anesthesia multiple gated acquisition scan mitral valve mitral valve area motor vehicle accident motor vehicie collision myocardial 02 consumption mitral valve prolapse molecular weight monozygotic


normal sodium not applicable nitrous oxide noradrenaline non·alcoholic fatty liver disease nonalcoholic steatohepatitis noradrenergic and specific serotonin antagonists neonatal alloimmune thrombocytopenia narrow band ultraviolet B narrow band untraviolet C neurogenic claudication National Cholesterol Education Program neocellular nevus nerve conduction studies nerve conduction velocity norepinephrine necrotizing enterocolitis neurofibromatosis nasogastric nasogastric tube non·Hodgkin's lymphoma neonatal intensive care unit noninvasive positive pressure ventilation natural killer nasolacrimal duct neonatal lupus erythematosus no light perception N·methyl·D-aspartate neuromuscular junction neonatal mortality rate neuroleptic malignant syndrome nonmelanoma skin cancers number needed to harm number needed to treat nitric oxide not otherwise specified nasopharyngeal nasopharyngeal carcinoma normal pressure hydrocephalus nothing by mouth, nil per os negative predictive value non·REM non·reassuring fetal heart rate nicotine replacement therapy


8 Abbreviations




Toronto Notes 2008


nephrotic syndrome normal saline nonsteroidal anti-inflammatory drugs non-small cell lung cancer normal sinus rhythm non-stress test non ST elevation myocardial infarction neural tube defects nitroglycerin nasotracheal tube nuchal translucency ultrasound nausea and vomiting nausea/vomiting and diarrhea neurovascular intact neurovascular status non-weightbearing not yet diagnosed New York Heart Association ova and parasites osteoarthritis on examination oxygen saturation occiput anterior osteoarthritis osteoclast activating factor obsessive compulsive disorder oral contraceptive pill obsessive-compulsive personality disorder oculus dexter once a day overdose right eye Ontario Drug Benefit oppositional defiant disorder opponens digiti minimi otitis externa Organization for Economic Co-operation and Development oral glucose challenge test oesophagogastro-duodenoscopy oral glucose tolerance test oral hypoglycemic agent Ontario Health Insurance Plan otitis media otitis media with effusion open neural tube defect occiput posterior opponens pollicis oral contraceptive pill olivopontocerebellar atrophy off pump coronary artery bypass oral polio vaccine odds ratio operating room open reduction internal fixation oculus sinister; left eye obstructive sleep apnea occiput transverse occupational therapy over the counter oculus uterque each eye





P PIE PA PA PAB PABA PAC PaCO, PACs progesterone physical exam posteroanterior pulmonary artery premature atrial beat para-aminobenzoic acid premature atrial contraction arterial partial pressure of carbon dioxide premature atrial contractions

post-anesthetic care unit phlegmasia alba dolens plasma anion gap Pan American Health Organization plasminogen activator inhibitor polyarteritis nodosa perinuclear anti-neutrophil cytoplasmic antibody arterial oxygen pressure partial pressure of oxygen in alveolar gas Papanicolaou pulmonary artery pressure pregnancy-associated plasma protein periodic acid-schiff reaction peripheral anterior synechiae pulmonary artery systolic pressure paroxysmal atrial tachycardia atmospheric pressure protein bound primary biliary cirrhosis percutaneous biliary drainage after meals peak concentration patient controlled analgesia posterior cerebral artery polychlorinated biphenyls phlegmasia cerulea dolens percutaneous coronary intervention polycystic kidney disease posterior cruciate ligament posterior capsular opacification partial pressure of carbon dioxide polycystic ovarian disease polycystic ovarian syndrome pneumocystis carinii pneumonia phenylcyclidine polymerase chain reaction proximal convoluted tubule pulmonary capillary wedge pressure Parkinson's disease personality disorder posterior descending (artery) parent ductus arteriosus pervasive developmental disorder phosphodiesterase postdural puncture headache proliferative diabetic retinopathy pulmonary embolus/embolism positive end expiratory pressure peak expiratory flow Prince Edward Island passive external rewarming pupils equal and reactive to light and accomodation positron emission tomography preeclampsia patellofemoral joint plain films patent foramen ovale pulmonary function tests plasma glucose prostaglandin prostaglandin E1 partial pressure of water periodic health examination posthemorrhagic hydrocephalus persistent hyperplastic primary vitreous peripherally inserted central catheter pelvic inflammatory disease pulmonary infilitration with eosinophilia pregnancy-induced hypertension posterior Interosseous nerve proximal interphalangeal joint Personal Information Protection and Electronic Documents Act posterior interventricular artery pyruvate kinase phenylketonuria palmaris longus


platelets evening polymyositis pontine micturition center premenstrual dysphoric disorder past medical history point of maximal impulse polymorphonuclear neutrophils proportional mortality rate premenstrual syndrome polymyositis paroxysmal nocturnal dyspnea post nasal drip primitive neuroectodermal tumour paroxysmal nocturnal hemoglobinuria parasympathetic nervous system peripheral nervous system oral, per os partial pressure of oxygen phosphate primary open angle glaucoma post-operative day post obstructive diuresis pro-opiomelanocortin post-operative nausea and vomiting post-partum depression purified protein derivative postpartum hemorrhage persistent pulmonary hypertension of the newborn proton pump inhibitor paramedian pontine reticular formation preterm premature rupture of membranes progressive systemic sclerosis positive predictive value positive pressure ventilation per rectum progesterone receptor pulmonary regurgitation packed red blood cells photorefractive keratectomy prolactin as needed premature rupture of membranes penicillin-resistant S. aureus penicillin-resistant Streptococcus pneumoniae proximal radio ulnar joint polycythemia rubra vera pulmonary stenosis progressive supranuclear palsy prostate specific antigen psoriatic arthritis primary sclerosing cholangitis poststreptococcal glomerulonephritis posterior superior iliac spine progressive supranuclear palsy progressive systemic sclerosis penicillin sensitive S. aureus paroxysmal supraventricular tachycardia physiotherapy prothrombin time percutaneous transluminal angioplasty pure tone audiometry percutaneous transhepatic cholangiography percutaneous transluminal coronary angioplasty percutaneous transluminal coronary interventional polytetra fluroethylene parathyroid hormone PTH-related peptides preterm labor post traumatic stress disorder partial thromboplastin time propylthiouracil peptic ulcer disease

Toronto Notes 2008






Abbreviations 9



posterior urethral valve psoralens and long wave ultraviolet radiaton pulmonary valve premature ventricular beat premature ventricular contractions peripheral vascular disease posterior vitreous detachment pulmonary vascular resistance potential years of life lost





each, every perfusion quality adjusted life year once a day every night, at bedtime four times a day quality of life quantitative sensory testing








routine and microscopy rule out rheumatoid arthritis right atrium right axis deviation right atrial enlargement radioactive iodine uptake recurrent abdominal pain right atrial pressure relative afferent pupillary defect renal artery stenosis reticular activating system right bundle branch block red blood cell renal blood flow right coronary artery renal cell carcinoma randomized controlled trial retinal detachment respiratory distress syndrome red blood cell distribution width reactive arthritis rapid eye movement radiofrequency rheumatoid factor risk factor renal function tests Rhesus right heart failure radio-immune assay right intercostal space reversible inhibitor of MAO-I reversible ischemic neurological deficit right internal mammary artery right internal thoracic artery Ringer's lactate right lower lobe right lower quadrant right lateral sternal border right middle lobe radionucleotide angiography ritonucleic acid Registered Nurses' Association of Ontario radionuclide cystogram recommended nutrient intake range of motion rupture of membranes retinopathy of prematurity retinitis pigmentosa retinal pigment epithelium renal plasma flow rapidly progressive glomerulonephritis


rapid plasma reagin rapid primary survey respiratory quotient relative risk respiratory rate relative risk reduction renal replacement therapy reflex sympathetic dystrophy rapid sequence induction respiratory syncytial virus radiation therapy reverse triiodothyronine renal tubular acidosis respiratory tract infection recombinant tissue plasminogen activator right upper lobe right upper quadrant residual volume right ventrical right ventricular assist device right ventricular end-diastolic pressure right ventricular failure right ventricular hypertrophy right ventricular outflow tract right ventricular outflow tract obstruction right vp.ntricular pressure right ventricular strain pattern right ventricular systolic pressure treatment




signs and symptoms side effects sinoatrial sinus arrhythmia spontaneous abortion subacute comhined degeneration subarachnoid hemorrhage hemoglobin oxygen percent saturation severe acute respiratory syndrome subacute bacterial endocarditis small bowel obstruction spontaneous bacterial peritonitis systolic blood pressure ster noclavicular subcutaneous spinocerebellar ataxia squamous cell carcinoma sickle cell disease sudden cardiac death short chain fatty acids slipped capital femoral epiphysis succinylcholine severe combined immunodeficiency spinal coni injury without radiologic abnormality small cell lung cancer sternocleidomastoid serum creatinine central venous oxygen saturation standard deviation single dose activated charcoal substitutp. decision maker selective dopamine re-uptake inhibitor Shy-Drager syndrome systolic ejection murmur selective estrogen receptor modulator sick euthyroid syndrome social economic status synovial fluid symphysis fundal height specific gravity small for gestational age sex hormones sex hormone binding globulin sonohysterography


sacroiliac syndrome of inappropriate antidiuretic hormone sudden infant death syndrome squamous intraepithelial lesion Stevens-Johnson Syndrome sublingual systemic lupus erythematosis speech language pathologist straight leg raise smooth muscle antibody superior mesenteric artery superior mesenteric vein sulfamethoxazole sentinel node biopsv sensorineural hearing lOSS substantia nigra pars compacta selective norepinephrine re-uptake inhibitor striatonigral degeneration sympathetic nervous system shortness of breath shortness of breath on exertion superior orbital fissure spreading pigmented actinic keratosis single photon emission computed tomography serum protein electrophoresis sun protection factor superficial punctate keratitis sinus rhythm stereotactic radiosurgery speech reception threshold Sjogren's syndrome A Sjogren's syndrome B subacute sclerosing panencephalitis selective serotonin re-uptake inhibitor sick sinus syndrome staphylococcal scalded skin syndrome sexually transmitted diseases ST elevation myocardial infection sexually transmitted infection subthalamic nucleus sodium thiopental Stevens-Johnson Syndrome split thickness skin graft sensitive thyroid-stimulating hormone stroke volume superior vena cava systemic vascular resistance supraventricular tachycardia septic work-up

T 1/2/3

trimester 112/3 half life t1/2 13 triiodothyronine T3RU T3 resin uptake T4 thyroxine TM thoracic aortic aneurysm TAB therapeutic abortion TACE transcateter arterial chemoembolization TAH total abdominal hysterectomy total abdominal hysterectomy-bilateral TAH/BSO salpingo-oophorectomy TB tuberculosis transbronchial biopsy TBB TBG thyroid binding globulin TBSA total body surface area TBUT tear break up time TBW total body water TC total cholesterol TC transcobalamin Tc99m MIBI technetium-99m methoxyisobatyl-isonitrile TCA trichloroacetic acid


10 Abbreviations







Toronto Notes 2008



tricyclic antidepressant transitional cell carcinoma tracheoesophogeal fistula traditional chinese medicine toxic dose - 50% therapeutic drug monitoring tetanus, diphtheria, polio tracheoesophageal thromboembolic disease transesophageal echocardiography tracheoesophageal fistula toxic epidermal necrolysis transcutaneous electrical neuro stimulation tubal embryo transfer triangular fibrocartilage complex triglyceride transposition of the great arteries total hip arthroplasty therapeutic index transient ischemic attack total iron binding capacity three times aday tetanus immune globulin tubulointerstitial nephritis transjugular intrahepatic portasystemic shunt total intravenous anesthesia total knee arthroplasty to keep vein open total lung capacity temporal lobe epilepsy tympanic membrane transient monocular blindness temporo mandibular joint trimethoprim trimethoprim-sulfamethoxazole tumour necrosis factor tumour/node/metastasis staging tetralogy of Fallot train of fcur toxoplasmosis; other: GBS, enterovirus, parvovirus B19, gonococcus, lyme, Candida; rubella; CMV; HSV, HI\( hepatitis, HPV; sypnilis tension-free obturator tape tissue plasminogen activator tropical pulmonary eosinophilia treponemal pallidum immobilization total parenteral nutrition thyroid peroxidase total peripheral resistance tricuspid regurgitation transfusion related acute lung injury transverse rectus abdominus myocutaneous thyrotropin releasing hormone transrectal ultrasound thyroid stimulating antibodies thyroid stimulating hormone thyroid stimulating immunoglobulin teaspoon thoracic spine toxic shock syndrome thrombin time transthoracic biopsy transthoracic echocardiography tissue transglutaminase transtubular potassium gradient transient tachypnea of the newborn thrombotic thrombocytopenic purpura transurethral needle ablation transurethral resection of bladder tumour transurethral resection of prostate tricuspid valve



tension-free vaginal obturator tape tension-free vaginal tape thromboxane 2 transformation zone thiazolidinedione


von Willebrand's factor Varicella-Zoster immunoglobulin Varicella-Zoster virus


unit urinalysis as directed urine output ultrasound unstable angina uterine artery embolization ulcerative colitis ulnar collateral ligament upper extremity upper esophageal sphincter unfractionated heparin upper gastrointestinal upper gastrointestinal (Gil bleed upper left sternal border upper motor neuron upper motor neuron lesion ointment urine osmolality urine protein electrophoresis ureteropelvic junction UV protection factor upper respiratory infection upper respiratory tract infection urinary tract infection ultraviolet ultraviolet wavelength A ultraviolet wavelength B ultraviolet wavelength C ureterovesical junction ultraviolet radiation




white blood cells Workers' Compensation Board Women's Health Institute Workplace Hazardous Materials Information System World Health Organization Wolff-Parkinson-White syndrome Workplace Safety and Insurance Board weight



radiation therapy



Zollinger-Ellison syndrome zygote intrafallopian transfer zygote-transfer Ziehl-Neelsen zinc protoporphyrin


ventricular fibrillation ventilation visual acuity volume of distribution vacuum assisted closure ventricular assist devices vaginal intraepithelial neoplasia vaginal birth after cesarean vertebrobasilar insufficiency vital capacity voiding cystourethrogram venereal disease research laboratory test for syphilis ventricular fibrillation visual field von Hippel Lindau syndrome vulvar intraepithelial neoplasia vasoactive intestinal peptide vitamin A visual internal urethrotomy very low density lipoprotein vanillyl mandellic acid vestibulo-ocular reflex vasopressin ventricular premature beat velopharyngeal insufficiency ventilation-to-perfusion vancomycin-resistant Enterococci ventricular septal defect vital signs routine ventricular tachycardia tidal volume venous thromboembolism vesicoureteral reflux von Willebrand's disease



Cardiology and Cardiovascular Surgery

Jeremy Cohen, Mona Moosavian and Praveena Sivananthan, chapter editors Lawrence Aoun and Sam Silver, associate editors Jeremy Adams, EBM editor Dr. Luigi Casella, Dr. Chi-Ming Chow, Dr. Jack Colman, Dr. Daryl Kucey and Dr. Anna Woo, staff editors
Basic Anatomy Review Coronary Circulation Cardiac Anatomy Differential Diagnoses of Common Presentations Cardiac Murmur Claudication Syncope Local Edema Generalized Edema Chest Pain Palpitations ST Segment Changes Dyspnea 3 Ischemic Heart Disease (IHD) 22 Chronic Stable Angina Acute Coronary Syndromes (ACS) Unstable Angina (UA)/Non-ST Elevation MI
ST-Elevation Myocardial Infarction (STEM!)
Treatment Algorithm for Chest Pain Sudden Cardiac Death Coronary Revascularization Percutaneous Coronary Intervention (PCI) Coronary Artery Bypass Graft (CABG) Surgery Off Pump Coronary Artery Bypass (OPCAB) Surgery Cardiac Transplantation Ventricular Assist Devices (VADs)


5 Cardiac Diagnostic Tests Electrocardiography (ECG) ECG Basics Approach to ECGs Rate Rhythm Axis Intraventricular Conduction Abnormalities Hypertrophy and Chamber Enlargement Ischem ia/lnfarction Miscellaneous ECG Changes Other Cardiac DiagnosticTests Cardiac Enzymes Ambulatory ECG Echocardiography Exercise Testing Nuclear Cardiology Cardiac Catheterization and Angiography Contrast-Enhanced CT Coronary Angiography Magnetic Resonance Imaging

Heart Failure...............................•......•........33
Congestive Heart Failure (CHF)
Sleep-Disordered Breathing
Myocardial Disease Dilated Cardiomyopathy (DCM)
Hypertrophic Cardiomyopathy (HCM)
Restrictive Cardiomyopathy (RCM)
Valvular Heart Disease Infective Endocarditis Rheumatic Fever Choice of Valve Prosthesis Summary of Valvular Diseases Pericardial Disease Acute Pericarditis Pericardial Effusion CardiacTamponade Constrictive Pericarditis Congenital Cardiac Disease 36




Arrhythmias 14 Mechanisms of Arrhythmias Bradyarrhythmias and AV Conduction Blocks SupraventricularTachyarrhythmias and Pre-excitation Syndromes Ventricula r Tachya rrhythmias Electrophysiology (EPS) Studies Electrical Pacing Implantable Cardioverter-Defibrillators (ICDs) Catheter Ablation

VASCULAR DISEASE Peripheral Arterial Disease Acute Arterial Occlusion/Insufficiency Chronic Arterial Occlusion/Insufficiency Hypertension 45


Toronto Notes 2008

Cardiology and CV Surgery C1


Cardiology and Cardiovascular Surgery
Pulmonary Hypertension Carotid Artery Disease Aortic Disease Aortic Dissection
Aortic Aneurysm
Peripheral Venous Disease Deep Venous Thromboembolism
Superficial Thrombophlebitis
Varicose Veins
Chronic Venous Insufficiency
Common Medications Landmark Cardiac Trials Summary Key Questions References R17



54 57 58


C2 Cardiology and CV Surgery

Toronto Notes 2008

Toronto Notes 2008

Basic Anatomy Review

Cardiology and CV Surgery C3

Basic Anatomy Review
Coronary Circulation
• arterial supply to the heart is from the right and left coronary arteries, arising from the root of the aorta (see Figures 1 and 2) • right coronary artery (RCA) • acute marginal branches • atrioventricular (AV) nodal artery • posterior interventricular artery (PIV) = posterior descending artery (PD) • left main coronary artery (LCA): two major branches • left anterior descending artery (LAD)
- septal branches
- diagonal branches
• left circumflex artery (LCx)
- obtuse marginal branches
• dominance of circulation • right-dominant circulation: PIV and at least one posterolateral branch arise
from RCA (80%)
• left-dominant circulation: PIV and at least one posterolateral branch arise from
LCx (15%)
• balanced circulation: dual supply of posteroinferior LV from RCA and LCx (5%) • the sinoatrial (SA) node is supplied by the SA nodal artery, which may arise from the RCA (60%) or LCA (40%) • most venous blood from the heart drains into the RA through the coronary sinus, although a small amount drains through thebesian veins into all four chambers, contributing to the physiologic R-L shunt

.) RAG 30'


" ,, ,, :1 ::



:: ::




v; /



left main coronary artery (LCA) left circumflex artery (LCx)
left anterior descending (LAD)
septal perforator

right coronary artery (RCA)

obtuse marginal diagonal

Av nodaI -+---FC-.".,,;;:--- ...... artery posterior interventricular Figure 1. Anatomy of the Coronary Arteries (right anterior oblique projection)

Legend LAD -= left anterior descending a. leX circumflex a. RCA -= right coronary a. PO = posterior descending a. SANA -= sinoatrial nodal artery RAO -= right anterior oblique plane LAO -= left anterior oblique plane


Michael Comn 0 2005

Figure 2. Spatial Orientation of the Coronary Arteries

,. sup. vena cava
2. info vena cava
3. tricuspid valve
4. pulmonary valve 5. pulmonary a.

6. ventricular septum 7.pulmonaryv.
8. mitral valve 9. aortic valve

1. parietal pericardium 6. sinoatrial node 2.pericardial cavity 7.atrioventricular node 3. visceral pericardium 8. bundle of His


4. myocardium
S. endocardium

9. R. Lbundle branches
10. Purkinje fibres

Figure 3. Circulation, Conduction and Layers

C4 Cardiology and CV Surgery

Basic Anatomy ReviewlDDx of Common Presentations

Toronto Notes 2008

Cardiac Anatomy



• layers of the heart • endocardium • myocardium • pericardium • visceral pericardium • pericardial space • parietal pericardium • valves • tricuspid valve (TV): separates RA and RV • pulmonic valve (PV): separates RV and PA • mitral valve (MY): separates LA and LV • the mitral valve has 2 cusps; all others have 3 • aortic valve (AV): separates LV and ascending aorta • conduction system • in the normal heart, rhythm is controlled by the SA node near the junction of the SVC and RA • impulses from the SA node travel through the atria ---+ AV node ---+ bundle of His • bundle of His splits into left and right bundle branches (LBB and RBB) • left bundle branch splits into anterior and posterior fascicles • RBB and fascicles of LBB give off Purkinje fibres which conduct impulses to ventricular myocardium


Differential Diagnoses of Common Presentations
Cardiac Murmur
• • • • • • • • • • • • • • • • • • • • • valvular heart disease ventricular septal defect patent ductus arteriosus arteriovenous fistula functional murmur atherosclerotic disease diabetic neuropathy venous disease (e.g. DVT, varicose veins) vasculitis (e.g. Buerger's disease, Takayasu's arteritis) neurospinal disease (e.g. spinal stenosis) reflex s)'mpathetic dystrophy osteoarthntis popliteal entrapment syndrome chronic compartment syndrome remote trauma acute myocardial ischemia (AMI) aortic stenosis hypertrophic cardiomyopathy (HOCM) increased vagal tone (vasovagal) hypovolemia • blood loss • venous insufficiency bradyarrhythrnia • sick sinus syndrome sinus node ischemia • AVblock • pacemaker dysfunction tachyarrhythrnia • Vfib • Torsade ianure de Pointes respiratory • hypoxia • hypercapnia metabolic • hypoglycemia neurologlCaf • stroke • migraine • seizure colloid cyst

Local Edema
• inflammation/infection • venous or lymphatic obstruction • thrombophlebitis • chronic lymphangitis • resection of regional lymph nodes • filariasis


Generalized Edema
• cardiac causes e.g. CHF • renal causes e.g. acute and chronic renal failure • vasodilators (especially CCBs) • hepatic causes e.g. cirrhosis • hypoalbuminenua, refeeding edema • hypothyroidism • exogenous steroids • pregnancy • estrogens


Chest Pain
• pulmonary • pneumonia • pulmonary embolism (PE) pneumothorax/hemothorax • empyema • pulmonary neoplasm bronchiectasis • TB • cardiac • MI/angina • myocarditis/pericarditis • Dressler's syndrome • gastrointestinal • esophageal: spasm, GERD, esophagitis, ulceration, achalasia, neoplasm

• • • •

• gastritis • pancreatitis biliary colic

Toronto Notes 2008

DDx of Common Presentations/Cardiac Diagnostic Tests

Cardiology and CV Surgery C5

• cardiovascular • acute Ml • CHF/LV failure Palpitations • aortic stenosis • elevated pulmonary venous • arrhythmias (PAB, PVB, SVT, VT) pressure • mitral valve prolapse • thyrotoxicosis • reduced CO • mitral stenosis • pheochromocytoma • respiratory • fever • left ventricular hypertrophy • airway disease with aortic regurgitation • asthma • hypertrophic cardiomyopathy • COPD exacerbation • upper airway obstruction • hypoglycemia (anaphylaxis, foreign body • drugs: tobacco, caffeine, alcohol, epinephrine, ephedrine, mucus plugging) aminophylline, atropine • parenchymal lung disease • ARDS ST Segment Changes • pneumonia • interstitial lung disease • ST Elevation • acute ST-elevation myocardial • pulmonary vascular disease infarction (STEMI) • PE • ventricular aneurysm • pulmonary HTN left bundle branch block (LBBB) • pulmonary vasculitis • pleural disease • acute pericarditis (diffuse ST changes) • pneumothorax • ischemia with reciprocal changes • pleural effusion post myocardial infarction (MI) • neuromuscular and chest wall disorders • vasospastic (Prinzmetal's) angina • hypothermia (Osborne waves) • C-spine injury • polymyositis, myasthenia gravis, • early repolarization (normal variant correlate with old ECGs) Guillain-Barre syndrome • kyphoscoliosis • ST depression • acute non-ST elevation myocardial • anxiety/psychosomatic
infarction (NSTEMI) or ischemia • severe anemia
• LVH or RVH with strain

• mediastinal • lymphoma • thymoma • vascular • dissecting aortic aneurysm • surface structures • costochondritis • rib fracture • skin (bruising, shingles) • breast

• post MI STEMI with reci,rrocal changes digitalis effect (' scooping") left or right bundle branch block • Wolff-Parkinson-White syndrome


Cardiac Diagnostic Tests
... v·.·.•. I....


Electrocardiography (ECG) ECG Basics
• the electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart recorded from the surface of the body • on the ECG graph • the horizontal axis represents time 1 mm (1 small square) = 40 msec
5 mm (1 large square) = 200 msec
• the vertical axis represents voltage
1 mm (1 small square) = 0.1 mV
10 mm (2 large squares) = 1 mV
• leads • standard 12-lead ECG • limb leads: I, II, III, aVL, aVR, aVF • precordial leads: V1-V6 • additional leads • right-sided leads: V3R-V6R (useful in RV jnfarction and dextrocardia)

Figure 4. ECG Grid

• Definition • Standard Leads


Figure 5. ECG Waveforms and Normal Values

C6 Cardiology and CV Surgery

Cardiac Diagnostic Tests

Toronto Notes 2008



to ECGs


Rate Calculation oExamples oPractice

Rate • nonnal = 60-l(l0 brm • regular rhytlill1 • to calculate the rate, divide 300 by number of large squares between 2 QRS complexes (there are 300 large squares in 1 minute: 300 X 200 msec = 60 sec), or dIvide 1500 by the number of small squares between 2 QRS complexes • irregular rhythm • rate = 6 x number of R-R i.lltf'rvals in 10 seconds (the "rhythm strips" are 10 seconds recordings) Rhythm • regular = R-R interval is the same across the tracing • irregular = R-R interval varies across the tracing • regularly-irregular = repeating pattern of varying R-R intervals • irregularly irregular = R-R intervals vary erratically • normal sinus rhythm (NSR) • P wave precedes each QRS; QRS follows each P wave • P wave axis is nonnal (positive in leads 1, aVF) • Rate between 60-100 bpm Axis • mean axis indicates the direction uf the mean vector • can be determined for any waveform (P, QRS, T) • the standard ECG reported QRS axis usually refers to the mean axis of the frontal plane. It indicates the mean direction of ventricular depolarization forces • QRS axis in the horJ7ontal plane is not routinely calculated. It is directed posteriorly and to the left • the transition from negative to positive is usually in lead V3 • QRS axis in the frontal plane (see Figure 6) • normal axis: -30" to gOo (i.e., positive QRS in leads 1and II) left axis deviation (LAD): axis <-3Qo o right axis deviation (RAD): axis >9Qo

Axis Definition ~ 0 Calculation method • Examples oPractice



Intraventricular Conduction Abnormalities
Right Bundle Branch Block (RBBB) • Complete RBBB • (,,2RS duration>120 msec • positive QRS in lead VI (rSR' or occasionally broad R wave) • broad S waves in leads 1, V5-6 (>40 msec) • usually secondary T wave inversion in leads Vl-2 • Incomplete RBBB • QRS duration >90 and <120 msec • in lead VI rsR', or rsr', with r' >30 msec Left Bundle Branch Block (LBBB) • Complete LBBB • QRS duration>120 msec • in leads I, aVL and usually V5 and V6, a broad notched or slurred R wave • deep broad S waves in leads Vl-2 • secondary ST-T changes (-w in leads with broad R waves, +ve in Vl-2) are usually present • LBBB usually masks ECG signs of myocardial infarction Left Anterior Fascicular Block (LAFB) (Left Anterior Hemiblock) • left axis deviation (-30° to -90°) • small q and prominent R in leads I and aVL • small r and prominent S in leads II, III, and aVF
Figure 7. Ventricular Conduction

Figure 6. GRS Axis on Frontal

Intraventricular conduction abnormalities • Examples


Left Posterior Fascicular Block (LPFB) (Left Posterior Hemiblock) • right axis deviation (110° to 180°) • small r and prominent S in leads I and aVL • small q and prominent R in leads II, III, and aVF Bifascicular Block • RBBB pattern • the first 60 msec (1.5 small squares) uf the QRS shows the pattern of LAFB or LPFB Nonspecific Intraventricular block • QRS duration >120 msec • absence of criteria for LBBB or RBBB

Toronto Notes 2008

Cardiac Diagnostic Tests

Cardiology and CV Surgery C7

Hypertrophy and Chamber Enlargement
• left ventricular hypertrophy (LVB) • S in VI + R in V5 or V6 >35 mm above age 40, (>40 mm for age 31-40, >45 mm for age 21-30) • RinaVL>llmm • R in I + S in III >25 mm • Rin V6>26mm • additional criteria: • LV strain pattern (ST depression and T wave inversion in leads I, aVL, V4-V6) • left atrial enlargement • right ventricular hypertrophy (RVH) • right axis deviation • R/S ratio >1 or qR in lead VI • RV strain pattern: ST segment depression and T wave inversion in leads Vl-2 • left atrial enlargement (LAE) • negative component of P wave in lead VI 2:1 mm wide and 2:1 mm deep additional criterion • P wave>120 msec, notched in lead II ("P mitrale") • right atrial enlargement (RAE): • P wave >2.5 mm in height in leads II, Ill, or aVF ("P pulmonale")
Hypertrophy and Chamber Enlargement • Examples

• ischemia • ST segment depression • T wave inversion • injury • transmural (involving the epicardium) - ST elevation in the leads facing the area injured/infarcted; transient ST elevation may occur in patients with coronary artery spasm (e.g. Prinzmetal angina) • subendocardial- marked ST depression in the leads facing the affeded area; it may be accompanied by enzyme changes and other signs of myocardial infarction

~ Ischemiallnfarction
• Examples

Acute days (avg. 3-5 hours) ST segment elevation Figure 8. ECG changes with infarction

Recent weeks-months T wave inversion

Old months-years (avg. > 6 months) Significant Os

• evolving infarction • "typical" sequential changes of evolving myocardial infarction • 1st - hyperacute T waves ( tall, symmetric T waves) in the leads facing the infarcted area, with or without ST elevation • 2nd - ST elevation (injury pattern) in the leads facing the infarcted area - usually in the first hours post infarct - in acute posterior infarction, there is ST depression in V1-V3 (reciprocal to ST elevation in the posterior leads, that are not recorded in the standard 12-lead ECG) • 3rd - significant Q waves (hours to days post-infarct) • 4th - inverted T waves (one day to weeks after infarction) • this classical sequence, however, does not always occur, e.g. - Q waves of infarction may appear in the very early stages, with or without ST changes - Non-Q wave infarction: there may be only ST or T changes, despite clinical evidence of infarction

C8 Cardiology and CV Surgery

Cardiac Diagnostic Tests

Toronto Notes 2008

• completed infarction • abnormal Q waves (note that wide Q waves may be found in III and aVL in normal individuals) • duration >40 msec (>30 msec in aVF for inferior infarction) • Q/QRS voltage ratio is >25% • abnormal R waves (R/S ratio>1, duration >40 msec) in VI and more frequently in V2 are found in posterior infarction (usually in association with signs of inferior and/or lateral infarction)
Table 1. Areas of Infarctionllschemia (right dominant anatomy)
Vessel Usually Involved Infarct Area left anterior descending ILAD) anteroseptal anterior anterolateral extensive anterior right coronary artery (RCAI infenor right ventncle posterior Mllassoc. with mf. Mil lateral isolated posterior MI Leads Vl, V2 V3, V4 I, aVL, V3-V6 I, aVL, Vl-V6
II, III, aVF V3R & V4R (right sided chest leads) Vl and V21prominent Rwaves)


I, aVL, V5-6 Vl and V21prominent Rwaves)

Miscellaneous ECG Changes
Electrolyte Disturbances • hypt'rkalemia (see Figure 9) • mild to moderate (K 5-7 mmol/L): tall peaked T waves • severe (K >7 mmol/L): progressiVt' changes: P waves flatten and disappear; QRS widens and may show bizarre patterns, axis shifts left or right; ST shift with tall T waves

Figure 9. Hyperkalemia

• hypokalemia (set' Figure 10) • ST segment depression, prolonged QT interval, low T waves, prominent U waves

Figure 10. Hypokalemia

• hypercalcemia: shortened QT interval • hypocalcemia: prolonged QT interval

Hypothermia • sinus bradycardia • when severe, prolonged QRS and QT intervals • atrial fibrillation willi slow ventricular response and other atrial/ventricular dysrhythmias • Osborne Jwaves: "hump-like" waves at tl1.e junction of the Jpoint and the ST segment

Figure 11. Osborne J Waves of a hypothermic patient

Pericarditis • early - diffuse ST segment elevation ± PR segment depression, upright T waves • later - isoelectric ST segment, flat or inverted T waves • tachycardia
Low Voltage • definition: total QRS height in precordial leads <10 mm and limb leads <5 mm • differential diaj?;ll.osis • myocardial disease • ischemia • infiltrative or dilated cardiomyopathy, myocarditis

Toronto Notes 2008

Cardiac Diagnostic Tests

Cardiology and CV Surgery Cq

• pericardial effusion thick chest wall/barrel chest: COPD, obesity • generalized edema nypothyroidism/myxedema inappropriate voltage standardization

Drug Effects
• digitalis • therapeutic levels may be associated with "dig effect" (see Figure 12): • 5T Liownsloping or "scooping" • T wave depressIon or inversion • QT shortening ± U waves • slowing of ventricular rate in atrial fibrillation • toxic levels associated with: • arrhythmias: paroxysmal atrial tachycardia (PAT) with conduction blocks; severe bradycardia in atrial fibrillation, accelerated junctional rhythms, PVCs, ventricular tachycardia • "reg:ularization" of ventricular rate in atrial fibrillation due to a junctional rhythm and AV dissociation • arniodarone, quInidine, phenothiazines, tricyclic antidepressants, antipsychotics, some antihistamines, some antibiotics: prolonged QT interval, U waves

Figure 12. Atrial fibrillation, 5T change due to digitalis ("digitalis effect")

Pulmonary Disorders
• cor pulmonale (often secondal)' to COPD) • low voltage, RAD, poor R wave progression • RAE and RVH witfl strain • multifocal atrial tachycardia (MAT) • massive pulmonary embolism (PE) • sinus tachycardia and atrial fibrillation/atrial flutter are the most common arrhythmias RAD, RVH with strain - most specific sign is 5 IC2JT3 (5 in I, Q and inverted T wave in Ill)

Other Cardiac Diagnostic Tests Cardiac Enzymes
• provide diagnostic & prognostic information and identify increased risk of mortality m acute coronary synaromes
Table 2. Cardiac Enzymes
Traponin I, Traponin T

1-2 days

Duration Elevated
Up to 2 weeks

DDx of Elevation
acute pulmonary embolism, heart failure, myocarditis, end stage renal disease myocardial infarction, myocarditis, pericarditis, muscular dystrophy, cardiac defibrillation, etc. liver disease (hepatitis, cirrhosis, Reye's syndromel, hepatic congestion, infectious mononucleosis, myocardial infarction, myocarditis, severe muscle trauma, dermatomyositis/ polymYOSitis, etc. infarction of: myocardium, lung, kidney; diseases of cardiopulmonary system, liver, collagen; hemolytic anemias, etc.
Use of B-Type N81riuretic Peptide in 1IIe EveluBtion end Menegemenl 01 AculBl)yspnee (BASEU (N Engl J Med 2004;350;647-54)
StJJdy. Prospective, randomized controlled trial. P8Ii8ntr.452 patients (mean age 71 yrs. 58% maleI with acute dyspnea; Patients with severe renal disease or cardiogenic shock were excluded. IrIt8rvrlntkxr. Patients were randomized to assessment including measurement of B·type natriuretic peptide or standard assessment. I'rinMry Outcrmw. Time to discharge and total cost of treatment. Rssult1t. Median time to discharge was significandy shorter in the intervention group when compared with the control group (8.0 vs. 11.0 days, p=O.OOI). Total cost was also significantly lower in the intervention group ($5410 vs. $7264, p=O.OO6I. In addition, the measurement of Btype natriuretic peptide significantly reduced the need for admission to hospital and intensive care. The 3O·day mortality rates were similar (10% vs. 12%, p=0.45). ConcIUlkms. In patients with acute dyspnea, measurement of B-type natriuretic peptide improves clinical outcomes (need for hospitalization or intensive care) and reduces time to discharge and total cost of treatment


1 day

3 days


2-3 days

4-5 days


5-6 days

12 days

• follow troponin q8h x 3 ± creatine kinase-MB (CK-MB) (depends on local laboratory protocol)



• indications for outpatient management: palpitations, syncope, antiarrhythmic drug monitoring, and arrhythmia surveillance in patients with documented or potentially abnormal rhythms, surveillance of non-sustained arrhythmias that can lead to prophylactic intervention

CI0 Cardiology and CV Surgery

Cardiac Diagnostic Tests

Toronto Notes 2008

• available teclmologies: • Holter morutor • battery operated, continually records up to 3 leads for 24-48 hrs • symptoms recorded by patient on Holter clock for correlation with ECG findings • continuous loop recorder (diagnostic yjeld 66-83%) • worn continuously and can record data before and after patient activation for symptomatic episodes • external and implantable devices • external devices can be transtelephonically downloaded • implantable loop recorder (ILR) - implanted subcutaneously to the right or left of the sternum; triggered by placing an activator over it; anterograde and retrograde recording time is programmable; cannot be transtelephonically downloaded; left in place for 14 to 18 months


Transthoracic Echocardiography (TIE)
• ultrasound beams are directed across the chest wall to obtain images of the heart • indications: evaluation of left ventricular ejection fraction (LVEF), wall motion abnormalities, myocardial ischemia and complications of MI, chamber sizes, wall thickness, valve morphology, proximal great vessels, pericardial effusion, unexplained hypotension, murmurs, syncope

Doppler Ultrasound
• method to assess blood flow patterns, direction and velocity • indications: documentation and quantification of valvular insufficiency or stenosis, intracardiac gradients and estimations of blood flow and cardiac output • an integral part of TIE and TEE

Transoesophageal Echocardiography (TEE)
• ultrasound probe inserted into the esophagus to allow for better resolution of the heart and its structures • better visualization of posterior structures, such as left atrium and mitral and aortic valves • invasive procedure, used to complement transthoracic echocardiography • indications: intracardiac thrombi, tumours, valvular vegetations (infective endocarditis), aortic dissection, aortic atheromas, prosthetic valve function, shunts, technically inadequate transthoracic studies

Stress Echocardiography
• echocardiography in combination with either physiologic (exercise treadmill testing) or pharmacologic (dobutamine infusion) stress • validated in demonstrating myocardial ischemia • provides information on the global left ventricular response to exercise • regional wall motion is analyzed at rest and with stress

Contrast Echocardiography
• contrast agents injected into the bloodstream to improve imaging of the heart • conventional agent: agitated saline (contains microbubbles of air) • allows visualization of right heart and intracardiac shunts, most commonly patent foramen ovale (PFO) • newer contrast agents are capable of crossing the pulmonary bed and achieving left heart opacification following intravenous injection

Intracardiac Ultrasound
• ultrasound probe inserted into the heart (usually the right atrium) • used in interventional procedures such as transcatheter atrial septal defect device closure

Intravascular Ultrasound
• ultrasound probe inserted into the coronary arteries or other vessels • occasionally used in coronary angiography to improve definition of coronary lesions

Toronto Notes 2008

Cardiac Diagnostic Tests

Cardiology and CV Surgery Cll

Exercise Testing
• exercise testing is a cardiovascular stress test using treadmill or bicycle exercise with electrocardiographic and blood pressure monitoring • ACC/AHA 2003 guidelines for use: • patients with intermediate (10-90%) pretest probability of CAD based on age, gender and symptoms • complete RBBB • ST depression <lmm at rest • difficult to interpret: WPW, V-paced rhythms, >1 mm ST depression at rest, complete LBBB • note: less useful in cases of marked resting ST-T abnormalities, LBBB, digoxin use, less accurate in women • exercise test results stratify patients into risk groups • low risk patients can be treated medically without invasive testing • intermediate risk patients may need additional testing in the form of exercise imaging studies or cardiac catheterization • high risk patients should be referred for cardiac catheterization

Absolute Contraindications to Exercise Testing
• • • • • • • • • • • • • • • • acute myocardial infarction (within two days) unstable angina not previously stabilized by medical therapy uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise symptomatic severe aortic stenosis uncontrolled symptomatic heart failure acute pulmonary embolus or pulmonary infarction acute myocarditis or pericarditis acute aortic dissection left main coronary stenosis hemodynamically significant aortic stenosis electrolyte abnormalities severe arterial hypertension tachyarrhythmias or bradyarrhythmias hypertrophic cardiomyopathy and other forms of outflow tract obstruction mental or physical impairment leading to inability to exercise adequately high-degree atrioventricular block

Relative Contraindications to Exercise Testing

Prognostic Markers
• maximum exercise capacity, markers related to exercise induced ischemia (exercise induced ST-segment depression, exercise-induced ST segment elevation (in leads without pathological Q waves and not in aVR) exercise-induced angina, and inadequate blood pressure response in post infarct patients • abnormalities in exercise capacity, systolic blood pressure response to exercise, and heart rate response to exercise are important findings. The most important electrocardiographic findings are ST depression and elevation • the most commonly used ECG criteria for a positive exercise test: ~1 mm of horizontal or downsloping ST-segment depression or elevation (alleast 60 to 80 msec after the end of the QRS complex)

Absolute Indications forTerminating Exercise Stress Test
• drop in systolic blood pressure of>10 mm Ilg from baseline despite an increase in workload, when accompanied by other evidence of ischemia • moderate to severe angina • ST elevation (>1 mm) in leads without diagnostic Q-waves (other than VI or aVR) • increasing nervous system symptoms (e.g. ataxia, dizziness, or near syncope) • signs of poor perfusion (cyanosis or pallor) • technical difficulties in monitoring ECG or systolic blood pressure • subject's desire to stop • sustained ventricular tachycardia

Nuclear Cardiology
• myocardial perfusion imaging (MPI) with gated single photon emission tomography (SPEeT) • role in evaluating myocardial viability, detecting ischemia, and simultaneously assessing perfusion and left ventricular function by ECG gated SPEeT

02 Cardiology and CV Surgery

Cardiac Diagnostic Tests

Toronto Notes 2008

.... ~



Images of the heart obtained during stress and at rest 3-4h later
• stress • exercise treadmill test (unless contraindicated) • vasodilator stress with intravenous drugs • dipyridamole (Persantine"'), adenosine • act to increase coronary flow • dobutamine • ~l selective agonist • acts to increase myocardial O 2 demand • commonly used for patients with obstructive airway disease • images • fixed defect - impaired perfusion at rest and during stress (infarcted) • reversible defect - impaired perfusion only during stress (ischemic)

Patients with normal perfusion studies at peak stress have a <1 %/year incidence of death nonfatal MI and are thus often spared further invasive evaluation for assessment of their symptoms.




Higher sensitivity and specificity compared to standard exercise ECG testing when used to diagnose CAD.

ACC/AHA 2003 Guidelines for Use
• stable angina, baseline ECG abnormalities, post-revascularization assessment, heart failure, patients unable to exercise, preoperative risk assessment for patients undergoing noncardiac surgery, and evaluation of the efficacy of revascularization in patients undergoing coronary artery bypass surgery or an interventional procedure

.... ~


The degree of severity shown on the scan reveals the likelihood of further cardiac event rates independent of the patient's history, examination, resting ECG, and stress ECG result.


• thallium-201 01 11, a K analogue) • technetium-99 (99'fc)-labelled tracer (sestamibilcardiolite™ or hexamibi/Myoview™)


ACC/AHA 2003 Guidelines for Stress Testing with Imaging (echocardiography or perfusion studies)
• for patients able to exercise (treadmill stress test): • h-eadmill test plus echocardiography or nuclear perfusion studies • patients with intermediate pretest probability of CAD who also have WPW or >1 mm ST depression at rest • patients with prior revascularization (CABG or PCI) • for risk stratification and planning of PCI in patients meeting the above criteria • for patients unable to exercise: • use dobutamine echocardiography or dipyridamole/adenosine perfusion (MPI) studies rather than treadmill test • for patients at intermediate risk of CAD or with prior revascularization • for risk stratification and planning of PCI in patients meeting the above criteria
Table 3. Sensitivity and Specificity of Various Stress Testing
Testing Modality Exercise ECG Planar Thallium MPI (exercise or pharmacologic stress) Thallium SPECT MPI (exercise or pharmacologic stress) Stress Echocardiography PET scanning Sensitivity 68 79 88 76 91 Specificity



Sensitivity and specificity of various stress testing modalities in the detection of coronary altery lesions. If positive, findings were confirmed with angiography. Derived from the meta-analysis by Garber AM and Solomon NA. Cost-effectiveness of a~ernative test strategies for the diagnosis of coronary artery disease. Ann Intern Med 1999; 130191:719-28.

Cardiac Catheterization and Angiography
• invasive: fluid filled catheters introduced perrutaneously into arterial and venous circulation under conscious sedation • arterial access most commonly through the femoral artery; radial approach gaining favour especially for obese and outpatients • venous access through the femoral vein or intemal jugular vein; multiple venous catheters can be safely inserted in the Sdme femoral vein • same day procedure as outpatient: • indications for prehospitalization: anticoagulation therapy, renal failure, diabetes, contrast allergy • catheterization permits direct measurement of intracardiac pressures, transvalvular and mean peak pressure gradients, valve areas, cardiac output, shunt data, oxygen saturations, and visualization of coronary arteries, cardiac chambers and great vessels

Toronto Notes 2008

Cardiac Diagnostic Tests

Cardiology and CV Surgery C13

Right Heart Catheterization • right atrial, right ventricular, pulmonary artery pressures are recorded Pulmonary Capillary Wedge Pressure • obtained by advancing the catheter to wedge into the distal pulmonary artery • records pressures measured from the pulmonary venous system • in the absence of pulmonary venous disease, will reflect left atrial pressure Left Heart Catheterization • systolic and end-diastolic pressure tracings recorded; left ventricular size, wall motion and ejection fraction can be assessed by injecting contrast into the left ventricle (left ventriculography) • cardiac output (measured by the Fick oxygen method and the indicator dilution method) Coronary Angiography (see Figure 13) • coronarY vasculature accessed via the coronary ostium

1 -Inferobasal
2 -Inferoaplcal




3 -Apical

4 - Anteroaplcal 5 - Anterobasal

Gold standard for localizing and quantifying CAD.

Figure 13. Coronary Angiogram Schematic

Prognosticators • angiographic variables may provide valuable information regarding lesion severity, complexity, location and prognosis Diagnostic Catheterization • outcomes related to complications for diagnostic catheterization should be <1 % • procedure related complications: vascular injury, renal failure, stroke, MI • mortality rate 0.1-0.2% • inadequate diagnostic procedures should occur in far fewer than 1% of cases • provocative pharmacological agents can be used to unmask pathology • fluid loading may unmask latent pericardial constriction • afterload reduction or inotropic stimulation may be used to increase the outflow tract gradient in hypertrophic cardiomyopathy • coronary vasoreactive agents (e.g. methylergonovine, acetylcholine) • a variety of pulmonary vasoreactive agents in primary pulmonary hypertension (e.g. oxygen, calcium channel blockers, adenosine, nitric oxide, or prostacyclin)




Hemodynamically significant stenosis is defined as 70% or more narrowing of the luminal diameter.

Contrast-Enhanced CT Coronary Angio


• fast RCG-synchronized multi-slice CT image acquisition in the heart has enabled non invasive imaging of the coronary arterial tree

Magnetic Resonance Imaging (MRI)
• offers high spatial rE-solution, eliminates the need for iodinated contra~l, cmd does not involve exposure to ionizing radiation • particular value in ilssessment of congenital cardiac anomalies, abnormalities of the aorta, and assessment of viable myocardium

C14 Cardiology and CV Surgery


Toronto Notes 2008


Mechanisms of Arrhy1;hmias
(I) Altered Impulse Formation
Two potentially arrhythmogenic processes: a) abnormal automaticity • automaticity is the property of the myocardial cell to generate an action potential. It is influenced by: • neurohormonal factors (sympathetic and parasympathetic) • abnormal metabolic conditions (e.g. hypoxia, acidosis, hypothermia) • electrolyte abnormalities • drugs (e.g. digitalis) • local ischemia/infarction • other cardiac pathology • abnormal automaticity may be: • altered automaticity (decreased or enhanced) of cells that are normally automatic, e.g. sinus node, AV node • the development of automaticity in cells that are not normally automatic e.g. ventricular muscle cells b) triggered activity ("afterdepolarization") • initiation of cardiac impulses during or after repolarization • afterdepolarization may be early or delayed • earlyafterdepolarization is associated with prolonged QT (as in some patients with the long QT interval syndrome) • delayed afterdepolarization may occur in digitalis intoxication and during myocardia ischemia

(II) Altered Impulse Conduction
a) re-entry (see Figure 14) • requires a loop circuit including areas with different refractory period and conduction velocity • responsible for reentrant tachyarrhythmias

Normal conduction

Unidirectional block at one of the limbs

Reentry setup

Figure 14. An Example of Reentry

b) conduction blocks • partial or total c) ventricular pre-excitation • accessory pathway connects atria and ventricles • atrial stimuli reach the ventricle earlier bypassing the AV node and the conducting system (see Pre-Excitation Syndromes, C19)

Toronto Notes 2008


Cardiology and CV Surgery C15

Bradyarrhythmias «60 bpm)
• Sinus brac!yl:ardia • Sinoatrial (SA) block • Sinus arrest • AV block (2nd & 3rd degree) • Junctional rhythm • Idloventrlcular rhythm

--------- ~

Regular Narrow QRS
• Sinus tachycardia • Atrial tachycardia • Junctional taChycardia • AVNRT • AVRT • Atrial flutter


Tachyarrhythmias (> 100 bpm)



• Atrial fibrillation • A flutter with variable block • Multlfocal atrial tachycardia

• SVT with aberrancy/BBB •Ventricular tachycardia

Figure 15. Clinical Approach to Arrhythmias

Bradyarrhythmias and AV Conduction Blocks
Sinus Bradycardia
• P axis normal (P waves positive in I and aVF) • rate <60/min • marked sinus bradycardia (<SO/min) may be seen in normal adults, particularly athletes, and in elderly individuals • caused by increased vagal tone or vagal stimulation; vomiting; episodes of myocardial ischemia or infarction (inferior MI); sick sinus node; increased intracranial pressure; hypothyroidism; hypothermia; drugs (beta-blockers, calcium blockers, etc.) • treatment: if symptomatic, atropine during acute episodes; atrial pacing for sick sinus node syndrome; if drug-induced, reduction or witFtdrawal of drugs

~ 'Examples



Sinus Arrhythmia (SA)
• normal P waves, with variation of the P-P interval • "respiratory SA" is normal: rate increases with inspiration, slows with expiration • "non-respiratory SA" is seen more often in the elderly, and when marked it may be due to sinus node dysfunction. Usually it does not require treatment

Sinus Pause/Sinus Arrest
• a temporary pause (>2 sec) without P wave • the P-P prolongation is not phasic or gradual (unlike sinus arrhythmia) and is not a multiple of the normal P-P interval (unlike sino-atrial block) • sinus arrest is prolonged or permanent • escape beats or rhythm may occur: • atrial escape: P waves with abnormal morphology • junctional escape: P waves not seen, or follow the QRS (retrograde P), rate 40-60 bpm • ventricular escape: no P wave; wide, abnormal QRS; slow rate (20-40 bpm)

Sick Sinus Syndrome (SSS)
• cl1aractelized by sinus node dysfunction (marked bradycardia, sinus pause/arrest, sinoatrial block) • t'requently associated with episodes of atrial tachyarrhythmias • when symptomatic, electronic pacemaker is indicated

AV Conduction Blocks
1st Degree AV Block
• prolonged PR interval (>200 msec) • frequently found among otherwise healthy adults • no treatment required

2nd Degree AV Block
• some of the atrial impulses are not conducted to the ventricles • second degree AV brock is further subdivided into:

CI6 Cardiology and CV Surgery


Toronto Notes 2008

Type I (Mobitz I) 2nd Degree AV Block
• a gradual prolongation of the PR interval precedes the failure of conduction of a P wave (Wenckebach phenomenon) • AV block is usually in AV node • frequently benign




Figure 16. Second Degree AV Block with Wenckebach Phenomenon (Mobitz I)

Type II (Mobitz II) 2nd Degree AV Block
• the PR interval is constant; there is an abrupt failure of conduction of a P wave • AV block is usually distal to the AV node • increased risk of high grade or 3rd degree AV block

. ........., 0r J"rv


II... V



Figure 17. Second Degree AV Block Mobitz II

2:1 AV block
• often not possible to determine whether the block is type I or type II • prolonged or repeated recordings may clarify the diagnosis


J.L.l,l'lo.- - ..1

11 -

~j-- ~I-· -Ak-l---{-

Figure 18. 2:1 AV Block

High Grade 2nd Degree AV Block
• 2 or more consecutive P waves that are not conducted • usually without progressive prolongation of PR intervals (type II pattern)

3rd Degree AV Block
• • • • • complete failure of conduction of the supraventricular impulses to the ventricles ventricular depolarization initiated by an escape pacemaker distal to the block QRS can be ndrrow or wide Ounctional vs. ventricular escape rhythm) PP and RR intervals are constant, variable PR intervals no relationship between P waves and QRS complexes (P waves "marching through")

Figure 19. Third degree AV Block (Complete Heart Block)

Toronto Notes 2008


Cardiology and CV Surgery C17

SupraventricularTachyarrhythmias and Pre-excitation Syndromes
Presentation • symptoms, when present, include: palpitations, dizziness, dyspnea, chest discomfort, presyncol?e/syncope • may preopitate congestive heart failure (O-fF), hypotension, or ischemia in patients with underlying disease • untreated tachycardias can cause cardiomyopathy (rare) • includes supraventricular and ventricular rhythms Supraventricular Tachyarrhythmias (SVT) • the term is used to designate any of the tachyarrhythmias that originate in the atria or AV junction, when a more specific diagnosis of its mechanism and site of origin cannot be made • characterized by narrow QRS, unless there is pre-existing BBB or aberrant ventricular conduction (abnormal conduction due to a change in cycle length) Sinus Tachycardia • sinus rhythm with rate>100 bpm • occurs in normal subjects with increased sympathetic tone (exercise, emotions, pain), alcohol use, caffeinated beverages, drugs (e.g. beta-adrenergic agomsts, anticholinergic drugs, etc.) • etiofogy: fever, hypotension, hypovolemia, anemia, thyrotoxicosis, heart failure, MI, shock, pulmonary embolism, etc. • treatment: treat underlying disease; consider ~-blocker if symptomatic, rate modifying CCB if ~-blockers contraindicated Premature Beats • premature atrial contraction (PAC) • ectopic supraventricular beat originating in the atria • P wave morphology of the PAC usually differs from that of a normal sinus beat • junctional premature beat • ectopic supraventricular beat that originates in the vicinity of the AV node • P wave is usually not seen or retrograde P wave may follow closely the QRS complex • treatment usually not required Atrial Flutter • rapid, regular atrial depolarization from a re-entry circuit within the atrium • atrial rate 250-350 bpm, usually 300 bpm • AV block usually occurs. It may be fiXed (2:1, 3:1, 4:1, etc.) or variable • etiology: CAD, thyrotoxicosis, MY disease, cardiac surgery, COPD, pulmonary embofism, pericarditis • ECG: sawtooth flutter waves in inferior leads (II, III, aVF); narrow QRS (unless aberrancy) • in atrial flutter with 2:1 block carotid massage (first check for bruits), Valsalva maneuver or adenosine may decrease AV conduction and bring out flutter waves • treatment: • acute: if unstable (e.g. hypotension, CHF, angina): electrical cardioversion if stable: (1) rate control: I)-blocker, diltiazem, verapamil, or digitalis, (2) chemical cardioversion: sotalol, amiodarone, type I antiarrhythmics (3) electrical cardioversion • anticoagulation gJ!idelines same as for Eatients with AFib (see AFib, CIS) long-term: antiarrhythmics, catheter ab ation

~ oExamples



Figure 20. Atrial Flutter with Variable Block

Multifocal Atrial Tachycardia (MAT) • irregular rhythm caused by presence of 3 or more atrial foci (may mimic AFib) • atrial rate 100-200 bpm; at least 3 distinct P wave morphologies and PR intervals vary, some P waves may not be conducted • occurs more commonly in patients with COPD, and hypoxemia; less commonly in patients with hypokalemia, hypoma~esemia, sepsis, theophylline or digitalis toxicity • treatment: treat the underlying cause; CCBs may De used (e.g. diltiazem, verapamil), ~-blockcrs usually contraindicated because of severe pulmonary disease • no role for electrical cardioversion, antiarryhthmics or ablation

C18 Cardiology and CV Surgery


Toronto Notes 2008

Atrial Fibrillation (AFib)
• most common sustained arrhythmia; incidence increases with age (8% of population over 80) • rapid, disorganized and asynchronous activity of atria due to simultaneous discharge and reentry at multiple atrial foci • cardiac function is affected (loss of atrial contraction, irregular and rapid ventricular response, decreased cardiac output and coronary flow) • symptoms: palpitation, fatigue, when acute and with rapid ventricular response may cause syncope and precipitate or worsen heart failure • may be asymptomatic • associated with thromboembolic events • etiology: HTN, CAD, valvular disease, pericarditis, cardiomyopathy, pericarditis, myocarditis, ASD, following surgery, PE, COPD, thyrotoxicosis, SSS (Sick Sinus Syndrome), alcohol intake ("holiday heart") • may present in young subjects without demonstrable disease ("lone AFib") and in the elderly without underlying heart disease • ECG findings: no organized P waves, chaotic baseline with fibrilla tory waves, irregularly irregular ventricular response, narrow QRS (unless aberrancy or previous BBB) • atrial rate 400-600jmin; ventricular rate depends on AV node conduction, typically 100-180 bpm when Lmtreated • wide QRS complexes due to aberranc.y may occur following a long-short cycle sequence ("Ashman phenomenon") • loss of atrial contraction - no "a" wave seen in JVP, no 54

AtrilII Fibrillation - AFfUlM trilII
(NEJM 2002; 347:182&-33.)









Study. Randomized. multicenter trial with mean follow-up of 3.5 years. f'lItienm 4060 patients (mean age 70 yrs, 61% male, 89% white) with atrial fibrillation and ahigh risk of stroke or death, in whom anticoagulant therapy was not contraindicated. ht8twnIim Rate control (using ~ers, verapamil, dittiazem, or digoxin alone or in combination) vs. rhythm controllusing an antiarrhythmic drug chosen by the treating physicianl. IIIain outcome: Overall mortality. ,.".,IIKThere was no difference in mortality between the two groups.There were more haspi· tal~ations and adVerse drug effects in the rhythm' control group. ConcIuIIon: Rate-control was as effective as rhythm-control in atrial fibrillation, and may be better tolerated. Anticoagulation should be continued.

Figure 21. Atrial Fibrillation

Management (adapted from ACC/AHA/ESC guidelines 2006)
Major objectives: 1) to control rate: beta-blockers, diltiazem, verapamil (in patients with heart failure digoxin, amiodarone) 2) to prevent thromboembolism • assess stroke risk: in patients with nonvalvular AFib determine CHADS2 score (see sidebar 09) • if no risk factors, ASA 81-325 mg daily • 1 moderate risk factor, ASA or warfarin (INR 2.0-3.0, target 2.5) • >1 moderate risk factor or any high risk factor (prior stroke, TIA or embolism, mitral stenosis, prosthetic valve), warfarin 3) to restore sinus rhythm Other objectives: - to prevent and manage myocardial and hemodynamic consequences of AFib - to identify and treat causes of AFib and associated conditions - to improve and maintain quality of life

PriIllllY prevention of Itroke in patients with etrIal fibriHation
The Cochrane Ubrary, Issue 3, 2003. Study: Meta·analysis of 5RCTs (2313 patientsl comparing warfarin vs. control in patients wtth non·valvular chronic atrial fibrillation and no history ofTIA or stroke. DlrtlI utnIcfioft: Inclusiorv'exclusion criteria, method of random~tion, masked versus openlabel intervention, intensity of anticoagulation and method of monttoring, antithrombotic agents in the control group, losses to follow-up, adherence to assigned therapy, and intention·to-treat analy· sis. IIIain IIlIIuIIK Warfarin therapy (mean INR 2.02.61 was associated with large, highly significant reductions in ischemic stroke (OR =0.34, 95% CI 0.23· 0.52),Therewas no significant increase in the rates of hemorrhage in the primary prevention cohorts. Cont:Iusioo: Adjusted-cose warfarin reduced stroke for patients with nonvalvular AFib, with no increased bleeding among participants in ran· damized clinical trials.

Newly Discovered AFib
• if the episode is self limited and not associated with severe symptoms, no need for antiarrhythmic drugs. Anticoagulants beneficial if risk for stroke is high • if AFib persists, 2 options: a) rate control and anticoagulants; b) cardioversion; if AFib >48 hrs, anticoagulation, for 3 weeks prior and 4 weeks after cardioversion. Long term anticoagulation as indicated by stroke risk stratification (CHADS2 score) • the AFFIRM study has shown no advantage in survival or quality of life from rhythm control vs. rate control

Recurrent AFiblPermanent AFib
• if episodes are brief or minimally symptomatic, antiarrhythmic drug may be avoided; rate control and antithromhotic therapy are appropriate • if symptoms are bothersome or episodes are prolonged, antiarrhythmic drugs (flecainide, propafenone or sotalol for patients with no or minimal heart disease; amiodarone for patients with LV dysfunction; beta-blockers, amiodarone and sotalol for CAD patients) • patients who have undergone at least one attempt to restore sinus rhythm may remain in AFib after recurrence: permanent AFib may be accepted (with rate control and antithrombotics as indicated by CHADS2 score)

Toronto Notes 2008


Cardiology and CV Surgery (1~

AV nodal re-entrant tachycardia (AVNRT) • sudden onset and offset • fast regular rhythm; rate 150-250 bpm • usually initiated by a supraventricular or ventricular premature beat • AVNRT accounts for 60-70% of all paroxysmal SVTs • retrograde P waves may be seen but are usually lost in the QRS complex • treatment • acute: Valsalva or carotid massage (check first for bruits), adenosine is first choice if unresponsive to vagal maneuvers; if no response, try metoprolol, digitalis, diltiazem; electrical cardioversion if patient hemodynamically unstable (hypotension, angina, or CHF) • long-term: 1st line: ~-blocker, diltiazem, digitalis, 2nd: anti-arrhythmic drugs (flecainide, propafenone), 3rd: catheter ablation

Ta~e 4. CHAlJS2 Risk Prediction tor Non-Valvula! /\lib (JAMA ZOOI; 2851221:2864-701
Risk Factor
Congestive Heart Failure Hypertension Age>75 Diabetes Stroke(TIA (prior)

1 1 1 1

2 Anticoagulotion Recommandetion aspirin 81-325 mg coumadin (lNR 2-3) coumadin (lNR 2-3)

CHADS Score 0·' 2-3 4-6

Stroke Risk (%/Vr) 1.9-2.B(low! 4.0-5.9Imod) 8.5182 (high)





The carotid massage is actually not a massage, but rather constant pressure directed posteriorly against the carotid artery for 5·10 seconds.

Figure 22. Pathways for AVNRT (see ECG Made Simple online for details)

Pre-excitation Syndromes
Wolff-Parkinson-White (WPW) Syndrome • congenital defect, present in 1.5-2/1000 of the general population • accessory bypass pathway (Kent bundle) connects atrIa and ventricle • activation through bypass pathway reaches the ventricle earlier than through the AV node and the normal conduction system • typical ECC pattern is due to the stimulation of the ventricle through the bypass tract • early activation, slow conduction in the ventricular myocardium produce the "delta wave" (initial slurred upstroke of QRS complex) • followed by the stimulus going throu9,h the AV node and the normal conduction svstem, generating a "fusion complex' • fCC features: • PR interval <120 msec. • "delta wave"(the leads showing the delta wave vary with the site of the bypass) • wide QRS complex due to the premature activation • secondary ST segment and T wave changes tachyarrythrnias may occur, most often AVRT and AFib AV re-entrant tachycardia (AVRT) • re-entrant loop via accessory yathway and normcll conuuction system • initiated by a premature atria or ventriculclr complex • orthodromic AVRT: stimulus from a premature complex travels up the bypass tract (V to A) and down the AV node (A to V). Narrow QRS complex (no delta wave because stimulus travels through normal conduction systpm) • antidromic AVRT: more rarply stimulus goes up the AV node (V to A) and down the bypass tract (A to V). Wide and abnormal QRS as ventricular activation is only via the bypass tract. • treatment: • acute: similar to AVNRT except avoid long-acting AV nodal blockers, e.g. digitalis & veraparni1 • long-term: for recurrent arrhythmias, ablation of the byPass tract is recommended. Drugs such as flecainide and procainmlde can be used Atrial Fibrillation in WPW Patients • as most atrial stimuli are conducted through the bypass tract, the ventricular rate is yery rapid (>200/min) and the QRS complex very wide • treatment: electrical cardioversion, IV procainamide or IV amiodarone • do not use drugs that slow AV node conduction (digitalis, beta blockers) as they may increase conduction through the bypass tract and precipitate VFib • long term: a1:>lation of bypass tract when possible

i wave i Delta
(slurring of the Rwave)

Figure 23. Delta wave ofWPW

Figure 24. WPW: bypass tract and
delta wave

C20 Cardiology and CV Surgery


Toronto Notes 2008

VentricularTachyarrh~hmias - - - - - - - - - - - - - ' ----Premature Ventricular Contraction (PVC) or Ventricular Premature Beat (VPB)
• QRS width >120 msec, no preceding P wave, bizarre QRS morphology • origin: LBBB pattern =RV site; RBBB pattern =LV site • PVCs may be benign but are usually Significant in the following situations: • consecutive (~3 = VT) or multiform (varied origin) • PVC falling on the T wave of the previous beat ("R on T phenomenon"): may precipitate ventricular tachycardia or VFib

Accelerated Idioventricular Rhythm
• ectopic ventricular rhythm • rate 50-100 bpm • more frequently occurs in the presence of sinus bradycardia, and is easily overdriven by a faster supraventricular rhythm • frequently occurs in patients with acute myocardial infarction or other types of heart disease (cardiomyopathy, hypertensive HD, valvular HD) but it does not affect prognosis and does not usually require treatment

Ventricular Tachycardia (VT)
• 3 or more consecutive ectopic ventricular complexes • rate >100 bpm (usually 140-200) • "sustained VT" if it lasts longer than 30 sec. • ECG characteristics: wide regular QRS tachycardia (QRS usually >140 msec); AV dissociation; bizarre QRS pattern. Also favour Dx of VT: left axis or right axis deviation; nonspecific intraventricular block pattern; monophasic or biphasic QRS in VI with RBBB; concordance in V1-V6 • occasionally during VT supraventricular impulses may be conducted to the ventricles generating QRS complexes with normal or aberrant supraventricular morphology ("ventricular capture") or summation pattern ("fusion complexes")



iI i\




\ , 11\ 1\1 \.i

'\ r


If\. v


II 1\


f\ , \


1(\ \ \ ( 1\ I i1 ~ !V







I( 1'\


Figure 25. VentricularTachycardia

Table 5. Clues fur Diflorontiating VT vs. SVT with Aberrancy" Clinical Cluas Presenting symptoms not helpful History of CAD and previous MI VT Physical Exam Cannon "a" waves VT Variable Sl VT Carotid sinus massage! adenosine terminates arrhythmia SVT** ECG Cluas AV dissociation Capture or fusion QRS width>140 msec Extreme axis deviation (left or right superior axis) Positive QRS concordance fR wave across chest leads) Negative QRS concordance (S wave across chest leads) Axis shift during arrhythmia

• treatment: • sustained VT (longer than 30 seconds) is an emergency, requiring immediate treatment • hemodynamic compromise - electrical cardioversion • no hemodynamic compromise - electrical cardioversion, lidocaine, amiodarone, type Ia agents (procainamide, quinidine)

Arrhythmias that may present as a wide QRS tachycardia
• • • • ventricular tachycardia SVT with aberrant conduction (rate related) SVT with preexisting BBB or nonspecific intraventricular conduction defect AV conduction through a bypass tract in WPW patients during an atrial tachyarrhythmia (e.g. atrial flutter, atrial tachycardia) • antidromic AVRT in WPW patients (see Pre-excitation Syndromes, C19)

VT VT VT may suggest

Torsade de Pointes
• polymorphic VT - "twisting of the points" • looks like usual VT except that QRS complexes "rotate around the baseline" changing their axis and amplitude • ventricular rate greater than 100, usually 150-300 • etiology: patients with prolonged QT intervals are predisposed • congenital long QT syndromes • drugs - e.g. Class IA (quinidine), Class III (sotalol), phenothiazines (TCAs), erythromycin, quinolones, antihistamines • electrolyte disturbances - hypokalemia, hypomagnesemia • nutritional deficiencies causing above electrolyte abnormalities • treatment: IV magnesium, temporary pacing, isoproterenol and correct underlying cause of prolonged QT, electrical cardioversion if hemodynamic compromise



if patient >65 and prevIous MI or structural heart disease, then chance of VT >95% Mav terminate VT in some patients with no structural heart disease

Toronto Notes 2008


Cardiology and CV Surgery C21

Figure 26. Torsades de Pointes

Ventricular Fibrillation (VFib)
• chaotic ventricular arrythmia, with very rapid irregular ventricular fibrilla tory waves of varying morphology • terminal event, unless advanced cardiac life-support (ACLS) procedures are promptly initiated to maintain ventilation and cardiac output, and electrical defibrillation is carried out • most frequent cause of sudden death • refer to ACLS algorithm for complete therapeutic guidelines

, Figure 27. Ventricular Fibrillation



V\ If







V 1"-/ ~ i'-'

Electrophysiolog (EPS) Studies

_ _ _ _ _ _ _ _ _ _.-J

• invasive test used to better characterize arrhythmias • mostly viewed as supplemental to ECG recordings which are commonly sufficient for diagnosis and management • provide useful information when ECG data are nondiagnostic or unobtainable • bradvarrhythmias: sinus node dysfunction, atrioventricular (AV) block, and intraventricular conduction delay • tachyarrhythmias: • mainly used to map tachyarrythmias for possible ablation or to assess inducibility of ventricular tachycardia

Electrical Pacing
• the decision to implant a pacemaker usually is based on symptoms of a bradyarrhythmia or tachyarrhythmia in the setting of heart disease

Pacemaker Indications
• SA node dysfunction (most common): symptomatic bradycardia +/- hemodynamic instability) • common manifestations include: syncope, near syncope, transient Iightheadedness, or severe fatigue • SA node dysfunction is commonly caused by one or more of the following: intrinsic disease within the sinus node (e.g. idiopathic degeneration, fibrosis, ischemia, or surgical trauma), abnormalities in autonomic nervous system function, and drug effects • AV nodal - infranodal block: Mobitz type II, complete heart block

Pacing Techniques
• temporary: transvenous Qugular, subclavian, femoral) or external pacing • permanent: transvenous into RA, apex uf RV or both • can sense and pace atrium, ventricle or both • new generation = rate responsive, able to respond to physiologic demand • biventricular • nomenclature e.g. "VVIR" 1. chamber paced (atrium, ventricle, dual) 2. chamber sensitive (atrium, ventricle, dual) 3. response to sensing (inhibit, trigger, dual (1&T» 4. programmability (e.g. rate responsive) 5. arrhythmia control (pace, shock, dual, none)

C22 Cardiology and CV Surgery

Arrhythmiasnschemic Heart Disease (lHD)

Toronto Notes 2008

Implantable Cardioverter Defibrillators (lCDs)
Implantable Defibrillator after MI •MADlY II (NEJM 2002; 346:877-83.1
SIUdy Randomized, unblinded, controlled trial (average follow-up 20 monthsl. PatienIs: 1232 patients (mean age 64 yrs, 84% men) with prior MI and LV ejection fraction 0.30 or less. Exclusions included NYHA class IV at baseline, and FDA approved indication for ICD. IntBnIIlIItioll: Prophylactic ICD vs. conventional medical therapy. Main outcomes: AlI-eause mortality. Results. The mortality rate was lower in the ICD group (HR 0.69, p~ 0.016). ConcIIIIion: In patients with previous MI and severe LV dysfunction, prophylectic ICD improves survival.

• sudden cardiac death (SCD) usually results from ventricular fibrillation (VFib), sometimes preceded by monomorphic or polymorphic ventricular tachycardia (VT) • rCDs detect ventricular tachyarrhythmias and are fughly effective in terminating VT/VFib and in aborting SCD • several studies demonstrate mortality benefit vs. antiarrhythmics in 2° prevention (AVID, CASH, CIDS) • benefit for 1° prevention of SCD in patients with ischemic & non-ischemic cardiomyopathy, depressed left ventricular ejection fraction (LVEF), prolonged QRS (MADIT-I, MADIT-ll, MUSTI, SCD-HeFT studies) • very expensive: ongoing trials to determine cost effectiveness of 1° prevention and define benefit in various subgroups • see Heart Failure, C33 for current treatment recommendations

Catheter Ablation


• radiofrequency (RF) energy: a low-voltage high-frequency form of electrical energy (similar to cautery). RF energy produces small, homogeneous, necrotic lesions approximately 'i-7 mm in diameter and 3-5 mID in depth


• paroxysmal svr • AVNRT: accounts for more than half of all cases • an extra pathway lies in or near the AV node, which creates a reentry circuit • accessory pathway (orthodromic reciprocating tachycardia): 30% of svr • reentrant rhythm, with an accessory AV connection as the retrograde limb • cured by targeting the accessory pathway • atrial flutter: flutter focus in RA • atrial fibrillation: potential role for pulmonary vein ablation • ventricular tachycardia: commonly arises from the right ventricular outflow tract and less commonly originates in the inferoseptal left ventricle near the apex (note: majority of cases of vr are dul" to scarring from previous MI and cannot be ablated)
appr~ximatel,r 1% of patients death. O.]-O.2~ cardiac: high grade AV block requiring permanent pacemaker, tamponade, pericarditis vascular: hematoma, vascular injury, thromboembolism, TIA/stroke pulmonary: pulmonary embolism

Major Complications
• • • • •

Ischemic Heart Disease (tHO)
• commonest cause of cardiovascular morbidity and mortality • atherosclerosis and thrombosis are by far the most important pathogenetic mechanisms • male:female ratio =2:1 with all age groups included (Framingham study), 8:1 for age <40, 1:1 for age >70 • peak incidence of symptomatic IHD is age 50-60 (men) and 60-70 (women) • for primary prevention of ischemic heart disease, please see Family Medicine, FM4 • risk factors as per Table 6

Table 6. Risk Factors For Atherosclerotic Heart Disease
Major Risk Factors
smoking diabetes mellitus (DMI hypertension IHTNI family history (FHx) of MI first degree male relative <55 or first degree female relative <60 hyperlipidemia

Minor Risk Factors
male, postmenopausal female obesity sedentary lifestyle hyperhomocysteinemia

Toronto Notes 2008

Ischemic Heart Disease (lHD)

Cardiology and CV Surgery C23

Pathophysiology of Atherosclerosis
Hypertension Hypercholesterolemia Cigarettes

endothelial injury

rt M""Ph'9' j ~ ""T~:m~,:I~
endothelial denudation

--+ cytokines and growth factors

"flO' •



muscle cells
& fibroblasts

"foam cells"


necrosis and release of degradative enzymes within atheroma

growth of atheroma




"Lipid Core" I

"Fibrous Cap" I


Figure 28. Pathophysiology of Atherosclerosis (Jon Kenny (920061

• chronic stable angina is most often due to a fixed stenosis caused by an atheroma • the acute coronary syndromes are the result of plaque rupture

Chronic Stable Angina
• symptom complex resulting from an imbalance between oxygen supply and demand in the myocardium • factors influencing supply: • luminal diameter (most important factor) • duration of diastole • hemoglobin


• SaOz
• factors influencing demand • heart rate • contractility • wall stress

Etiology and Pathophysiology
• decreased myocardial oxygen supply • atherosclerosis, vasospasm tachycardia (-!- duration of diastole) • anemia • hypoxemia • congenital anomalies • increased myocardial oxygen demand • tachycardia • hyperthyroidism (1' contractility, l' HR) • myocardial hypertrophy, aortic stenosis (1' wall tension)

Canadian Cardiovascular Society Ices) FunclionaI Qassification of Angine Class I: ordinal'( physical activity (walking, climbing stairsl does not cause angina; angina with strenuous, rapid, or prolonged activity Class II: slight limitation of ordinal'( activity: angina brought at >2 blocks on level or climbing ~ 1flight of stairs or by emotional stress Class III: marl<ed limitation of ordinal'( activity: angina brought on at ~2 blocks on level or climbin sl flight of stairs Class IV: inability to carl'( out any physical activity without discomfort; angina may be present at rest

Signs and Symptoms
• typical: retrosternal chest pain, tightness or discomfort radiating to left (± right) shoulder/arm/neck/jaw, associated with diaphoresis, nausea, anxiety • Levine's sign: clutching fist over sternum when describing chest pain • anginal equivalents: dyspnea, acute left ventricular failure, flash pulmonary edema • predictably precipitated by the "3 E's": Exertion, Emotion and Eating • brief duration, lasting <10-15 minutes and typically relieved by rest and nitrates

The most powerful features that increase the likelihood of MI are ST-segment elevation, new Q-wave, chest pain radiating to both the right and left arm simultaneously, presence of an S3 and hypotension. The most powerful features that decrease the likelihood of MI are normal ECG report, pleuritic chest pain, pain reproduced on palpation, sharp or stabbing chest pain, and positional chest pain.
(Is This Patient Having aMyocardial Infarction? JAMA 1998; 280: 1256-63.)

Clinical Assessment (ACC 2002 Guidelines)
• • • • history, physical and directed risk factor assessment labs: Hb, fasting glucose, fasting lipid profile ECG (at rest and during episode of chest pain if possible) CXR (suspected heart failure, valvular disease, pericardial disease, aortic dissection/aneurysm, or signs or symptoms of pulmonary disease) • stress testing (see Cardiac Diagnostic Tests, ell) or angiography

C24 Cardiology and CV Surgery

Ischemic Heart Disease (IHD)

Toronto Notes 2008

• echocardiography: • to assess systolic murmur suggestive of aortic stenosis (AS), mitral regurgitation (MR) and/or hypertrophic cardiomyopathy (HCM) • to assess LV function in patients with Hx of prior MI, pathological Q waves, signs or symptoms of congestive heart failure (CHF)

Differential Diagnosis • cardiovascular • aortic dissection • pericarditis • respiratory (e.g. PE, pneumothorax, pneumonia) • gastrointestinal (e.g. peptic ulcer disease, gastroesophageal reflux disease, esophagitis, esophageal spasm, esophageal rupture) • musculoskeletal (e.g. rib fracture, costochondritis, muscle spasm) • neurological (e.g. herpes zoster) • psychiatric (e.g. anxiety) Treatment (ACC 2002 Guidelines) • goals of treatment: reduce myocardial oxygen demand or increase oxygen supply • lifestyle modification, treatment of risk factors, enrollment in an exercise program • enteric coated ASA (ECASA), clopidogrel when ASA absolutely contraindicated • I3-blockers (first line therapy - decrease overall mortality) • increase coronary perfusion and decrease demand (HR, contractility) and BP (afterload) • cardioselective agents are preferred (e.g. metoprolol, atenolol) to avoid peripheral effects (inhibition of vasodilation and bronchodilation via (32 receptors) • avoid intrinsic sympathomimetics (e.g. acebutolol) which increase demand • nitrates - used for symptomatic control, no clear impact on survival • decrease preload (venous dilatation) and afterload (arteriolar dilatation), and increase coronary perfusion • maintain daily nitrate-free intervals to prevent nitrate tolerance (tachyphylaxis) • calcium channel blockers (CCBs) (second line or combination) • increase coronary perfusion and decrease demand (HR, contractility) and BP (afterload) • caution: verapamil/diltiazem combined with (3-blockers may cause symptomatic sinus bradycardia or AV block • ACE inhibitors (ACEIs) • not used to treat angina -- however, cmgina patients tend to have risk factors for cardiovascular disease which do warrant use of an ACEI (e.g. hypertension, diabetes, proteinuric renal disease, previous MI with LV dysfunction) • class IIa evidence of benefit in all patients at high risk for cardiovascular disease • class I evidence in patients with concomitant DM, renal dysfunction or LV systolic dysftmction • growing evidence for angiotensin II receptor blockers (ARBs) when ACEIs are contraindicated • ACEIs do not treat symptoms of angina • statins (see Endocrinology. E15, Family Medicine. FM6 for target lipid guidelines) • revascularization (see Coronary Ri'1Jasculari;;ation, C29) • diagnosis: exercise stress test, nuclear imaging, cardiac CT, or coronary angiography Recommendations for Coronary Angiography (ACCIAHA 2002 Recommendations) • disabling (CCS classes III and IV) chronic stable angina despite medical therapy • high-risk criteria on clinical assessment or non-invasive testing • sudden cardiac death, serious ventricular arrhythmia, or CHF • uncertain diagnosis or prognosis after noninvasive testing • inability to undergo non-invasive testing VARIANT ANGINA (Prinzmetal's Angina) • myocardial ischemia secondary to coronary artery vasospasm, with or without atherosclerosis • uncommonly associated with infarction or LV dysfunction • typically occurs between midnight and 8 AM, unrelated to exercise, relieved by nitrates • typically ST elevation on ECG • diagnose by provocative testing with ergot vasoconstrictors (rarely done) • treat with nitrates and CCBs

• • • • typical symptoms of angina but normal angiogram may show definite signs of ischemia with exercise testing thought to be due to inadequate vasodilator reserve of coronary resistance vessels better prognosis than overt epicardial atherosclerosis

Toronto Notes 2008

Ischemic Heart Disease OHD)

Cardiology and CV Surgery C25

Acute Coronary Syndromes (ACS)
• coronary atherosclerosis with superimposed thrombus on ruptured plaque • other causes of unstable angina: • coranalY thrombuembolism (e.g. infective endocarditis, intracavity thrombus, paradoxical embolism) or cholesterol embolism • severe coronary vasospasm • coranary dissection • severe anemia

Spectrum of ACS
• unstable angina (UA)/non-ST elevation myocardial infarction (NSTEMI) • ST elevation myocardial infarction (STEM!) • sudden cardiac death

• history and physical • note that up to 30% of MIs are unrecognized or "silent" due to atypical symptoms - most common in DM, elderly, post-heart transplant (because of denervation) • ECG,CXR • labs • serum markers for myocardial damage • CBC, INR/aPTT, electrolytes and magnesium, creatinine, urea, glucose, serum lipids • draw serum lipids within 24-4R homs because values are unreliable from 2 to 48 days post-MI • cardiac enzymes (see Cardiac Enzymes, C9)

Unstable Angina (UA)/Non ST Elevation MI



• syndrome of acute plaque rupture and thrombosis with incomplete or transient vessel occlusion • unstable angina is clinically defined by any of the following: • accelerating pattern of pain: l' frequency, l' duration, with -.j., exertion, -.j., response to treatment • angina at rest • new onset angina • anguld post-MI or post-procedure (e.g. percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABGD • NSTEMI is clinically defined by the presence of 2 of 3 criteria: • symptoms of angina/ischemia • rise and fall of serum markeli-; of myocardial necrosis • evolution of ischemic ECG changes (without ST elevation or new LBBB) • acute phase of UA/NSTEMI: • risk of progression to MI or th(' JE'velopment of recurrent MI or death is highest in the early period • at 1 to 3 months after the acute phase, most patients resume a clinical course similar to that in patients with chronic stable coronary disease • majority of NSTEMIs do not result in the development of Q waves

A Rendomized Triel of lDw-Oose Aspirin in !he Primery Prevention of Cerdiovasculer Oiseese in

(N Engl J Med2l105;352:1293-13(4).

Management of NSTEMI (ACC/AHA 2002 AND ACCP 2004)
Anti-platelet and anticoagulation therapy • ASA (initially 162-325 mg chewed followed by 81-162 mg OD), clopidogrel300 mg loading dose then 75 mg OD if ASA contraindicated • subcutaneous low molecular weight heparin (LMWH) or IV unfractionated heparin UFH (LMWH is preferable to UFH except in renal failure or if CABG is planned within24h) • if PCI is planned: clopidogrel 600 mg loading dose and GP IIblIIIa inhibitor IV ESSENCE trial: 20% mortality benefit for enoxaparin and ASA vs. UFH and ASA General measures and anti-ischemic therapy • bed rest, cardiac monitoring, oxygen • nitroglycerin SL followed by IV • morphineIV

Study. Prospective. randomized, placebo-controlled trial. PBtierrts. 39,876 women 45 years of age or older (median age 55 yrs) with no history of major chronic illness. IntsrventiOtr. Patients were randomized to receive either l00mg of aspirin on alternating days or placebo. Primsry Outcome: Incidence of major cardiovascular events (nonfatal MI, nonfatal stroke or death from cardiovascular causes!. Rssu/t$; There was a non-significant trend toward fewer events of the primary composite outcome in the aspirin group compared with placebo (4n vs. 522, RR.O.91, p.O.131. Those in the aspirin group were at significantly reduced risk of stroke (RR.Q.83, p.O.04. NNT.3911. but were at significantly increased risk of GI bleed ing requiring transfusion (RR.1.4, p.O.02, NNH.553). The two groups had similar risks of fatal or nonfatal MI and death from cardiovascular causes. However, subgroup analysis revealed a significantly reduced risk of major cardiovascular event, ischemic stroke and MI in women 65 years of age or older receiving aspirin. Conclusions. In women 45 years of age or older, aspirin reduces the risk of stroke but has no effect on the risk of MI or death from cardiovascular causes.

C26 Cardiology and CV Surgery

Ischemic Heart Disease (IHD)

Toronto Notes 2008


Treatment of NSTEMI -BEMOAN":

Enoxaparin Morphine


• I3-blockers (first dose IV) followed by oral administration • non-dihydropyridine CCB in absence of severe LV dysfunction in patients with continuing or frequently recurring ischemia when ~-blockers are contraindicated (evidence suggests that CCBs do not prevent Ml or decrease mortality) • ACEI • for patients with LV dysfunction or CHF • for all ACS patients with diabetes (class I) • for all post-ACS patients (class ITa) Risk stratification • history, physical, cardiac enzymes, ECe • non-invasive stress testing, echocardiography • angiography Conservative vs. invasive strategies (FRISC II, TACTICS-TIMI 18, RITA 3, ICTUS) • early coronary angiography ± revascularization if possible is recommended in UA/NSTEMl with any of the following high-risk indicators (class I): • recurrent angina/ischemia at rest despite intensive anti-ischemic therapy CHF or l V dysfunction • hemodynamic instability high TIMl risk score (see sidebar) • sustained VT • dynamic ECe changes • high-risk findings on non-invasive stress testing PCl within the previous 6 months repeated presentations for ACS despite Tx and without evidence of ongoing ischemia or high risk features (class IIa) Post-discharge therapy • education, risk factor modification • drugs required in hospital to control ischemia should be continued after discharge in patients who do not undergo revascularization • Rx: ECASA 81-162mg OD and/or clopidogrel 75mg OD (at least 1 month), ~-blocker, stalin, ACEJ and/or ARB ± warfarin x 3 months if high risk (large anterior MI, l V thrombus, LVEF <30%, history of VTE, chronic AFib) • nitrates for symptomatic relief of ongoing angina if necessary • aldosterone antagonist if: • on ACEl • LVEF<40% • symptomatic HF or DM • Cr <221 flm/L (2.5 mgldL) for men or <177 flill/L (2.0 mgldL) for women • serum K <5.0 mmol/L (significant mortality decrease seen within 30 days - EPHESUS trial)

TIMI Risk Score for UAlNSTEMI
Hiltorl~1 Age ~65yrs ~3


risk factors for CAD Known CAD (stenosis ~50%1 Aspirin use in past 7days 1 1 1 (0-71

I'reHntItion Recent 1$24 hr) severe angina ST-segment deviation ~.5 mm t cardiac markers Risk Score =Total Points

CAD =coronary artery disease NSTEMI =non ST-segmenl e1avation myo<ardial infarction TIMI =thrombolysis in myocardial infarction UA =unstable angina

ST Elevation Myocardial Infarction (STEMI)
• syndrome of acute plaque rupture and thrombosis with total coronary occlusion resulting in myocardial necrosis • STEMl is clinically defined by new ischemic ECe changes plus one or both of ischemic symptoms and elevated cardiac enzymes • ECe criteria: • ST elevation in 2 contiguous leads (:2:1 mm in limb leads or ;::2 mm in precordial leads) or • new BBB (left or right) • see Electrocardiography, C5

Management of STEMI (ACC/AHA 2004 guidelines)
Initial Goals • relieve ischemic pain • assess hemodynamic state and correct abnormalities • initiate reperfusion therapy with PCI or thrombolysis • antithrombotic therapy to prevent rethrombosis (of plaque or incompletely stenosed vessels) Long Term Goals • ACEI to prevent LV remodelling • beta blockers to prevent recurrent ischemia and VT/VF • statins to slow disease progression • anticoagulation if l V tfuombus or chronic AFib

Toronto Notes 2008

Ischemic Heart Disease (IHD)

Cardiology and CV Surgery C27

Acute Management • note: after the diagnosis of STEMI is made, do not wait for results of further investigations before implementing reperfusion therapy • goal: thrombolysis (EMS-to-needle) WIthin 30 minutes or PCI (EMS-to-balloon) within 90 minutes depending on capabilities of hospital At Hospital • bedrest, telemetry, oxygen • nitroglycerin sUblinguaJ or IV • morphine IV • ASA 162-325mg chewed • if PeI is planned: clopidogrel 300 mg loading dose then 75 mg OD, GP IIb/llIa inhibitor IV • 24-48 hrs of high dose LMWH (or unfractionated heparin if the patient will undergo PCI or CABG, will receive no revascularization therapy or will be thrombolysed with teneeteplase, alteplase or reteplase) • no benefit of LMWH versus ASA in patients given streptokinase, anistreplase or urokinase (class lIb evidence) • continue high dose LMWH followed by oral anticoagulation at discharge if at high risk for thromboembolic event (large anterior MI, A Fib, severe LV dysfunction, CHF, previous DVT or PE, or ECHO evidence of mural thrombus) • j:l-blocker (first dose IV) followed by oral administration. Contraindications to betablockers include: acute bronchospasm, significant hypotension, significant pulmonary congestion or significant conduction disease. If bradycardia is present, consider administering atropine (COMMIT/CCS2 trial: 1'mortality in patients with hemodynamic compromise with early beta-blockers given IV) • select and implement reperfusion strategy Reperfusion Options • if skilled PCI practitioners are available, early PCI (::::12 hrs after symptom onset and <90 mins after presentation) has been shown to improve mortality versus thrombolysis, with fewer intracranial hemorrhages and recurrent MIs (ACC/AHA Class I recommendations) • fibrinolysis preferred if the patient presents within 12 hrs of symptom onset, has contraindications to PCI, or PCI cannot be administered within 90 mins by a skilled practitioner (ACC/AHA 2004 Guidelines) • categorization of PCI in management of STEMI: • primary: PCI without prior administration of thrombolytic therapy data suggest that when available and performed in experienced centres, primary PCI is the method of choice to establish reperfusion GAMA 2004;291:736-39) • rescue: PCI following failed thrombolytic therapy (diagnosed clinically when, upon completion of thrombolytic infusion, ST segment elevation fails to resolve below half its initial magnitude and patient still having CP)
Table 7. Contraindications and Cautions for Fibrinolysis in STEMI
Absolute Prior intracranial hemorrhage Known structural cerebral vascular lesion Known malignant IC neoplasm Significant c1osed·head or facial trauma 1:;3 months) Ischemic stroke 1$3 months) Active bleeding Suspected aortic dissection Relative Chronic, severe, poorly controlled hypertension Uncontrolled hypertension IsBP>180, dBP>110) Current anticoagulation Noncompressible vascular punctures Ischemic stroke 123 months) Recent internal bleeding (~2-4 weeks) Prolonged CPR or major surgery (~3 weeks) Pregnancy Active peptic ulcer

Enoxaparin \/8111US Unfractionlllld Heperin with RbrinoIyIiI for ST-Eleylltion Myocerdial InI1Irction IN Engl J Med2006:354:1477-88)

Study. Prospective, randomized, controlled multicentre trial. I'etienI11; 20,479 patients Imedian age 60 yrs. 77'10 malel with STEMI who were scheduled to undergo fibrinolysis. 1ntBtventiotr. Patients were randomized to receive either enoxaparin Of weight based u"fractionated heparin in addition to thrombol· ysis and standard therapies. Primery 0u1J:0mB: Death or recurrent nonfatal MIJO days post-event 1hJsuJtr. Tha composite primary outcome occurred less often in the enoxeparin group compared with those who received unfraction· ated heparin (9.9'10 vs. 12.0'10, p<O.OOI, NNT=47). Taken seperately, there was a trend toward reduced monality (6.9'10 vs. 7.5'10, p=O.1l) and a significant reduction in nonfatal reinfarction (3.0'10 vs. 4.5'10, p<O.OOl) in the eno.aparin group. The risk of major bleeding was significantly increased in the eno.aparin group (2.1'10 Ys. 1.4'10, p<O.OOl, NNH=1421. Concluliolr. In patients with STEMI receiving thrombolysis, enoxaparin is superior to unfreetionated heparin in preventing recurrent nonfatal MI and may lead to a small reduction in monality.

Long Term Management/Secondary prevention
• education • Iisk factor modification • anti-platelet agents/anticoagulants • ECASA 81-162 mg OD indefinitely if not contraindicated ± clopidogrel 75 mg OD • warfarin (target INR 2.0-3.0 for 3 months) if large anterior MI, especially with LV aneurysm, or if LV thrombus seen on echo • ACEI - decrease mortality • prevent adverse ventricular remodeling • recommended for asymptomatic patients, even if LVEF >40% (HOPE trial) • recommended for: (ACC/AHA 2004 Guidelines) • symptomatic CHF, reduced LVEF «40%), anterior MI • use ARBs in patients who are intolerant of ACEIs • p-blockers (first line therapy - decrease mortality) • start immediately and continue indefinitely if no contraindications

C28 Cardiology and CV Surgery

Ischemic Heart Disease UHD)

Toronto Notes 2008

• CCB (NOT recommended as first line treahnent) • diltiazem and verapamil are contraindicated in MI with associated LV dysfunction (both are negative inotropes and negative chronotropes) • short acting nifedipine is contraindicated (no longer available in Canada) • aldosterone antagonists • EPHESUS trial showed significant mortality benefit of eplerenone by 30 days • ACC/AHA 2004 class I recommendation for use of any aldosterone antagonist in patients meeting criteria (see C26) • nitrates (alleviate ischemia but do not improve outcome; use caution in right-sided MI patients who are pre-load dependent) • statin • irrespective of lipid levels (MRCIBHF) • risk stratification (Figure 29) • initial intensive treahnent with high dose atorvastatin showed benefit within 30 days of therapy (PROVE_IT TIMI22 Trial) • pre-discharge ECHO to assess LV dysfunction

Resting LVEF is a useful prognostic factor.

Prognosis • 5-15% of hospitalized patients will die • risk factors • infarct size/severity • age • co-morbid conditions • development of heart failure or hypotension • post-discharge mortality rates • 6-8% within first year, half of these within first 3 months 4% per year following first year • risk factors • LV dysfunction • residual myocardial ischemia • ventricular arrhythmias • history of prior MI • resting T,VEF is most useful prognostic factor • complications as per Table S
Post·Infarction Risk Stratification

High-Risk (30-35%) -prior MI -CHF -Recurrent Ischemia -High-Risk Arrhythmia IntermediatefLow-Risk (65-70%)

Non-invasive Stress Testing

Cudi"" Catheterization
*notc: ECHO done routinely posr-Ml


Ischemia or Poor Functional Status 1 -1 Normal Results No further testing at this time


Figure 29. Post-Infarction Risk Stratification Table 8. Complications of Myocardial Infarction

~) (1
Complications of MI uCRASH PAOu: Cardiac Rupture Arrhythmia Shock Hypertension/Heart failure Pericarditis/Pulmonary emboli Aneurysm OVT

Complication Arrhythmia 1. tachycardia 2. bradycardia

Etiology sinus, AFib, VI; VFib sinus, AV block

Presentation first 48 hrs first 48 hrs 1-7 days 1-7 days 1-7 days within 48 hours anytime anytime 7·10 days, up to 6months 1-7 days

Therapy see Arrhythmias, C14

Myocardial Rupture 1. LV free wall transmural infarction 2, papillary muscle (-+MR) inferior infarction 3. ventricular septum I-+VSD) septal infarction ShockiCHF Post·infarct Angina Recurrent MI Thromboembolism Pericarditis (Dressler's syndromel infarction or aneurysm persistent coronary stenosis multivessel disease reocclusion mural/apical thrombus DVT inflammatory autoimmune

surgery surgery surgery inotropes, intra-aortic balloon pump aggressive medical therapy PClorCABG see above anticoagulation ASA

2-8 weeks

Toronto Notes 2008

Ischemic Heart Disease (lHD)

Cardiology and CV Surgery C29

Treatment Algorithm for Chest Pain
Chesl Pain

1. Morphine prn


2. O
3. 4. 5. 6.
Initial enzymes normal No Ischemic EKG changes


ASA 162-325mg chewed Nitroglycerin SL EKG Cardiac Enzymes


Observe: Analgesia prn Serial EKGs and ~ enzymes recurrent pain, ~ serial studies


ST segment depression (UA) Positive enzymes with no EKG changes (NSTEMI)

! !


,. 2. 3. 4. 5. 6. Beta-blocker Enoxaparin (LMWH) Morphine prn Oxygen ASA (if not already gIven) Nitroglycerin IV

Initially treat as per UAI NSTEMI


consider reperfusion



riSkl stratify
low ,.,5....




high risk

Pain resolves, S8rial studies nonnal

Stress Test

Steess T e s t !
Cardiac Catheterization Coronary Revascutarization "'va


,~ ",'
stress test


lugh rIsk


consider other causes of' chest pain






! -..

Risk Factor Modification & life-tong anti-anginal therapy

.. see "conservative vs. invasive strategies" in text o see "post-infarct risk stratification" in text ++ see Mreperfusion options" in text

Adapted from Cecil Essentials of Medicine 6th Ed. Andreoli and Carpenter. p.l01 (2004) with permission from Elsevier

Figure 30. Treatment Algorithm for Chest Pain

Sudden Cardiac Death
• unanticipated, non-traumatic cardiac death in stable patient, within 1 hour of symptom onset; ventricular fibrillation is most common cause


• primary cardiac pathology • ischemia/MI • LV dysfunction • severe ventricular hypertrophy • hypertrophic cardiomyopathy (HCM) • AS • long QT syndrome • congenital heart disease

• • • • • acute - resuscitate with prompt CPR and defibrillation investigate underlying cause (cardiac catheterization, electrophysiologic studies) treat underlying cause anti-arrhythmic drug therapy: amiodarone, ~-blockers lCD

Coronary Revascularization Percutaneous
Corona~ Intervention

(PCI) -,-::'_-,""",,"-'

• interventional tedmique aimed at relieving significant coronary stenosis • main techniques: balloon angioplasty, stenting • less common techniques: rotational/directional/extraction atherectomy

• medically refractory angina • acute coronary syndromes • primary/rescue PCI for STEMl

C30 Cardiology and CV Surgery

Ischemic Heart Disease (IHD)

Toronto Notes ZOOS

Balloon Angioplasty and Intracoronary Stenting
• coronary lesions dilated with balloon inflation • majority of patients receive intracoronary stent(s) to reduce recurrence (restenosis) of lesion(s) • primary success is >90% • major complication is restenosis, felt to be due to elastic recoil and neointimal hyperplasia (occurs in 20%) • recent development: drug-eluting stents (DES) • coated with antiproliferative drugs (sirolimus, paclitaxel) • aim to prevent neointimal hyperplasia and restenosis • problem of late stent thrombosis with DES

Adjunctive Therapies
• ASA and heparin decrease post-procedural complications • further reduction in ischemic complications has now been demonstrated using GplIb/IIIa inhibitors in coronary angiography and stenting (abciximab, eptifibatide, tirofiban) • following stent implantation, patients treated with ASA and clopidogrel • dual antiplatelet therapy (ASA and ciopidogrel) needed at least 12 months after DES

Procedural Complications
• mortality and emergency bypass rates <1% • nonfatal MI: approximately 2-3%

COronary Artery Bypass Graft (CABG) Surgery
• the objective of CABG is complete revascularization of the myocardium; goals include relieving symptoms (angina, heart failure) and thus improving quality of life, and/or prolonging life

Choice of R ••valCularization

Advantages of Pel over CABG • less invasive technique • less periprocedural morbidity and mortality • Shorter periprocedural hospitalization
Advantages of CABG over Pel • Greater ability to achieve complete revascularization • less need for repeated revascularization procedures

Indications for Pel over CABG • Single or double-vessel disease • Inability to tolerate surgery Indications for CABG over Pel • Triple-vessel or left main disease • Diabetes mellitus • Plaque morphology unfavourable for PC1

• Class I: there is evidence and/or general agreement that a given procedure or treatment is useful and effective: • CABG • significant left main artery disease • triple vessel disease, survival benefit in patients with abnormal LV function (EF <50%) • two-vessel disease with Significant proximal left anterior descending (LAD) disease and with abnormal LV function (EF <50%) or demonstrable ischemia on noninvasive testing • one or two vessel disease without significant LAD disease who have survived sudden cardiac death or sustained VT • CABG orPCI • patients with one or two vessel disease without Significant LAD disease but with a large area of viable myocarclium and high risk criteria on noninvasive testing • recurrent stenosis associated with a large area of viable myocardium or high risk criteria on noninvasive testing • Class IIa: weight of evidence/opinion is in favour of usefulness/efficacy • CABG or PCI • one vessel disease with significant proximal LAD • repeat CABG for multiple saphenous vein graft stenosis, with high risk criteria on noninvasive testing, especially when LAD graft at risk. PCI may be appropriate for focal lesions, or multiple lesions in poor surgical candidates • one or two vessel disease without Significant proximal LAD disease but with a moderate area of viable ischemia on noninvasive testing

Operative Issues
• isolated proximal disease in large coronary arteries (>1.0-1.5 mm) is ideal for bypass surgery; small, diffusely diseased coronary arteries are not suitable for bypass surgery • arteries with severe stenoses (>50% diameter reduction) are bypassed, except those of small calibre «1 mm in diameter)

Toronto Notes 2008

Ischemic Heart Disease (IHD)

Cardiology and CV Surgery C31

Table 9. Risk Factors for CABG Mortality and Morbidity
Risk Factors for CABG Mortality
Idecreasing order of significance) • urgency of surgery (emergent or urgent) • reoperation • older age • poor left ventricular function Isee belowl • female gender • left main disease • others include catastrophic conditions (cardiogenic shode, ventricular septal rupture, ongoing CPRI, dialysis-dependent renal failure, end-stage COPD, diabetes, cerebrovascular disease, and peripheral vascular disease

• left ventricular function is an important determinant of outcome of all heart diseases • patients with severe LV dysfunction usually have poor prognosis, but surgery can sometimes dramatically improve LV function • assess viability of non-functioning myocardial segments using thallium myocardial imaging, PET scanning or MRI

Conduits for CABG
• saphenous vein grafts (SVG) • at 10 years, 50% occluded, 25% stenotic, 25% angiographically normal • left internal thoracic/mammary artery (LITA/LIMA) • LIMA to LAD is the gold-standard; excellent long term patency (90-95% at 15 years), improved event-free survival (angina, MI), decreased late cardiac events; no increase in 0perative risk • right internal thoracic/mammary artery (RITA/RIMA) • used in bilateral ITA grafting; pedicled RIMA patency comparable to LIMA (free RIMA patency less) • patients receiving bilateral ITAs have less risk of recurrent angina, late myocardial infarction, angioplasty, reoperation and death; however, higher rates of sternal infection, dehiscence and mediastinitis especially in elderly, obese or diabetic patients • radial artery (free graft) • approximately 85-90% patency at 5 years • prone to severe vasospasm postoperatively due to muscular wall; patients often placed on CCB (e.g. nifedipine XL 20 mg aD) postoperatively • right gastroepiploic artery • good long term patency (80-90% at 5 years) • primarily used as an in situ graft to bypass the RCA • use limited because of the fragile quality of the artery, other technical issues, increased operative time (laparotomy incision) and incisional discomfort with associated ileus • for Y0unger patients «60 years of age), complete arterial revascularization is preferred due to longer term graft patf'ncy • redo bypass grafting • operative mortality 2-3 times higher than first operation • 10% perioperative MI rate • reoperation undertaken only in symptomatic patients who have failed medical therapy and in whom angiography has documented progression of the disease • increased risk with redo-sternotomy secondary to adhesions which may result in laceration to aorta, RV, lMA and other bypass grafts

Cleveland Clinic Clinical Scoring System for Post-CABG Outcomes PI10perative FiClDr Score Emergency Case Creatinine 141-167 umolll Creatinine>168 umoVL Severe LV dysfunction Reoperation Mitral regurgitation Age 65·74 Age >75 Prior vascular surgery


Hematocrit <34% Aortic Stenosis Weight <65 kg Oiabetes Cerebrovascular Disease



4·7% 10% 18% 23% >50%

0·2% 2·4% 5% 7% >25%

3-5 6 7-9 lOt

'Morbidity defined as myocardial infarction requiring use of

IABp, mechanical ventilation for 3. days, neurological
deficit. oliguric or anuric renal failure, Of serious infection.

Adapted from Higgins et al Stratification of morbidity and mortality outcome by preoperative risk factors in coronary anery bypass patients. JAMA, lfi7:234-8, 1m

Off-Pump Coronary Artery Bypass (OPCAB) Surgery
• despite the success of CABG with cardiopulmonary bypass (CPB), the deleterious effects of CPB include: stroke and neurocognitive defects (microembolization of gaseous and particulate matter) immunosuppression systemic inflammatory response Ic~ading to: • myocardial dysfunction • renal dysfunction • neurological injury • respiratory dysfunction • coagulopathies

C32 Cardiology and CV Surgery

Ischemic Heart Disease (IHOl/Cardiac Transplanatation

Toronto Notes 2008

• OPCAB avoids the use of CPB by allowing surgeons to operate on a beating heart • stabilization devices allow local cardiac wall motion fixation around the distal anastomotic site (e.g. Genzyme Immobilizer) while positioning devices allow the surgeon to lift the beating heart to access the lateral and posterior vessels (Medtronic Octopus and Starfish system) • procedure is safe and well tolerated by most patients; however, OPCAB surgery remains technically more demanding and has a steeper learning curve • use in poor candidates for CPB who have: calcified aorta, poor LVEF, severe peripheral vascular disease (PVD), severe COPD, CRF, coagulopathy, transfusion issues (i.e. Jehovah's Witness), good target vessels, anterior/lateral wall revascularization, target revascularization in older, sicker patients • absolute contraindications include: hemodynamic instability, poor quality target vessels including intramyocardial vessels, diffusely diseased vessels and calcified coronary vessels • relative contraindications include: cardiomegaly/CHF, critical left main disease, small distal targets, recent or current acute Ml, cardiogenic shock, LVEF <35% • OPCAB decreases in hospital morbidity (decreased incidence of chest infection, inotropic requirement, supraventricular arrhythmia), blood product transfusion, ICU stay, length of hospitalization, and decreased CK-MB and troponin I levels • no Significant difference in terms of survival at 2 years, frequency of cardiac events (MI, PC!, CHF, recurrent angina, redo CABG) or medication usage when compared to on-pump CABG

Cardiac Transplantation
• for end-stage heart disease; majority due to ischemic cardiomyopathy (60%) or idiopathic cardiomyopathy (20%), and minority due to valvular or congenital problems • worldwide I-year survival is 79%, 5-year survival about 60%, annual mortality rate of4% • donor hearts are considered from patients up to age 50-55 • matching is according to blood type, body size and weight (should be within 25%), and HLA tissue matching (if time allows)

Indications for Surgery
• severe cardiac disability despite maximal medical therapy (recurrent hospitalizations for CHF, NYHA III or N, peak metabolic oxygen consumption <15 ml/kg/min) • symptomatic cardiac ischemia refractory to conventional treatment (unstable angina not amenable to CABC or angioplasty with LVEF <30%; recurrent, symptomatic ventricular arrhythmias) • exclusion of all surgical alternatives to cardiac transplantation (revascularization for significant reversible ischemia, valve replacement for critical aortic valve disease, valve replacement or repair for severe MR)

• emotionally stable with social support • medically compliant and motivated • contraindications: incurable malignancy, major systemic illness, irreversible major organ disease (e.g. renal, hepatic), active systemic infection (e.g. Hep C, HN), obesity, irreversible pulmonary hypertension (pulmonary vascular resistance [PVR] >6 Wood units), severe COPD (FEV 1 <1 L), or active drug addiction or alcoholism • typically age <70 years

• rejection • common, however less than 5% have serious hemodynamic compromise • no noninvasive tests to detect rejection, and the gold standard remains endomyocardial biopsies • risk of acute rejection is greatest during the first 3 months after transplant • infection • leading cause of morbidity and mortality after cardiac transplantation • risk peaks early during the first few months after transplantation and then declines to a low persistent rate • allograft coronary artery disease • approximately 50% develop graft CAD within 5 years of transplantation • the most common cause of late death following transplantation

Toronlo !'Joles 2008

Cardiac TransplanatationlHeart Failure

Cardiology and CV Surgery C33

• malignancy • develop in 15% of cardiac transplant recipients • second most common cause of late death following transplantation • cutaneous neoplams most common, followed by non-Hodgkin's lymphoma and lung cancer • immunosuppressive medication side effects

Ventricular Assist Devices (VADs)


• indications • bridge to transplantation • postoperative mechanical support when unable to separate from cardiopulmonary bypass despite inotropic and rABP support • postoperative cardiogenic shock • can support the left (LVAD), right (RVAD) or both ventricles (BiVAD) • works by decompression of the ventricle, resulting in decreased myocardial oxygen consumption, permitting recovery of the myocardium that is not irreversibly injured • long-term implantation is being studied for its effectiveness in transplant and non-transplantable patients

Heart Failure
Congestive Heart Failure (CHF)

• forwClfd heart failure - heart unable to maintain adequate cardiac output to meet demands and/or able to do so only by elevating filling pressure • backward heart failure - heart unable to accommodate venous return resulting in vascular congestion (systemic or pulmonary) • heart failure can involve left side of heart (left heart failure), right side (right heart failure) or both (biventricular failure) (See Table 10) • pulmonary edema - severe pulmonary congestion 2° to backwards left-heart failure • components of ineffective ventricular filling (diastolic dysfunction) and/or emptying (systolic dysfunction) • most cases associated with poor cardiac output (low-output heart failure); however, some not due to intrinsic cardiac disease but instead due to increased demand (high-out put heart failure)

• primary insults (myocyte loss, overload) ~ pump dysfunction, which leads to: • remodeling (dilatation, hypertrophy) • neurohumoral activation -> necrosis and apoptosis • both pathways result in further damage (restarting the cycle), and edema, tachycardia, vasoconstriction, congestion • Lompensatory response to myocardial stress (perpetuate disease process) • pressure overload (e.g. HTN, aortic stenosis) ~ hypertrophy • volume overload (e.g. aortic regurgitation) -> cardiac dilatation • systemic response to ineffective circulating volume • activation of sympathetic nervous and renin-angiotensin-aldosterone systems result in • salt and water retention with intravascular expansion • increased heart rate and myocardial contractility • increased afterload




Dichotomies of Heart Failure:
Forward vs. Backward Left-sided vs. Right-sided Systolic dysfunction vs. Diastolic dysfunction Low output vs. High output

Systolic Dysfunction (impaired ventricular ejection)
• impaired myocardial contractile function (e.g. MI, myocarditis, dilated cardiomyopathy) -> decreased ejection fraction (LVEF) and stroke volume (SV) decreased cardiac output (CO) • findings: apex beat displaced, S3, l' heart size on CXR, W LVEF, LV dilatation

Diastolic Dysfunction (impaired ventricular filling)
• 1/3 of all HF patients have normal systolic function (i.e. normal ejection fraction) • causes of decreased compliance: • transiently by ischemia (relaxation of myocardium is active and requires ATP) • permanently by severe hypertrophy (HTN, AS, HCM), restrictive cardiomyopathy (RCM), or Ml


C34 Cardiology and CV Surgery

Heart Failure

Toronto Notes 2008

What are the five most common causes of CHF1 1. coronary artery disease (60·70%) 2. idiopathic (20%) often in the form of dilated cardiomyopathy 3. valvular (e.g. A5, AR and MR) 4.HTN 5. alcohol (may cause dilated cardiomyopathy)

• increased l.V filling pressures produce venous congestion upstream (i.e. pulmonic and systemic venous congestion) • findings: HTN, apex beat sustained, 54, normal-sized heart on CXR, LVH on ECG/echo, normal LVEF

High-Output Heart Failure
• caused by demand tor increased cardiac output • often exacerbates existing heart failure or decomfensates a patient with other cardiac pathology, but is infrequently a primary cause 0 heart failure • differential diagnosis: anemia, thiamine deficiency (beriberi), hyperthyroidism, A-V fistula or I.-R shunting, Paget's disease of bone, renal disease, hepatic disease

Etiologies of Primary Insults
• consider predisposing, precipitating and perpetuating factors • see sidebar for top five etiologies • less common causes of CHF • toxic e.g. doxorubicin, radiation, uremia, catecholamines • infectious e.g. Chagas' disease (very common cause in South America), Coxsackie virus, HIV • endocrine e.g. hyperthyroidism, OM, acromegaly • infiltrative e.g. sarcoidosis, amyloidosis, hemochromatosis • genetic e.g. HCM, Friedreich's Ataxia, muscular dystrophy • congenital heart disease • metabolic e.g. thiamine deficiency, selenium deficiency • peripartum

Use ejection fraction to grade LV dysfunction: Grade I (EF >60%) (Normal) Grade II (EF = 40-59%). Grade III (EF = 21·39%) Grade IV (EF ~20%)

Precipitants of Symptomatic Exacerbations
• consider natural progression of disease vs. new precipitant, and search for reversible cause • see sidebar for differential diagnosis ("HEART FAILED")
The most common cause of right heart failure is left heart failure

Table 10. Signs and Symptoms of Lvs. R Heart Failure
Left Failure Low cardiac output (forwardI fatigue syncope systemic hypotension cool extremities slow capillary refill peripheral cyanosis pulsus alternans mitral regurgitation 53 dyspnea, onhopnea, PND cough crackles Right Failure (Right heart failure can mimic most of the symptoms of forward left heart failure if decreased RV output leads to LV underfillingl

"The best findings for detecting increased filling pressure are jugular venous distension and radiographic redistribution." "The best findings for detecting systolic dysfunction are an abnormal apical impulse, radiographic cardiomegaly, Qwaves or LBBB on an electrocardiogram~ "Diastolic dysfunction is difficult to diagnose but is associated with elevated blood pressure during heart failure:'
ICan the Clinical Examination Diagnose Left· Sided Heart Failure in Adults? JAMA 1997;

tricuspid regurgitation 53 (right-sidedl peripheral edema elevated JVP with AJR and Kussmaul's sign hepatomegaly pulsatile liver

Venous congestion (backward)

• identify and assess precipitating factors and treatable causes of CHF • blood work - CBc, electrolytes, BUN, creatinine ± TSH, ferritin, B-natriuretic peptide (BNP) • ECG (look for chamber enlargement, arrhythmia, ischemia/infarction) • CXR - see Diagnostic Medical Imaging, DM4 • echocardiography - LVEF, cardiac dimensions, flow or wall motion abnormalities, valvular disease, pericardial effusion • radionuclide angiography (MUGA) - LVEl-' • myocardial perfusion scintigraphy (thallium or sestamibi SPECT)


New York Heart Association (NYHAl Functional Classification of Hean FaiUl1l
• Class I: ordinary physical activity does not cause symptoms of HF • Class II: comfortable at rest, ordinary physical activity results in symptoms • Class III: marked limitation of ordinary activity; less than ordinary physical activity results in symptoms • Class IV: inability to carry out any physical activity without discomfort; symptoms may be present at rest

TREATMENT Acute Management of Pulmonary Edema ("LMNOP")
• • • • • • treat acute precipitating tactors (e.g. ischemia, arrhythmias) L - Lasix™ (furosemide) dose varies from 40-500 mg IV M .. morphine 2-4 mg IV - decreases anxiety, venodilation (decreases preload) N .. nitroglycerin (topical/TV) 0 - oxygen P - positive airway pressure (CPAP or BiPAP) - decreases preload and need for ventilation • P - position - sit patient up with legs hanging down unless patient is hypotensive

Toronto Notes 2008

Heart Failure

Cardiology and CV Surgery C35

• other vasodilators/inotropes as necessary in ICU setting • nitroprusside (N) • hydralazine (PO) • sympathomimetics • dopamine - low dose causes selective renal vasodilation (high potency D 1 agonist) - medium dose provides inotropic support (medium potency ~1 agonist) - high dose increases systemic vascular resistance (SVR) (low potency <Xl agonist), which in most cases is undesirable • dobutamine - selective inotrope (~1 agonist) and arterial vasodilator (<Xl antagonist) • phosphodiesterase inhibitors (milrinone) - inotropic effect and vascular smooth muscle relaxation (decreased SVR), similar to dobutarnine - adverse effect on survival when used as long-term oral agent • consider PA catheter to monitor pulmonary capillary wedge pressure (PCWP) if patient is unstable or a cardiac etiology is uncertain (PCWP >18 indicates likely cardiac etiology) • mechanical ventilation as needed • rarely used but potentially life-saving measures: • intra-aortic balloon pump (IABP) • L or R ventricular assist device (LVAD/RVAD) • cardiac transplant


Precipitants of Heart Failure "HEART FAILED":
HTN (common) Endocarditis/environment (e.g. heat wavel Anemia Rheumatic heart disease and other valvular disease Thyrotoxicosis Failure to take meds {very commonI Arrhythmia (commonl Infectionlischemialinfaretion (commonI Lung problems WE, pneumonia, CaPOI Endocrine (pheochromocytoma, hyperaldosteronism) Dietary indiscretions (commonl

Long Term Management of Heart Failure (ACCIAHA 2005 Guidelines)
Conservative Measures • symptomatic measures • oxygen in hospital, bedrest, elevation of head of bed • lifestyle measures (grade B evidence) • diet, exercise, DM control, smoking cessation, -.j., alcohol consumption, patient education, sodium and fluid restriction • multidisciplinary heart failure clinics (grade B evidence) • for management of individuals at higher risk, or with recent hospitalization Pharmacological Therapy • vasodilators • ACEIs: standard of care - slow progression and improve survival (CONSENSUS, SOLYO, SAVE trials) • all symptomatic patients functional class II-N (grade A) • all asymptomatic patients with LVEF <40% (grade A) • post-MI (see IHD section) • target dose as used in mortality trials, or maximum tolerated dose • angiotensin II receptor blockers (ELITE-II, CHARM, Val-HeFT trials) • second line to ACEI if not tolerated (grade B), or as adjunct to ACEI if ~-blockersnot tolerated (grade A) • hydralazine and nitrates (Ve-HeFT-I trial) • second line to ACEI, decrease in mortality not as great as with ACEI (Ve-HeFT-1I trial) • ~-blockers: standard of care - slow progression and improve survival (metoprolol: MERIT; carvedilol: US-CARVEDILOL, COPERNICUS trials) • class I-III with LVEF <40% (grade A) • stable class N patients (grade A) • note: should be used cautiously, titrate slowly because may initially worsen CHF • aldosterone antagonists: mortality benefit in severe CHF (spironolactone: RALES; eplerenone: EPHESUS trial) • spironolactone for class lIlb and N CHF already on ACEI and loop diuretic (grade A) • eplerenone may be considered if intolerable endocrine side effects • note: potential for life threatening hyperkalemia • monitor K after initiation and avoid if Cr >220 J.!mollL or K >5.2mmol/L • diuretics: symptom control, management of fluid overload • furosemide (40-500 mg OD) for potent diuresis • metolazone may be used with furosemide to increase diuresis • spironolactone for class IIIb and N CHF already on optimal therapy (grade A) • furosemide, metalozone, and thiazides oppose the hyperkalemia induced by ~-blockers, ACEIs, ARBs, and aldosterone antagonists

"LMNOp· Treatment of Pulmonary Edema Lasix™ Morphine Nitroglycerin Oxygen Positive airway pressure

Overwhelming evidence supports use of ACEls in combination with carefully titrated beta blockers in chronic systolic heart failure. Spironolactone reduces mortality in some subgroups. (ces 2003)

C36 Cardiology and CV Surgery

Heart FailurelMyocardial Disease

Toronto Notes 2008

• inotropes: digoxin improves symptoms and decreases hospitalizations, no effect on mortality (DIG trial) • indications: patient in sinus rhythm and symptomatic on ACEI (grade A), or CHF and atrial fibrillation (grade B) • patients on digitalis glycosides may worsen if these are withdrawn • anti-arrhythmic drugs: for use in CHF with arrhythmia • can use amiodarone, ~-blockcr, or digitalis (grade B) • anticoagulants: warfarin for prevention of thromboembolic events • prior thromboembolic event or atrial fibrillation (grade B) • possible benefit in other patients with LVEF <30% or LV thrombus (controversial) • CCBs (equivocal effect on survival) - not currently recommended • selected drugs contraindicated in CHF: • NSAIDs, class I/IIl antiarrhythmic agents, metformin, thiazolidinediones, cGMP phosphodiesterase inhibitors (sildenafil, vardenafil, tadalafil) with borderline low blood pressure
Procedural Interventions

• resynchronization therapy: symptomatic improvement with biventricuIar pacemaker (MIRACLE trial) • consider if QRS >13U ms, T,VEF <35%, and severe symptoms despite optimal therapy (grade B) • greatest benefit likely with marked LV enlargement, MR, QRS >150 ms, high diuretic requirement • ICD: mortality benefit in 1° and 2° prevention of SCD (MADIT-I, MUSTI, MADIT-II trials) • prior MI, optimal medical therapy, LVEF <30%, clinically stable (grade B) • prior MI, NSVT, LVEF 30-40%, EPS inducible VT (grade B) • LVAD/RVAD (see Ventricular Assist Devices, C33) • cardiac transplantation (see Cardiac Transplantation, C32) • valve repair if patient is a good surgical candidate and has significant valve disease contributing to CHF (see Valvular Heart Disease, C40)

Sleep-Disordered Breathing
• 45-55% of patients with CHF have sleep disturbances, including Cheyne-Stokes breathing and sleep apnea (central or obstructive) • associated with a worse prognosis and greater LV dysfunction • nasal continuous positive airway pressure (CPAP) is effective in treating Cheyne-Stokes respiration/sleep apnea with improvement in cardiac function and symptoms

Myocardial Disease
Definition of Cardiomyopathy (CMP):
• intrinsic or primary myocardial disease not 2° to congenital, hypertensive, coronary, valvular, or pericardial disease • usually classified as dilated, hypertrophic or restrictive cardiomyopathy (functional classification) • LV dysfunction 2° to MI often termed "ischemic cardiomyopathy", but this is not a true cardiomyopathy (i.e. primary myocardial disorder) since the primary pathology is CAD


Dilated Cardiomyopathy (DCM)
Definition Etiology
• • • • • •


• dilation and impaired systolic function of one or both ventricles idiopathic (presumed viral or genetic) -50% of DCM alcohol familial uncontrolled tachycardia collagen vascular disease: SLE, PAN, dermatomyositis, progressive systemic sclerosis infectious: viral (Coxsackie B, HIV), Chagas disease, Lyme disease, Rickettsial diseases, acute rheumatic fever • neuromuscular disease: Duchenne muscular dystrophy, myotonic dystrophy, Friedreich's ataxia

Toronto Notes 2008

Myocardial Disease

Cardiology and CV Surgery C37

• • • • •

metabolic: uremia, nutritional deficiency (thiamine, selenium, camitine) endocrine: hyper/hypothyroidism, DM, pheochromocytoma peripartum toxic: cocaine, heroin, glue sniffing, organic solvents dmgs: chemotherapies (anthracycline, cyclophosphamide), anti-retrovirals, chloroquine, clozapine • radiation induced • may present as • CHF • systemic or pulmonary emboli • arrhythmias • sudden death (major cause of mortality due to fatal arrhythmia)

Signs and Symptoms

• ECG - variable ST-T wave abnormalities, poor R wave progression, conduction defects (e.g. BBB), arrhythmias (non-sustained VT) • CXR - global cardiomegaly (globular heart), signs of CHF • echo - 4-chamber enlargement, global hypokinesis, depressed LVEF, MR and TR, mural thrombi • endomyocardial biopsy - not routine, used to mle out a treatable cause • angiography - in selected patients to exclude ischemic HD

• treat underlying disease: e.g. abstinence from EtOH • treat CHF: see Heart Failure, C33 • thromboembolism prophylaxis: anticoagulation with warfarin • indicated for: AFib, history of thromboembolism or documented thrombus • LVEF <30% (controversial) • treat symptomatic or serious arrhythmias • immunize against influenza and S. pneumoniae • consider surgical options (eg. LVAD, transplant, volume reduction surgery) in appropriate candidates with severe, refractory disease

• depends on etiology • better with reversible underlying cause, worst with infiltrative diseases, HIV, dmg-induced • cause of death usually CHF or sudden death 20 to ventricular arrhythmias • systemic emboli are significant source of morbidity

Hypertrophic Cardiam apathy (HCM)
• defined as unexplained ventricular hypertrophy (not due to systemic HTN or AS) • most causes involve asymmetric pattern of hypertrophy (septal hypertrophy most common)

Etiology and Pathophysiology
• histopathologic features are myocyte disarray, hypertrophy, and interstitial fibrosis • cause is felt to be a genetic defect involving one of the cardiac sarcomeric proteins (>200 mutations associated with AD inheritance, incomplete penetrance) • prevalence of 1/500 - 1/1000 in general population

Hemodynamic Classification
• hypertrophic obstructive cardiomyopathy (HOCM): dynamic LV outflow tract (LVOT) obstruction, either resting or provocable • non-obstmctive hypertrophic cardiomyopathy: no LVOT obstmction • many patients may have diastolic dysfunction (impaired filling, decreased ventricular compliance)

Signs and Symptoms (of HOeM)
• clinical manifestations: asymptomatic (common therefore screening important), SOBOE, angina, presyncope/syncope (due to LV outflow obstruction or arrhythmia), CHF, arrhythmias, SCD • pulses: rapid upstroke, bifid carotid pulse (in HOCM) • precordial palpation: PMI localized, sustained, double impulse, 'triple ripple' (triple apical impulse in HOCM), LV lift

C38 Cardiology and CV Surgery

Myocardial Disease

Toronto Notes 2008

• precordial auscultation: normal or paradoxically split S2, 54, harsh systolic diamond-shaped murmur at LLSB or apex, enhanced by squat to standing or Valsalva (murmur secondary to LVOT obstruction and associated mitral regurgitation)

• ECG - LVH, high voltages across precordium, prominent Q waves or tall R wave in VI, P wave abnormalities • echo - asymmetric septal hypertrophy (less commonly apical), systolic anterior movement of mitral valve and MR • cardiac catheterization (usually performed only when patient being considered for invasive therapy)

• avoid factors which increase obstruction, including volume depletion and strenuous exertion • treatment of HOCM • medical agents: ~-blockers, disopyramide, verapamil (only in patients with no resting/provocable obstruction) • patients with drug-refractory symptoms: • surgical myectomy • septal ethanol ablation • dual-chamber pacing • treatment of ventricular arrhythmias - amiodarone or lCD • first-degree relatives ot patients with HCM should be screened annually during adolescence (physical, ECG, 20 echo), then serially every 5 years

• potential complications: AFib, VT, CHF, sudden death (most common cause of SCD in young athletes) • major risk factors for sudden death • history of survived cardiac arrest/sustained VT • family history of multiple sudden deaths • other factors associated with increased risk of sudden cardiac death: • syncope • non-sustained VT on ambulatory monitoring • marked ventricular hypertrophy


Restrictive Cardiomyo~athy(RCM)
• restricted ventricular filling in a non-dilated, non-hypertrophied ventricle 2° to myocardial abnormality (stiffening, fibrosis and/or decreased compliance)

• • • • infiltrative: amyloidosis, sarcoidosis non-infiltrative: scleroderma, idiopathic myocardial fibrosis storage diseases: hemochromatosis, Fabry's disease, glycogen storage diseases endomyocardial: • endomyocardial fibrosis, LoeHier's endocarditis or eosinophilic endomyocardial disease • radiation heart disease • carcinoid syndrome (may have associated TV or PV dysfunction)

Clinical Manifestations
• CHF (usually with preserved LV systolic function), arrhythmias • elevated JVP with prominent x and y descents, Kussmaul's sign • 54

• • • • • ECG -low voltage, non-specific, diffuse ST-T wave changes ± nonischemic Q waves CXR - mild cardiac enlargement echo cardiac catheterization -1' end-diastolic ventricular pressures endomyocardial biopsy - to determine etiology (especially for infiltrative RCM)

Toronto Notes 2008

Myocardial Disease

Cardiology and CV Surgery C39

• • • • exclude constrictive pericarditis treat underlying disease supportive care and treatment for CHF, arrhythmias heart transplant - might be considered for CHF refractory to medical therapy

• depends on etiology

Myocarditis ______~---------~-----_..I
Definition • inflammatory process involving the myocardium; cardiomyopathy

important cause of dilated

• idiopathic • infectious • viral (most common): Coxsackie B, echovirus, poliovirus, HN, mumps • bacterial: S. aureus, C. perfringens, C. diphtheriae, Mycoplasma, Rickettsia • fungi • spirochetal (Lyme disease - Borrelia burgdorferi) • Chagas disease (Trypanosoma cruzi), toxoplasmosis • toxic: catecholamines, chemotherapy, cocaine • hypersensitivity, eosinophilic: drugs (antibiotics, diuretics, lithium, clozapine), insect/snake bites • svstemic diseases: collagen vascular diseases (SLE, RA, others), sarcoidosis, autoimmune • other: giant cell myocarditis, acute rheumatic fever

Signs and Symptoms
• • • • • • constitutional illness acute CHF chest pain - due to pericarditis or cardiac ischemia arrhythmias systemic or pulmonary emboli sudden death

• ECG - non-specific ST-T changes ± conduction defects • bloodwork • increased CK, troponin, LDH, and AST with acute myocardial necrosis ± increased WBC, ESR, ANA rheumatoid faclor, complement levels • blood culture, viral titres and cold agglutinins for Mycoplasma • CXR - enlarged cardiac silhouette • echo - dilated, hypokinetic chambers, segmental wall motion abnormalities • myocardial biopsy (in limited cases)

• • • • • • • • • • supportive care restrict physical activity treat CHF treat arrhythmias anticoagulation treat underlying cause if possible usually self-limited and often unrecognized, many recover sudden death in young adults may progress to dilated cardiomyopathy few may have recurrent or chronic myocarditis


C40 Cardiology and CV Surgery

Myocardial DiseaseNalvular Heart Disease

Toronto Notes 2008

Table 11. SummaryTable for CHF and Myocardial Disease Congestive Heart Failure & Myocardial Disease Systolic Heart Failure Diastolic Heart Failure
Dilated Cardiomyopathy Secondary Causes
Idiopathic, infectious le.g. myocarditis!. Alcohol, Familial, Collagen vascular disease, etc. Hypertrophic Cardiomyopathy
Restrictive Cardiomyopathy

Secondary Causes Hypertension, Diabetes, Valvular le.g. ASI, Post-MI, Transiently by ischemia, etc.

Coronary artery disease, MI, Genetic disorder affecting Diabetes, Valvular cardiac sarcomeres Imost le.g. AR, MRI common cause of sudden cardiac death in young athletes)

Amyloidosis, Sarcoidosis, Scleroderma. Hemochromatosis, Fabry's, Pompe's Disease, Loeffler's, etc.

Valvular Heart Disease
Infective Endocarditis (IE)
• see Infectious Diseases, ID14

Rheumatic Fever
• see Pediatrics. P55

for . . . . . 1IIOCIende IOl'lic ItInoIiI

A bIdIide cIinicllI prd:llon rule


Prognosis • acute complications: myocarditis (DCM/CHF), conduction abnormalities (sinus tachycardia, A Fib), valvulitis (acute MR), pericarditis (not usually constrictive pericarditis) • chronic complications: rheumatic valvular heart disease - fibrous thickening, adhesion, calcification of valve leaflets resulting in stenosis/regurgitation, increased risk of IE ± thromboembolism • onset of symptoms usually after 10-20 year latency from acute carditis of rheumatic fever • mitral valve most commonly affected

Type: Blinded cross sectional study Who: 124 patients of an ambulatory cardiology c1in~. Patients were examined for. 1) munnur over the right clavicle; 21 munnur loudest at second right intelcostal space 31 reduced intensity of 52; 4) reduced volume of the carotid pulse 51 delayed carotid upstroke. MelhodI: Patien1s were examined by blinded investigators, and the c1in~1 examination findings were compared to findings on subsequent ed1ocardiography. Moderate to severe aortic stenosis was defined as avalve area <1.2 em' or apeak intensity gradient of >25 mmHg. 1IeIuIII: Absence of amunnur over the right clavicle ruled out aort~ stenosis while presence of ~ of the 4associated symptoms ruled in aortic stenosis (LR=40I. ConclUIioIII: Bedside techniques can accurately rule in and rule out moderate to severe iIOflic stenosis. Etchells E, GlennsV, Shadowitz 5, Bell C, 5iu 5. J Gen Intsm Med. 1998 Oct;13(101:699-704. DepaTtment of Medicine,Toronlo Hospital, Ont,

Choice of Valve Prosthesis
Table 12. Mechanical Valve vs. Bioprosthetic Valve
Mechanical Valve
• Good durability • Less preferred in small aortic root (stenoticl • Increased risk of thromboembolism (1-3%/yearl: long-term anticoagulation with warfarin • Target INR aortic valves: 2.0-3.0 mitral valves: 2.3-3.5 • Increased risk of hemorrhage: 1-2%/year

Bioprosthetic Valve
Limited long-term durability (mitrakaortic) Good flow in small aortic root sizes Decreased risk of thromboembolism: long-term anticoagulation not needed for aortic valves Some recommendation for limited anticoagulation for mitral valves Decreased risk of hemorrhage


of Valvular Diseases


• see Table 13 (next page)

Table 13. Valvular Heart Disease
Valve Disorder Biology

Pathophysiology Outflow obstruction ~ increased EOP -'concentric lVH -'lVfailure

Symptoms Exertional angina, syncope, dyspnea, PND, orthopnea, penpheral edema

Physical Exam Narrow pulse pressure, brachial-radial delay, pulsus palVus ettardus, sustainedPMI Auscultation: crescendo-decrescendo SEM radiating to Rclavicle &carotid, musical qualilyat apexlGaliavardin phenomenonl, S4, soft S1 wi paradoxical splilting, S3lJatel Waterhammer pulse,bisferiens pulse, femoral-brachial sBP >10 IHill's testl, hyperdynamic ape~ displaced PM I,

IlM!stigations ECG: lVH &strain,lBBB,LAE, Afib CXR:post-stenotic aortic root dilatation, calcdied valve,lVH,LAE, CHf ECHO: reduced valve area, pressure gradient lVH, reduced lVfunction

Treatment Asymptomatic: serial ECHOs,IE prophyla~s,avoid exertion Symptomatic:avoidnilrates/arterial dilators &ACEls in severe AS Surgery it symptomatic or lVdysfunction

Surgical Options Valve replacement -aortic rheumatic valve disease & trileafletvalve ---minimal calcification Decalcification/debridement -until AV replacement -pregnancy -balloon valvuloplasty lin youngl

Prognosis Asymptomatic: near nonmal survival Angina: <5years Syncope: <3 years Dyspnea: <1 years Complications: IE

0 0




Congenilallbicuspid,unicuspidvalvel. calcification Iwear andtearl, rheumatic disease AVA: NoH cm'; severe ASo<1.0cm'; crilicalASsO,Bcm'

Z 0 ;;r

N 0 0 00


Supravalvulac aortic root disease IMarlan's,atherosclerosis& dissecting aneurysm, connective

Volume overload ~ lV dilatation ~ increased SV, high sBP &low dBP ~

VawulaccongeniiallbicuspidAV, largeVSOl,lE Acute Onset IE,aortic dissection, trauma, failed prosthetic valve

overload ~ lVH 1J0w dBP ~ -j,coronaryperfusionl

Usual~ only becomes symptomatic late in disease when lVfailure develops Dyspnea, orthopnea, PND, syncope, angina

Auscultation: early decrescendo diastolic murmur at llSB Icuspl or RlSB laortic rootl,best heard silting, leaning tOlWard, on full expiration, softSI,absentS1, S3IJatei wide pulse pressure SOBOE, orthopnea, fatigue, palpilations, peripheral edema, malar flush, pinched and blue facieslsevere MSI Afib,no"a"waveonJVp,leftparasternal Idt palpable diastolic thrill at apex Auscultation: mid-diastolic rumble at ape~ best with bell in lLD position following exertion, loud SI, OS following loud P11heard best during expirationl, long munmur & A1-0S intelVal short correlate with worse MS

ECG: lVH,LAE CXR: lVH,LA~ aortic root dilatation ECHO/TTE: quantify AR,leaflet or aortic root anomalies Cath: d>40 yrs and surgical candidate Exercise testing: hypotension with exercise

Asymptomatic: serial ECHOs,lE proph0axis, afterloadreduction IAGEls if nonmallV functionl Symptomatic: avoid exertion, treatCHf Surgery if: NYHA class III-IV CHf, lVEf <50% witlvWithout symptoms,lncreasinglVsile

Valve replacement Chronic progressionrrom ---most patients asymptomatic mild-moderate AR Valverepaic ~ severe AR over 10 years or more Symptomatic 0 4year sUlVival -limiledrole ---repair of vawes to improve SevereAcuteo>1 year survival coaptation in on~ 10-30% Aortic root replace IBentall proced,l: --when ascending aortic aneurysm oresent -valved conduilused Percutaneous balloon vawuloplasty -young rheumatic pts&goodleaflet morphology -asymptom pts with mod-sev MS, new-onset ARb, pulmon HTN Contraindication: -left atrial thrombus -fJlOd-sevMR Open Mitral Commissurotomy: -If mild calcd +leafleVchordal thickening ---restenosis in 50% p1s in Byrs Vawereplacement ---mod-sevcalcd &sev scarred leaflets Asymptomatic MVA narrowmg over 15-10 years followed by progressively symptomatic CHf andincapacilation


Rheumatic disease most common cause;congenilallrarel Severe MS is MVA <1,1 cm'

MS ~ fixed CO &LAE ~ 'tLA

resistance &CHf; worse with Afib InoatIialkickl,tachycardia I-j,atrial emptyingtimel &pregnancy l'1'preloadl

ECG: NSRiAfib,LAE IP mitralel, RVH, RAD CXR: LAE, CHF, MV calcification ECHO/TTE: valvular anomalies Cath: concurrent CAD d>40 yrs Imalelor>50yrslfemalel

Avoidexertion,feverl,NA pressurel,treatAfiband CHf, increase diastolic filling time


proph0axis Surgery it NYHA class III-IV CHf and failure of medical theraoy luStJal1y MVA <11 cm'1







<I> <I>



Mitral valve prolapse Congenilal cleft leaflets, lV dilatation/aneurysm ICHF, DCM, myocarditisl,IEabscess,Marlan's syndrome, HOCM, acute MI, myxoma, MV annulus calcification, chordae/papillarymuscle trauma!ischemia/rupture, rheumatic disease

Reduced CO ~ increased lV & LA pressure ~ lV &LA dilatation ~ CHf &pulmonary HTN

Dyspnea, PNO, orthopnea, palpitations, peripheral edema

Displaced,hyperdynamic apex, left parasternalldt apical thrill Auscullation: holosystolic murmur at apex, radiating to axilla +1mid-diastolic rumble, loud S1 m pulmonary HTNI. S3

ECG: LAE, left atrial delay Ibifid Pwavesl, +1-lVH CXR: lVH, LAE, pulmonary venous HTN ECHO: severily of MR,lV function, leaflets Swan-Ganz: prominent LA V wave

Asymptomatic: serial ECHOs, IEproph0axis Symptomatic: -j,preload Idiureticsl, -j, afterload IACElsl for severe MR &poor surgical candidate; stabilizeacuteMRwithvasodilators blfsurgery Surgery if: acute MR with CHf, papillary muscle rupture, NYHA class III-IV CHf, Afib,lVEf <00%, increasing lVsize,atrial fibrillation, earlier surgery d vawerepairable

Valve repair: Chronic MR: Asymptomatic progression for many years before onset CHf or Afib; ->75% of p1s with MR &myxomatous Acute MR with pulmonary HTN and MV disease IMVPI -annuloplaslyrings, leaflet repair, cardiogenic shock approx, 00% chordae transfers/shorten/replacement mortalily Vawereplacement -Iailure of repair -ileavi~calcified annulus Advantage of Repaic -low rate of endocarditis, no anticoagulation, lesschanceofre-operation


~ ~


e: e:






Table 13. Valvular Heart Disease (cotinued)
Valve DisonIBf EIioIogy

Prolonged,stabbing chest pain, dyspnea, anxiety/panic,palpnations,fatigue, presyncope

Physical Exam Ausculation: mid-systolic click Ibillowing of mnral leaflet into lA; tensing of redundant valve tissuel; mid to late systolic murmuratapex,accentuated by Valsalva or squat-to-stand maneu.e'~

Investigations ECG: non-specitic ST-Twave changes, PSVT, ventricular ectopy ECHO: systolic displacement of thickened MV leaflets into lA

Traatmant Asymptomatic: no treatment reassurance Symptomatic: Il-blockers and avoidance of stimulants Icaffeinel for anxiety, IE prophylaxis it MR, anticoagulation it systemic emboli Preload reduction (diuretics) Surgery it usual~ on~ it other surgery needed le.g. MVRI

Surgical Dptions NoneunlesssevereMR

Prognosis Excellent prognosis, typical~ benign; risks of IE, armythmias, thromboembolism it associated with MR However, small %have severe MR, requiring management


Myxomatous degeneration of

crowd orifice; Marlan's syndrome; pectus excavatum, slraightback syndrome, other MSK abnormalities; 2-6% of population If>MI

MV displaced into lA during systole; no causal mechanisms found for symptoms


Rheumatic disease, congennal, carcinoid, fibroelastosis

Increased RA pressure ~ fixed CO and RA dilatation ~ right hean failure

Peripheral edema, fatigue, palpnations

Prominent "a" waves in JVP, +Va ECG: RAE abilominojugular refle~ Kussmaul's sign, CXR: dilatation of RA without diastolic rumble 4th left intercostals space pulmonary anery enlargement ECHO: diagnostic "cv" waves in JVp, +Va abdominojugular refle~ Kussmaul's sign, holosystolic murmur at LLSB accentuated by inspiration, left parasternal lift Systolic murmur at 2nd lICS, pulmonary

Commissurotomy Valve Replace: -if severely diseased valve -bioprosthesisprelerred

Asymptomatic for many years; most successful~ treated medical~

i ... '"
ttl ttl ttl



RV dilatation, IE ilV drug use!, meumaticdisease,congennal IEbsteinanomalYI,carcinoid

PUlmonary HTN .., RV dilatation "'rightheanfailure

Peripheral edema, fatigue,palpnations

ECG: RAE, RVH, Afib CXR: RAE, RVenlargement ECHO: diagnostic

Preload reduction Idiureticsl

Asymptomatic for many years; most


surgery needed le.g. MVRJ

s:1 '" '" '"


Usually congenital, meumatic diseaselrarel,carcinoid

Increased RV pressure ~ RV hypenrophY""ightheanfailure

Chest pain, syncope, fatigue, oeripheraledema

ECG: RVH CXR: prominent pulmonary ane';es enlarged RV ECHO: diagnostic

Balloon valvuloplasty it severe symptoms

Percutaneousoropen balloon valvuloplasty

Mild congennal PS is usually asymptomatic and non-progressive; moderate-severe PS may progress to symptomatic disease and require treatment CHF and right hean failure uncommon unless associated with severe pulmonary HTN


Pulmonary HTN, IE, meumatic disease, tetrology of fal~, post-repair

Increased RVvolume "'increased wall tension'" RV hypertrophy .., right heanfailure

Chest pain, synco~e, laugue, peripheral edema

Ear~ diastolic murmur at LLSB, Graham Steell idiastolicl murmur 2nd and 3rd lICS increasing with inspiration lit due to pulm HTNI

ECG: RVH 00: prominent pulmonary aneries il pulmonary HTN; enlarged RV ECHO:diagnosnc

Rare~ requires treatment valve replacement it severe

Pulmonary valve replacement

~ 8

z o 1I ...,


Toronto Notes 2008

Pericardial Disease

Cardiology and CV Surgery C43

Pericardial Disease
Acute Pericarditis
Etiology of PericarditislPericardial Effusion • idiopathic is most common: usually presumed to be viral • infectious • viral: Coxsackie virus A, B (most common), echovirus • bacterial: S. pneumoniae, S. aureus
• • • • • • •
• TB • fungal: histoplasmosis, blastomycosis post-MI: acute (direct extension of myocardial inflammation, 1-7 days), Dressler's syndrome (autoimmune, 2-8 weeks) post-cardiac surgery (e.g. CABG), other trauma metabolic: uremia (common), hypothyroidism neoplasm: Hodgkin's, breast, lung, renal cell carcinoma, melanoma collagen vascular disease: SLE, polyarteritis, RA, scleroderma vascular: dissecting aneurysm other: drugs (e.g. hydralazine), radiation, infiltrative disease (sarcoid)

Signs and Symptoms • diagnostic triad: chest pain, friction rub, and ECG changes • pleuritic chest pain - alleviated by sitting up and leaning forward • pericardial friction rub - may be uni-, bi- or triphasic • ± fever, malaise Investigations • ECG - initially diffuse elevated ST segments ± depressed PR segment, the elevation in the ST segment is concave upwards ---> 2-5 days later ST isoelectric with T wave flattening and inversion • CXR - normal heart size, pulmonary infiltrates • ECHO - assess pericardial effusion Treatment • treat the underlying disease • anti-inflammatory agents (high dose NSAIDs/ASA, steroids if severe or recurrent); analgesics Prognosis • complications: recurrence, atrial arrhythmia, pericardial effusion, tamponade, constrictive pericarditis (uncommon)

Pericardia. Effusion
Etiology • transudative (serous) • CHF, hypoalbuminemia/hypoproteinemia, hypothyroidism • exudative (serosanguinous or bloody) • causes similar to the causes of acute pericarditis • may develop acute effusion secondary to hemopericardium (trauma, post MI myocardial rupture, aortic dissection) • physiological consequences depend on type and volume of effusion, rate of effusion development, and underlying cardiac disease Signs and Symptoms • may be asymptomatic or similar to acute pericarditis • dyspnea, cough • extra-cardiac (esophageal/recurrent laryngeal nerve/tracheo-bronchial/phrenic nerve irritation) • JVP increased with dominant "x" descent • arterial pulse normal to decreased volume, decreased pulse pressure • auscultation: distant heart sounds ± rub

C44 Cardiology and CV Surgery

Pericardial Disease

Toronto Notes 2008

• • • • ECG -low voltage, flat T waves CXR - cardiomegaly, rounded cardiac contour ECHO (procedure of choice) - fluid in pericardial sac pericardiocentesis - definitive method of determining transudate vs exudate, identify infectious agents, neoplastic involvement

• mild: frequent observation with serial echocardiograms, treat the cause, anti-inflammatory agents for inflammation • severe: may develop cardiac tamponade


Cardiac Tamponade

..... ~

, .}-------------,


Clanic quartet of tamponade: hypotension, increased JVp, tachycardia, pulsus paradoxus.

• major complication of rapidly accumulating pericardiaI effusion; cardiac tamponade is a clinical diagnosis • any cause of pericarditis but especially trauma, malignancy, uremia, idiopathic, proximal aortic dissection with rupture



•. l - - - - - - - - - - - - ,

• high intra-pericardial pressure'" decreased venous return --> decreased diastolic ventricular filling --> decreased CO --> hypotension & venous congestion

Beck's triad: hypotension, increased JVP, muffled heart sounds.

Signs and Symptoms
• • • • tachypnea, dyspnea, shock pulsus paradoxus (inspiratory fall in systolic BP >10 mmHg during quiet breathing) JVP "x" descent only, absent "y" descent hepatic congestion/peripheral edema

• ECG - electrical altemans (pathognomonic variation in R wave amplitude), low voltage • ECHO - pericardial effusion, compression of cardiac chambers (RA and RV) in diastole • cardiac catheterization

• pericardiocentesis - ECHO or ECG-guided • pericardiotomy • avoid diuretics and vasodilators (these decrease venous return to already under-filled RV --> decrease LV preload .--> decrease CO) • fluid administration may temporarily increase CO • treat underlying cause


Constrictive Pericarditis
• chronic pericarditis resulting in fibrosed, thickened, adherent, and/or calcified pericardium • any cause of acute pericarditis may result in chronic pericarditis • major causes are post-viral, TB, radiation, uremia, post-cardiac surgery, idiopathic

Signs and Symptoms
• dyspnea, fatigue, palpitations • abdominal pain • may mimic CliF (especially right-sided HF) • ascites, hepatosplenomegaly, edema • increased JVP, Kussmaul's sign (paradoxical increase in JVP with inspiration), Friedreich's sign (prominent "y" descent) • BP usually normal • precordial examination: ± pericardial knock (early diastolic sound) • see Table 14 for differentiation from cardiac tamponade

• • • • ECG - non-specific: low voltage, flat T wave, ± AFib CXR - pericardial calcification, effusions ECHO/CT/MRI - pericardial thickening cardiac catheterization

Toronto Notes 2008

Pericardia! Disease/Congenital Cardiac DiseaseNascular Disease

Cardiology and CV Surgery C45

• medical: diuretics, salt restriction • surgical: pericardiectomy (if refractory to medical therapy)

Table 14. Differentiation of Constrictive Pericarditis vs. Cardiac Tamponade
Characteristic Constrictive Pericarditis Tamponade

JVP Kussmaul's sign pulsus paradoxus pericardial knock hypotension

"y" > "x" present uncommon present variable

/Ix" > y " absent always absent severe

Congenital Cardiac Disease
• see Pediatrics, PI8. Note: more adults than children now live with congenital heart defects

Table 15. Common Congenital Heart Defects
I. Pure obstructive lesions 1. Pulmonic stenosis II. Simple left-to-right shunts (acyanotic lesions with increased pulmonary blood flow)

2. 3. 4. 5.

Mitral stenosis Aortic stenosis Coarctation of the aorta Interrupted aortic arch

1. Patent ductus arteriosus 2 Atrial septal defect 3. Ventricular septal defect 4. Endocardial cushion defect IAV canal) 5. Aortopulmonary window
IV. Complex cyanotic defects (mixing defects)

III. Right-to-Ieft shunts (cyanotic defects with decreased pulmonary blood flow)

1. 2. 3. 4. 5.

Tetralogy of Fallot Pulmonary atresia with ventricular septal defecl Pulmonary atresia with intact ventricular septum Tricuspid atresia Ebstein's anomaly

1. 2. 3. 4. 5. 6.

Double outlet right ventricle Univentricular heart (double inlet left ventricle) Transposition of the great arteries Total anomalous pulmonary venous connection Truncus arteriosus Hypoplastic left heart syndrome

V. Coronary artery congenital defects

1. Anomalous origin of coronary artery 2. Coronary artery fistula 3. Ostial stenosis
';dapted from Bojar RM. Manual of perioperative care in cardiac surgery, 3'd edition. Massachusetts: Blackwell Science Inc., 1999.

VASCULAR DISEASE Peripheral Arterial Disease
Acute Arterial Occlusion/lnsufficiency ----...,.---Definition
• acute occlusion/rupture of a peripheral artery • urgent management required: >6 hours results in irreversible ischemia and mvonecrosis • lo~ver extremity> upper extremity; femoropopliteal > aortoiliac

• embolus • cardiac embolus (80-90%): history of MI <3 months, valvular disease, AFib, cardiomyopathy, endocarditis, atrial myxoma • arterial embolus: proximal arterial aneurysm, alheroembolism • venous embolus (intracardiac shunt); may have Hx of OCP use . • Hx of TIAs/strokes • thrombus • atherosclerotic, congenital anomaly, infection, hematological disorders and stasis • trauma • arterial catheterization, intra-arterial drug injection induced, aortic dissection, severe venous thrombophlebitis, prolonged immobilization • idiopathic

C46 Cardiology and CV Surgery

Vascular Disease

Toronto Notes 2008

Clinical Features
• general • pain in lower extremity progressing within hours to a feeling of cold, numbness, loss of function and sensation • symptoms (6 P's) - all may not be present • Pain: absent in 20% of cases due to prompt onset of anesthesia and paralysis • Pallor: within a few hours becomes mottled cyanosis • Paresthesia: light touch (small fibres) lost first then sensory modalities (large fibres) • ParalysislPower loss: most important, heralds impending gangrene • Polar (cold) • Pulselessness: not reliable • embolus vs. thrombus - dramatically different treahnent • see Table 16
Table 16. Differentiation of arterial embolism and thrombosis
Presentation Onset loss of function/sensation Hx of claudication Atrophic changes Contralateral limb pulses Embolus Acute Prominent No No Yes Thrombus Progressive, acute-on-chronic less profound Yes Yes Decreased or absent

• CXR, ECG, arteriography

• immediate heparinization with 5000 ill bolus and continuous infusion to maintain PIT >60 seconds • absent power and sensation - emergent revascularization • present power and sensation - work-up (including angiogram) • definitive treatment • embolus: embolectomy • thrombus: thrombectomy ± graft, ± bypass • irreversible ischemia: amputation • identify and treat underlying cause • continue heparin post-op, start warfarin post-op day 1 for 3 months

• compartment syndrome with prolonged ischemia; requires fasdotomy • renal failure and multi-organ failure due to toxic metabolites from ischemic muscle

• 12-15% mortality rate • 5-40% morbidity rate (amputation)

Chronic Arterial Occlusionllnsufficiency

• predominantly due to atherosclerosis: primarily lower extremities with symptoms related to the location of obstruction

Risk Factors
• major: smoking, DM, hyperhomocysteinemia • minor: HTN, hyperlipidemia, family history, obesity, sedentary lifestyle, male gender

Clinical Features
Signs of peripheral vascular insufficiency "SJCVO": Symmetry of leg musculature Integrity of skin Colour of toe nails Varicose veins Distribution of hair

• claudication: 3 components • pain with exertion: usually in calves or any exercising group • relieved by short rest: 2 to 5 minutes, and no postural changes necessary • reprodUcible: same distance to elicit pain, same location of pain, same amolmt of rest to relieve pain • pulses may be absent at some locations • signs of poor perfusion: hair loss, hypertrophic nails, atrophic muscle, skin ulcerations and infections, slow capillary refill, prolonged pallor with elevation and rubor on dependency, venous troughing (collapse of superficial veins of foot) • other manifestations of atherosclerosis: CVD, CAD, impotence, splanchnic ischemia

Toronto Notes 2008

Vascular Disease

Cardiology and CV Surgery C47

Differential Diagnosis
• osteoarthritis (OA): worse at night and varies day-to-day • neurogenic claudication: due to spinal stenosis or radiculopathy; pain very similar but relieved by longer rest and postural changes • varicose veins: localized pain, typically less severe, after exercise and never at rest; related to the presence and site of varices • inflammatory processes: Buerger's disease, Takayasu's arteritis • other: popliteal entrapment (e.g. tumour, Baker's cyst), radiation injury, remote trauma

• non-invasive • ankle-brachial index (ABI) (grade lA recommendation): measure brachial and ankle pressures bilaterally (use highest value) generally, ABl <0.90 abnormal, rest pain appears at <0.3 (see Table 17)
Table 17. Ankle-Brachial indices and degrees of ischemia
ABI recording Degree of Ischemia

>0.95 0.85 - 0.94 0.50-0.84 0.26-0.49 <0.25 >1.2

normal/no ischemia mild moderate severe consider limb salvage suspect wall calcification (most common in diabetics)

• CTA and MRA - excellent correlation with arteriography, where available, can replace it for intervention planning (lA recommendation) • Doppler segmental pressures and pulse volume recordings, transcutaneous oxygen studies (photoplethysmography) treadmill exercise claudication test and real-time Duplex scanning considered by vascular specialist (Grade 3C) • invasive • arteriography (gold standard): defines site and size of occlusion, and collateral flow status, operative planning tool

Treatment (see Figure 31)
• conservative • risk factor modification (smoking cessation improves prognosis, treatment of HfN, hyperlipidemia and/or DM) • exercise program - develops collateral circulation, improves exercise tolerance • foot care (especially DM) • pharmacotherapy: anti-platelet agents (ECASA, clopidogrel or ticlopidine) cilostazol (cAMP-phosphodiesterase inhibitor with anti-platelet and vasodilatory effects, now available in Canada) • pain relief: opiate analgesia (morphine sulphate), supplemented by NSAIDs; if opiate analgesia inadequate, possibility of lumbar sympathectomy • surgical/interventional • indications: claudication interfering with lifestyle, rest pain, pre-gangrene, gangrene • surgical options: endovascular (stenting/angioplasty) or arterial bypass grafts • bypass graft sites: aortofemoral, axillofemoral, femoropopliteal, distal arterial • graft choices: in situ graft - reversed vein graft, synthetic polytetrafluoroethylene graft (Gor-Tex™) or Dacron® • amputation: if not suitable for revascularization and persistent serious infections and/or gangrene

• conservative therapy: 60-80% improve, 20-30% stay the same, 5-10% deteriorate, 5% will require intervention within 5 years, <4% will require amputation

C48 Cardiology and CV Surgery

Vascular Disease/Aortic Disease

Toronto Notes 2008

Aortobifemoral bypass graft

Axillobifemoral bypass graft

Figure 31. Treatment options for critical limb ischemia. (A) Algorithm for the treatment of critical limb ischemia. (B) Surgical treatment options for the treatment of aortoiliac disease.
Modified from Beard JD. Chronic lower limb ischaemia. BMJ. 2000;320:854-857.

• see Family Medicine. FM32

Pulmonary Hypertension
• see Respirology, R17

Carotid Artery Disease
• see Neurosurgery, NS19

Aortic Disease Aortic Dissection


• tear in aortic intima allowing blood to dissect between the aortic intima and media; acute <2 weeks, chronic >2 weeks

Classification (see Figure 32)
• DeBakey • Type I - involves ascendmg and descending aorta • Type II - ascending aorta omy (stops at the mnominate artery) • Type IlIA - descenaing thoracic aorta only (distal to left subclavian artery and proximal to diaphragm) • Type IITB - Type IlIA plus abdominal aorta • Stanford' • Type A - involves ascending aorta and aortic arch; requires emergency surgery Type B - only involves aorta distal to subclavian artery; emergency surgery orily ifcomplications of dissection (requires long-term follow-up to assess aneurysm size)

• most common: damage to aortic media (smooth muscle and elastic tissue), leading to degenerative/cystic manges due to h)'pertension • oilier: cystic medial necrosis, atherosclerosis, connective tissue disease (Marfan's, Ehlers-DanIos), congenital conditions (coarctation of aorta, bicuspid aortic valves, patent ductus arteriosus), infection, trauma, arteritis (Takayasu's)

Toronto Notes 2008

Aortic Disease

Cardiology and CV Surgery C49

Epidemiology • incidence of 5.2 in 1 000 000 • male:female = 3.2:1.0 • small increased incidence in African-Canadians (related to higher incidence of hypertension) • lowest incidence in Asians

Debakey: Stanford:

Type I

Type II

'-Type A----.l

Debakey: Stanford:

Type lilA

Type 1118

'-Type S--.:..:...J

Figure 32. Classification of Aortic Dissection

Clinical Features • sudden onset searing chest pain that radiates to back with: • hypertension (75-85% of patients) • asymmetric BPs and pulses between arms ischemic syndromes due to occlusion of aortic branches: coronary (MI), carotids (ischemic stroke, Homer's syndrome), splanchnic (ischemic gut) • "unseating" of aortic valve cusps (new diastolic murmur in 20-30%) • rupture into pleura (dyspnea, hemoptysis) or peritoneum (hypotension, shock) or pericardium (cardiac tamponade) • renal insufficiency • lower limb ischemia (cold legs) Investigations
• CXR:

• • • •

• pleural cap • widened mediastinum • left pleural effusion with extravasation of blood TEE: can visualize aortic valve and thoracic aorta but not abdominal aorta ECC: LVH (90%), ± MI, pericarditis, heart block CT, aortography, MR - definitive imaging studies bloodwork: LDH (rio ischemic gut), amylase (rio pancreatitis)

Treatment • pharmacologic • sodium nitroprusside and ~-blocker to lower BP and decrease cardiac contractility • surgical • resection of intimal tear, reconstitution of flow through true lumen, replacement of the affected aorta with prosthetic graft, correction of any predisposing factors (e.g. bicuspid aortic valve, PDA, etc) • post-operative complications: renal failure, intestinal ischemia, stroke, paraplegia, persistent leg ischemia, death Type A: requires emergent surgery with cardiopulmonary bypass, may require hypothermic circulation for transverse arch dissections, valve replacement and coronary re-implantation for aortic root involvement, initial involvement rate is 2% per hour • Type B: mitially mana!?ed medically - 10-20% require urgent operation for complications (expanSIon, rupture, compromise of branch arteries, refractory HTN, or ongoing pain)

Aortic Aneurysm

Definition of Aneurysm • localized dilatation of an artery that is beyond its normal diameter (2x diameter) • true aneurysm: involving all vessel wall layers (intima, media and adventitia) • false aneurysm: disruption of the aortic wall or the anastomotic site between vessel and graft with containment of blood by fibrous capsule made of surrounding tissue • aneurysms can rupture, thrombose, embolize or erode and fistulize


CSO Cardiology and CV Surgery

Aortic Disease

Toronto Notes 2008

• thoracic (TAA): ascending, transverse arch, descending • thoracoabdominal • abdominal (AAA)

• medial degeneration, atherosclerosis, expansion of chronic dissections, metabolic/endocrine, mycotic (Salmonella, Staphylococcus, usually suprarenal), neoplastic, cystic medial necrosis, trauma, aortitis (vasculitis), connective tissue disease (Marfan syndrome, Ehlers-Danlos)



•.1 - - - - - - - - - - - - ,

• incidence 4.7 to 31.9 per 100 000 for AAA and 5.9 per 100 000 for TAA • high risk groups: • 65 years and older • male:female = 3.8:1 • peripheral vascular disease, CAD, CVD family history of AAA

ClassicTriad of Ruptured AAA o pain o hypotension o pulsatile abdominal mass

Clinical Features
• conunon presentation: due to acute eXfansion or disruption of wall • syncope, pain (chest, abdomina, flank, back) • hypotenslOn • palpable mass above the umbilicus, pulsatile abdominal mass in two directions • airway or esophageal obstruction, hoarseness (left recurrent laryngeal nerve paralysis), hemoptysis, or hematemesis distal pulses may be intaet • 75% asymptomatic (discovered incidentally) • unconunon presentation • partial bowel obstruction • ureteric obstruction and hydronephrosis • Glbleed (duodenal mucosal hemorrhage, aortoduodenal fistula) • aortocaval fistula • distal embolization (blue toe) • associated diseases • hypertension, PVD, CAD, COPD, renal insufficiency

75% of aortic aneurysms are
found incidentally.

• • • • abdominal D/S (100% sensitive, up to ± 0.6 em accuracy in size determination) CT (accurate visualization, size determination) MRI (accurate visualization, limited access) aortogram (not for diagnosis because false negative normal lumen size due to thrombus formation; indicated for associated renovascular HTN, peri-renal AAA, visceral angina, iliac disease) • Doppler/Duplex (r/o vascular tree aneurysms elsewhere)

Conservative • cardiovascular risk factor reduction: smoking cessation, HTN control, DM and hyperlipidemia control • regular exercise • watchful waiting, D/S q b months Surgical • when risk of rupture greater than or equal to risk of surgery • risk of rupture aepends on: 1. size 2. rate of enlargement >0.4 cm/yr 3. symptoms, comorbidities (HTN, COPD, dissection), smoking • elective AAA repair mortality: 2-5%, elective TAA repair mortality <10% (highest with proximal aortic and thoracoabdominal repairs) • consider revascularization for patients with CAD before elective repair of aneurysm • indications: • general: ruptured, symptomatic, mycotic, associated with acute Type A aissection or complicated Type B dissection or when risk of rupture is greater than risk of surgery (size >5.5 em or >2x normal lumen size) • ascending thoracic aortic aneurysms • symptomatic, enlar~g, diameter >5.5 em or >2x normal lumen size, >4..'1 em & aortic regurgitation (annuloaortic ectasia); ~ em in Marfan syndrome • contraindications: life expectancy <1 year, terminal disease (e.g. cancer), Significant co-morbidities (recent Ml, unstable angina), decreased mental acuity, advanced age

Risk of AAA Rupture Size 1-year rupture risk <4 em 0"10 4-4.99 em 1% 5-5.99 em 11% 6-6.99 em 25%

Toronto Notes 2008

Aortic DiseaselPeripheral Venous Disease

Cardiology and CV Surgery C51

• surgical options: • open surgery (laparotomy) with graft replacement (see Figure 33) • possible complications - early: renal failure, spinal cord injury (paraparesis or paraplegia), impotence, arterial thrombosis, anastomotic rupture or bleeding, peripheral emboli - late: graft infection/thrombosis, aortoenteric fistula, anastomotic (pseudo) aneurysm • endoluminal graft placement under image guidance • newer procedure • high success rates in patients with suitable anatomy and experienced centres • advantages: decreased morbidity and mortality, procedure time, need for transfusion, leU admissions, length of hospitalization, and recovery time • disadvantages: endoleak rates as high as 20-30%, device failure increasing as longer follow-up periods are achieved, re-intervention rates 10-30%, cost-effectiveness is an issue (devices are very expensive) • complications - early: immediate conversion to open repair, groin hematoma, arterial thrombosis, iliac artery rupture, and thromboemboli - late: endoleak, severe graft kinking, migration, thrombosis, rupture of aneurysm

Figure 33. Replacement of an infra renal abdominal aortic aneurysm with a synthetic bifurcation graft. (AI Arterial clamps are placed at the proximal end of the aneurysm (below the left renal vein) and the common iliac arteries. (BlThe aneurysmal segment is replaced with a synthetic bifurcation graft and the outer wall of the aorta is closed over the graft,

Peripheral Venous Disease
Deep Venous Thromboembolism
• see Hematology. H28

Superficial Thrombophlebitis
• erythema, induration, and tenderness along the superficial vein; usually spontaneous but can follow venous cannulation


• suppurative phlebitis (complication of intravenous cannulation; associated with fever, chills) • trauma • inflammatory: varicose veins, migratory superficial thrombophlebitis, Buerger's disease, SLE



and CV Surgery

Peripheral Venous Disease

Toronto Notes 2008

• hematologic: polycythemia, thrombocytosis • neoplastic: occult malignancy (especially pancreatic) • idiopathic



Clinical Features
• most common in greater saphenous vein and its tributaries • pain and cord-like swelling along course of involved vein • areas of induration, erythema and tenderness correspond to dilated and often thrombosed superficial veins • complications: • simultaneous DVT (up to 20% of cases), pulmonary embolus (rare unless DVT) • recurrent superficial thrombophlebitis


Migratory superficial thrombophlebitis is often asign of underlying malignancy.

• non-invasive tests (e.g. Doppler Ultrasonography) to exclude associated DVT

• conservative • bedrest and elevation of limb • moist heat, compression bandages, mild analgesic, anti-inflammatory and anti-platelet (e.g. ASA), ambulation • surgical excision of involved vein • indication: failure of conservative measures (symptoms that persist over 2 weeks) • suppurative thrombophlebitis: broad-spectrum IV antibiotics and excision

Varicose Veins
• distention of tortuous superficial veins resulting from incompetent valves in the deep, superficial, or perforator systems • distribution: greater saphenous vein and tributaries (most common), esophagus, anorectum, scrotum

• primary • main factor: inherited structural weakness of valves • contributing factors: increasing age, female gender, OCP use, occupations requiring long hours of standing, pregnancy, obesity • secondary • deep-venous valvular insufficiency and incompetent perforating veins • malignant pelvic tumours with venous compression • congenital anomalies - arteriovenous fistulae

• most common form of venous disorder of lower extremity • 10-20% of population

Clinical Features
• • • • • • diffuse aching, fullness/tightness, nocturnal cramping aggravated by prolonged standing (end of day), premenstrual visible long, dilated and tortuous superficial veins along thigh and leg ulceration, hyperpigmentation, and induration (secondary varicosities) associated esophageal varices (GI bleed), hemorrhoids, varicocele Brodie-Trendelenberg test (valvular competence test) • with patient supine, raise leg and compress saphenous vein at thigh; have patient stand; if veins fill quickly from top down then incompetent valves; use multiple tourniquets to localize incompetent veins

• recurrent superficial thrombophlebitis • hemorrhage: external or subcutaneous • ulceration, eczema, lipodermatosclerosis, and hyperpigmentation

• largely a cosmetic problem • conservative: elevation of leg and/or elastic stockings • surgical: high ligation and stripping of the long saphenous vein and its tributaries, sclerotherapy, endovenous laser therapy (EVLT)

Toronto Notes 2008

Peripheral Venous Disease

Cardiology and CV Surgery C53

• • • • natural history benign, slow with predictable complications almost 100% symptomatic relief with treatment if varicosities are primary good cosmetic results with treatment significant post-operative recurrence, especially with sclerosing agent injection

Chronic Venous Insufficiency
• chronic elevation of deep venous pressure and blood pooling in lower extremities


• calf muscle pump dysfunction and valvular incompetence (valvular reflux) due to phlebitis, varicosities, or DVT • venous obstruction • AV fistulas, venous malformations

Clinical Features
• • • • • pain (most common), ankle and calf edema - relieved by foot elevation pruritis, brownish hyperpigmentation (hemosiderin deposits) stasis dermatitis ulceration: shallow, above medial malleolus, weeping (wet), painless, irregular outline signs of DVT/varicose veins/thrombophlebitis

• ambulatory venous pressure measurement (gold standard) • Doppler D/S (most commonly used) • photoplethysmography

• conservative • elastic compression stockings, leg elevation, avoid prolonged sitting/standing • ulcers: zinc-oxide wraps, split-thickness skin grafts, antibiotics, debridement • surgical • if conservative measures fail, or if recurrent/large ulcers • surgical ligation of perforators in region of ulcer, greater saphenous vein stripping • venous bypass if short segment obstruction

• obstruction of lymphatic drainage resulting in edema with high protein content

• 1° • Milroy's syndrome • infection: filariasis (#1 cause worldwide), post-operative • malignant infiltration: axillary, groin or intrapelvlc radiation/surgery (axillary, groin LN removal): #1 cause in North America

Clinical Features
• classically non-pittine; edema • impaired limb mobility; discomfort/pain; psychological distress

• avoid limb injury (can precipitate or worsen lymphedema) • skin hygiene • daily skin care with moisturizers • topical treatment of fungal infection; systemic treatment of bacterial infection • external support • intensive: compression bandages • maintenance: lymphedema sleeve • exercise • gentle daily exercise of affected limb, gradually increasing ROM • must wear a sleeve/bandages when doing exercises • massage and manual lymph drainage therapy

• if left untreated, becomes resistant to treatment due to subcutaneous fibrosis • cellulitis causes rapid increase in swelling: can lead to sepsis and death





~ ~
Table 18. Commonly Used Cardiac Therapeutics
Drug class



Medlanism of action


Side effects
Dry cough, 10% hypotension, fatigue, hyperkalemia, renal insufficiency, angioedema

Contraindications Bilateral renal artery stenosis, pregnancy

ANGIOTENSIN CONVER'I1NG ENZYME INHI8ITORS (ACElsI enalapril (Vasotec~ I, perindopril (Coversyl~ I,

Inhibit ACE·mediated co~;ersion of angiotensin I to angiotensin II (AT III, :ausing peripheral vasodilation and decreased aldosterone synthesis Bled< AT II receptors, causing similar effects to ACEls Bled< ~adrenergic receptors, decreasing HR, Bp, contractility, and myocardial oxygen demand, slow conduction through the AV node

HTN, CAD, CHF, post·MI, OM

ANGIOTENSIN II RECEPTOR BLOCKERS IARBS) candesartan, irbesartan, valsartan I\-IlLOCKERS ~, antagonists ~,I\l, antagonists a,i)l,1\l, antagonists ~, antagonists with ISA Benzothiazepines Phenylalkylamines (non-dihydropyridinesl Dihydropyridines atenolol, metoprolol, bisoprolol propranolol labetalol, carvedilol acebutalol dihiazem verapamil

Same as ACEls, although evidence is generally less for ARBs. Often used when ACEls are not tolerated. HTN, CAD, acute MI, post·MI, CHF, Afib, SVT

Similar to ACEIs, but do not cause dry cough

Same as ACEls


Hypotension, fatigue, light·headedness, depresson, bradycardia, hyperkalemia, brondlOspasm, impotence, depression of counterregulatory response to hypoglycemia, exacerbation of Raynaud's phenomenon and claudication bradycalllia, edema Negative inolrope

Sinus bradycardia, 2'" or 3" degree heart bled<, hypotension, WPW. Caution in asthma, claudication, Raynaud's phenomenon, and CHF lin CHF, start low and go slowl

'" e:



Bled< smooth muscle and myocardial calcium manne~ causing effects similar to ~Ied<ers Also vasodilate Bled< smooth muscle calcium mannels causing peripheral vasodilation HTN, CAD, SVT. diastol~ dysfunction Sinus bradycardia, 2'" or 3" degree heart bled<, hypotension, WPW, CHF



amlodipine INorvasc~l,
nifedi~ne (Adalat~1.


Hypotension, eclema, ffushing, headame, Iight·headedness

Severe aortic stenosis and liver failure

felodipine IPiendil~1 DIURETICS Thlazides hydrochlorthiazjde, mlorthalidone metalazone furosemide (Lasix~'I Reduce Na reabsorption in the OCT HTN (drugs of mo~ for uncomplicated HTNI Hypotension, hypokalemia, polyuria Sulfaaliergy, pregnancy

Loop diuretics

Blocks NaiK ATPase in the loop of Henle

CHF, pulmonary or peripheral edema

Hypovolemia, hypokalemic metabolic alkalosis

Hypovolemia, hypokalemia

Aldosterone receptor antagonists

spironolactone, eplenerone

Antagonize aldosterone receptors

HTN, CHF, hypokalemia

Edema, hyperkalemia, gynecomastia

Renal insufficiency, hyperkalemia, pregnancy

8" Z

~ ::s


Table 18. Commonly Used Cardiac Therapeutics (continued)
DNg class
Digoxin (lanoxin~1


-3 o

Mechanism of action
Inhibit NaiX-ATPase, leading to increased intracellular Na and Ca concentration and increased myocardial contractility, Also slows conduction through the AV node Antagonizes vitamin K, leading to decreased synthesis of cloning factors II, VII, IX, and X Antithrombin III agonist, leading to de;:reased cloning factor activity

Side effects
AV block, tachyarrhythmias, bradyarrhythmias, blurred or yellow vision Ivan Gogh syndromel. anorexia, nausea and vomiting



1'" or 3" degree AV bliXX ,hypokalemia, WPW

'" r->


Coumarins wartann lCoumadin"1 Atrial fibrillation, LV dysfunction, prosthetic va~es Bleeding Iby far the most important side effectl, paradoxical thrombosis, skinne;:rosis Bleeding, o~eoporosis, hepann-induced thrombocytopenia iless in LMWHsl Recent surgery or bleeding, bleeding diathesis, pregnancy


unfractionated heparin low mole;:ular weight hepanns ILMWHsl: daltepann, enoxapann, tinzaparin

Acute MI; when immediate anticoagulant effect needed

Recent surgery or bleeding, bleeding diathesis, thrombocytopenia, renal insufficiency (for LMWHsl

ANI1PlAmETS Salicylates

ASA (Aspirin" I
c1opidogrel (~avix ;'1
ticlo~dine (TIclid~ I

Irreversibly acetylates platelet COX-" preventing thromboxane A2-mediated platelet aggregation Blocl< platelet ADP receptors

CAD, acute MI, po~-Ml,


and CABG

Bleeding, GI upset gastrointestinal ulceration, impaired renal pertusion

Active bleeding or peptic ulcer disease


Acute Ml, post-Ml, po~-PCI and CABG

Bleeding, thrombotic thrombocytopenic purpura, neutropenia Iticlo~dinel

Active bleeding or PUD

GP IIbnlla inhibitors

eptffibatide, tirofiban, abciximab aheplase, reteplase,
tenacte~ase, ~repto~nase

Blocl< binding of fibrinogen to GP IIbnlla Convert circulating plasminogen to plasmin, which lyses cross-linked fibrin Relax vascular smooth muscle, producing venous and arteriolar dilation

Acute Ml, particularty if PCI,s planned


Recent surgery or bleeding, bleeding diathesis



Acute STEMI CAD, MI, CHF (isosorbide dinnrate plus hydralazinel

Bleeding Headache, dizziness, weakness, postural hypotension

See Table 7. C1l Concurrent use of cGMP phosphodiesterase inhibitors, angle closure glaucoma, increased ICP Liver or muscle disease





Statins atorvastatin lLipitor W I, pravastatin (Pravachol"I, rosuvastatin (Crestor" I. simvestatin IZocor"1 Inhibit hydroxymethylglutaryl CoA reductase, which Dyslipidemia 11' prevention of CADI. CAD, po~-Ml catalyzes the rate-limiting step in cholesterol synthesis Myalgia, rhabdomyolysis, abdominal pain





e: e:




C56 Cardiology and CV Surgery

Common Medications

Toronto Notes 2008





2 slow Ca influx

Kefflux /


--------------- ----------------------------------------;.-.
4 Na influx


cc :2: W :2:

Figure 34. Representative Action Potential Table 19. Antiarrhythmic* drugs (Vaughn-Williams Classification)
Class Agent
quinidine procoinamide disopyramide lidocaine mexiletine propafenone flecainide encoinide propranolol metoprolol etc,


Side Effects
Torsades de Pointes laillal, diarrhea lupus-like syndrome anti-cholinergic effe<:ts confusion, stupor, seizures GI upset, tremor exacerbation ofVT lalllci negative inotropy lalllci bradycordia and heart blod< lalllc) bronchospasm. negative inotropy. bradycordia, AV block, impotence, fatigue photosensitivity. pulmonary toxicity, hepatotoxicity, thyroid disease, 1'INR for side effects of sotalol: Il- blod<er effects, Torsades de Pointes bradycardia. AV blod< hypotension

Mechanism of Action
' moderate Na channel blod<ade 'slows phase 0upstroke 'prolongs repolarization, slowing conduction ' mild Na channel blod<ade ' shonens phase 3repolarization 'marked Na channel blod<ade ' markedly slows phase 0upstroke

Mnemonic for anti-arrythmic Drug claaifieation: Some Block Potassium Channels (I-Sodium ca, II-~ blocker, 111Potassium ca, Iv-cca







'Il-blod<er 'decreases phase 4depolarization


amiodarone" sotalol


' blocl<s Kchannel ' prolongs phase 3repolarization, which prolongs effective refractory period


verapamil diltiazem


*All antiarrhythmics have potential to be proarrhythmic

'CCS 'slows phase 4spontaneous depolarization, slowing AV node conduction "amiodarone has class I. II, III, and IV properties

Table 20. Actions of Alpha and Beta Adrenergic Receptors
Adapted from the Family Practice Notebook (

Alpha Receptors Targot System

Beta Recaptors Alpha 2

Alpha 1

'constriction of vascular smooth muscle 'constriction of skin, skeletal muscle and splanchnic vessels

''I' myocordial contractility
'accelerate SA node

, oj, vascular smooth muscle


''I' myocordial contractility
,oj, heart rate

'peripherally act to modulate 'accelerate ectopic pacemakers vessel tone 'vasoconstrict and dilate; oppose Alpha 1vasoconstrictor activity , bronchodilation

Respiratory Dermal Ocular Gastrointestinal Genitourinary 'pilomotor smooth muscle contraction 'apocrine constriction , radial muscle contraction 'inhibition of myenteric plexus 'anal sphincter contraction 'pregnant uterine contraction , penile and seminal vesicle ejaculation 'urinary bladder contraction Metabolic 'smooth muscle wall relaxation 'fat cell lipolysis 'stimulation of renal renin release 'ciliary muscle relaxation

' bladder wall relaxation 'uterine relaxation

'stimulate gluconeogenesis and glycogenolysis at the liver 'fat cell lipolysis

, gluconeogenesis , glycogenolysis

Toronto Notes 2008

Common MedicationslLandmark Cardiac Trials

Cardiology and CV Surgery C57

Table 21. Commonly Used Drugs that Act on Alpha and Beta Adrenergic Receptors
Adapted from the Family Practice Notebook I Alpha Receptors Mechanism of Action Agonist
01 01 and a2

Beta Receptors




and ~


Phenylephrine Metlioxamine

Epinephrine Norepinephrine Phentolamine

Norepinephrine Dobutamine Metoprolol Acebutolol Alprenolol Atenolol Carvedilol

Isoproterenol Epinephrine Propranolol Timolol Nadolol Pindolol

Albuterol Terbutaline Butoxamine


Plazasin Phenoxybenzamine



Landmark Cardiac Trials
Table 22. Congestive Heart Failure
Trial VeHEFT-l SOlVD Reference Results Hydralazine &isorbide dinitrate decreased mortality in patients with CHF. Addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for CHF in patients with chronic CHF and decreased ejection fractions. Enalapril deere,sed mortality compared to hydralazine &isorbide dinitrate in patients with CHF. When added to digoxin, diure-ti,,>, and an ACE inhibitor, carvedilol reduced the risk of cardiovascular related death and hospitalization in patients with CHE Amlodipine had no significant mortality benefit over placebo in CHE but may decrease mortality in patients with non-ischemic dilated cardiomyopathy. Digoxin decreased rate of hospitalization, improved symptoms and exercise capacity, but had no mortality benefit in patients with CHE Compared to captopril, losartan was associated with lower all-cause mortality in CHF patients over 65. Metoprolol added to ACE inhibitors and diuretics significantly reduced morbidity and mortality in NYHA class II-IV CHF. Spironolactone in addition to standard treatment significantly reduced mortality in patienls with NYHA class III-IV CHF. In elderly CHF patients, losartan was not superior to captopril in improving all-cause mortality, but was significantly better tolerated. Compared with metoprolol, carvedilol was associated with areduction in all cause mortality. Carvedilol in addition to standard treatment significantly reduced the risk of death or hospitalization in patients with severe CHF. In addition to standard therapy, eplerenone la selertive aldosterone blocker) reduced morbidity and mortality in patients with post-acute MI heart failure. The risk of hyperkalemia was increased. BNP was more accurate than clinical evaluation in identifying heart failure as cause of dyspnea NTproBNP level lower than 300 pg/mU was optimal for ruling out heart failure, with anegative predictive value of 99% regardless of age

NEJM 1986; 341:1547-52. NEJM 1991; 325:293-302.


NEJM 1991; 325:303-10.


NEJM 1996; 334:1349-55.


NEJM 1996; 335:1107-14.


NEJM 1997; 336:525-31


Lancet 1997; 349:747-52.


Lancet 1999; 353:2001-7.


NEJM 1999; 341:709-17.


Lancet 2000; 355:1582-7.


Lancet 2003: 362: 7-13.


NEJM 2001; 344:1651-58


NEJM 2003; 348:1309-21.


NEMJ 2002; 347:161-167


Am JCardio/2005; 95:948-54

C58 Cardiology and CV Surgery

Landmark Cardiac Trials/Summary Key Questions

Toronto Notes 2008

Table 23. Ischemic Heart Disease
Trial Reference Results


NEJM 1997; 337:447-52. NEJM 1998; 339:436-443.

Compared to unfractionated heparin, enoxaparin significantly reduced the risk of death, MI, or recurrent angina in patients with unstable angina or non-Q-wave MI. In patients with ACS who did not have persistent S1-elevation, eptifibatide Igp lib/Ilia inhibitorl in addition to standard therapy significantly reduced the risk of death or non-fatal MI at 4, 7, and 30 days. The risk of bleeding was increased. Patients with multivessel disease treated with CABG or PTCA had similar 5-year mortality rates. Those treated with PTCA were more likely to require subsequent revascularization. CABG conferred asurvival benefit in diabetics. In patients without LV dysfunction who had CAD, Hx of CVD, PVD, or DM +I other CVD risk factor, ramipril significantly reduced the risks of death, MI and stroke. Clopidogrel plus aspirin significantly reduced the risk of CVD death, non·fatal MI, or stroke, in patients with mild MI or unstable angina, compared to aspirin alone. The risk of major bleeding was increased. No mortality benefit for early IV administration of Il-blockers in STEMI, if also undergoing vascularization. Increased mortality in patients with hemodynamic compromise. Medical therapy is equivalent to PCI plus medical therapy for patients with stable CAO


NEJM 1996; 335:217-25.


NEJM 2000; 342:145-53. NEJM 2001; 345:494-502.


J Am Call Cardiol 2005;


NEMJ2007; 356(15):1503-1516

Summary Key Questions
1. 2. What are the 2most common clinical conditions encountered in cardiology? What are some clinical conditions in cardiology that require urgent diagnosis and treatment? What inrtial investigations should be performed in a patient with suspected cardiac disease? What are components of the long-term management of stable coronary artery disease? What is the treatment of acute NSTEMI?

Ischemic heart disease and heart failure. Both are chronic diseases wrth superimposed acute events. Myocardial infarction, unstable arrhythmias, sudden cardiac death, infective endocarditis, cardiac tamponade, acute arterial occlusion, aortic dissection, and ruptured aortic aneurysm. Electrocardiography, chest radiography, and cardiac enzymes. Subsequent tests may include ambulatory ECG, echocardiography, myocardial perfusion imaging, exercise stress testing, and coronary angiography. "ABCDE"; ASA and ACEI , ~-blocker and BP control, cigarette cessation and cholesterol lowering, diet and diabetes management, education and exercise. Oxygen, morphine, nitrates, ASA, ~-blockade, heparin, and clopidogrel. Patients with STEMI should also receive thrombolysis or primary PCI. Lifestyle intervention, ACEI, ~-blockers, aldosterone antagonists, diuretics, and possibly digoxin. 'lMNOP": Lasix™, morphine, nitrates, oxygen, positive airway pressure and positioning. GERD/PUD, pneumonia and costochondritis. Normal Pwave morphology, progressive prolongation of PR interval until Pwave is dropped, normal QRS complex. Pulsus parvus et tardus, crescendo-decrescendo SEM loudest over right second intercostal space and radiating to the clavicle and carotid, sustained apical impulse. AFib: irregularly irregular, chaotic baseline, disorganized Pwaves; Flutter: regular rhythm, dysmorphic Pwaves, variable AV conduction (2:1, 3:1, 4:1), sawtooth pattern in inferior leads. Prolonged QT interval. Cardiac relaxation is an active process that requires ATP and therefore Oz. Decreases symptoms, reduces hospitalizations. It has no mortality benefit.





What is the long-term management of heart failure? What is the acute management of pulmonary edema? What are 3 common, non-cardiac causes of chest pain? What ECG changes are seen in Mobitz Type I (Wenckebach's) second degree heart block?

7. 8.


10. What are 3 classic physical exam findings of severe aortic stenosis?
11. How can one distinguish Aflutter from Afib on ECG?

12. What is the predisposing factor for the development of Torsades de Pointes? 13. How can ischemia lead to transient congestive heart failure?

14. What is the role for digoxin in the
treatment of congestive heart failure?

Toronto Notes 2008

Summary Key QuestionsIReferences

Cardiology and CV Surgery C59

15. Name 3 classes of medications that have been shown to reduce mortality in CHE 16. What is the difference in the pathophysiology of chronic, stable angina, and the acute coronary syndromes? 17. Both NSAIDs and ASA inhibitthe same enzyme (COX-l I. Why is only ASA used for long-term anti·platelet therapy? 18. Name 4 contraindications to the use of


ACEls, Spironolactone.

Chronic stable angina is due to a stable stenosis, while ACS is due to adynamic stenosis Ii.e. plaque rupture). ASA irreversibly inhibits COX-l which permanently shuts off thromboxane (pro-platelet aggregation activity) synthesis as thromboxane is made within platelets. Platelets have no nuclei (no DNA) to regenerate the COX·l enzyme. Significant bradycardia, significant pulmonary edema, severe asthma, 2nd or 3rd degree heart block. Creatinine Kinase-Myocardial Band. This is the clinical presentation of amyloidosis. This can result in CHF due to restrictive cardiomyopathy. In this situation, the EF is usually maintained.

19. Which cardiac enzyme peaks most rapidly? 20. A patient presents with macroglossia His liver is enlarged, he has unexplained nephrotic syndrome and he is complaining of shortness of breath. Rales are ausculated over his lung fields bilaterally. What do you predict his ejection fraction will be, and why? 21. Which infectious agent is the most common cause of infectious myocarditis? 22. What is the treatment for varicose veins? 23. Thrombolysis is preferred in which clinical scenarios? 24. A recent immigrant from the tropics presents with pulmonary infiltrates, eosinophilia and unilateral leg edema. What is the likely diagnosis?

Coxsackie. Elevation and stockings, ligation and stripping of veins, sclerotherapy and endovenous laser therapy. In an early presentation of STEMI, when there are contraindications to PC I, when PCI is not available. Filariasis.

Ischemic Heart Disease
Cannon CR, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. NEJM 2004;350(151:1495-504. Lindahl, B., et al. Markers of Myocardial Damage and Inflammation in Relation to Long-Term Mortality in Unstable Coronary Artery Disease. New England Journal of Medicine. 2000; 343:1139-1141 Pitt B., et al. Eplerenone, aselective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. NEJM 2003; 348114):1309-21. Rauch, u., et al. Thrombus Formation on the Atherosclerotic Plaques: Pathogenesis and Clinical Consequences. Annals of Internal Medicine. 2001; 134: 224-238. The Arterial Revascularization Therapies Study Group. Comparison of Coronary-Artery Bypass Surgery and Stenting for theTreatment of Multivessel Disease. New England Journal of Medicine. 2001; 344:1117-1124. Turpie, A. G. G. and Antman, E. M. Low-MolecularWeight Heparins in theTreatment of Acute Coronary Syndromes. Archives of Internal Medicine. 2001; 161: 1484-1490. Yeghiazarians, Y, Braunstein, J. B., Askari, A., and Stone, RH. Review Article: Unstable Angina Pectoris. New England Journal of Medicine. 2000; 342:101-114.

Nuclear Canliology
LeeTH and Boucher CA. Noninvasive tests in patients with stable coronary artery disease (Reviewl. NEngl J Med 2000;344:1840-5.

Feldman AM and McNamara D. Myocarditis (Review). NEngl J Med 2000; 343:1388-98.

ACCIAHA guidelines for percutaneous coronary intervention. Circulation. 2001;103:3019-3041. ACCIAHA 2002 guideline update for the management of patients with unstable angina and non-SI-segment elevation myocardial infarction. (Available at: htto;liwww.acc.orgl ACCIAHA Guideline update for the Diagnosis and Management of Chronic Heart Failure in the Adult. Circulation 2005; 112:e154. ACCIAHA guidelines for the management of patients with ST-elevation myocardial infarction: areport of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardiallnfarctionl. Circulation 2004; 110(9):e82-292. Antman EM et al. ACCIAHA Guidelines for the Management of Patients with ST-elevation Myocardial Infarction - summary: A Report of the American College of Cardiology. American Heart Association Task Force on Practice Guidelines. Circulation. 2004; 110-588. CCS. 2001 Canadian cardiovascular society consensus guideline update for the management and prevention of heart failure. Canadian Journal of Cardiology.2001;17(suppE):5-24. Aurigemma, GP et al. Clinical Practice, Diastolic Heart Failure. NEJM 2004; 351:1091 - The American College of Cardiology (clinical guidelines, etc). Cardiovascular Society 2005 Consensus Conference Peripheral Aterial Disease (Draftl. - Cardiology Online (requires registrationl. Heart Valve Repair Online. Beard JD. Chronic lower limb ischemia. BMJ. 2000;320:854-851 Fuchs JA. Atherogenesis and the Medical Management of Atherosclerosis. In Vascular Surgery 4th edition, Robert B. Rutherford Ed. 1995. WB.

C60 Cardiology and CV Surgery


Toronto Notes 2008

Saunders Co., Toronto. pp 222-234. Harrington RA et al. AntithromboticTherapy for Coronary Artery Disease: the Seventh ACCP Conference on Antithrombotic and ThrombolyticTherapy. Chest. 2004; 126 13 suppll:513s-584s. May J, White GH, and Harris JP The complications and downside of endovascular therapies. Adv Surg 35: 153-72,2001. Schmieder FA and Comerota AJ. Intermittent c1~udication: magnitude of the problem, patient evaluation, and therapeutic strategies. Am J Card 87lSuppll: 30-130, 2001. Way LW, Doherty GM, editors. Current Surgical Diagnosis and Treatment, 11" edition. Lange Medical Books/McGraw-Hill. 2004. Yang SC, Cameron DE, editors. Current therapy in thoracic and cardiovascular medicine. McGraw-Hili Inc, 2004. Ambulatory ECG Peter J. Zimetbaum, MD, and Mark E. Josephson, MD, Zimerbaum, P, Josephson, M. The Evolving Role of Ambulatory Arrhythmia Monitoring in General Clinical Practie. Annals of Internal Medicine. 130 (101.1999. Kadish AH, Buxton AE, Kennedy HL. ACClAHA clinical competence statement on electrocardiography and ambulatory electrocardiography: a report of the ACClAHAlACP-ASIM task force on clinical competence. Circulation. 104:3169 -3178.2001. Krahn, A., Klein, G., Skanes, A.,Yee, R. Insertable Loop Recorder Use for Detection of Intermittent Arrhythmias. Pacing and Clinical Electrophysiology. 27 151. 2004 StressTesting Allison,1, Bardsley, Behrenbeck,1, Christian, 1, Clements, I., Edwards, B., Gibbons, R., rvliller,1, Oh, J., Pellikka, P, Roger, v., Squires, R., Weissler, A. 1996 Mayo Foundation for Medical Education and Research. 71(1): 43-52. 1996. GIBBONS ET AL. Exercise Testing Guidelines. JACC. 30 111:260-315. 1991


Echocardiography Picano, E. Stress Echocardiography:A historical perspective. Am J Med. 114:126-130. 2003. Heatlie, G., Giles, M. Echocardiography and the general physician. Postgrad Med. J. BO;84-B8. 2004. Cheitlin, M. ACClAHAIASE 2003 Guideline Update for the Clinical Application of Echocardiograohy: Summary Article. Journal of the American Society of Echocardiography. 16 1101. 2003. Gowda, R., Khan, I., Sacchi,1, Patel, R. History of the evolution of echocardiography. International Journal of Cardiology. 97 11): 1-6. 2004. Nuclear Cardiology Sabharwal, N. Lahiri, A. Role of myocardial perlusion imaging for risk stratification in suspected or known coronary artery disease. Heart. 89:129112912003. , Beller, G., Zaret, B. Contributions of Nuclear Cardiology to Diagnosis and Prognosis of Patients with Coronary Artery Disease. Circulation. 2000.

Danias, P, Roussakis, A. loannidis J. Cardiac imaging Diagnostic perlormance of coronary magnetic resonance angiography as compared against conventional x-ray angiography A meta-analysis Journal of the American College of Cardiology 44121: 1867-1876. 2004.

Schoepf, J., Becker, C., Ohnesorge, B., Yucel, K. CT of Coronary Artery Disease. Radiology. 232:16-312004. Samberg, J. Arrhythmia Therapy. Lippincott Williams &Wilkins, Inc. 9161: 537-542. 2002.

Hayes, D., Furman, S Cardiac Pacing: How it Started, Where We Are, Where We Are Going. Journal of Cardiovascular Electrophysiology. 1515) 2004. Zipes et al. ACClAHATask Force Report Guidelines for Clinicallntracardiac Electrophysiological and Catheter Ablation Procedures. JACC. 26 (2): 555-573. 1995. Wellens, J. Cardiac Arrhythmias: the quest for acure. Journal of the American College of Cardiology. 44 (6): 1155-1163. 2004. Conti, J. ACC 2005 Annual Session Highlight. Cardiac Arrhythmias. Journal of the American College of Cardiology. 45 1111:B30-B32. 2005. Keane, D. New Catheter Ablation Techniques for theTreatment of Cardiac Arrhythmias. Cardiac Electrophysiology Review. 6:341-348. 2002. Skanes, A., Klein, G., Krahn, A. Yee, R. Cryoablation: Potentials and Pitfalls. J Cardiovasc Electrophysiol. 15:528-534. 2004. Packer, D. Evolution og Mapping and Anatomic Imaging of Cardiac Arrhythmias. Journal of Cardiovascular Electrophysiology. 15 (7). 2004. Zipes, O. The year in electrophysiology. Journal of the American College of Cardiology. 43(71:1306-1324. 2004. Ryan TJ, Faxon Dp, Gunnar RM, et al. Guidelines for percutaneous Percutaneous AngiographylPCl transluminal coronary angioplasty: arepOil of the American College of Cardiology/Am Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures Subcommittee on PercutaneousTransluminal Coronary angioplastyl. JAm Coli CardioI.12:52~5.


O'Neil Dixon, S., Grines, C. The year in interventional cardiology. Journal of the American College of Cardiology. 45 (71:1117-1134. 2005. Bashore et al. ACClSCA&1 expert concensus document. American College of CardiologylSociety for Cardiac Angiography and Interventions Clinical Expert Consensus Document on Cardiac Catheterization Laboratory Standards. Journal of the American College of Cardiology. 37181:2170-2214. 2001. Bairn, D. New devices for percutaneous coronary intervention are rapidly making bypass surgery obsolete. Lippincott Williams &Wilkins, Inc.19161: 593-597. 2004. Cardiovascular Surgery -The American College of Cardiology Iclinical guidelines, etcl - Cardiology Online (requires registration) Repair Online Alexander Pand Giangola G. Deep venous thrombosis and pulmonary embolism: Diagnosis, prophylaxis, and treatment. Ann Vase Surg 13: 31827,1999. Beard JD. Chronic lower limb ischemia. BMJ. 2000;320:854-B51 Bojar RM. Manual of perioperative care in cardiac surgery, 3rd edition. Massachusetts: Blackwell Science Inc., 1999. Cheng DCH, DavidTE eds. Perioperative care in cardiac anesthesia and surgery. Austin: Landes Bioscience, 1999. Coulam CH and Rubin GO. Acute aortic abnormalities. Semin Roentgenol 36: 148-64, 2001. Crawford ES and Crawford JL. Thoracoabdominal Aortic Aneurysm. In: Vascular surgery: Principles and Practice 2nd edition, Veith FJ, Hobson RW, Williams RA, and Wilson SE Eds 1994. McGraw-Hili Inc,Toronto. Fuchs JA. Atherogenesis and the Medical Management of Atherosclerosis. In Vascular Surgery 4th edition, Robert B. Rutherford Ed. 1995. WB Saunders Co., Toronto. pp 222-234. Freischlag JA. Abdominal Aortic Aneurysms. In: Vascular surgery: Principles and Practice 2nd edition, Veith FJ, Hobson RW, Williams RA, and Wilson SE Eds 1994. McGraw-Hili Inc,Toronto. Hallett JW Jr. Abdominal aortic aneurysm: natural history and treatment. Heart Dis Stroke 1: 303-8, 1992. Hallett JW Jr. Management of abdominal aortic aneurysms. Mayo Clin Proc 75: 395-9, 2000. Harlan BJ, Starr A, Harwin FM. Illustrated handbook of cardiac surgery. NewYork: Springer-Verlag Inc., 1996. May J, White GH, and Harris JP The complications and downside of endovascular therapies. Adv Surg 35: 153-72,2001. Pitt MPI and Bonser RS. The natural history of thoracic aortic aneurysm disease: An overview. J Card Surg 12ISuppl): 270-8, 1997 Powell JT and Brown LC. The natural history of abdominal aortic aneurysms and their risk of rupture. Adv Surg 35: 173-85,2001. Rosen CL andTracy JA. The diagnosis of lower extremity deep venous thrombosis. Em Med Clin NAm 19: 895-912, 2001. Schmieder FA and Comerota AJ. Intermittent claudication: magnitude of the problem, patient evaluation, and therapeutic strategies. Am J Card 87 (Suppll: 30-130, 2001. Verma S, Szmitko PE, et al. Clinician Update: Shoulrl radi~1 arteries be used routinely for coronary artery bypass grafting? Circulation. 2004;110:e40-e46. Way LW, Doherty GM, editors. Current Surgical Diagnosis and Treatment, 11'" edition. Lange Medical Books/McGraw-HilI. 2004. Yang SC, Cameron DE, editors. Current therapy in thorocic and cardiovascular medicine. McGraw-Hili Inc, 2004.



Clinical Pharmacology
Hanna Bielawska and Evan Kwong, chapter editors Deana Hathout and Rirudaman Minhas, associate editors Jai Shah, EBM editor Dr. Paul Oh, staff editor
General Principles Drug Nomenclature Phases of Clinical Testing Drug Administration and Site of Action Overview of Drug Disposition Pharmacokinetics (ADME) Absorption Mechanisms of Drug Absorption Factors Affecting the Rate and Extent of Drug Absorption Bioavailability Hepatic First-Pass Effect Efflux Pump Distribution Factors Affecting the Rate and Extent of Drug Distribution Volume of Distribution Principles of Protein Binding Depots Barriers Metabolism (Biotransformation) Drug Metabolizing Pathways Factors Affecting Drug Biotransformation Elimination Routes of Drug Elimination Pharmacokinetics Calculations Time-course of Drug Action Half-life Steady State Clearance Elimination Kinetics Pharmacokinetics Equations Pharmacodynamics Dose-Response Relationship Efficacy Potency Effects of Drugs on Receptors Agonists Antagonists Effectiveness and Safety Therapeutic Index (TI)


Therapeutic Drug Monitoring (TDM) .. .11 Adverse Drug Reactions (ADRs) Type A Type B Approach to Suspected ADRs 12

Variability in Drug Response Autonomic Pharmacology Parasympathetic Nervous System (PNS) Sympathetic Nervous System (SNS) Opioid Analgesic Equivalencies Summary Key Ouestions References 13 14

16 17 18


Toronto Notes 2008

Clinical Pharmacology CPI

CP2 Clinical Pharmacology

General Principles

Toronto Notes 2008

General Principles
Drug Nomenclature
• chemical name: describes the chemical structure; the same in all countries (e.g. N (4-hydroxyphenyl) acetamide) • drug company code: a number; usually for drugs that are not yet marketed • non-proprietary (generic) name: shortened form of chemical name; listed in pharmacopoeia (e.g. acetaminophen) • proprietary (trade) name: the brand name or registered trademark (e.g. TylenoJTM) • street name: slang term used for a drug of abuse

Phases of Clinical Testing
• phase 1 • first administration to healthy human volunteers, following animal studies; to determine pharmacokinetics and pharmacodynamics • phase II • first administration to patients, small studies; to determine therapeutic efficacy, dose range, pharmacokinetics, pharmacodynamics • phase III • double blind, large sample; to compare a new drug to placebo or standard of care, safety and efficacy • phase IV • post-marketing surveillance, wide distribution; to determine rare adverse reactions, effects of long-term use, determine ideal dosing

Drug Administration and Site of Action -----'
• choice of route of administration depends on: • properties of the drug • local and systemic effects (limiting action or adverse events) • desired onset and/or duration of action • patient characteristics


'.'\----------..., ~
each, every onceltwicelthree times! four times a day at bedtime beforelafterlwith meals as necessary drops ointment as directed rightlleft/each eye right/left/each ear

Table 1. Routes of Drug Administration
Route Oral (POI Advantage Convenient, easy to administer Large surface area for absorption Inexpensive relative to parenteral administration Rapid onset of action No hepatic first-pass effect Almost no hepatic first-pass effect Convenient if patient is NPO, vomiting or unconscious Direct to systemic circulation No hepatic first-pass effect Slow infusion or rapid onset of action Easy to titrate dose Direct to specific organs Iheart, brainl No hepatic first-pass effect Depot storage if oil-based =slow release of drug Aqueous solution = rapid onset of action Non-irritating drugs, small volumes Constant, even absorption Alternative to IV Disadvantage Drug metabolism by gastrointestinal secretions Incomplete absorption Hepatic first-pass effect Potential GI irritation Must be lipid soluble Must be non·irritating Short duration of action Inconvenient Irritation at site of application Erratic absorption Requires IV access, aseptic technique Hard to remove once administered Vascular injury, extravasation Expensive Risk of infection, bleeding Risk of infection, bleeding, vascular complications Pain at site of injection Pain at site of injection Smaller volumes than 1M May have tissue damage from multiple injections

Common Letin Abbrevi~
odlbidltid/qid qhs aclpclcc prn

Buccal Sublingual (SLI

Rectal (PRI

ung ud

Intravenous IIV)


Intra-arterial Intramuscular 11M) Subcutaneous (SCI

Intrathecal Inhalation

Direct into cerebrospinal fluid (CSFI Infection Bypass blood-brain barrier IBBB) and blood-CSF barrier Possibility of brain herniation and coning Immediate action in lungs Rapid delivery to blood Local or systemic action No hepatic first-pass effect Easy to administer Localized Limited systemic absorption Drug absorption through intact skin Rapid onset of action No hepatic first-pass effect Local effect Must be a gas, vapour or aerosol


Effects are mainly limited to site of application


Irritation at site of application Delayed onset of action Hydrophilic drugs are not easily absorbed Risk of infection

Others: Intraperitoneal, Intra-articular

Toronto Notes 2008

General PrincipleslPharmacokinetics (ADME)

Clinical Pharmacology CP3

Overview of Drug Disposition

Pharmacokinetics + - the study of 'kinetics', or movement of a drug in the body - subdivided into ADME: absorption, distribution, metabolism and elimination

Pharmacodynamics - the study of drug effect: the interaction of a drug with its receptor and the resultant effect - includes: dose-response relationships, drug-receptor binding

Pharmacokinetics (ADME)
• definition: the relationship between drug administration, the time-course of distribution, and the concentration achieved in the body • the manner in which the body handles a drug • examines the rate and extent at which drug concentrations change in the body by observing: • input processes • absorption • output processes responsible for drug delivery and removal from the body • distribution, metabolism (biotransformation), elimination

• definition: movement of the drug from the site of administration into the plasma • important for the main routes of administration, except IV




Mechanisms of Drug Absorption
• most drugs are absorbed into the systemic circulation via passive diffusion • other mechanisms: active transport, facilitJted diffusion, pinocytosis/phagocytosis

Factors Affecting the Rate and Extent of Drug Absorption
• partition coefficient of the drug (Poil/water), i.e. the relative solubility of a drug in oil (lipid) vs. water • drugs with high lipid solubility can rapidly diffuse across cell membranes (e.g. anesthetics are very lipid soluble and therefore have a rapid onset of action) • local blood flow at the site of administration (sublingual vessels provide Significant blood flow and therefore rapid absorption) • moleLlllar size • drugs with a small molecular weight (MW) absorb faster than high MW drugs • pH and drug ionization • drugs are weak acids (e.g. acetylsalicylic acid) or weak bases (e.g. ketoconazole); therefore, they have an ionized and non-ionized form • pH and pKa determine the ratio of ionized:non-ionized forms (Henderson-Hasselbach equation) • non-ionized forms cross cell membranes much faster than ionized forms • total surface area for absorption • the small intestine has villi, which inL'TeaSe the surface area for absorption, making it the primary site of absorption fur most oral drugs

Partition Coefficient (PI 'the ratio of adrug's solubility in lipid as compared to water , more relevant when thought of in terms of adrug's solubility in membrane as compared to extracellular fluid 'a large Pmeans that adrug is highly soluble in lipid and will thus cross membranes easily, i.e. highly absorbed




Drug Ionization and tha Handel'lOll-llassalbach Equation
Ionization reaction for aweak acid' HA! A +H'; pK, =pH +log IHAlA) (Henderson-Hasselbach equation) For aweak acid of pK, =4,4, at agastric pH of 1.4, non-ionized:ionized =HAk = 1: 0.001 Therefore, drug is mainly non-ionized and diffuses across membrane Ionization reaction lor aweak base' BH'! B+H'; pKa =pH +log IBH'IBI

Bioavailability (F)
• definition: the fraction of drug that reaches the systemic circulation in an unchanged state following administration • factors affecting bioavailability: • drug absorption • metabolism in the gut wall • hepatic first-pass effect • IV and intra-arterial dose have 100% bioavailability (F = 1) • Jrugs with a low bioavailability may be ineffective orally (e.g. penicillin G is destroyed by gastric enzymes and needs to he administered IV)

.... . ' " \ - - - - - - - - - - - - ,
The amount of drug that reaches the systemic circulation (bioavailability) is highly dependent on absorption and the first-pass effect. Properties of the drug, route of administration and patient factors should be considered to ensure clinical effectiveness.


Hepatic First-Pass Effect
• definition: the metabolism of a drug by the liver, following absorption, but before it reaches systemic circ.ulation • occurs with PO administration of a drug: GI tract (absorption) --. portal vein --> liver (first-pass metabolism) --> systemic circulation

CP4 Clinical Pharmacology

Pharmacokinetics (ADME)

Toronto Notes 2008

• significant first-pass effect can drastically reduce a drug's bioavailability • occurs to much lesser extent with PR administration, because drug absorbed in colon bypasses the portal system: colon (absorption) -> internal pudendal veins -> IVC -> systemic circulation • drugs with a high hepatic first-pass effect include: • levodopa, morphine, propranolol, lidocaine, organic nitrates • drugs with low hepatic extraction (little or no first pass effect) include: • diazepam, digoxin, phenytoin, warfarin

Efflux pump • p-glycoprotein (pgp) is a protein in the GI tract that acts as an efflux pump involved in the transport of drugs out of cells • overexpression of pgp blocks intestinal absorption of certain hydrophobic drugs • some tumours also overexpress pgps leading to multi-drug resistance to chemotherapeutic agents

• definition: process by which drugs move between different body compartments and to the site of action • major body fluid compartments: plasma, interstitial fluid, intracellular fluid, transcellular fluid (e.g. CSF, peritoneal, pleural) • tissue compartments: fat, brain
Total Body Water 60% of body weight

..------=..----'-----, --------..,.----:=-----"-----,,,---,Extracellular Fluid ,6- 20% Intracellular Fluid 40-44%

Intravascular Plasma 4%


Interstitial Fluid 12-15%

Figure 1. Distribution ofTotal Body Water (TBW)

Factors Affecting the Rate and Extent of Drug Distribution • physicochemical properties of the drug (e.g. partition coefficient) • pHoffluid • plasma protein binding • binding within compartments • cardiac output • regional blood flow • percentage body fat Volume of Distribution (Vd) • actual Vd: the anatomic volume of body fluid into which a drug wiJI distribute • maximum 'actual Vd ' = total body water (40L for average adult) • apparent Vd: the theoretical volume of body fluid into which a drug will distribute • a calculated value that does not correspond to an anatomical space • the value takes into account drug distribution into tissues and protein binding • this value is used in dosing patients • for example, amiodarone distributes into total body water (TBW = actual Vd = 40 L), but it also distributes to and cuncentrates in fat tissues; this gives it an apparent Vd of 400 L, i.e. to achieve a given plasma concentration of amiodarone, we dose as if the drug distributes into 400 L of body fluid Principles of Protein Binding • drug molecules in the blood exist in two forms: 1) bound to plasma proteins • acidic drugs bind to albumin • basic drugs bind to OJ-acid glycoprotein 2) free • only free drug can leave the circulation, distribute into tissues and exert an effect • free drug is subject to metabolism and elimination

Toronto Notes 2008

Phannacokinetics (ADME)

Clinical Phannacology CPS

• within the plasma, the fraction of free drug is in equilibrium with the fraction of bound drug, i.e. as free drug leaves the circulation, more drug unbinds to equilibrate with the portion that is left • the fraction of drug that is bound is determined by: • drug concentration • drug affinity for protein binding site • number of binding sites/protein concentration • saturation of binding sites may result in a large increase in concentration of free drug, which could cause toxicity • in hypoalbuminemia (liver failure or nephrotic syndrome), the dose of highly binding drugs must be lowered to avoid toxicity • multiple drugs and endogenous substances can compete for the same protein binding sites, leading to increased free drug concentration and increased effect/toxicity • e.g. ASA displaces acidic drugs that are highly protein bound such as phenytoin, therefore increasing the risk of toxicity; sulfonamide displaces bilirubin from protein binding sites: this can lead to jaundice and, in neonates, kerructerus • in general, only drugs that are highly protein bound (>90%) are involved in drug interactions due to competitive binding

,,} - - - - - - - - - - , .

Special consideration must be given in dosing patients in hypoalbuminemic states to prevent drug toxicity. Highly protein·bound drugs will exert agreater effect in these patients than in healthy individuals because of higher levels of free drug. Examples of highly protein binding drugs: warfarin, digoxin, diazepam, furosemide, amitriptyline.


'., - - - - - - - - - - - , )
lin Flctor. Governing

Depots • a body compartment (e.g. a type of tissue) where drug molecules tend to be stored • fat is a depot for very lipid soluble drugs (e.g. diazepam) • some oil-based medications are injected 1M for slow release (e.g. depot medroxyprogesterone) Barriers (relative) • body structures that limit or prevent diffusion of drug molecules • placenta • blood brain barrier (BBB) - barrier composed of tight junctions (between capillary endothelial cells) and astrocytes • need to consider dosing route if drugs are meant to cross these barriers

Penetration of BBB 1. Small molecular size «500 Da~ons) 2. High lipid solubility 3. Active transport mechanisms

.... .)------------,
Common Drugs thlt Cross BBB include: • General anesthetics • Alcohol • Nicotine • Caffeine • l:Dopa • Narcotics • Psychotropic medications


Metabolism (Biotransformation)
• • • • •


definition: chemica! transformation of a drug in vivo main site of biotransformation in the body: liver other sites: GI tract, lung, plasma, kidney goa! is to make compounds more hydrophilic to enhance renal elimination as a result of the process of biotransformation • a pro-drug may be activated to an active drug (e.g. nitroglycerin to nitric oxide) • a drug may be changed to another active metabolite (e.g. codeine to morphine) • a drug may be changed to a toxic metabolite (e.g. halogenated alkenes to toxins) • a drug may be inactivated (e.g. procaine to PABA)




Drug Metabolizing Pathways • phase I (P450) reactions • introduce or unmask polar chemical groups on a parent compound in order to increase water solubility (e.g. oxidation-reduction, hydrolysis, hydroxylation reactions) • mediated by cytochrome P450 enzymes found in the endoplasmic reticulum or cell cytoplasm • product of the reaction can be excreted or undergo phase II reactions • phase II (conjugation) reactions • conjugation with polar endogenous substrates (e.g. glucuronidation, glutathione conjugation, sulfation) • increases water solubility and renal elimination Factors Affecting Drug Biotransformation • genetic polymorphism of metabolizing enzymes • individuals may metabolize drugs faster or slower depending on their genotype • this may lead to toxicity or ineffectiveness of a drug at a normal dose • genetic diversity in CYP2D6 results in phenotypes that correspond to poor, intermediate, extensive, and ultra rapid metabolizers of drugs using this enzyme pathway (e.g. SSRIs, ~-blockers, opiates, neuroleptics) • for example, isoniazid is metabolized by N-acetylation; therefore, patients with the "slow acetylator" phenotype are predisposed to peripheral neuropathy from isoniazid toxicity

Cytochrome P450 System The P450 enzymes are asuperfamily of heme proteins that are grouped into families and subfamilies according to their amino acid sequence. These proteins are responsible for the metabolism of drugs, chemicals and other xenobiotics.

Nomenclature: CYP3A4 ·CYP· =cytochrome P450 protein lstArabic # =family letter =subfamily 2nd Arabic #=isoform The CYPI, CYP2, and CYP3 families metabolize most drugs in humans. The most important isoforms are CYP3A4 and CYP2D6; therefore. anticipate drug interactions if prescribing drugs using these enzymes.

CP6 Clinical Pharmacology

Pharmacokinetics (ADME)

Toronto Notes 2008




Some Common Examples of P4liO Inhibiton and Inducers P450 Inhibitors metronidazole erythromycin (macrolidesl cimetidine, ciprofloxacin ketoconazole isoniazid, indinavir naringin or bergamottin (bioftavenoid in grapefruitl P450 inducer. phenytoin phenobarbital rifampin smoking

..... , . ) - - - - - - - - - - - - - ,
The very young and the very old are very sensitive to the actions of drugs.


• enzyme inhibition due to competition from other drugs and micronutrients • inhibition of CYP3A4 is particularly important as it leads to an increased concentration of the substrate drug • erythromycin, ketoconazole, indinavir and grapefruit juice inhibit CYF3A4 and predispose a patient to drug toxicity from other medications metabolized by this pathway • many other enzyme inhibitors exist (valproic acid, ciprofloxacin) • enzyme induction • certain medications enhance gene transcription leading to an increase in the activity of a metabolizing enzyme • one drug may stimulate multiple P450 isoenzymes simultaneously • by inducing the P450 enzyme system, a drug may induce its own metabolism (e.g. carbamazepine) and/or induce other drugs' metabolism (e.g. phenobarbital can induce the metabolism of oral contraceptives and bilirubin) • many other potent enzyme inducers exist: e.g. phenytoin, dexamethasone • liver dysfunction caused by disease • hepatitis, alcoholic liver disease, biliary cirrhosis, and hepatocellular carcinoma may decrease drug metabolism; however, due to the liver's reserve, the reduction in metabolism may not be clinically significant • renal disease • age • neonates and the elderly have reduced ability to biotransform, therefore adjust dosing accordingly • nutrition • decreased protein and fatty acid ingestion decreases P450 biotransformation • vitamin and mineral deficiencies may also affect metabolizing enzymes • alcohol • inhibition of P450 with acute ingestion of alcohol • chronic alcohol consumption can induce the P450 enzyme and increase the generation of the toxic metabolite and hepatocellular damage • smoking • cigarette smoke induces CYF1A2 thereby increasing the metabolism of some drugs (e.g. smokers may require higher doses of theophylline because it is metabolized by CYP1A2)

• definition: removal of drug from the body
Avoid toxicity from drug or metabolite accumulation by adjusting adrug's dosage according to the elimination char· acteristics of the patient le.g. in renal impairment).

Routes of Drug Elimination
• kidneys • main organ of drug excretion • two mechanisms for renal elimination: 1) glomerular filtration • a passive process • only the free drug fraction can be filtered • rate of drug filtration depends on GFR, the degree of protein binding of the drug, and size of drug 2) tubular secretion: • an active process that is saturable • the protein-bound fraction, as well as the free drug, can be secreted • two distinct transport mechanisms for weak acids and weak bases i) acids: penicillin, salicylic acid, probenecid, chlorothiazide ii) bases: quinine, quaternary ammonium compounds (e.g. choline) • drugs may competitively block each other's secretion if both use the same secretion system (e.g. probenecid was historically used to reduce the excretion of penicillin and increase its levels) • tubular reabsorption: drugs can be passively reabsorbed back to the systemic circulation, countering elimination mechanisms • elimination rate depends on renal function, which decreases with age and is affected by many disease states; renal function is assessed clinically using serum creatinine (SCr) levels • thus, in those with renal impairment, dosage adjustments may be required for medications affected by renal elimination • the Cockcroft-Gault equation can estimate creatinine clearance (CrCl) in adults 20 years of age and older: • for males, CrCl (mLimin) = [(140 - age in yrs) x Weight (kg)] x 1.2 SCr (flmol/L) • for females, above equation x 0.85


',}----------.., ,
Cockcroft-Gault equation to esti·
mate erCl using U.S. units

(]40 - age in vrsl xWeight (kg)
SCr (mgJdL) x 72 for females, muitip/y above by 0.85

Toronto Notes 2008

Pharmacokinetics (ADME)

Clinical Pharmacology CP7

• stool • some drugs and metabolites are actively excreted in the bile (e.g. corticosteroids) or directly into the intestinal tract from systemic circulation • enterohepatic circulation • counteracts stool elimination • some glucuronic acid conjugates are excreted in the bile and hydrolyzed in the intestines by bacteria; this results in the release of the drug in its original form and allows for systemic reabsorption • can substantially prolong the duration of drug in the body • lungs • elimination of anesthetic gases and vapours by exhalation • sweat, saliva, tears (e.g. rifampin) • saliva concentrations of some drugs parallel their plasma concentration




It takes 5 half-lives to reach steady state with repeated dosing or to eliminate a drug once dosing is stopped.



Pharmacokinetics Calculations
• definition: the quantitative description of the rates of the various steps of drug disposition, i.e. how drugs moVE' through the body • the pharmacokinetic primiples of ADME (absorption, distribution, metabolism and elimination) can be graphically represented on the concentration vs. time graph (see Figure 2)

o u

® .Di


1. Absorption Phase 2. Peak Absorption 3. Post-Absorption stribution Phase 4. Elimination Phase Ha~·I~e based on this

" o

Time to Peak Absorption

Figure 2. Time Course of Drug Action

Time-Course of Drug Action
• many kinetic parameters are measured using IV dosing, thus there is no absorption phase and distribution for most drugs is rapid • therefore, elimination is the main process measured • the concentration axis is converted to a 10g1O concentration to allow for easier mathematical calculations (see Figure 3)
~Co = concentration

at time 0





1l c:

Time (hrsl

= slope

Half-Life (t 1/2 )
• definition: the time it takes for the blood level of a drug to fall to one-half (50%) of the level measured at some prior time • for most drugs, half-life correlates with the elimination phase • in general it takes five half-lives to either reach steady state with repeated dosing, or for drug elimination once dosing is stopped

'" .3

Steady State
• the concentration at which the same amount of drug entering the system is eliminated from the system • time is important for therapeutic monitoring since drug levels are reliable only when the drug has reached this steady state (see Figure 4) • any change in drug dose and/or interval will change the steady state level • special situations • drugs with a long half-life and the clinical need to rapidly increase the blood concentration may be addressed by giving a loading dose (e.g. phenytoin) • drugs with a very short half-life and the need for a long term effect; multiple, frequently repeated doses are too inconvenient, so use a continuous infusion (e.g. nitroprusside, insulin, heparin)

Figure 3. Log Concentration vs. Time Graph (IV bolus dose)
Steady state of adrug with t", of 3hrs. It takes about 15 hrs (5xt,,1 to reach asteady state. Steady State

• a quantitative measurement of the rate of removal of a substance from the body • clearance = volume of body fluid from which a substance is removed per unit of time • consider: • clearance from a specific part of the body • total body clearance


Time (hrs)

Figure 4. Steady State of a Drug

Elimination Kinetics
• first-order kinetics (the most common type) • a constant fraction of drug is eliminated per unit time • the amount of drug eliminated is based on the concentration of drug present • this relationship is linear and predictable • zero-order kinetics (less common, assoLiated with toxicities) • non-linear kinetics • a constant amount (number of molecules) of drug is eliminated per unit time • clearance slows as drug concentration rises • some drugs can follow first-order kinetics until elimination is saturated (usually at large doses) at which point the clearance decreases • some drugs follow non-linear kinetics at therapeutic levels (e.g. phenytoin)

Time (hrs)

Figure 5.

First and Zero Order Kinetics. In first order kinetics (solid line/, a constant fraction of the drug is eliminated per unit time; in zero order kinetics (dashed linel. a constant amount of the drug is eliminated per unit time.

CP8 Clinical Pharmacology

Pharmacokinetics (ADMEl/Pharmacodynamics

Toronto Notes 2008

Pharmacokinetics Equations
• Volume of Distribution (Vd) Vd = dose/concentration at time 0 • Slope (A.) rise/run log (C] ~)/(t2

- t1 )

..... '

. !l - - - - - - - - - - - - ,

• Elimination Rate Constant (k): proportion of drug removed per unit time • k = - slope x 2.303 • Clearance (Cl): amount of body fluid cleared per unit time • Cl=kxVd • Half-life (t1/2) = 0.693 x 11k = 0.693 x Vd/Cl • Ideal Body Weight (IBW) • for males = 50 kg + [2.3 kg x (no. of inches >5 ft)] • for females = 45.5 kg + [2.3 kg x (no. of inches >5 ft)] • Loading Dose (LD) • LD = IBW x doselkg or • LD = Cp x Vd/F where

For unit conversion factors, please see Appendix: Common Unit Conversions.

Cp = target plasma drug concentration Vd = volume of distribution F = bioavailability (F = 1 for IV drugs)

• Maintenance Dose (MD) • MD = IBW x Dose per kg/t (dosing interval) • with renal impairment: • MD = CrCl (patient)/ CrC! (normal) x dose for normal patient or • MD = Cp x CrCI/ F (where CrCl = creatinine clearance)

Dose-Response Relationship
• efficacy and potency are two important pharmacodynamic characteristics of a drug • the principles of efficacy and potency can be quantified using dose-response curves • with gradual dose-response relationships, the response of the drug reflects the number of receptors that are effectively occupied

..... ' . ! - - - - - - - - - - - - , l

Efficacy venus Potency
• Efficacy measures adrug's maximal effect and is independent of concentration • Potency measures the concentration of adrug needed to produce acertain effect

Efficacy • a measure of the ability of a drug to elicit an effect at its receptor • independent of concentration • measured as Em•• = the maximal response that a drug can elicit (see Figure 6) • e.g. if Drug A causes a greater maximum intensity of response than Drug B (regardless of dose), then Drug A is more efficacious than Drug B • reflects drug response under ideal circumstances (e.g. controlled clinical trial) Potency • a measure of the effect produced by a certain concentration of a drug • measured as ED 50 (or EC so) = the effective concentration of a drug needed to produce 50% of the maximal possible effect (see Figure 6) • one may compare the ED50 of two or more drugs that have paraUellog dose-response curves • the drug that reaches its ED so at the lower dose is the more potent • if the potency of a drug is low, this may be overcome by increasing the dose of the drug (e.g. 30 mg vs. 1.5 mg); this is not problematic provided that the higher dose not cause adverse side effects

Toronto Notes 2008


Clinical Phannacology CP9





g so
~ Q)



~ B


(both B andC

are less potent









Log of dose


..., '"

c '": g


Figure 6. Log Dose-Response Curve Illustrating Efficacy and Potency

Effects of Drugs on Receptors
• drugs that act on specific receptors can be broadly classified as agonists or antagonists (see Figure 7)

Agonists • drugs that bind to endogenous ligands and exert an effect • have two main properties: • affinity: the ability of the agonist to bind to the receptor (e.g. the ~2-agonist salbutamol binds to ~2-re('eptors) • efficacy: the ability to cause a response via the receptor interaction (e.g. binding of salbutamol to ~2-receptors results in activation of smooth muscle relaxation) • full agonists: can elicit a maximal effect at a receptor • partial agonists: can only elicit a partial effect, no matter how high the concentration, i.e. have reduced efficacy as compared to full agonists Antagonists • drugs that have affinity (can bind to a receptor), but no efficacy • these are drugs that block the action of an agonist or of an endogenous ligand • chemical antagonism • direct chemical interaction between agonist and antagonist prevents agonist binding to receptor (e.g. chelating agents for removal of heavy metals) • functional antagonism • interaction of two agonists that act at different receptors independent of each other but have opposite physiological effects • e.g. acetylcholine at the muscariniC' receptor decreases HR, constricts pupil, stimulates intestinal motility; whereas epinephrine at the adrenergic receptor increases HR, dilates pupil, decreases intestinal motility • reversible competitive antagonism (most common in clinical practice) (see Figure 8) • antagonist binds to the same receptor as the agonist, thus displacing it • the antagonist binds reversibly • increasing the concentration of agonist can overcome the antagonism through competition • irreversible antagonism • competitive (see Figure 8) • irreversible binding of the antagonist to the same receptor as the agonist • blocks the agonist from binding • e.g. acetylsalicylic acid is a C'OmpE'titive irreversible antagonist of cyc!ooxygenase • non-competitive (see Figure 9) • binding of antagonist to an alternate site, separate from but usually near to the agonist receptor • binding of antagonist produces allosteric effects which change the ability of the agonist to bind • e.g. organophosphates are non-competitive irreversible antagonists of acetylcholinesterase

CPlO Clinical Pharmacology


Toronto Notes 2008




ANTAGONIST BINDING 1) Competitive reversible binding

Receptor AnlJgonist binding REVERSIBLE BINDING

concentration of agonist

antagonist binding

2) Competitive irreversible bindinq

Agonist Antagonist





c::>000tJ c::>



Agonist cannot bind receptor which

is irreversibly
blocked by antagonist

Antagonist binding

3) Non-competitive irreversible binding
Antagonist bound to alternative site prevents
agoni!>t from

Agonist Antagonist

binding to receptor


Antagonist binding


o Adrian Yen (2006)

Figure 7. Mechanism of Agonists and Antagonists


A -> C increasing dose of competitive antagonist. At each dose of antagonist, increasing the concentration of agonist can overcome the inhibition

Dose of Agonist

Figure 8. The Log Dose-Response Curve for Competitive Reversible Antagonism

Response A -> D increasing dose of irreversible antagonist.


Dose of Agonist

With one dose of antagonist, increasing dose of agonist does not completely overcome antagonism, as seen in B. Eventually with high enough antagonist concentrations, no amount of agonist can elicit a response, as seen in D.

Figure 9. The Log Dose-Response Curve for Non-Competitive Irreversible Antagonism

Toronto Notes 2008

Pharmacodynamicsffherapeutic Drug Monitoring

Clinical Pharmacology CPU

Effectiveness and Safety
• the two most clinically relevant properties of any drug are effectiveness and safety • effectiveness • similar to efficacy but in real populations, i.e. not experimental studies • safety • LD so (Lethal Dose - 50%): the dose of a drug needed to cause death in 50% of a test population of subjects (usually rodents) • TOso (Toxic Dose - 50%): the dose needed to cause a harmful effect in 50% of a test population of subjects

Therapeutic Index (TI)

• defined as TOsolED so (see Figure 10) • ret1ects the "margin of safety" for a drug - the likelihood of a high dose causing serious toxicity/death • the larger the Tl, the safer a drug (e.g. amoxidllin has a wide Tl, therefore therapeutic monitoring is not needed, whereas warfarin has a narrow 11 and must have accurate therapeutic monitoring) • factors can change the EDs<Y LDso or the TOso : • presence of interacting drugs • changes in drug absorption, distribution, metabolism, elimination

------.....;----~---~~-----~Drugs with anarrowTI have ahigh likeli· hood of causing toxicity and need thera· peutic monitoring.




EDso TDso Log Dose




Log Dose

The therapeutic index (TDsoiEDsol is a measure of the margin of safety of a given drug.

Drug A has a much narrower therapeutic index than Drug S. The dose of Drug Arequired to achieve a100% therapeutic response will be toxic in 50% of patients. For Drug S, this is only 10%.

Figure 10. ED 50 ,TD so ' and the Therapeutic Index (Til

Therapeutic Drug Monitoring (TOM)
• definition: using serum drug concentration data to optimize drug therapy (e.g. dose adjustment, monitor compliance) • TOM is often used for drugs that have: • narrow therapeutic index (TI) • unpredictable dose-response relationship • significant consequences associated with therapeutic failure or toxicity • wide interpatient pharmacokinetic variability • serum drug samples are usually taken when the drug has reached steady state (e.g. trough level- the lowest level before the next dose), therefore sampling times are generally before the next dose • examples of drugs whose levels need to be monitored: warfarin (via INR monitoring rather than serum levels), digoxin (if patient symptomatic), lithium, heparin, carbamazepine, phenytoin, theophylline

CP12 Clinical Phannacology

Adverse Drug Reactions

Toronto Notes 2008

Adverse Drug Reactions (ADRs)


• in Canada, an estimated 1.6% of patients admitted to hospitals experience a serious


In Canada, an estimated 1.6% of patients admitted to hospitals experience aserious adverse drug reaction.

adverse drug reaction • classification of adverse drug reactions • type A: predictable, dose-related • type B: unpredictable, not dose-related

Type A
• side effects: excessive but characteristic pharmacological effect from usual dose of a drug (e.g. ~-blockers causing bradycardia) • overdose/toxicity: exaggerated but characteristic pharmacological effect from supratherapeutic dose • teratogen: drug may produce developmental defects in fetus • characteristics: • account for more than 80% of all ADRs • extension of pharmacological effect • dose-related and generally not severe • usually do not require discontinuation • dose reduction or titration may help minimize effect

• idiosyncratic: uncharacteristic response to drug, unrelated to pharmacology (e.g. sulfa-containing medications) • pseudoallergenic: mimics immune-mediated reaction • allergic/immune-mediated: does not occur on first exposure (up to 7 d), immediate with subsequent exposure, may occur with low dose, resolves within 3-4 days of discontinuation • characteristics: • usually more severe • usually require discontinuation • not dose-related

pproaCfi to Suspecte(f AD s
• history and physical examination: signs/symptoms of the reaction (e.g. rash, fever, hepatitis, anaphylaxiS, etc.), timing, risk factors, medication history, dechallenge (response when drug is removed) and rechallenge (response when drug is given again) • check with literature, Health Canada and FDA; contact the pharmaceutical company • differentiate between drug therapy vs. disease pathophysiology • treatment: stop the drug, supportive care, symptomatic relief • Canadian Adverse Drug Reaction Monitoring Program: • should report all suspected ADRs which are: 1) unexpected; 2) serious; or 3) reactions to recently marketed drugs (on the market < 5 years) regardless of nature or severity

Toronto Notes 2008

Adverse Drug ReactionsNariability in Drug Response

Clinical Pharmacology CP13

Table 2. Sample of Clinically Relevant Adverse Drug Reactions and Interactions
Drug(s) Adverse Drug Reaction Comments

Beta blockers Vancomycin

Bradycardia Red Man Syndrome

Dose dependent Pruritic erythematous rash on upper body Related to rapid infusion of first dose Not considered"allergy" Switch ACEI to ARB Life threatening

ACEI Sulfa drugs

Cough Stevens-Johnson Syndrome Toxic Epidermal Necrolysis Rash


Many children with EBV infection will develop a rash when given amoxicillin ; this is NOT a true penicillin allergy Many other drugs interact with warfarin

Warfarin with acetaminophen or amiodarone Aminoglycosides Acetaminophen Valproic acid Chinese herbs

Increased INR

Ototoxicity and nephrotoxicity Hepatotoxicity

Dose dependent Many other drugs are hepatotoxic (e.g. statins, OCPs, isoniazid)

Variability in Drug Response
• each person is unique in their dosing requirements • recommended patient dosing is based on clinical research and represents mean values for a select population • the majority of patients will experience the desired therapeutic effect of a drug with minimal ADRs on the recommended dose, but not all patients will achieve this effect • dosing may need to be adjusted, or the medication may need to be changed altogether • the causes of individual variability in drug response are many, but can be broadly divided into problems with intake, pharmacokinetics, and pharmacodynamics • a variety of factors may increase or decrease a patient's response to a medication at a given dose • more than one factor may be affecting a patient; be open minded and flexible when prescribing and dosing medication • some possible causes of variable responses to a drug: • intake • compliance/adherence - if a patient is non-compliant (non-adherent), consider why and try to find a solution - e.g. dosing schedule is too hard to follow; medication is non-palatable; medication is too expensive • pharmacokinetics • absorption - is the patient not absorbing due to vomiting, diarrhea or steatorrhea? - is the hepatic first pass effect too high due to enzyme induction, or too low because of liver disease? - is change in absorption due to drug interactions (e.g. calcium carbonate chelates iron) • distribution - does the patient have a very high or low percentage body fat? - is the BBB intact or disrupted?

CP14 Clinical Pharmacology

Variability in Drug Response/Autonomic Pharmacology

Toronto Notes 2008

• metabolism - is the patient elderly or a neonate? - various effects possible - does the patient have a certain genetic polymorphism? - patient may lack enzymes to metabolize drugs (e.g. acetylcholinesterase deficiency, CYP polymorphism) - does the patient have liver dysfunction? - is metabolism increased due to enzyme induction or decreased due to enzyme inhibition? • elimination - is there kidney or liver dysfunction? - is there obstruction of the bile elimination pathway? • pharmacodynamics • is the variability due to genetic variability in drug response? (e.g. malignant hyperthermia due to specific anesthetic agents) • is the variability due to drug interactions? (e.g. polypharmacy) • does this person have a disease process that affects drug pharmacodynamics? • is this person tolerant to the medication?

Autonomic Pharmacology

Sympathetic (SNS) • Fight or Flight
Figure 11. Subdivisions of the Peripheral Nervous System

Parasympathetic (PNS) • Rest and Digest

• most organs are innervated by both sympathetic and parasympathetic nerves; these have opposing effects (see Figure 12) • sympathetic and parasympathetic efferent fibers originate bilaterally in lateral hom of the spinal cord • almost all autonomic nervous system (AN5) efferent tracts are divided into pregangliOniC and postganglionic nerves:

preganglionic nerves


ganglionic synapse -> postganglionic nerve


synapse on target organ

• sympathetic preganglionic fibers originate in the spinal cord at spinal levels Tl-L3, and terminate in one of two ganglia: 1) paravertebral ganglia, i.e. the sympathetic trunk, that lie in a chain close to the vertebral column 2) pre-vertebral ganglia, i.e. celiac and mesenteric ganglia, that lie within the abdomen • parasympathetic preganglionic fibers originate in the spinal cord in the lower brainstem and in the sacral spinal cord at levels 52-54; they terminate in the ganglionic cells located near or within the target organ • both sympathetic and parasympathetic pre-ganglionic nerves release acetylcholine (ACh) • post-ganglionic sympathetic nerves release norepinephrine (NE), while post-ganglionic parasympathetic nerves release ACh • the exception are post-ganglionic sympathetics to sweat glands, and to a few skeletal muscles and blood vessels, which also release ACh

Toronto Notes 2008

Autonomic Phannacology

Clinical Phannacology CPIS



A Constricts pupil C Slows heart rate E Stimulates peristalsis G Stimulates intestinal mobility I Contracts bladder


StImulates salvation Constricts bronchi Stimulates bile Relaxes rectum

1 Dilates pupil

2 Inhibits salvation
4 Dilates bronchi 6 Stimulates metabolism

3 Accelerates heart (ate and improves contractility 5 Stimulates se<retion of adrenaline and noradrenaline 7 Inhibits peristalsis 9 Contracts rectum

and glucose release
8 Inhibits intestinal mobility

10 Relaxes bladder
e Yona Gellert 2007

Figure 12. Autonomic Nervous System

Parasympathetic Nervous System (PNS)
• acetylcholine (ACh) is the neurotransmitter of the parasympathetic nervous system • ACh receptors include: • nicotinic (pre-ganglionic) located in autonomic ganglia, and nicotinic (post-ganglionic) in the adrenal medulla and neuromuscular junction (NMJ) • muscarinic (only post-ganglionic) • M 1 located in the CNS • M2 receptors located on smooth muscle, cardiac muscle and glandular epithelium • acetylcholine action is terminated by metabolism in the synaptic cleft by acetylcholinesterase and in the plasma by pseudocholinesterase • e.g. acetylcholinesterase inhibitors are used to increase ACh levels in conditions such as myasthenia gravis or Alzheimer's disease

Sympathetic Nervous System (SNS)
• norepinephrine is the major neurotransmitter of the SNS • receptors include: • ~l predominately in cardiac tissue • ~2 predominately in smooth muscle and glands • a 1 predominately on post-synaptic receptors in smooth muscles and glands • ~ predominately on pre-synaptic terminals, where they feed back to inhibit sympathetic nervous system response; also exist as post-synaptic terminals in the brain, uterus and vascular smooth muscle • norepinephrine action is terminated by reuptake by the presynaptic membrane, diffusion from the synaptic cleft and degradation by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)

CP16 Clinical Phannacology

Autonomic Phannacology/Opioid Analgesic Equivalencies

Toronto Notes 2008

Table 3. Direct Effects of Autonomic Innervation on the Cardiorespiratory System
Organ Heart
1. Sinoatrial Node 2. Atrioventricular Node 3,Atria 4. Ventricles
~, ~,

Sympathetic Nervous System Receptor Action

Parasympathetic Nervous System Receptor Action

l' HR l' Contractility l' Contractility


-J,HR -J, Conduction -J, Contractility -J, Contractility

Blood Vessels 1. Skin, Splanchnic 2, Skeletal Muscle
3. Coronary

a"a, a


a" a"

Constriction Constriction Dilatation Constriction Dilatation


Dilatation Dilatation Dilatation Dilatation Dilatation

Lungs 1. Bronchiolar Smooth Muscle 2. Bronchiolar Glands

<x" ~,


Relaxation l'Secretion


Contraction Stimulation

Opioid Analgesic Equivalencies
Table 4. Opioid Equivalent Doses

Generic Name Morphine

Proprietary Name MSIR1M ("immediate release' I PO); MS Contin1M , M-Eslon1M Icontrolled release PO!: various names for IV form

Oral (mg) 30-60

IV (mg) 10

Comments - Parenteral 10 mg morphine is usual standard for comparison, -Morphine PO:IV =60:10 for opioid na'ive patient. 30:10 for others. - Do not crush, break, or chew oral controlled release morphine.

When prescribing narcotics, remember: N narcotic (e.g. morphine 5mg PO q4hl B breakthrough (e.g. morphine 2.5 mg PO qlh prnl A anti-emetic (e.g. dimenhydrinate 12.5 mg PO q4h) l laxative (e.g. senokot PO qhs)

Codeine Codeine Contin'" ,

Tylenol #1.#2,#3 CYP2D6 polymorphisms)

200 120 . Metabolized to morphine 1-7-10% of Caucasians are non· metabolizers, due to generics - Limited by potential toxicities of the acetaminophen with which it is often combined. · No additional benefit at doses ,.200 mg,


OxyContin" Oxy IR'';, Endocodone"'; Percocet"', Percodan '" [combination with ASA or acetaminophen) Vicodin", Lortab'"



· Often formulated in combination with acetaminophen/aspirin - Use caution if administrating additional acetaminophen or aspirin,



Not Available

• Limited by potential toxicities of the acetaminophen or ibuprofen with which it is combined, · Ouiak onset of action and thus highly addictive -PO especially useful for initial dose titration and prn supplementation. -N form often used subcutaneously.









· Not a1st line opioid, May cause seizures due to the accumulation of normeperidine, its breakdown product. -It should not be used longer than 48 h nor more than 600 mgl24 h - Contraindicated with MAOls, - Rarely used anymore

Toronto Notes 2008

Opioid Analgesic Equivalencies/Summary Key Questions

Clinical Phannacology CP17

Table 4. Opioid Equivalent Doses (continued)
Generic Neme

Proprietary Name

Oral (mg)
Not Available

IV (mg)



• Minimal experience outside the hospital setting - Usually for stable pain, especially in patients with GI dysfunction

Fentanyl Itransdermall


Transdermal 50 ~gIh patch =Morphine 100 mg PO/24 h=16 mg PO q4h =1.4 mglh IV 20 10



• long, variable half·life, which may complicate titration



. long half·life with relatively short dosing interval

• • • • • •

when converting from one opioid to another, use 50-75% of the equivalent dose to allow for incomplete cross·tolerance rapid titration and prn use may be required to ensure effective analgesia for the first 24 hours dose equivalencies provided in the above table are approximate; individual patients vary the opioids often used to manage mild to moderate pain include codeine, hydrocodone, and oxycodone moderate to severe pain is often managed using morphine, hydromorphone, oxycodone, fentanyl, methadone, or levorphanol note that usual starting therapeutic doses are lower than those listed above

Summary Key Questions
Questions 1. What are the four steps, in order, of pha rmacokin'etics? Answers ADME

=absorption, distribution, metabolism, excretion

2. What are the factors affecting absorption? Partition coefficient of the drug, local blood flow at the site of administration, molecular size, pH, total surface area for absorption 3. What are the two most important CYP isoforms involved in drug metabolism? 4. How long does it take for a drug to reach steady state? CYP3A4 and CYP2D6; anticipate drug reactions Five half-lives

5. What is the difference between an agonist Agonist =a drug that binds to endogenous ligand (affinity) and and an antagonist? exerts an effect lefficacyl Antagonist = a drug that has affinity but no efficacy 6. What is the difference between efficacy and potency? Effectiveness? Efficacy is a drug's maximal effect independent of concentration and can only be determined in clinical studies Potency is a concentration needed to produce a given effect Effectiveness is like efficacy, but in the real-life clinical setting TD50/ED50; relationship between toxic and effective doses, i.e. a measure of 'margin of safety' of a drug warfarin, digoxin, lithium, heparin, carbamazepine, phenytoin, theophylline Type A = excessive but predictable pharmacological effect (side effects) from usual dose of drug Type B =idiosyncratic and unpredictable reactions unrelated to pharmacology of drug Compliance, decreased absorption, liver or biliary dysfunction, drug interactions, percentage of body fat. age, genetic polymorphism, kidney disease

7. What is therapeutic index? 8. What are some medications with a narrow therapeutic index? 9. What is the difference between type A and type B adverse drug reactions?

10. What are some factors that affect variability in drug response?

CPIS Clinical Pharmacology


Toronto Notes 200S

Baker GR, Norton PG, Flintoft Vet al. The Canadian Adverse Events Study: the incidence of adverse events among hospital patients in Canada. CMAJ 2004; 170:1678-86. Canadian Adverse Drug Reaction Monitoring Program ICADRMPI Adverse Reaction Database Hardman JG and Limbird LR (edsl (19961. Goodman and Gilman's the Pharmacological Basis ofTherapeutics (9th edl. McGraw-Hili, NewYork. Hardy B, Bedard M (20021. Serum Drug Concentration Monitoring. In: Compendium of Pharmaceuticals and Specialties 2002. Repchinsky Cled.l. Canadian Pharmacists Association, Ottawa. Kalant Hand Roschlau W leds) 11999). Principles of Medical Pharmacology 16th ed.). Oxford University Press, NewYork. Katzung BG led) (2001). Basic and Clinical Pharmacology 18th ed.). McGraw-Hili Companies, NewYork. Rang H, Dale M, Ritter J ledsl (1999). Pharmacology 14th ed.). Churchill Livingstone, Edinburgh.


Renita Ahluwalia and Naomi Driman, chapter editors Deana Hathout and Ripudaman Minhas, associate editors Jai Shah, EBM editor Dr. Neil H. Shear, staff editor
Introduction to the Skin Skin Anatomy Skin Function Definitions Primary Morphological Lesions Secondary Morphological Lesions Other Morphological Lesions Patterns and Distribution Differential Diagnoses of Common Presentations Common Skin Lesions Cysts Fibrous Lesions Hyperkeratotic Lesions Vascular Lesions Pigmented Lesions Miscellaneous Lesions Acneiform Eruptions Acne Vulgaris/Common Acne Perioral Dermatitis Rosacea Dermatitis (Eczema) Asteatotic Dermatitis Atopic Dermatitis Contact Dermatitis Dyshidrotic Dermatitis Nummular Dermatitis Lichen Simplex Chronicus Seborrheic Dermatitis Stasis Dermatitis Papulosquamous Diseases Lichen Planus Pityriasis Rosea Psoriasis Vesiculobullous Diseases Bullous Pemphigoid Pemphigus Vulgaris Dermatitis Herpetiformis Porphyria Cutanea Tarda



Infections Bacterial Infections Superficial Skin (Epidermal) Deeper Skin (Dermal) Common Hair Follicle Infections Sexually Transmitted Infections Dermatophytoses Parasitic Infections Viral Infections Yeast Infections Pre-Malignant Skin Tumours


36 36


Malignant Skin Tumours Basal Cell Carcinoma (BCC) Cutaneous T-cell Lymphoma Leukoplakia Malignant Melanoma (MM) Squamous Cell Carcinoma (SCC) Heritable Disorders Ichthyosis Vulgaris Neurofibromatosis (NF) Vitiligo Skin Manifestations of Internal Conditions Autoimmune Disorders Endocrine Disorders HIV Malignancy Others Nails and Disorders of the Nail Apparatus







Alopecia (Hair Loss) Hair Growth Non-Scarring (Non-Cicatricial) Alopecia Scarring (Cicatricial) Alopecia Pediatric Exanthems Erythema Nodosum Pruritus Wounds and Ulcers Common Medications Topical Steroids Sunscreens and Preventable Therapy Dermatological Therapies Summary Key Questions References


44 45
46 46

Drug Eruptions 24 Erythema Multiforme (EM), Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) Drug Hypersensitivity Syndrome Exanthematous Eruptions Fixed Drug Eruption Photosensitivity Eruptions Serum Sickness-Like Reaction Angioedema Urticaria



Toronto Notes 2008

Dennatology D1

D2 Dermatology

Introduction to the Skin

Toronto Notes 2008

Introduction to the Skin
Skin Anatomy
Layers of the Epidermis
·Californians Like Girls in String Bikinis·



arrector pili muscle hair follicle

~~=~~~~~~=s J stratum corneum
::::::J stratum lucidurn
~ stratum granulosum

•] ~~~!i>:.~~f!'C:.t:I.~,
til • f ]

stratum spinosum

~~iiii~ jJ ::~~~;~:'J ..m; '.;W'' '] j
S~~~~~:a~~g p

stratum basale


aneous adipose tissue

sweat gland


{i ~

Figure 1. A cross-section of the various layers of skin. Epidermal layer is detailed in A.

• divided anatomically into epidermis, dermis, and subcutaneous tissue • epidermis • avascular: receives its nutrition from the dermal capillaries • derived from keratinoeytes with the youngest presenting at the 'base' (see layers Figure lA) • cells progress from stratum basale to stratum corneum in about four weeks • stratum basale (germinativum): mitotic figures that give rise to keratinoeytes • stratum spinosum (prickle cells): junctions in this layer (tonofilaments) give the epidermis its strength • stratum granulosum: Hat cells containing basophilic granules which characterize skin • stratum lucidum: comprised of transparent layers of packed dead cells • stratum corneum: flat scales of the resistant protein keratin • other epidermal cells include melanoeytes, Langerhans cells, and white blood cells • dermis - comprised of connective tissue divided into two regions: • papillary: contains numerous capillaries that supply nutrients to the dermis and epidermis • reticular: provides a strong structure for skin; consists of collagen bundles woven together along with elastic fibres, fibroblasts, and macrophages • subcutaneous tissue (subdermal) • consists primarily of lipid in fat cells

Skin Appendages
• epidermal in origin; can extend into the dermis • include hair, nails, and cutaneous glands (sebaceous glands, apocrine and eccrine sweat glands)

Cutaneous Glands
• sebaceous gland - part of pilosebaceous unit, produces sebum which is secreted into the hair follicle via the sebaceous duct, where it covers the skin surface (protective function). Sebum has some antifungal properties • found over entire skin surface except palms and soles • apocrine sweat gland - apocrine duct empties into hair follicle above sebaceous gland • found in axillae and perineum • main function is to produce scent • eccrine sweat gland - not part of pilosebaceous unit • found over entire skin surface except lips, nail beds and glans penis • important in temperature regulation via secretion of sweat to cool skin surface

Toronto Notes 2008

Introduction to the SkinlDefinitions

Dennatology D3

Skin Function
• protection • with continuous recycling and avascularity, the skin is a barrier to numerous insults: • UV radiation, mechanical/chemical insults, pathogens, and dehydration • thermal regulation • insulation to maintain body temperature in cool environments • via hair and subcutaneous adipose tissue • dissipation of heat in warm environments • via increased activity of sweat glands and increased blood flow within the vascular network of the dermis • sensation • largest sensory organ of the body with touch, pain, and temperature sensation • metabolic function • vitamin D synthesis (via melanocytes) • energy storage (mainly in the form of triglycerides)

Primary Morphological Lesions
• an initial lesion that has not been altered by trauma or manipulation, and has not regressed
Table 1. Types of Lesions
Elevated Fluid-filled Lesions Flat Lesion Palpable Deep (dermal) Raised Superficial Lesion



<1 em Diameter
Macule (e.g. freckle I Nodule (e.g. dermatofibromal Papule (e.g. wart)


em Diameter

Vesicle (e.g. herpes simplex virus (HSV)I Bulla (e.g. bullous pemphigoidI Patch (e.g. vitiligo) Tumour (e.g. lipoma) Plaque (e.g. psoriasis)

Describe 8 lesion with SCALDA Sire Colour (e.g. hyperpigmented, hypopigmented, erythematous) A rrangement (e.g. solitary, linear, reticulated, grouped, herpetiform) Lesion morphology (see Table 1) Distribution (e.g. dermatomal. intertriginous, symmetrical! asymmetrical, follicular) A Iways check hair, nails. mucous membranes and intertriginous areas

• • • • • • •

cyst: a nodule containing semisolid or fluid material erosion: a disruption of the skin involving the epidermis alone, heals without scarring indurated: descriptive term for a lesion that is hard or firm pustule: an elevated lesion containing purulent fluid (white, grey, yellow, green) scar: replacement fibrosis of dermis and subcutaneous tissue (hypertrophic or atrophic) ulcer: a disruption of the skin that extends into the dermis or deeper; heals with scarring wheal: a special form of papule or plaque that is blanchable and transient, formed by edema in the dermis (e.g. urticaria)

Secondary Morphological Lesions


• develop during the evolutionary process of skin disease, or are created by manipulation or complication of primary lesion (e.g. rubbing, scratching, infection) • crust: dried fluid (serum, blood, or purulent exudate) originating from a lesion (e.g. impetigo) • scale: excess keratin (e.g. seborrheic dermatitis) • fissure: a linear slit-like cleavage of the skin • excoriation: a scratch mark • lichenification: thickening of the skin and accentuation of normal skin markings (e.g. chronic atopic dermatitis) • xerosis: dryness of skin, eyes and mouth • atrophy: histological decrease in size and number of cells or tissues resulting in thinning or depression of the skin

D4 Dermatology

DefinitionsfDifferential Diagnosis of Common Presenting Problems

Toronto Notes 200S

Other Morphological Lesions
• comedones: collection of sebum and keratin • open comedone (blackhead) • closed comedone (whitehead) • purpura: extravasation of blood into dermis resulting in hemorrhagic lesions; non-blanchable • petechiae: small pinpoint purpura • ecchymoses: large flat purpura • telangiectasia: dilated superficial blood vessels; blanchable

Patterns and Distribution
• • • • • • • • •

annular lesions: ring shaped e.g. granuloma annulare follicular lesions: involving hair follicles guttate lesions: "drop like" lesions found on the skin (e.g. guttate psoriasis) Koebner phenomenon: isomorphic response, appearance of lesions at an injury site e.g. molluscum, lichen planus, psoriasis, warts reticular lesions: lesions following a net-like pattern (e.g. livedo reticularis) satellite lesions: lesions scattered outside of primary lesion serpignous lesions: lesions following a snake-like pattern target (iris) lesions: concentric ring lesions (like a dartboard, e.g. erythema multiforme) other descriptive terms used: discrete, clustered, linear, confluent, dermatitic

Differential Diagnoses of Common Presentations
Table 2. Differential Diagnosis of Common Presenting Problems
lesion Discrete Red Papule Infectious Folliculitis Furuncle Scabies Inflammatory Acne vulgaris Lichen planus Rosacea Psoriasis Urticaria Dermatitis (atopic, contact, nummular, seborrheic) Discoid lupus Lichen planus Psoriasis DrugIToxin Bites/stings Miscallaneous Vascular: hemangioma, pyogenic granuloma Other: dermatofibroma, milaria rubra

Red Scales

Pityriasis rosea Secondal)' syphilis Tinea


Neoplastic: mycosis fungoides

Brown Macule

Post·inllammatol)' UV Radiation: hypo/hyper pigmentation actinic/solar lentigo, freckle tephelidel Cat-Scratch disease Impetigo Viral: HSV, zoster, varicella, molluscum, coxsackie Scabies Bullous impetigo Acute contact dermatitis Dyshidrotic eczema

Congenital: cafe-au-lait spots, congenital nevus, epidermal/junctional nevus Neoplasia: lentigo maligna. malignant melanoma, pigmented BCC Other: dermatits herpetiformis, porphyria cutanea tarda



Acute dermatitis EM/SJSITEN Lupus erythematosus Acne vulgaris Rosacea Dyshidrotic eczema Pustular folliculitis Pustular psoriasis Allergic stomatitis EM/SJSITEN Lichen planus Seronegatives SLE

Drug eruption

Autoimmune: bullous pemphigoid, pemphigus vulgaris Other: dermatitis herpetiformis, porphyria cutanea tarda Other: hidradenitis suppurativa


Candida Dermntophyto. Impetigo Sepsis Varicella Aspergillosis CMV Coxsackie CI)'ptococcosis HSV/HZ HIV TB Syphilis Plague Syphilis T8 Tularemia

Oral Ulcer

Chemotherapy Radiation therapy

Autoimmune: pemphigus vulgaris Congenital: XXV Hematologic: sickle cell disease Neoplasia: BCC, SCC

Skin Ulcer

RA, SLE, vasculitis Ulcerative colitis (pyoderma gangrenosuml

Autoimmune: necrobiosis lipoidica diabeticorum le.g. DMI Congenital: XXV Hematologic: sickle cell disease Neoplasia: SCC Vascular: arterial, neurotropic, pressure, venous, aphthous, leukoplakia, traumatic

Toronto Notes 2008

Common Skin Lesions

Dermatology D5

Common Skin Lesions
Table 3. Cysts

I- ~

1lenooidCj1t Rne, congenRaI hamartom~





Thii walled CjSI lined IIith siralified squamous e¢helium andfillOOllithilenleOOtifl


fiom~int~lendonsOOath, tal~aOlll:llUSt'/sI\\tien

ilenleOOtin Pore ArisefiomirdusklilolepNleOllis



MostCOlt'JOOllartaneousCjSl Youth-nidage

2"'most common artaooousCjSl



EtioIogyf PathopIrysioIog




Pril1\1n~ arisl! from ~1lI\YJtelji~ ~b in epidemnaloradnexalepitheliJm; SecooIariiyfrom~isIeri ... u1reration,

MaybelXJSi'liaomatic S91s &Symptoms Round, yjlow~lKoloured, s~grolli ... rno~le,firm,

or coSlrelic procedures

scalp, lacks central ""nctum

Most com~ 10000 ~ laternl third of eyeblow 01 midline under nose


'·1 mm superficial,whnetoyellow
su~dermalllilPUlesllXUringon ~1~,d1eeks,ardfureftead~

transiOCefll; adear gelatinous mlMdrnaybeextnllid





m newborns Sjl1Il1aneous~ lesoi.!s in filSt 4weeks of Ide


Irxreareinsi2eardlllmbefowr inil'!9r;rICj







Incision ard expression of COI1lent


Mu~~e facial mil~ respords 10 tlJlital retinoidthernllf

Fibrous Lesions
DERMATOFIBROMA DefinitionlPathophysiology
• button-like benign dermal tumour due to fibroblast proliferation in dermis



• unknown; often associated with history of minor trauma or insect bites

• adults, F>M

Differential Diagnosis
• blue nevus, dermatofibrosarcoma protruberans, Kaposi's sarcoma, malignant melanoma

Signs and Symptoms
• firm, red-brown, solitary, well-demarcated dermal papules or nodules with central dimpling and hyperpigmentation • most are asymptomatic but itchy, tenderness is common • site: legs> arms> trunk • Fitzpatrick's sign: pressure causes skin retraction (dimple)

• no treatment usually needed (excise if bothersome or diagnosis uncertain) • cryotherapy if certain of diagnosis

• benign outgrowth of skin

D6 Dermatology

Common Skin Lesions

Toronto Notes 2008

• middle-aged and elderly, F>M, obese

Signs and Symptoms
• small, soft, skin-coloured or tan, pedunculated papule or papilloma, 1-10 mm • sites: neck, axillae, and trunk

• clipping, cautery


Hyperkeratotic Lesions
• benign neoplasm of epidermal cells

• unusual <30 years old • autosomal dominant inheritance

Differential Diagnosis
• malignant melanoma (lentigo maligna, nodular melanoma), melanocytic nevi, pigmented BCC, solar lentigo, spreading pigmented actinic keratosis

Signs and Symptoms (usually asymptomatic)
• round/oval, well-demarcated, discrete waxy papule/plaque, ± pigment, warty surface, "stuck on" appearance • sites: face, trunk, upper extremities (may occur at any site except palms or soles) • colour varies (wmte to pink to jet hlack) • surface crumbles when picked

Clinical Course
• over time, increase in pigmentation, "stuck on" plaque appears warty

• biopsy only if diagnosis uncertain

• none required, but often sought for cosmetic or physical ("in the way") reasons • liquid nitrogen • curettage



• common, persistent, keratotic lesions with malignant potential

Types of Actinic Keratoses lAKsl
• eJYlhematous - typical AK lesion • hypertrophic -thilier, rough papule/plaque • cutaneous hom • actinic cheilitis -confluent AKs on the lip • pigmented •flat, tan-brown, scaly plaque • spreading pigmented • proliferative • conjunctival -type of pinguecula or pterygium

• UV radiation damage to keratinocytes from repeated sun exposure (especially UVB) • pleomorpmc keratinocytes, parakeratosis, and atypical keratinocytes

• common with increasing age, M>F • skin phototypes I-ill (see Table 21) • melanin is protective

Differential Diagnosis
• Bowen's disease, chronic cutaneous lupus erythematosus, superficial basal cell carcinoma

Signs and Symptoms
• • • • discrete yellow-brown, scaly, adherent patches on a background of sun damaged skin sandpaper-like, gritty sensation felt on stroking these lesions <1 em, round/oval sites: areas of sun exposure - face, ears, scalp if bald, neck, sun exposed limbs

Toronto Notes 2008

Common Skin Lesions

Dermatology 07

Clinical Course Investigations

• may transform into see (1-10%) • biopsy lesions that are refractory to treatment '-

• 5-FU (fluorouracil) cream applied for 2-3 weeks, Aldara™ (imiquimod) cream applied "for 8-10 weeks • liquid nitrogen

• epithelial neoplasm with atypical keratinocytes in epidermis • considered a clinically distinct variant of a well-differentiated see capable of spontaneous regression

• >50 years, rare under 20 years • skin phototypes I-III (see Table 21)

• associated with human papilloma virus (HPV) • associated with UV radiation and chemical carcinogens (tar, mineral oil)

Differential Diagnosis Signs and Symptoms

• see (grows slower - months)
• erythematous, skin-coloured, firm, dome-shaped nodule with central keratin-filled crater, smooth surface (resembles an erupting volcano) • lesion is quite tender during the proliferative phase • sites: sun-exposed skin

Clinical Course
• • • • rapidly grows to -2.5 em in 6 weeks, with keratotic plug in centre of nodule by 6 weeks attains full size in <4 months, may spontaneously regress in <10 months disfiguring scar after regression rarely, keratoacanthomas show intravascular and perineural invasion, and lymph node metatasis

• surgical excision is advisable given lack of features predicting prognosis • curettage and electrocautery • if on lip treat as see

Vascular Lesions
• benign proliferation of vessels in the dermis • red or blue nodules that blanch with pressure • treatment options: argon laser, tattooing, cosmetics, excision with skin expansion





Treatment of Hemangiomas of

Natural history for most is spontaneous resolution, however, 10% require treatment due to functional impairment (visual compromise, airway obstruction, high output cardiac failure) or cosmetic disfigurement. Oral corticosteroids are the first-line therapy.

• vascular malformation of dermal capillaries that follow a dermatomal distribution

• congenital • associated with Sturge Weber syndrome (VI, V2 distribution)

• 0.3% incidence

Signs and Symptoms
• follows dermatomal distribution, rarely crosses midline • red to blue macule present at birth • most common site: nape of neck

D8 Dermatology

Common Skin Lesions

Toronto Notes 2008

Clinical Course • papules/nodules may develop in adulthood, no involution Treatment • laser or camouflage (Le. make-up) SALMON PATCH (NEVUS SIMPLEX) Definition • pink-red irregular patches resulting from dilation of dermal capillaries • midline macule on glabella known as "Angel Kiss," on nuchal region known as "Stork Bites" Epidemiology • 1/3 newborns Clinical Course • tend to regress spontaneously Treatment • no treatment required CAVERNOUS HEMANGIOMA (CAPILLARYNENOUS/LYMPHATIC MALFORMATIONS) Definition • deeply situated proliferation of thick-walled blood vessels, venous malformation without endothelial proliferation Signs and Symptoms • soft, compressible, bluish, subcutaneous mass that feels like a bag of worms when palpated • site: anywhere (distribution may indicate underlying cranial abnormality) Clinical Course • can ulcerate • tend to persist, generally do not involute Treatment • surgical removal ANGIOMATOUS NEVUS (STRAWBERRY NEVUs/CAPILLARY HEMANGIOMA) Definition • benign vascular proliferation of endothelial lining Epidemiology • congenital (usually occur within 1st month of life) Signs and Symptoms • redlblue nodules Clinical Course • appears by age 9 months, increases in size over months, then regresses • 50% of lesions resolve by 5 years old • Kasabach-Merritt syndrome (consumptive thrombocytopenia if hemangioma enlarges rapidly) Treatment • can excise if not gone by school age • systemic corticosteroids and INF-a may be indicated for rapidly growing lesions SPIDER ANGIOMA (SPIDER TELANGIECTASIA) Definition • central arteriole with slender branches resembling legs of a spider

Toronto Notes 200S

Common Skin Lesions

Dermatology 09

• associated with hyperestrogenic state (e.g. in hepatocellular disease, pregnancy, oral contraceptive pill (OCP))




Differential Diagnosis
• ataxia telangiectasia, hereditary hemorrhagic telangiectasia, telangiectasia in systemic scleroderma

Aspider angioma will blanch when the tip of apaperclip is applied to the centre of the lesion.

Signs and Symptoms
• faintly pulsatile, blanchable, red macule • sites: face, forearms, and hands

• electro or laser surgery

• benign vascular neoplasm

• >30 years old

Signs and Symptoms
• bright red to deep maroon, dome-shaped vascular papules, 1-5 mm • site: trunk • less friable compared to pyogenic granulomas

Clinical Course
• increase in number over time

• no treatment usually needed • laser or electrocautery for small lesions • excisions of large lesions if necessary

• rapidly developing hemangioma

• <30 years old

• proliferation of capillaries with erosion of epidermis and neutrophilia

Differential Diagnosis
• glomus tumour, nodular malignant melanoma, SCC, nodular BCC

Signs and Symptoms
• bright, red, dome-shaped sessile or pedunculated nodule • sites: fingers, lips, mouth, trunk, toes

Clinical Course
• lesions bleed frequently and persist for months

• • • • surgical excision with histologic examination electrocautery laser cryotherapy

Pigmented Lesions
SEBORRHEIC KERATOSIS (see Hyperkeratotic Lesions, D6) MELANOCYTIC NEVI (MOLES) (see Table 5)
• be suspicious of new pigmented lesions in individuals over age 40 • average number of moles per person: 18-40

010 Dermatology

Common Skin Lesions

Toronto Notes 2008

• • • • • purpura (e.g. solar, ASA, anti-coagulants, steroids, hemosiderin stain) post-inflammatory melasma melanoma fixed drug eruption

Table 4. Pigmented Lesions
Solar Lentigo (Aging spots, Liver Spotsl Benign melanocylic proliferation in an area of previous sun damage Mongolian Spot Freckles (Ephelides) Becker's Nevus


Congenital hyperpigmented macule

Commonly acquired Asymptomatic pigmented hyperpigmented macules hamartoma secondary to sun exposure Increased melanin within basal layer keratinocyles Increased melanin in basal cells

Pathophysiology Increased number of Ectopic melanocytes in melanocytes in dermal· dermis epidermal junction due to chronic sun exposure Epidemiology Most common in 99% occurs in Asian Caucasians >40 years old and Aboriginal infants Skin phototype I-III Lentigo maligna, seborrheic keratosis, pigmented solar keratosis Well demarcated brownl black irregular macules Sites: sun-exposed skin especially dorsum of hands and feet N/A

Skin phototypes Iand II M>F (most common in blonde Often becomes noticeable at and red haired individuals) puberty Junctional nevi Juvenile lentigines N/A

Diffenential Diagnosis

Signs and Symptoms

Grey-blue macule Commonly on lumbosacral area; usually asingle lesion

Usually <5 mm Sharply demarcated light brown-ginger macules Lesions multiply &grow darker with sun exposure

Light brown macule/patch with apapular verrucous surface & sharply demarcated borders Sites: trunk and shoulders Hair growth follows onset of pigmentation and is localized to areas of pigmentation Benign lesion extends for 1-2 years and then remains stable. only rarely fading Cosmetic management as desired (usually too large to remove)

Clinical Course Laser therapy, shave and Tneatment excisions. cryotherapy

Usually fades in early childhood but may persist into adullthood

Do not require treatment and usually fade in the winter. Broad-spectrum sunscreens may prevent the appearance of new freckles


'.'}-------------, ,


Miscellaneous Lesions
KELOID Definition
• excessive proliferation of collagen following trauma to skin; tissue extends beyond boundaries of scar

MisceH_u. Common Skin Lesion.
SyrIngoma Small. firm, skin-coloured papules found mainly around eyelids and upper chest due to benign growth of eccrine sweat glands. Removal is lor cosmetic purposes only.

• predilection for darker skin • M=F

Congan~allesionsof ~1e head made up of skin and appendagesl components which are present at birth or shortly thereafter. Prophylactic excision at puberty is done due to high frequency of neoplastic changes in adulthood.

Signs and Symptoms
• • • • • skin-coloured or red-bluish papules/ nodules; firm and small with claw-like extensions different from a hypertrophic scar that is confined to the injured skin may continue to expand in size for years can be pruritic and painful sites: earlobes, shoulders, sternum, scapular area

Morphea Sclerotic dermal plaques with violaceous borders and central hypopigmantation of idiopathic origin. Askin biopsy is done to confirm the diagnosis. Treatment consists of sun protection and lOpical. oral or injected steroids depending on symptoms and severity.

• intralesional corticosteroid injections • cryotherapy • silicone compression

Table 5. Melanocytic Nevi Classification
Congenital Nevus Age of Onset • birth Description • sharply demarcated pigmented brown plaque with regularl irregular contours ± coarse hairs ·>1.5cm • rule out leptomeningeal involvement if on head/neck • benign neoplasm of pigment-forming nevus cell • well circumscribed, round, uniformly pigmented maculeslpapules ·<1.5cm •can be classified according to site of nevus cells Isee below) • flat, irregularly bordered, uniformly tan-dark brown, sharply demarcated smooth macule • domed, regularly bordered, smooth, round, tan-dark brown papule • face, trunk, extremities, scalp • NOT found on palms or soles • soft, dome-shaped, skin-eoloured to tan/brown papules or nodules, often with telangiectasia • sites: face, neck • childhood •variegated macule/papule with irregular indistinct borders and focal elevation '>6mm • risk factors: positive family history 100% lifetime risk of malignant melanoma with 2blood relatives with melanoma (0.8% risk for general population) • brown oval I round papules surrounded by hypomelanosis • same sites as neocellular nevus INCN) • spontaneous involution with regression of centrally located pigmented nevus • uniformly blue to blue-black macule/papule with smooth border '<6mm • melanocytes at dermal-epidermal junction above basement membrane • melanocytes at dermal-epidermal junction; migration into dermis • melanocytes exclusively in dermis Histology • nevomelanocyles in epidermis Iclustersl and dermis Istrands)

Z • surgical excision if suspicious, due to increased risk of developing melanoma





Acquired Melanocytic Nevus

• early childhood to age 40 • involute by age 50

• excisional biopsy required if on scalp, soles, mucous membranes, anogenital area, or if variegated colours, irregular borders, pruritic, bleeding, exposed to trauma • same as above

Junctional Nevus

Compound Nevus

• same as above

Dermal Nevus

• same as above

Dysplastic Nevus (Clark's Melanocytic Nevusl

• hyperplasia and proliferation of melanocyles in the basal cell layer

• follow q2-6 months with colour photographs • excisional biopsy if lesion changing or highly atypical

[ =


• dermal or compound neocellular nevus INCN) surrounded by hypomelanosis, lymphocytes, histocytes • pigmented melanocytes and melanophages in dermis • none required • excision if colour variegated or irregular borders • associated with vitiligo, metastatic melanoma • remove if suddenly appears or has changed

Halo Nevus

• first 3decades


Blue Nevus

•childhood and late adolescence







012 Dermatology

Acneiform Eruptions

Toronto Notes 2008


Acneiform Eruptions
Acne Vulgaris/Common Acne
Definition and Clinical Features


• a common inflammatury pilosebaceolls disease categorized with respect to severity Type I - comedonal, sparse, no scarring Type II - comedonal, papular, muderate ± little scarring Type III - comedonal, papular, and pustular, with scarring Type IV - nodulocystic acne, risk of severe scarring • predilection sites: face, neck, upper chest, and hack • epidemiology • common during the teen years • severe disease affects males lOx more frequently than females • incidence decreases in adult life

• increased sebum production • sebum is comedogenic, an irritant, and is converted to free fatty acids (FFA) by microbiallipases made by anaerobic diphtheroid Propionibacterium acnes • free fatty acids + bacteria inflammation + delayed hypersensitivity reaction hyperkeratinization of follicle lining with resultant plugging -+ inflammatory papules and comedones

Exacerbating Factors
• menstruationlhormonal factors (androgens increase sebum production) • OCP: specifically those containing progestins with significant androgenic effects (norethindrone acetate, levo/norgestrel) • topical acnegenic agents • steroids, tars, oi.ntments, greasy cosmetics, etc. • systemic meds: lithium, phenytoin, steroids, halogens (chloracne), androgens, iodides, bromides, danazol • NB: foods are not a major aggravating factor

Differential Diagnosis
• folliculitis, keratosis pilari.s (upper arms, face, thighs), perioral dermatitis, rosacea
Table 6. Acne Treatments and Mechanisms of Action

Topical Therapies
Drug name

Mechanism of Action

Generally regarded as unsafe in lactation local skin reactions include burning, peeing, dryness, pruritus, erythema Dry skin, contact dermatitis. Apply to the point of dryness and erythema, but not discomfort See above See above

clindamycin phosphate le.g. DalacinT"'1 Lincosamide antibiotic; inhibits protein synthesis erythromycin
benzoyl peroxide Macrolide antibiotic; inhi~ts protein synthesis Protein oxidant with bactericidal effect

BenzaClin'" gel
ertthromycin +benzoyl peroxide

1% c1indamycin and 5% benzoyl perox~e
3% e~1hromycin and 5% benzoyl peroxide

IBenzamycin'"J adapalene tretinoin (e.g. Retin-A"'I
Comedolytic Comedolytic less irrnating than tretinoin. No interaction with sun, expensive Sun sensitivity and irritation

Toronto Notes 2008

Acneiform Eruptions

Dermatology 013

Table 6. Acne Treatments and Mechanisms of Action (continued)
AftertDtJical treatnen1li have failed, add oral antibiotics, such astetrecycUna 1500 mg PI) dailtto bidl, ary1!lromytin 1500 mg PO bid}, Antibiotics require 3-6 mon1tls of use befllre assessing efficacy, May also consider honnonal1herapy, ~cluding antiandlllll8n& Drug name Machanism of Action Systemic antibiotic cyproterone: potent anti-androgenic, progestogenic and antigonadatrophic activity ethinyl estradiol: increases level of sex hormone binding globulin ISHBGI, reducing circulating plasma levels of androgens

Use caution with regard to drug interactions: do not use with isotretinoin Not to be used as the sole treatment or the first treatment Aher 35 years of age, estrogen/progesterone should only be considered in exceptional circumstances, carefully weighing the rislobenefit ratio with physician guidance Also used for other androgen-dependent symptoms, including sebormea, alopecia, and mild hirsotism,

cyprotel1llle acetatHt!lirrj\ eslBdij ID~nePl

SEVERE ACNE After attempting the above, consider systemic retinoids

iloIreUioillAccutane Rochelll,Oarus'"l

-------------------------~ l , l - - - - - - - - - - - - - - , Retinoid that inhibits sebaceous Teratogenic: contraindicated during pregnancy • \.1
gland function and keratinization Baseline lipid profile and hepatic enzvmes before treatment May transient~ exacerbate acne, Drug may be discontinued at 16-20 _ks when nodule count has dropped by >70%, Asecond course may be initiated aher 2months prn, Rafractol'( cases may require 3of more courses of isotretinoin, Highly unsafe in pregnancy; general~ regarded as unsafe in lactation, May cause depression, Signed informed consent is needed when prescribing

Drug name

Mechanism of Action



Isotretinoin &Upids
Case reports indicate isotretinoininduced hypertriglyceridemia can be successfully controlled with concurrent hypolipidemic therapy,

Perioral Dermatitis
• distinctive pattern of discrete erythematous micropapules that often become confluent, forming inflammatory plaques on perioral and periorbital skin


• 15-40 years old • predominantly females

Signs and Symptoms
• initial lesions usually in nasolabial folds • symmetry common • rim of sparing around vermilion border of lips

Exacerbating Factors
• inappropriate use of potent topical corticosteroids

• topical: metronidazole 0.75% gel or 0.75-1 % cream to area bid • systemic: tetracycline

• chronic acneiform, inflammatory skin disease



Guidelines for the DiagllOlil of ROIlIC88
Presence of one or more of the following primary features: Flushing (transient erythemal Nontransient erythema Papules and pustules Telangiectasia May include one or more of the following secondary features: Burning or stinging Plaque Dry appearance tdema Ocular manifestations Peripheral location Phymatous changes

• unknown

• although found in all skin types, fair skin is most commonly affected (10% prevalence in Sweden) • 30-50 years old • F>M

Signs and Symptoms
• differentiated from acne by the absence of comedones typically affecting the convexities of the central face, especially forehead, nose, cheeks and chin • may also affect the scalp, neck, and the upper part of body

014 Dennatology

Acneifonn EruptionsfDennatitis (Eczema)

Toronto Notes 2008

.... . } - - - - - - - - - - - - - , ~
Subtypes end Verients of RoSlCII end Their CherlCtlriltiCi


Elythrometotl1llllliec:tlltic Flushing, persistent central facial erythema ± telangiectasia

• dome-shaped red papules with or without pustules that often occur in crops • pustulation and papulation may develop contributing to a florid and ruddy complexion • non-transient erythema is the commonest sign of rosacea • in longstanding rosacea, signs of thickening, induration, lymphedema in the skin may become apparent • phyma: a distinct swelling caused by lymphedema and hypertrophy of subcutaneous tissue, and particularly affects the nose (rhinophyma) • ocular changes are common in rosacea: conjunctivitis, keratitis, iritis

Persistent central facial erythema Transient, central facial papules or pustules or both

Exacerbating Factors
• heat, cold, wind, sun, stress, drinking hot liquids, alcohol, caffeine, spices (triggers of vasodilatation)

PhymItoUi Thickening skin, irregular surface nodularities and enlargement Nose, chin, forehead, cheeks or ears

Clinical Course
• • • • • characterized by remissions and exacerbations all forms of rosacea can progress from mild to moderate to severe unclear whether or not a given patient can change from one subtype to another initially flushing (transient erythema) with a burning sensation is common early diagnosis and prompt treatment are recommended to prevent worsening

Foreign body sensation in the eye, burning or stinging, dryness, itching, ocular photosensi· tivitv, blurred vision, telangiectasia of the sclera or other parts of the eye, or periorbital edema

• avoid topical corticosteroids • cosmetic camouflage • telangiectasia: treated by physical measures; vessels can be ablated using electrical hyfrecators, vascular lasers, and intense pulsed light therapies • phymas: treated by physical ablation or removal; paring, electrosurgery, cryotherapy, laser therapy (C0 2, Argon, Nd:YAG)

VARIANT GllnulollIItoul Noninflammatory, hard; brown, yellow, or red cutaneous papules or nodules of uniform size

Specific Rosacea Treaments
1st Line Oral tetracyclines (250-500 mg PO bid) Topical metronidazole Oral erythromycin (250-500 mg PO bid) 2nd Line Topical clindamycin Topical erythromycin 2% solution Topical benzoyl peroxide Oral metronidazole Ampicillin 3rd Line Oral retinoids Topical sulfur

Dermatitis (Eczema)
• inflammation of the skin

Signs and Symptoms
• • • • symptoms include pruritus and pain acute dermatitis: papUles, vesicles subacute dermatitis: scaling, crusting chronic dermatitis: after lots of scratching, lichenification, xerosis and fissuring


Asteatotic Dermatitis
Definition and Clinical Features
• diffuse, mild pruritic dermatitis secondary to dry skin • very common in elderly, especially in the winter (a.k.a. "winter itch") but starts in the fall

• skin rehydration with moisturizing routine • ± mild corticosteroid creams

Atopic Dermatitis (Eczema)
• subacute and chronic eczematous reaction associated with Type I (IgE-mediated) hypersensitivity reaction (release of histamine) and Th2 cellular response producing prolonged severe pruritus

Toronto Notes 2008

Dermatitis (Eczema)

Dermatology 015

Etiology • associated with personal or family history of atopy (asthma, hay fever, anaphylaxis, eosinophilia) • polygenic inheritance: one parent >60% chance for child; two parents >80% chance for child • frequently affects infants, children, and young adults • females only slightly more at risk than males (1.3:1 over the age of 2 years) • almost 15% of children in developed countries under the age of 5 are affected; half of these cases are diagnosed by 1 year of age • half of all patients with AD are over 18 years of age • the earlier the onset, the more severe and persistent the disease • long-term condition with 1/3 of patients continuing to show signs of AD into adulthood • childhood onset and inheritable forms are associated with a defect in the protein filaggrin Signs and Symptoms • inflammation, lichenification, excoriations are secondary to relentless scratching • atopic palms: prominent palmar creases • associated with • keratosis pilaris (hyperkeratosis of hair follicles, "chicken skin") • xerosis • occupational hand dryness • patients usually suffer from three flares per year Distribution • infant (onset at 2-6 months old): face, scalp, extensor surfaces • childhood (>18 months): flexural surfaces • adult: hands, feet, flexures, neck, eyelids, forehead, face, wrists Investigations • no prerequisite investigations to diagnose atopic dermatitis • may consider: skin biopsy, immunoglobulin serum levels (often elevated serum IgE level), patch testing, and skin prick tests to look for contact or environmental allergies Treatment • majority of cases are mild and easily managed • goal: reduce signs and symptoms, prevent or reduce recurrences, and provide longterm management to prevent progression from early disease to full AD flare • treatment maximized (i.e. less flare-ups, modified course of disease) if diagnosis made early and treatment plan individualized • individualized based on age, severity, sites and extent of involvement, presence of infection, previous responses to therapy • reassure patients that although there is no complete cure, the disease can be controlled • avoid triggers of AD: irritants (detergents and solvents, certain clothing, water hardness), inappropriate bathing habits (long hot showers), microbes (5. aureus), stress, sweating, contact allergens, and environmental aeroallergens (dust mites) • enhance barrier function of the skin • simplest and most important aspect of controlling AD • involves regular application of moisturizers +/- diluted corticosteroid wetwrap dressings • emollients hydrate the skin and reduce itching • twice daily application is recommended even in absence of symptoms, especially after bathing or swimming • bathing promotes hydration when followed by the application of moisturizers to the skin • consider psychological support for some patients

D16 Dermatology

Dermatitis (Eczema)

Toronto Notes 2008

1 Initial assessment of disease history, extent and severity (Impact on family, psychological distress)

Adjunctive therapy "Avoidance of triggers "Treat bacterial superinfections (topical or oral antibiotics) " Antihistamines "Psychological interventions

Patient education, dally emollient use


Acute control of flare "Topical corticosteroids or topical calcineurin inhibitor (pimecrolimus or tacrolimus)

Maintenance therapy If disease is persistent and/or frequent recurrences "Use topical corticosteroid or calcineurin inhibitor at earliest sign of flare "Long-term maintenance use of calcineurin inhibitors

~ .,

Disease remission (no signs or symptoms)

Severe refractory disease
-Azathioprine -Methotrexate ·Oral cyclosporin ·Oral steroids

·Potent topical steroids -Psychotherapeutics

Figure 2. Atopic dermatitis treatment algorithm
Adapted from: Ellis C, et al. ICCAD II Faculty. International Consensus Conference on Atopic Dermatitis II (ICCAD III: clinical update and current treatment strategies. Br J Dermato/. 2003; 148ISuppl 63):3·10.

• anti-inflammatory therapies a) topical corticosteroids: • effective, rapid symptomatic relief for acute flares • different formulations and potencies suitable for nearly any area of skin • best applied immediately after bathing • control inflammation with a potent topical steroid; prescribe a milder one following resolution of acute flare • systemic immunosuppression may be needed in severe cases • flares may respond to systemic anti-staphylococcal therapy • side effects: • skin atrophy, purpura, striae, steroid acne, perioral dermatitis, and glaucoma when used around the eyes b) topical immunomodulators: • long-term management • calcineurin inhibitors such as pimecrolimus (ElideFM) and tacrolimus (Protopic™) • block calcineurin and inhibit inflammatory cytokine transcription in activated T-cells and other inflammatory cells • significant adverse events may include skin burning and transient irritation • provide good long-term management of AD with advantages over long-term corticosteroids • rapid, sustained effect in controlling pruritus • produce no skin atrophy • safe for the face and neck • no significant systemic toxicities associated with their use

Prognosis • 50% clear by age 13, few persist >30 years of age Complications • infections are common: diagnose early and treat appropriately (Le. antibiotic, antifungal, antiviral therapy); infections must be resolved before applying anti-inflammatory treatments • topical mupirocin or fusidic acid is often sufficient • oral antibiotics (i.e. cloxacillin, cephalexin) for widespread S. aureus infections

Toronto Notes 2008

Dermatitis (Eczema)

Dermatology 017

Contact Dermatitis
• cutaneous inflammation from the interaction between external agent(s) and the skin
Table 7. Contact Dermatitis
Irritant Contact Dermatitis Mechanism of reaction toxic injury to skin; non-immune mechanism acute: quick reaction, sharp margins (e.g. from acidl alkali exposure! cumulative insult: slow to appear, poorly defined margins le.g. from soap! majority; will occur in anyone given sufficient concentration of irritants palmar surface of hand usually involved minority; patient acquires susceptibility to allergen that persists indefinately dorsum of hand usually involved; often discrete area of skin involvement many allergens are irritants, so may coincide with irritant dermatitis Allergic Contact Dennatitis cell-mediated delayed (Type IV) hypersensitivity reaction



NickelSullal! NeomytilSulfate BaisamolPeru fragraocenix



TapT.. AIIIgena _Identified byThe North American Contaclllennllilia GnJup Tilt Substance Allergic
I8IClianI (%I 141 foond in some jewelJy, buckles
most comon~ usad top~alantibiotic

Type of reaction

lU 11.7

hagrancematerial anix 01 eight dilferent fragranceCOl1ljlO!lenls which was dmIoped toalWwfor allergen testing it cosmetics aCOl1ll1Ollpreservative that ~ used it vaccines, contact lens solution, cosmetics used in jewellery, dentist1y,thiosulfate

Frequency of contact dermatitis

Area of involvement




soaps, weak alkali, detergents, organic solvents, alcohol, oils Avoidance of irritants Compresses Barrier moisturizers Topical! oral steroids

Sodilm gold



Patch testing to determine specific allergen Avoid allergen and its cross-reactants Wet compresses soaked in Burow's solution (drying agent) Steroid cream (hydrocortisone 1%, betamethasone valerate 0.05% or 0.1% cream; bid) Systemic steroids prn (prednisone 1mgJ1<g, taper over 2weeks!



acolourless gas foond in many woripIaces, cosmetics,

resins,plasUcbollles OuatemilllH5

acomponent in many shampoos,moislIKizers, comflliooersandsoaps ahard metalfOllndin cosmetics,jeweliely, butlllns,tooIs atopical antibiotic

Dyshidrotic Dermatitis
• "tapioca pudding" papulovesicular dermatitis of hands and feet, followed by painful crackling/fissuring





• NOT caused by hyperhidrOSiS (excessive sweating) • emotional stress may precipitate the dermatitis

Signs and Symptoms
• • • • • acute vesicular lesions that coalesce into plaques, which dry and develop scaling acute stage often very itchy secondary infection common lesions heal with desquamation and may lead to chronic lichenification sites: palms and soles ± dorsal surfaces of hands and feet

• topical • high potency corticosteroid with saran wrap occlusion to increase penetration • intralesional triamcinolone • systemic • prednisone in severe cases • antibiotics for secondary S. aureus infection

Nummular Dermatitis
Definition and Clinical Features
• • • •

_ _ _ _ _~




annular, coin-shaped, pruritic, erythematous plaques dry, scaly, lichenified often associated with atopy and dyshidrotic dermatitis secondary bacterial infection common

• moisturization • potent corticosteroid ointment e.g. Cyclocort™ ointment bid

018 Dermatology

Dermatitis (Eczema)/Papulosquamous Diseases)

Toronto Notes 2008


Lichen Simplex Chronicus
Definition and Clinical Features
• chronic dermatitis resulting from continued rubbing/scratching of skin • may develop secondarily to another pruritic skin disease • lichenified (thickened) skin

• treat pruritus to break the itch-scratch cycle • antihistamines, topical antipruritics • topical corticosteroids (extremely potent)


Seborrheic Dermatitis
• greasy, erythematous, yellow, non-pruritic scaling papules and plaques; occurs in areas rich in sebaceous glands

• possible etiologic association with the yeast Pityrosporum ovale

• common in infants and at puberty • increased incidence in immunocompromised patients e.g. HIV • in adults, can cause dandruff (pityriasis sicca)

Signs and Symptoms
• infants - one possible cause of "cradle cap" • children - may be generalized with flexural and scalp involvement • adults - scalp: diffuse in areas of scalp margin with yellow to white flakes, pruritus, and underlying erythema • sites: scalp, eyebrows, eyelashes, beard, face, trunk, body folds, genitalia • face: eyebrows, sides of nose, posterior ears, glabella • chest: over sternum

• face: NizoraJTM cream OD + mild steroid cream OD or bid • scalp: salicylic acid in olive oil or Derma-Smoothe FSTM lotion (peanut oil, mineral oil, fluocinolone acetonide 0.01%) to remove dense scales, 2% ketoconazole shampoo (NizoraI™), ciclopirox (Stieprox™) shampoo, selenium sulfide (e.g. Selsun™) or zinc pyrithione (e.g. Head and Shoulders™) shampoo, steroid lotion (e.g. betamethasone valerate 0.1% lotion bid)


Stasis Dermatitis
Definition and Clinical Features
• persistent skin inflammation of the lower legs with brown pigmentation, erythema, xerosis, and scaling • associated with venous insufficienLy

• • • • support stockings rest and elevate legs moisturizer to treat xerosis mild topical corticosteroids to control inflammation

• ulceration (common in medial malleolus), secondary bacterial infections

Papulosquamous Diseases

Lichen Planus
• acute or chronic inflammation of mucous membranes or skin characterized by violaceous papules, especially on flexural surfaces

Toronto Notes 2008

Papulosquamous Diseases

Dermatology DI9

• association with hepatitis C • may be triggered by severe emotional stress

Signs and Symptoms
• small, polygonal, flat-topped, shiny, violet papules; resolves with hyperpigmented macules • Wickham's striae: greyish lines over surface; pathognomonic • sites: wrists, ankles, mucous membranes in 60% (mouth, vulva, glans), nails, scalp • mucous membrane lesions: lacy, whitish reticular network, milky-white plaques/papules; increased risk of SCC in erosions and ulcers • nails: longitudinal ridging; dystrophic • scalp: scarring alopecia • spontaneously resolves in weeks or lasts for years (mouth and shin lesions) • Koebner phenomenon: develops in areas of trauma


The 6 POI of Lichen Planul
Purple, Pruritic, Polygonal, Peripheral, Papules, Penis

• • • • topical corticosteroids with occlusion or intradermal steroid injections short courses of oral prednisone (rarely) photochemotherapy for generalized or resistant cases oral retinoids for erosive lichen planus in mouth

Pityriasis Hosea
Definition and Clinical Features
• acute, self-limiting, erythematous eruption characterized by red, oval plaques/patches with central scales that do not extend to edge of lesion • sites: trunk, proximal aspects of arms and legs • long axis of lesions follows parallel to ribs producing "Christmas tree" pattern on back • varied degree of pruritus • most start with a "herald" patch which precedes other lesions by 1-2 weeks


• human herpes virus 7 (at least in some cases)

• no treatment needed; clears spontaneously in 6-12 weeks • topical corticosteroids when post-inflammatory pigmentation is a concern

• • • • • plaque psoriasis guttate psoriasis erythrodermic psoriasis pustular psoriasis psoriatic arthritis


PSORIASIS: Pathophysiology
Pink papuleSJ1llaqueSJ1linpoint bleeding IAuspitz sign)/Physical injury (Koebner phenomenonl Silver scalelSharp margins OnycholysislOil spots Rete Ridges with Regular elongation Itching Arthritis/Abscess (Monro)/Autoimmune Stratum corneum with nuclei Immunologic Stratum granulosum absent

Differential Diagnosis
• atopic dermatitis, mycosis fungoides (cutaneous T-cell lymphoma), seborrheic dermatitis, tinea

• a common chronic and recurrent disease characterized by well-circumscribed erythematous papules/plaques with silvery-white scales, mostly at sites of repeated trauma

• decreased epidermal transit time from basal to horny layers • shortened cell cycle of psoriatic and normal skin ---> excess keratinization with scales


,,l - - - - - - - - - - - , ,

• multifactorial inheritance

Woronoff's Ring Woronoff's ring: blanched halo that surrounds psoriatic lesions after topical or phototherapy treatments.

020 Oennatology

Papulosquamous Diseases

Toronto Notes 2008

",' ,


P80riuis Treatment Approach
1st line Topical corticosteroids (moderate to very potent) Topical Vitamin Danalogues Topical Retinoid CoalTarTherapy Anthralin (dithranoll Topical Salicylic Acid

Signs and Symptoms • worse in winter (lack of sun and humidity) • Koebner phenomenon (isomorphic response): induction of new lesion by in)ury • Auspitz' sign: bleeds from minute points when scale is removed • sites: scalp, extensor surfaces of elbows and knees, trunk, nails, pressure areas • usually non-pruritic • exacerbating factors: drugs (lithium, ethanol, chloroquine, ~-blockers), sunlight, stress, obesity Treatment • preventative measures: avoid sunburns, avoid drugs that exacerbate the condition (~-blockers, lithium, curticosteroid rebound phenomenon, interferon, etc.) • first-line treatment mainly involves topical treatments, usually prescribed if less than 5-10% of the budy surfaces are involved. If the affected area is >10%, use topical medications as adjuncts to phototherapy or systemic drugs • systemic treatments should be considered if: • psoriatic lesions cover> 10% of the body surface area • unsuccessful topical therapies • disease is causing psychological distress
Table 8. TopicalTreatment of Psoriasis

2nd line Phototherapy PUVA, UVB, Narrowband UVB Cyclosporin Methotrexate Acitretin

3rd line
Biological therapies (alefacept, etanercept, infliximab, etc.)

Reduce fissure formation Remove scales Inhibits DNA synthesis, increases cell turnover Binds to skin 1,25-dihydroxyvitamin D3 to inhibit keratinocyte proliferation Reduce scaling and thickness Retinoid derivative UVB 290-320 nm or 311 nm Narrow Band UVB INBUVCI

Petrolatum is effective


,)------------, alcipotriol is avitamin Dderivative. Dovobet™ = calcipotriene combined with betamethasone dipro-portionate and is considered to be the most potent topical psoriatic therapy.


salicylic acid 1-12% tar ILCD: Liquor carbonis detergensl 20% coal tar solution calcipotriene (Dovonex '. , Dovobet".: I

Poor long term compliance

Not to be used on face or skin folds

corticosteroid ointment

Use appropriate potency steroid in different areas for degree of psoriasis Use on nails Use with topicals

tazarotene ITazarac™llgellcreaml UVB


')---:::PUV-:-::-A-=-P1o=--ra-1 c-'ns--:::lp::"'-----,
and long-wlVll UV radiation IUVAI

Table 9. SystemicTreatment of Psoriasis
methotrexate psoralens and long wave ultraviolet radiation (PUVA) acitretin cyclosporine "Narrow band" UVB 1311-312 nm)

Adverse Effects
Bone marrow toxicity, hepatic cirrhosis Pruritus, burning, cataracts, skin cancer Alopecia, cheilitis, teratogenicity, epistaxis, xerosis, hypertriglyeridemia Renal toxicity, hypertension, immunosuppression Well tolerated

Psora len photochemotherapy is used for treatment of psoriasis as well as anumber of other dermatologic disorders. Psoralens, which are linear furocoumarins found in plants and made synthetically, are applied topically via solutionslcreamslbaths or given orally followed by UVA exposure at awavelength of 350-360 nm. The therapeutic effect of PUVA in psoriasis is due to the conjunction of psoralens with epidermal DNA which inhibits DNA replication and causes cell cycle arrest.

Table 10. "Biologicals" approved in Canada
Treatment Route Dosing Schedule
weekly weekly twice weekly initially once every 2weeks -every 2months



",', ,
Case reports indicate that patients inadequately controlled or intolerant to etanercept may benefit from switching to efalizumab.

alefaceptlAmevive™) efalizumab IRaptiva™) etanercept IEnbreI™)' adalimumab IHumira™J'


++1/2 +++


infliximab IRemicade™I' IV 'Can also be used to treat Psoriatic Arthritis


Toronto Notes 2008

Papulosquamous DiseasesNesiculobuilous Diseases

Dermatology 021

Definition and Clinical Features
• discrete, scattered salmon-pink scaling papules • sites: generalized, sparing palms and soles • often antecedent streptococcal pharyngitis

• UVB phototherapy, sunlight, lubricants • penicillin V or erythromycin if Group A
~-hemolytic Strt>ptococcus

on throat culture

Definition and Clinical Features
• • • • generalized erythema with fine desquamative scale on surface associated symptoms: arthralgia, severe pruritus may present in patient with previous mild plaque psoriasis aggravating factors: lithium, ~-blockers, NSAIDs, antimalarials, phototoxic reaction, infection

• hospitalization, bedrest, IV fluids, sun avoidance, monitor fluid and electrolytes • treat underlying aggravating condition • methotrexate, PUVA, retinoids

Definition and Clinical Features
• sudden onset of erythematous macules and papules which evolve rapidly into pustules, very painful • can be generalized or localized to palms/soles • patient usually has history of psoriasis; may occur with sudden withdrawal from steroid therapy

• as above

• 5 categories • asymmetric oligoarthropathy • distal interphalangeal (DIP) joint involvement (predominant) • rheumatoid pattern - symmetric polyarthropathy • psoriatic arthritis mutilans (most severe form) • predominant spondylitis or sacroiliitis

Vesiculobullous Diseases
Bullous Pemphigoid
• chronic autoimmune bullous eruption characterized by pruritic, tense, subepidermal bullae on an erythematous or normal skin base

~---~--~~~--~---Pemphigul Vulgaris vs. Bullous Pemphigoid. 5 =Superficial at the junction

• IgG produced against dermal-epidermal basement membrane leads to subepidermal bullae

o =Deeper

• 60-80 years old • associated with malignancy (rarely)

D22 Dermatology

Vesiculobullous Diseases

Toronto Notes 2008

Signs and Symptoms
• sites: flexor aspect of foreanns, axillae, medial thighs, groin, abdomen, mouth (33%)

• immunofluorescence shows deposition of IgG and C3 at basement membrane • anti-basement membrane antibody (IgG) (pemphigoid antibody detectable in serum)

• generalized bullous eruption heals without scarring • can be fatal

• • • • prednisone ± steroid-sparing agents (e.g. azathioprine) topical potent steroids (clobetasol) may be as effective as systemic steroids tetracycline ± nicotinamide is effective for some cases dapsone for milder cases

Pemphigus Vulgaris



• autoimmune blistering disease characterized by flaccid, non-pruritic epidennal bullae/vesicles on an erythematous or nonnal skin base


',, - - - - - - - - - - - , }

• IgG produced against epidennal desmoglein 3 leads to intraepidennal bullae

Pemphigu8 Foliaceu8 An autoimmune intraepidermal blistering disease that is more superficial than pemphigus vulgaris due to antibodies against desmoglein 1, an intracellular adhesion molecule. Appears as crusted patches and erosions which can initially be managed with topical steroids if localized. Active widespread disease is treated like pemphigus vulgaris.

• 40-60 years old, patients are often Jewish, Mediterranean, Asian • associated with thymoma, myasthenia gravis, malignancy, and use of D-penicillamine

Signs and Symptoms
• • • • may present with erosions and secondary bacterial infection sites: mouth (90%), scalp, face, chest, axillae, groin, umbilicus Nikolsky's sign: sliding or rubbing pressure on skin -> separation of epidennis Asboe-Hanson sign: pressure applied to bulla extends bulla laterally

• immunofluorescence: shows IgG and C3 deposition intraepidermally • circulating serum anti-desmoglein IgG antibodies

Prognosis and Clinical Course
• • • • initially mouth lesions, followed by skin lesions first localized (6-12 months) then generalized lesions heal with hyperpigmentation but no scar may be fatal unless treated with immunosuppressive agents

• prednisone 2.0-3.0 mglkg until no new blisters, then 1.0-1.5 mglkg until clear, then taper • steroid-sparing agents - azathioprine, methotrexate, gold, cyclophosphamide, cyclosporine, intravenous immunoglobulin (MG), mycophenolate mofetil • plasmapheresis for acutely high antibody levels


Dermatitis Herpetiformis
• intensely pruritic grouped papules/vesicles/urticarial wheals on an erythematous base • almost always excoriated, rarely seen as blisters

• 90% have HLA 88, DR3, DQWZ • 90% associated with gluten-sensitive enteropathy (celiac) (80% are asymptomatic) • 30% have thyroid disease; some have intestinal lymphoma or iron/folate deficiency

Toronto Notes 2008

Vesiculobullous Diseases

Dennatology D23

• 20-60 years old, M:F =2:1

Signs and Symptoms
• sites: extensor surfaces of elbowslknees, sacrum, buttocks, scalp • lesions grouped, bilaterally symmetrical • pruritus, burning, stinging

• dapsone for pruritus • gluten-free diet

Table 11. Summary of Vesiculobullous Diseases
Pemphigus Vulgaris Antibody Site Infiltrate Treatment Association
IgG Intercellular space

Bullous Pemphigoid
IgG Basement membrane

Dennatitis Herpetiformis
IgA Dermal Neutrophils Gluten-free diet/dapsone Gluten enteropathy Thyroid disease Intestinal lymphoma

Eosinophils and neutrophils Eosinophils High dose steroids cyclophosphamide Moderate dose steroids cyclophosphamide

Thymoma, myasthenia Malignancy (rarely) gravis, malignancy (paraneoplastic pemphigus)

h ria Cutanea Tarda
• autosomal dominant or sporadic skin disorder associated with the presence of excess heme, characterized by tense vesicleslbullae in photoexposed areas subjected to trauma

• associated with alcohol abuse, DM, drugs (estrogen therapy, NSAID), HN, hepatitis C, increased iron indices

• 30-40 years old, M>F

Signs and Symptoms
• facial hypertrichosis, brown hypermelanosis vesicles, and bullae in photodistribution (dorsum of hands and feet) • sites: light-exposed areas subjected to trauma, dorsum of hands and feet, nose, and upper trunk

• • • • urine + 5% HCl shows orange-red fluorescence under Wood's lamp (UV rays) 24-hour urine for uroporphyrins (elevated) stool contains elevated coproporphyrins immunofluorescence shows IgE at dermal-epidermal junctions

• discontinue aggravating substances (alcohol, estrogen therapy) • phlebotomy to decrease body iron load • low dose hydroxychloroquine if phlebomy contraindicated

D24 Dermatology

Drug Eruptions

Toronto Notes 2008

Drug Eruptions
Erythema Multiforme (EM), Stevens-Johnson Syndrome (SJS),Toxic Epidermal Necrolysis (TEN)
• disorders with varying presence of characteristic skin lesions, blistering and mucous membrane involvement • note that EM is considered to be distinct from SJS and TEN (no longer considered part of a spectrum)


,, ,)------------,
Erythema multiforme is aclinical diag· nosis. Resonable evidence exists for the follo.wing as precipitating factors: • HSV (Predominant precipitating factorl • Histoplasma capsulatum • Ort virus

Table 12. Comparison of Erythema Multiforme, Stevens.Johnson Syndrome,Toxic Epidermal Necrolysis
Erythema Multiforme (EM)
Lesion • macules/papules with central vesicles • classic bull's-eye pattern of concentric light and dark rings Itargetlesionsl • bilateral and symmetric • all lesions 'pp€,r within 72 hours • "oedema • lesion "fixed" for at leasr 7dilYs • dorsa of hands onn forearms • mucous membrane involvement llips, tongue. buccal mucosal • extremities with face> trunk • involvement of palms and soles • burning and stinging • recurrences • secondary bacterial infection

Stevens-Johnson Syndrome (SJS) Toxic Epidennal Necrolysis (TEN)
• EM with more mucous membrane • severe mucous membrane involvement involvement. and ~istering •"Atypical lesions' -red circular • •atypical lesions" - 50% have no patm with dark purple center target lesions •"sicker" Ihigh fever) • diffuse el'{thema then necrosis and • sheet·like epidermal detamment in <10% sheet·like epidermal detatllment in




• generalized vnth prominent face and trunk involvement • palms and soles may be spared

• generalized • nails may also shed

Other Complications

• scarring. contractu res, eruptive • tubular necrosis and acute renal nevornelanocytic nevi, corneal failure, epithelial erosions of scarring. blindness. phimosis and vaginal tramea synemiae • prodrome 1-14 days prior to eruption with fever and flu·like illness • high fever >38"C

Constitutional symptoms

• weakness. malaise


• mfection - HSV, or Hisrop/asma

• 50% are drug·related INSAJDs,


• 80% are definitely drug related anticonvulsants, sulfonamides, penicillinsl • <5% are due to viral infection. • occurs up to 1-3 weeks after drug immunization exposure with more rapid onset upon rechallenge

Differential diagnosis

• gianturticaria,granulorna annulare, mycosIs fungoides. vasculitis

• scarlet fever. phototoxic. eruption, GVHD. SSSS. exfoliative derrnatitis. Kawasaki disease, paraneoplastic pemphigus

• scarlet fever, phototoxic eruption. GVHD, SSSS. exfoliative dermatitis

Course and Prognosis

• lesion; last 2weeks "lid heal without complicatiuns

• 4-6 week course

• 3Q% mortality due to fluid loss.
regrowth of epidermis by 3weeks, secondary infection • as for Stevens-Johnson syndrome • admitto burn unn • debride frankly necrotic tissue • consider IVIG

• 5% mortality


• symptomatic ire,tment loral antihistamines, oral antacidsl • corticosteroids in severely ill Icontroversiall • prophylactic oral acyclovir for 6-12 months for herp€s simplex virus IHSVI·associated EM with frequent recurrences

• prolonged hospitalization • withdraw susp€ct drug • intravenous fluids • corticosteroids - controversial • infection prophylaxis • considerlVIG GVHD =Graft Versus Host Disease

SSSS = Staphylococcal Scalded Skin Syndrome

Drug Hypersensitivity Syndrome
• initial fever, followed by symmetrical bright red exanthematous eruption that may lead to internal organ involvement (hepatitis, arthralgia, nephritis, pneumonitis, lymphadenopathy, and/or hematologic abnormalities) • classically the patient dpvelops the syndrome 10 days after first exposure to the drug • siblings at risk • sulfonamides and anticonvulsants (phenytoin, phenobarbital, carbamazepine, lamotrigine) most common • 10% mortality if undiagnosed and untreated

Toronto Notes 2008

Drug Eruptions

Dermatology D25

Exanthematous Eruptions (Maculopapular EruptionsJMorbilliform) - - _ . ---'• • • • • symmetrical, widespread, erythematous patches or plaques with or without scales the "classic" and most common adverse drug reaction often starts on trunk or on areas of sun exposure may progress to generalized exfoliative dermatitis especially if the drug is continued associated with penicillin, sulfonamides, phenytoin (in order of decreasing probability)


Fixed Drug Eruption
• sharply demarcated erythematous oval patches on the skin or mucous membranes • sites: face, mucosa, genitalia • with each exposure to the drug, the patient develops erythema at the same location as before (fixed location) • antimicrobials (tetracycline, sulfonamides), anti-inflammatories, psychoactive agents (barbiturates), phenolphthalein are most common causes


• phototoxic reaction: "an exaggerated sunburn" confined to sun-exposed areas • photoallergic reaction: an eczematous eruption that may spread to areas not exposed to light • chlorpromazine, doxycycline, thiazide diuretics, procainamide


Serum Sickness-Like Reaction ----~• a symmetric drug eruption resulting in fever, arthralgia, lymphadenopathy, and skin rash • usually appears 5-10 days after drug • skin manifestations: usually urticaria; can be morbilliform • cefaclor most common in kids; buproprion (Zyban™) in adults



• deeper swelling of the skin involving subcutaneous tissues often with swelling of the eyes, lips, and tongue • mayor may not accompany urticaria • can have hereditary or acquired forms; acquired form occurs with urticaria • hereditary angioedema - does not occur with urticaria • onset in childhood; 80% have positive family history • recurrent attacks; 25% die from laryngeal edema • triggers: minor trauma, emotional upset,. temperature changes • treatment: prophylaxis with danazol or stanozolol • epinephrine pen to temporize until patient reaches hospital in acute attack




• • •

typically erythematous flat-topped, palpable lesions varying in size with circumscribed dermal edema associated with mast cell release of histamine may be pruritic individual lesion lasts <24 hrs

(also known as "Hives"; see Table 13 for classification) • transient, red, pruritic well-demarcated wheals • second most common type of drug reaction, though can be due to many other things • due to release of histamine from mast cells in dermis • each lesion lasts less than 24 hours, though condition may be chronic • can also result after physical contact with allergen

.... . } - - - - - - - - - - - - - ,
The name urticaria dates back to the 18th century where contact with nettles (Urtica dioica) was believed to cause swelling and burning of skin.


026 Dennatology

Drug Eruptions/Infections

Toronto Notes 2008

Table 13. Classification of Urticaria
Type Acute Urticaria >2/3 of cases Attacks lasts <6 weeks Individual lesion <24 hrs Approach to Diagnosis Drugs especially aspirin, NSAIDs Foods nuts, shellfish, eggs, fruit Idiopathic Infection Insect stings Percutanous absorption cosmetics, work exposures Stress Systemic diseases systemic lupus erythematosis (SLE), endocrinopathy, neoplasm IgE-dependent: trigger associated Idiopathic (90% of chronic urticaria patients) Drugs (antibiotics, hormones, local anesthetics) Physical contact (animal saliva, plant resins, latex, metals, lotions, soapl Insect stings Ibees, wasps, hornets) Aeroallergens Foods and additives Parasitic infections Direct mast cell release Opiates, muscle relaxants, radio-contrast agents Complement-mediated Serum sickness, transfusion reactions Infections, viral/bacterial (>80% of urticaria in pediatric patients) Urticarial vasculitis Arachidonic acid metabolism ASA, NSAIDs Physical Dermatographism (friction, rubbing skin), cold lice cube, cold water), cholinergic (hot shower, exercisel, solar, pressure (shoulder strap, buttocks), aquagenic (exposure to water), adrenergic (stress), heat Other Mastocytosis, urticaria pigmentosa Idiopathic Infections Hepatitis Autoimmune diseases SLE Drug hypersensitivity cimetidine and diltiazem

..... , ) - - - - - - - - - - - - - ,


Mastocytosis (Urticaria Pigmentosa)
Rare disease due to excessive infiltration of the skin by mast cells. It manifests as many reddish·brown elevated plaques and macules. Applying pressure to a lesion pro· duces a wheal surrounded by intense erythema termed Darier's sign, due to mast cell degranulation. This occurs within minutes.

Chronic Urticaria <1/3 of cases Attacks last >6 weeks Individual lesion lasts <24 hrs

Vasculitic Urticaria Lesions last >24 hrs Painful, non-pruritic Requires biopsy

Bacterial Infections


• often involve the epidermis, dermis, hair follicles or periungual region • may also be systemic

Toronto Notes 2008


Dennatology D27

Superficial Skin (Epidermal)
Table 14. Comparison of Impetigo Vulgaris and Bullous Impetigo
Impetigo Vulgaris Definition and Clinical Features
• acute purulent infection which appears vesicular and progresses to golden yellow "honey-crusted" lesions surrounded by erythema • sites: commonly involves the face, arms, legs and buttocks • agent: Group A ~ hemolytic Streptococcus (GAS). S. aureus, or both • preschool and young adults living in crowded conditions, poor hygiene, neglected minor trauma

0-,. ~ ~

Bullous Impetigo
• scattered, thin-walled bullae containing clear yellow or slightly turbid fluid with no surrounding erythema • sites: trunk, intertriginous areas, face


• S. aureus group II elaborating exfoliating toxin


• neonates and older children, can be epidemic

Differential Diagnosis' infected eczema, HSV, varicella virus Investigations
• Gram stain and culture of blister fluid or biopsy • remove crusts, use saline compresses and topical antiseptic soaks bid • topical antibacterials such as 2% mupirocin or fusidic acid tid, continued for 7-10 days after resolution • systemic antibiotics such as cloxacillin or cephalexin for 7-10 days

• bullous drug eruption, pemphigus vulgaris, bullous insect bites, thermal burns • Gram stain and culture of blister fluid or biopsy


• cloxacillin for 7-10 days • topical antibacterials such as fusidic acid or mupirocin, continued for 7-10 days after oral antibiotic is stopped • complication: high levels of toxin in immunocompromised or young children may lead to generalized skin peeling or SSSS

Deeper Skin (Dermal)
Table 15. Comparison of Erysipelas and Cellulitis
Erysipelas Lesion •upper dermis •may be confluent, erythematous, raised, warm plaque •very painfullonce called 51. Anthony's firel •face and legs •GAS Cellulitis •lower dermis/subcutaneous fat •unilateral erythematous flat lesion, often with vesicles poorly demarcated, not uniform~ raised •tender •commonly legs •GAS, S. aureus (large sized wounds!, H. influenzae Iperiorbitall, Pasteurella muftocida (dog/cat bitel •fever, leukocytosis, lymphadenopathy (less commonl •less likely


Distribution Etiology

Systemic Symptoms Complications

•fever, chills, headache, weakness (more serious) •scarlet fever, streptococcal gangrene, fat necrosis, coagulopathy •spreads through lymphatics •first line: penicillin, cloxacillin or cefazolin •second line: c1indamycin or cephalexin •if allergic to penicillin use erythromycin


•first line: cloxacillin or cefazolinlcephalexin •second line: erythromycin or clindamycin •children: cefuroxime •diabetes mellitus (OMI(foot infections): trimethoprim· sulfamethoxazole ITMPISMX) and metronidazole

• clinical diagnosis therefore rarely do skin/blood culture. • if suspect necrotizing fasciitis, do immediate biopsy and frozen section histopathology. • differential diagnosis: deep vein thrombosis [OVT) (less red, less hot, smootherl, superficial phlebitis, contact dermatitis, photosensivity reaction, stasis dermatitis, panniculitis, vasculitis

D28 Dermatology


Toronto Notes 2008

Common Hair Follicle Infections
Table 16. Comparison of Superficial Folliculitis, Furuncles and Carbuncles
Superficial Folliculitis Definition • superficial infection of the Furuncles (Boils) Carbuncles

hair follicle • pseudofolliculitis: inflammation of follicle due to friction, irritation, or occlusion

• red, hot, tender, inflammatory nodules involving subcutaneous tissue that arises from a hair follicle • sites: hair-bearing skin (thigh, neck, face, axillae, perineum, buttocks)

• deep-seated abscess formed by multiple coalescing furuncles • lesions drain through multiple points to the surface


• normal non-pathogenic bacteria (Staphylococcusmost common; Pseudomonas - hot tubl • Pityrosporum • acute lesion consists of a dome-shaped pustule at the mouth of hair follicle • pustule ruptures to form a small crust • sites: primarily scalp, shoulders, anterior chest, upper back, other hairbearing areas • antiseptic (Hibitane) • topical antibacterial (fusidic acid, mupirocin, or erythromycin) • oral cloxacillin for 7-10 days

• S. aureus

• S. aureus

Signs and Symptoms

• develops as a red, tender nodule with central yellowish point, which forms over summit and ruptures


• incise and drain large • Same as for furuncles carbuncles to relieve pressure and pain • if afebri Ie: hot wet packs, topical antibiotic • if febrile/cellulitis: culture blood and aspirate pustules (Gram stain and C&S) • cloxacillin for 1-2 weeks (especially for lesions near external auditory canal/ nose, with surrounding cellulitis, and not responsive to topical therapy)


sexually Transmitted Infections
SYPHILIS Definition and Clinical Features
• sexually transmitted infection caused by Treponema pallidum characterized initially by a painless ulcer (chancre) • transmitted sexually, congenitally, or rarely, by transfusion • following inoculation, becomes a systemic infection with secondary and tertiary stages

Toronto Notes 2008


Dermatology D29

Table 17. Stages of Syphilis
Primary Syphilis Clinical Features
• single red, indurated, PAINLESS chancre, that develops into painless ulcer with raised border and scanty serous exudate • chancre develops at site of inoculation after 3 weeks of incubation and heals in 4-6 weeks; chancres may also develop on lips or anus • regional non-tender lymphadenopathy appears <1 week after onset of chancre • DDx: chancroid painful HSV - multiple lesions

Secondary Syphilis

Tertiary Syphilis

• 2-6 months after primary • extremely rare infection (patient may not • 3-7 years after secondary recall presence of primary • main skin lesion: chancre) 'Gumma' - a granulomatous • associated with generalized non-tender nodule lymphadenopathy, splenomegaly, headache, chills, fever, arthralgias, myalgias, malaise, photophobia • lesions heal in 1-5 weeks and may recur for 1year • three types of lesions: 1) macules and papules, flat top, scaling, non-pruritic, sharply defined, circular/annular rash DDx: pityriasis rosea, tinea corporis, drug eruptions, lichen planus 2) condyloma lata: wart-like moist papules around genital/perianal region 31 mucous patches: macerated patches mainly found in oral mucosa

Investigations • cannot be based on • VDRL positive and Diagnosis clinical presentation alone • FTA-ABS +ve; -ve after 1 year • VDRL negative - repeat weekly following appearance of chancre for 1 month • darkfield +ve in all • fluorescent treponemal secondary syphilis except antibody-absorption (FTA-ABSI macular exanthem test has greater sensitivity and may detect disease earlier in course • darkfield examination spirochete in chancre fluid or lymph node aspirate Treatment
• penicillin G, 2.4 million units 1M, single dose • as for primary syphilis • treatment: penicillin G, 2.4 million units 1M weekly

• disseminated gonococcal infection

Etiology • Neisseria gonorrheae Signs and Symptoms
• • • • hemorrhagic, tender, pustules on a purpuric/petechial background sites: distal aspects of extremities associated with fever, arthritis, urethritis, proctitis, pharyngitis and tenosynovitis conjunctivitis if infected via birth canal

• notify Public Health authorities and screen for other sexually transmitted infections (STIs) • cefixime 400 mg PO (drug of choice) or ceftriaxone 125 mg 1M




• infection of skin, hair and nails caused by dermatophytes (fungi that live within the epidermal keratin and do not penetrate deeper structures)

Etiology and Pathophysiology • Trichophyton, Microsporum, Epidermophyton species (Pityrosporum is a superficial yeast)
• digestion of keratin by dermatophytes results in scaly skin, broken hairs, crumbling nails

• skin scrapings, hair, and nail clippings analyzed with potassium hydroxide (KOH) prep --+ look for hyphae and mycelia

D30 Dermatology


Toronto Notes 2008

• topicals as first line agents for tinea corporis/cruris and tinea pedis (interdigital type) e.g. clotrimazole or terbinafine cream applied OD or bid, until one week after complete resolution of lesions • oral therapy is indicated for onychomycosis or tinea capitis [e.g. terbinafine (LamisiJTMliver toxicity, cyp 2D6 inhibitor) or itraconazole (Sporanox™ - heart failure reported, cyp 3A4 inhibitor)]
Table 18. Different Manifestations of Dermatophyte Infection
Definition and Clinical FeatlJres Tinea Capitis Differential Diagnosis Investigations • Wood's light examination of hair: green fluorescence only for Microsporum infection • culture of scales/hair shaft • microscopic examination of a KOH preparation of scales or hair shafts Treatment • griseofulvin x 8 weeks or terbinafine (LamisjiTM) x 2-4 weeks

• superficial fungal infection • alopecia areata, psoriasis, of scalp, eyelashes, and seborrheic dermatitis, eyebrows involving hair trichotillomania shafts and follicles • round, scaly patches of alopecia, possibly with broken off hairs • a kerion (boggy, elevated, purulent inflamed nodule/ plaque) may form • this may be secondarily infected by bacteria and result in scarring • affects children (mainly black), immunocompromised adults • very contagious and may be transmitted from barber, hats, theatre seats, pets • pruritic, scaly, round/oval plaque with active erythematous margin and central clearing • site: trunk, limbs, face • scaly patch/plaque with a well-defined, curved border and central clearing on medial thigh • does not involve scrotum • pruritic, erythematous, dry/macerated granuloma annulare, pityriasis rosea, psoriasis, seborrheic dermatitis

Tinea Corporis


Tinea Cruris

• topicals - 1% c1otrimazole or • microscopic examinations of KOH prep of scales scraped 2% miconazole; both are bid from active margin shows for 2-4 weeks hyphae • scales can be cultured • same as for tinea corporis • topicals - 1% c1otrimazole or 2% miconazole; both are bid for 2-4 weeks

I"Jock Itch"'

• candidiasis (involvement of scrotum and has satellite lesions!. contact dermatitis, erythrasma

Tinea Pedis (Atillete's Foot)

• pruritic scaling and/or • atopic dermatitis, contact maceration of the web spaces dermatitis, dyshidrotic and powdery scaling of soles dermatitis, erythrasma, • acute infection: interdigital intertrigo (interdigitall, (esp. 4th web space) red/white psoriasis scales, vesicles, bullae, often with maceration • may present as flare-up of chronic tinea pedis • frequently become secondarily infected by bacteria • chronic: non-pruritic, pink, scaling keratosis on soles and sides of foot • heat, humidity, occlusive footwear are predisposing factors

• same as for tinea corporis

• topicals -1% clotrimazole or 2% miconazole; both are bid for 2-4 weeks

Toronto Notes 2008


Dennatology D31

Table 18. Different Manifestations of Dermatophyte Infection (continued)
Definition and Clinical Features TInea Manuum Differential Diagnosis Investigations
• same as for tinea corporis

• topicals - 1%c1otrimazole or 2% miconazole; both are bid for 2-4 weeks

• acute: blisters at edge of • atopic dermatitis, contact red areas on hands dermatitis, granuloma annulare, psoriasis • chronic: single dry scaly patch • primary fungal infection of the hand is actually quite rare: usually associated with tinea pedis • crumbling, distally • Psoriasis, lichen planus, dystrophic nails; yellowish, contact dermatitis, traumatic opaque with subungual onychodystrophies, bacterial hyperkeratotic debris infections • toenail infections usually precede fingernail infections • T rubrum (90% of all toenail infections)

TInea Unguium IDnychomycosisl

• KOH prep of scales from subungual scraping shows hyphae on microscopic exam • subungual scraping or nail clippings may be cultured on Sabouraud's agar

• terbinafine (LamisiI™) (6 weeks for fingernails, 12 weeks for toenails) • itraconazole (Sporanox™) 7 days on, then 3 weeks off (2 pulses for fingernails, 3 pulses for toenails)

Parasitic Infections
SCABIES Definition
• a transmissible parasitic skin infection due to Sarcoptes scabiei, a mite, characterized by superficial burrows, intense pruritus (especially nocturnal), and secondary infection

• • • • • risk factors: sexual promiscuity, crowding, poverty, nosocomial immunocompromised: "Crusted (Norwegian) Scabies"; all over body, millions of mites scabies mite remains alive 2-3 days on clothing/sheets incubation = 1 month, then begin to itch re-infection followed by hypersensitivity in 24 hours

Differential Diagnosis
• asteatotic eczema, dermatitis herpetiformis lvesicles, urticaria, eosinophilia, no burrows), lichen simplex chronicus (neurodermatitis)

Signs and Symptoms
• primary lesion: superficial linear burrows • secondary lesions: small urticarial crusted papUles, eczematous plaques, excoriations • sites: axillae, groin, buttocks, hands/feet (especially web spaces), sparing of head and neck (except in infants)

• microscopic examination of root and content of burrow with KOH for mite, eggs, feces

• bathe, then apply permethrin 5% cream (i.e. Nix™) or pyrethran 1% (Kwellada PTM) from neck down to soles of feet (must be left on for 8-14 hours and may require second treatment 7 days after first treatment) • change underwear and linens; wash with detergent in hot water cycle then machine dry • ± antihistamine • treat family and contacts • pruritus may persist for 2-3 weeks due to prolonged hypersensitivity reaction

LICE (PEDICULOSIS) Definition and Clinical Features
• intensely pruritic red excoriations, morbilliform rash, caused by louse (a parasite) • scalp lice: nits (i.e. louse eggs) on hairs • red excoriated skin with secondary bacterial infection, lymphadenopathy • pubic lice: nits on hairs • excoriations • body lice: nits and lice in seams of clothing • excoriations and secondary infection mainly on shoulders, belt-line and buttocks

032 Dermatology


Toronto Notes 200S

Differential Diagnosis
• bacterial infection of scalp, seborrheic dermatitis

• permethrin 1% (Nix™ cream rinse) (ovicidal) or pyrethran 1% (RC & Cor™, Kwellada-PTM shampoo) • comb hair with fine-toothed comb using dilute vinegar solution to remove nits • repeat in 7 days • bedding, clothing and towels should be changed and washed with detergent in hot water cycle then machine dried

~ Viral Infections


Signs and Symptoms
• herpetiform (i.e. grouped) umbilicated vesicles on an erythematous base caused by HSV • vesicles located on skin or mucous membranes • transmitted via contact with erupted vesicles or via asymptomatic viral shedding • primary • children and young adults • usually asymptomatic; may have high fever, regional lymphadenopathy, malaise • followed by antibody formation and latency of virus in nerve root ganglion • secondary • recurrent form seen in adults; much more common than primary • prodrome of tingling, pruritus, pain • triggers for recurrence: fever, sunburn, physical trauma, menstruation, emotional stress, upper respiratory tract infection (URTI)

• 2 biologically and immunologically different subtypes: HSV-l and HSV-2

• most commonly "cold sores" (grouped vesicles which quickly burst and commonly occur at the muco-cutaneous junction) • recurrent on face, lips but NOT on mucous membranes (unlike aphthous ulcers)

• treat during prodrome to~revent vesicle formation • topical antiviral (Zovirax ) cream, apply 5-6x/day, 4-7 days for facial/genital lesions • oral antivirals are far more effective and have an easier dosing schedule


• sexually transmitted; incubation 2-20 days • gingivostomatitis (entire buccal mucosa involved with erythema and edema of gingiva) • vulvovaginitis (edematous, erythematous, extremely tender, profuse vaginal discharge) • urethritis (watery discharge in males) • recurrent on vulva, vagina, penis, lasting 5-7 days • diagnosis • -ve darkfield, -ve serology for syphilis, -ve bacterial cultures • Tzanck smear shows multinucleated giant epithelial cells with Giemsa stain • tissue culture and electron microscopy of vesicular fluid • skin biOpsy • antibody titres increase one week after primary infection only (no increase with recurrent lesions)

Both HSV-l and HSV-2 can occur on face or genitalia.

Differential Diagnosis of Genital Ulcerations • Candida balanitis, chancroid, multiple syphilitic chancres Treatment of HSV-2
• rupture vesicle with sterile needle • wet dressing with aluminum subacetate solution, Burow's compression, or betadine solution • acyclovir: 10 days for 1st episode • famciclovir and valacyclovir may be substituted and have better enteric absorption • in case of herpes genitalis, look for and treat any other sexually-transmitted infections

Toronto Notes 2008


Dermatology D33

• dendritic corneal ulcer • herpes simplex encephalitis • HSV infection on atopic dermatitis causing Kaposi's varicelliform eruption (eczema herpeticum)

• EM

• dermatomal infection caused by varicella zoster in a person who has already had the primary infection (chicken pox)



Risk Factors
• immunosuppression, old age, occasionally associated with hematologic malignancy


Signs and Symptoms
• unilateral dermatomal eruption occurring 3-5 days after pain and paresthesia of that dermatome • vesicles, bullae, and pustules on an erythematous, edematous base • lesions may become eroded/ulcerated and last days-weeks • pain is pre-herpetic, synchronous with rash, or post-herpetic • severe post-herpetic neuralgia often occurs in elderly • involvement of tip of nose suggests eye involvement

Herpes Zoster typically involves a single dermatome; lesions rarely cross the midline.

• thoracic (50%), trigeminal (10-20%), cervical (10-20%); disseminated in HIV patients

Differential Diagnosis
• before thoracic skin lesions occur, must consider other causes of chest pain, contact dermatitis, localized bacterial infection, zosteriform herpes simplex virus (more pathogenic for the eyes than varicella zoster)

• compresses with normal saline, Burow's, or betadine solution • analgesics (NSAIDs, amitriptyline) • for patients over 50 years old, with severe acute pain or ophthalmic involvement: famciclovir or valacyclovir for 7 days or acyclovir for 7 days if immunocompromised; must initiate within 72 hours to be of benefit • use gabapentin 300-600 mg PO tid • early and sufficient treatment helps reduce the incidence of post-herpetic neuralgia

MOLLUSCUM CONTAGIOSUM Definition and Clinical Features
• discrete dome-shaped and umbilicated pearly, white papules caused by DNA pox virus (molluscum contagiosum virus (MeV)) • sites: eyelids, beard (likely spread by shaving), neck, axillae, trunk, perineum, buttocks

• common in children and AIDS patients • transmission: direct contact, auto-inoculation, sexual

• • • • topical cantharidin (a keratolytic) liquid nitrogen cryotherapy curettage Aldara™ (immune system modulation)

D34 Dermatology


Toronto Notes 2008

·'}---w.-rt-vs-.C=-o-m-vs-.C,....-II-ou-.---, Dimnguilhing feItu,.. of Coma, Clllou.... end WIrtI Coma lund.rIying bony protuber.nce) Pairing reveals awhitish yellow central translucent keratinous core Clllou... Pairing reveals layers of yellowish keratin with no thrombosed capillaries or interrup· tion of epidermal ridges Verruca vulg.ri. (W.rtI) Pairing reveals multiple bleeding points and thrombosed capillaries

Table 19. Different Manifestations of HPV Infection
Definition and Clinical Features Verruca Vulgaris ICommon Wartsl Differential Diagnosis
• hyperkeratotic, elevated discrete • molluscum contagiosum, seborrheic keratosis epithelial growths with papillated surface caused by HPV - at least 80 types are known • located at trauma sites: fingers, hands, knees of children and teens • paring of surface reveals punctate, red·brown specks (dilated capillaries) • hyperkeratotic, shiny, sharply marginated growths • commonly caused by HPV 1, 2, 4,10 • located at pressu re sites, heads of metatarsal, heels, toes • paring of surface reveals red·brown specks (capillaries). interruption of epidermal ridges • multiple discrete, skin coloured, flat topped papules grouped or in linear configuration • common in children • commonly HPV 3, 10 • sites: face, dorsa of hands, shins, knees • skin·coloured pinhead papules to soft cauliflower like masses in clusters on genitalia and perianal areas • commonly HPV 6 and 11 • HPV 16, 18, 31, 33 cause cervical dysplasia, squamous cell cancer and invasive cancer • often occurs in young adults, infants, children • can be asymptomatic, lasting months to years • highly contagious, transmitted sexually and non-sexually (e.g. Koebner phenomenon via scratching, shaving). and can spread without clinically apparent lesions • Investigations: acetowhitening: subclinical lesions seen with 5% acetic acid x 5 minutes and hand lens • Complications: fairy·ring warts (satellite warts at periphery of treated area of original warts) • need to scrape ("pare") lesions to differentiate wart from callus and corn




Treatment for akin w.rta Fir.t Une Therepill salicylic acid preparations (patches, solutions, creams, ointments) silver nitrate stick topical cantharone glutaraldehyde occlusive methods (duct tape) Second Line Therepill liquid nitrogen cryotherapy topical imiquimod Third Une Therepill curettage cautery surgery laser oral cimetidine (particularly children) topical5·fluorouracil topicaltretinoin (flat warts) localized heat therapy intralesional bleomycin (plantar warts)

Verruca Plantaris (Plantar Wartsl and Verruca Palmaris IPalmar Wartsl

Verruca Planae (Flat Warts)

• syringoma, seborrheic keratosis, molluscum contagiosum, lichen planus

Condyloma Acuminata IGenital Wartsl

• condyloma lata (secondary syphilitic lesion, darkfield strongly +ve). molluscum contagiosum




Treetment for Anogenitll werta Firat line therepill imiquimod 5% cream podophyllotoxin (solution, cream, or gel) podophyllin resin cryotherapy Second line therepill trichloroacetic acid topical 5-fluorouracil electrodessication surgical excision (with cold steel or scissors) CO,laser

Toronto Notes 2008


Dermatology D35

Table 20. Treatment of Warts
Treatment Type of Wart

Notes dyschromia, pain, 10-30 seconds scar, recurrence CO, and Nd: Vag lasers keratolytic irritation, blisters, hyperpigmentation irritation, blisters, scar erythema, erosions, ulcers, pain pain, naillossldystrophy, Raynaud's phenomenon causes an allergiclhypersensitivity reaction erythema, burning, erosion 65-90% resolve spontaneously over several years over the counter (OTC!. use with occulsion irritation best in children cantharidin +podophyllin +salicylic acid

oestructive liquid nitrogervl:lectrodessication surgery laser Caustic Acids cantharidin Itopicall mono-di-and tri-chloracetic acid Chemotherapeutic Agents podophyllotoxin* bleomycin (intralesionall* Hypersensitivity Agents dinitrochlorobenzene (DNCSI Immune Response Modifiers 5% imiquimod cream (Aldara T")* Miscellaneous no treatment salicylic acid 40% minimum !retinoin Itopical)* cimetidine lorall* canthrone plus duct tape ± occlusion/callous scraping/paring
• = Avoid

All Resistant Resistant Small, common Common Genital Common Common, plantar Genital Common Common, plantar Flat Resistant Common, plantar

in pregnancy

Yeast Infections
CANDIDIASIS Candidal paronychia
• painful red swellings of periungual skin mucous membranes • glossitis (thrush), balanitis, vulvovaginitis


Candidal intertrigo
• macerated/eroded erythematous patches that may be covered with papules and pustules, located in intertriginous areas often under breast, groin, or interdigitally • peripheral "satellite" pustules • predisposing factors - obesity, diabetes, systemic antibiotics, immunosuppression, malignancy • intertrigo starts as non-infectious maceration from heat, moisture and friction; evidence that it has been infected by Candida is a pustular border • treatment: keep area dry, miconazole cream bid until rash clears

• chronic asymptomatic superficial ftmgal infection with brown/white scaling macules

Etiology and Pathophysiology • Pityrosporum ovale (Malassezia furfur)
• microbe produces carboxylic acid ...... inflammatory reaction inhibiting melanin synthesis yielding variable pigmentation

Epidemiology • Pityrosporum ovale also associated with folliculitis and seborrheic dermatitis
• predisposing factors: summer, tropical climates, Cushing's syndrome, prolonged corticosteroid use

Signs and Symptoms
• affected skin darker than surrounding skin in winter, lighter in summer (does not tan) • sites: upper trunk most common

• KOH prep of scales for hyphae and spores

• scrub off scales with soap and water • selenium sulfide body lotion • ketoconazole cream or PO daily for 10 days

036 Dermatology

Pre-Malignant Skin TumourslMalignant Skin Tumours

Toronto Notes 2008

.... ' . I - - - - - - - - - - - , }

Pre-Malignant Skin Tumours
• nevus sebaceous: salmon-coloured waxy plaques on scalp; 10% become basal cell carcinomas (BCC) • actinic keratosis: See D6; 1-10% become squamous cell carcinoma (SCC) • dysplastic nevi: See Table 5 • giant, congenital hairy nevi: 10% malignant melanoma • lentigo maligna may transform into malignant melanoma (MM)

Work-up of Nonmelenome Skin tancers (NMSCI
History: duration, growth rate,
family/personal hx of skin cancer, prior therapy to the particular lesion Physicel: determine exact location, size, whether circumscribed, tethering to deep structures, full skin exam,lymph node exam (basosquamouslSCCsI Biopty: if shallow lesion/shallow therapy considered, do shave biopsy; otherwise punch biopsy

Malignant Skin Tumours
Table 21. Skin Phototypes (Fitzpatrick)
Phototypes Sun Exposure Colour of Skin
White White White

Skin's Response to Sun Exposure

I II 1\1


Pale brown Brown Dark brown/black

Always burns, never tans Always burns, little tan Slight burn, slow tan Slight burn, faster tan Rarely burns, dark tan Never burns, dark tan

Basal Cell Carcinoma
• malignant proliferation of basal cells of the epidermis (primarily tangential growth) • subtypes: noduloulcerative, pigmented, superficial, sclerosing

• • • • 75% of all malignant skin tumours >40 years, increased prevalence in the elderly M>F, skin phototypes rand II, chronic cumulative sun exposure usually due to UV light, therefore >80% on face may also be caused by scar formation, radiation, trauma, arsenic exposure or genetic predisposition (Gorlin syndrome)

Differential Diagnosis
• intradermal melanocytic nevus, nodular malignant melanoma (biopsy), sebaceous hyperplasia, SCC

Signs and Symptoms
• noduloulcerative (typical) • skin-coloured papule/nodule with rolled, translucent ("pearly") telangiectatic border and depressed/eroded/ulcerated centre • pigmented variant • flecks of pigment in translucent lesion with surface telangiectasia • may mimic malignant melanoma • superficial variant • scaly plaque with fine telangiectasia at margin • sclerosing variant • flesh/yellowish-coloured, shiny papule/plaque with indistinct borders
.... '

. I) - - - - - - - - - - - - ,

• electrodessication and curettage • surgical excision ± microscopically controlled surgery (Mohs surgery - unique minimally invasive stepwise excision) • radiotherapy (less traumatic, useful in areas difficulty to reconstruct; requires skilled physician because of many complications) • cryotherapy • life-long follow-up • 95% cure rate if lesion is less than :2 cm in diameter • slow growing lesion, locally invasive and rarely metastatic «0.1%) • imiquimod 5% cream (AldaraTM) can be used for primary superficial lesions if surgical management is inappropriate

Margilll • smeller lelions: electro-dessication and curettage with 203 mm margin of normal skin • deep infiltrltlve 1&Iions: surgical excision with 3-5 mm margins beyond visible and palpable tumour border; may require skin graft or flap

Toronto Notes 2008

Malignant Skin Tumours

Dermatology D37

Cutaneous 'J:.Cell Lymphoma
• T-cell lymphoma, first manifested in skin


• >50 years old, M:F 2:1

Differential Diagnosis
• nummular dermatitis, psoriasis

Signs and Symptoms
• two major forms: • Mycosis Fungoides (limited superficial type) • characterized by erythematous patches/plaques/nodules/tumours which could be pruritic, poikiloderma ("cigarette-paper skin") • leonine facies (caused by extensive infiltration) • mildly symptomatic, usually excellent prognosis • Sezary Syndrome (widespread systemic type) • rare variant characterized by universal erythroderma ("redman syndrome"), lymphadenopathy, WBC >20 x 109 cells per litre with Sezary cells • hair loss, pruritis • fatigue, fever, often fatal

• skin biopsy (histology, lymphocyte antigen "cell" markers, TcR gene arrangement) • blood smear looking for Sezary cells or flow cytometry (e.g. CD4: CDS >10 is Sezary) • imaging (for systemic involvement)

• Mycosis Fungoides • topical steroids and/or PUVA, narrow band (311-313 mm), UVB (NBUVB) • Sezary Syndrome • oral retinoids and intE'rferon, extra-corporeal photophoresis • may need radiotherapy -> total skin electron beam radiation • may maintain on UV therapy

• white plaque or patch that is not characterized pathologically or clinically as any other disease • seen as a precancerous or premalignant condition • oral form is strongly associated with tobacco usE' and alcohol consumption

• 1-5% prevalence in adult population after 30 years of age; peak at age 50 • M>F, fair-skinned • most common oral mucosal premalignant lesion

Differential Diagnosis
• lichen planus, oral hairy leukoplakia

Signs and Symptoms
• sharply demarcated borders, homogeneous or speckled white plaque • most often found on floor of mouth, soft palate, and ventral and lateral surfaces of the tongue

• biopsy is mandatory because it is a premalignant lesion

• low risk sites (buccal/labial mucosal or hard palate): eliminate carcinogenic habits, follow-up • moderate/dysplastic lesions: excision, cryotherapy

D38 Dermatology

Malignant Skin Tumours

Toronto Notes 2008

Malignant Melanoma



• malignant neoplasm of pigment forming cells (melanocytes and nevus cells) • several different subtypes based on pathology (see below)
Does this Patient have a Mole or Melanoma?
JAMA 1998; 279\9): 696-701.

• incidence 1:100 • risk factors: numerous moles, fair skin, red hair, positive personal/family history, large congenital nevi, familial dysplastic nevus syndrome (100%) • most common sites: back (M), calves (F) • worse prognosis if: male, on scalp, hands, feet, late lesion, no pre-existing nevus present

ABCDE checklist: A· Asymmetry B· Border (irregularl C· Colour (varied) D· Diameter (increasing or >6 mml E· Enlargement, elevation
Sensitivity 92% (CI82-96%! Specificity 100% (CI54-100%!

Signs and Symptoms
• malignant characteristics of a mole: see mnemonic"ABCDE" • sites: skin, mucous membranes, eyes, CNS

Prognostic Indicators
• ulceration or microulceration upstages risk • number of nodes more important than size of nodes • sentinel node status is single most important prognostic factor for recurrence and survival

Lentigo maligna (premalignant lesion)
• malignant melanoma in situ (normal and malignant melanocytes confined to the epidermis) • 2-6 cm, tan/brown/black uniformly flat macule or patch with irregular borders • lesion grows radially and produces complex colours • sites: face, sun exposed areas • 1/3 evolve into lentigo maligna melanoma

~, Risk Factors for Melanoma
(no SPF is a SIN)
• Sun exposure • Pigment traits (blue eyes, fair/red hair, pale complexion) • Freckling • Skin reaction to sunlight (increased incidence of sunburn! • Immunosuppressive slates (e.g. renal transplantation! • Nevi (dysplastic nevi; increased number of benign melanocytic nevil

Lentigo maligna melanoma (15% of all melanomas)
• malignant melanocytes invading into the dermis • flat, brown, stain-like lesion that gradually enlarges with loss of skin surface markings • with time, colour changes from uniform brown to dark brown with black and blue hues • found on all skin surfaces, especially those chronically exposed to sun • not associated with preexisting acquired nevi

Superficial spreading melanoma (60-70% of all melanomas)
• atypical melanocytes initially spread laterally in the epidermis then invade the dermis • irregular, indurated, enlarging plaques with red/white/blue discolouration, focal papules and nodules • ulcerate and bleed with growth

Nodular melanoma (30% of all melanomas)
• atypical melanocytes that initially grow vertically with little lateral spread • uniformly ulcerated, blue-black, and sharply delineated plaque or nodule • rapidly fatal

Acrolentiginous melanoma (5% of all melanomas)
• ill-defined dark brown, blue-black macule • palmar, plantar, subungual skin • melanomas on mucous membranes have poor prognosis

,,' ,


• excisional biopsy preferable, otherwise incisional biopsy • remove full depth of dermis and extend beyond edges of lesion only after histologic diagnosis • beware of lesions that regress - tumour is usually deeper than anticipated • lymph node dissection shows survival advantage if nodes uninvolved • chemotherafY (cis-platinum, BCG), high dose interferon a for stage II (regional) and stage II (distant) disease • radiotherapy is curative for uveal melanomas, palliative for bone and brain metastases

Node diaection for letiont >10 mm
• assess sentinel nodes • if macroscopically or microscopically positive, alymph node dissection should be preformed prior to wide excision of the primary melanoma to ensure accurate lymphatic mapping

American Joint Committee on Cancer Staging System Based on Breslow's Thickness of Invasion
• T1 <1.0 mm

• T2 1.01-2.0 mm
• T3 2.01-4.0 mm • T4 > 4.0 mm • a = no ulceration; b = ulceration

• • • •

Stage I Stage II Stage III Stage IV

5-year survival 90% Tla - T2a 70% T2b - T4b any nodes 45% 10% any mets

Toronto Notes 2008

Malignant Skin TumourslHeritable Disorders

Dermatology 039

Squamous Cell Carcinoma
• a malignant neoplasm of keratinocytes (primarily vertical growth)

• primarily on sun-exposed skin in the elderly, M>F, skin phototypes I and II, chronic sun exposure • predisposing factors include UV radiation, ionizing radiation therapy/exposure, immunosuppression, PUVA, atrophic skin lesions, chemical carcinogens such as arsenic, tar and nitrogen mustards

Differential Diagnosis
• BCe, Bowen's disease, melanoma, nummular eczema, psoriasis

Signs and Symptoms
• indurated erythematous nodule/plaque with surface scale/crust, and eventual ulceration • more rapid enlargement than BCC • sites: face, ears, scalp, forearms, dorsum of hands

• surgjcal excision with primary closure, skin flaps or grafting • lifelong follow-up (more aggressive treatment than BCC)

• prognostic factors include: immediate treatment, negative margjns, and small lesions • SCCs tha t arise from actinic keratosis metastasize less frequently (-1%) than other SCCs (e.g. arising de novo in old burns) (2-5% of cases) • overall control is 75% over 5 years, 5-10% metastasize

• erythematous plaque with a sharply demarcated red and scaly border

Signs and Symptoms
• often 1-3 em in diameter and found on the skin and mucous membranes • evolves to SCC in 10-20% of cutaneous lesions and >20% of mucosal lesions

• biopsy required for diagnosis • as for BCC • topical5-fluorouracil (Efudex™) or imiquimod (Aldara™) used if extensive and as a tool to identify margjns of poorly defined tumours

Heritable Disorders
Ichthyosis Vulgaris
• a generalized disorder of hyperkeratosis leading to dry skin, associated with atopy and keratosis pilaris


• 1:300 incidence • autosomal dominant inheritance • associated with atopic dermatitis

2 A.D.
atopic dermatitis and autosomal dominant

Signs and Symptoms
• "fish-scale" appearance especially on extremities with sparing of flexural creases, palms and soles, scaling without inflammation

• immersion in bath and oils • emollient or humectant creams, and creams or oils containing urea

040 Dermatology

Heritable Disorders

Toronto Notes 2008



(Type I; von Recklinghausen's Disease)


• autosomal dominant disorder with excessive and abbormal proliferation of neural crest elements

• autosomal dominant inheritance • incidence 1:3,000

Signs and Symptoms
• diagnostic criteria include 1) more than 6 cafe-au-Iait spots >1.5 em in an adult, and more than 5 cafe-au-Iait spots >0.5 em in a child under age 5 2) axillary freckling 3) iris hamartomas (Lisch nodules) 4) optic gliomas 5) neurofibromas, and others • associated with pheochromocytoma, astrocytoma, bilateral acoustic neuromas, bone cysts, scoliosis, precocious puberty, developmental delay, and renal artery stenosis

• follow closely for malignancy, transformation of neurofibroma to neurofibrosarcoma • excise suspicious or painful lesions • see Pediatrics, P83

• primary pigmentary disorder characterized by hypopigmentation and depigmentation

• 1% incidence, polygenic • 30% with +ve family history

• associated with other autoimmune disease especially thyroid disease, DM, Addison's disease, pernicious anemia • may be precipitated by trauma (Koebner phenomenon)

Signs and Symptoms
• acquired destruction of melanocytes characterized by sharply marginated white patches • sites: extensor surfaces and periorificial areas (mouth, eyes, anus, genitalia) • associated with streaks of depigmented hair, chorioretinitis

• rule out other autoimmune diseases: autoimmune thyroiditis, pernicious anemia, Addison's disease, Type I DM • Wood's lamp to detect lesions

• sun avoidance and protection • topical immunomodulator (i.e. tacrolimus, pimecrolimus) or a topical steroid for 6-12 months prior to attempting phutotherapy • camouflage preparations • PUVA • "bleaching" normal pigmented areas (total white colour) if widespread loss of pigmentation

Toronto Notes 2008

Skin Manifestations of Internal Conditions

Dermatology 041

Skin Manifestations of Internal Conditions
Table 22. Skin Manifestations of Internal Conditions
AUTOIMMUNE DISORDERS Buerger's disease Cutaneous lupus erythematosus Dermatomyositis Polyarteritis nodosa Rheumatic fever Scleroderma Systemic lupus erythematosus

Related Dennatoses
Superficial migratory thrombophlebitis, pallor, cyanosis, gangrene, ulcerations Sharply marginated annular or psoriaform bright red plaques with scales, telangiectasia, marked scarring, diffuse non-scarring alopecia Periorbital and perioral violaceous erythema, heliotrope with edema, Gottron's papules Iviolaceous flat-topped papules with atrophy), periungual erythema, telangiectasia, calcinosis cutis Polyarteritic nodules, stellate purpura, erythema, gangrene, splinter hemorrhages, livedo reticularis Peteclliae, urticaria, erythema nodosum, erythema multiforme, rheumatic nodules Raynaud's, nonpitting edema, waxy/shinynense atrophic skin (morpheaI, ulcers, cutaneous calcification, periungual telangiectasia, acrosclerosis Malar erythema, discoid rash (erythematous papules or plaques with keratotic scale, follicular plugging, atrophic scarring on face, hands, and arms!. hemorrhagic bullae, palpable purpura, urticarial purpura, patclly/diffuse alopecia, mucosal ulcers, photosensitivity Pyoderma gangrenosum Generalized hyperpigmentation or limited to skin folds, buccal mucosa and scars Moon facies, purple striae, acne, hyperpigmentation, hirsutism, atrophic skin with telangiectasia Infections (boils, carbuncles, candidiasis, S. aureus, dermatophytoses, tinea pedis and cruris, infectious eczematoid dermatitisl, prurnus, eruptive xanthomas, necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic foot, diabetic bullae, acanthosis nigricans, calciphylaxis Moist, warm skin, seborrhea, acne, nail atrophy, hyperpigmentation, toxic alopecia, pretibial myxedema, acropaclly, onycholysis Cool, dry, scaly, thickened, hyperpigmented skin: toxic alopecia with dry, coarse hair, brittle nails, myxedema, loss of lateral 1/3 eyebrows Viral (HSV, HZV, HPV, cytomegalovirus, molluscum contagiosum, oral hairy leukoplakia), bacterial limpetigo, acneiform folliculitis, dental caries, cellulitis, bacillary epithelioid angiomatosis, syphilisl, other (candidiasis) Seborrhea, psoriasis, pityriasis rosea, vasculitis



(Hereditary Skin DiIonlenl

Gene DefectIIleficie Syndrome
Cholesterol metabolism disorders Keratinization enzyme deficiencies Keratin disorders CHILD syndrome

Lamellar icllthyosis

Epidermolysis bullosa simplex Carvajal syndrome KID syndrome Darier disease, Hailey-Hailey disease Ehlers-Danlos syndrome Wemer syndrome

Desmoplakin disorders Connexin defects Calcium pump deficiencies

Ulcerative colitis IUCI ENDOCRINE DISORDERS Addison's disease Cushing's syndrome Diabetes mellitus

Collagen defects

RecQ DNA helicase deficiencies DNA repair disorders

Hyperthyroid Hypothyroid HIV Infections

Xeroderma pigmentosum

Protein-tyrosine Cowden syndrome phosphatase deficiencies

Inflammatory dermatoses Malignancies MAUGNANCY Adenocarcinoma Gastrointestinal {Gil Cervix/anus/rectum Carcinoma Breast GI Thyroid BreasVGU/lung/ovary Lymphoma/Leukemia Hodgkin's Acute Leukemia Multiple Myeloma OTHERS Liver disease


Kaposi's Sarcoma, lymphoma, BCC, SCC, malignant melanoma

Peutz-Jeghers: pigmented macules on lips/oral mucosa Pagers Disease: eroding scaling plaques of perineum

Pagers Disease: eczematous and crusting lesions of breast Palmoplantar keratoderma: thickened skin of palms/soles Sipple's Syndrome: multiple mucosal neuromas Dermatomyositis: heliotrope erythema of eyelids and purplish plaques over knuckles

Ataxia Telangiectasia: telangiectasia on pinna, bulbar conjunctiva Icllthyosis: generalized scaling especially on extremities Bloom's Syndrome: butterlly erythema on face, associated with short stature Amyloidosis: large, smooth tongue with waxy papules on eyelids, nasolabial folds and lips, as well as facial petechiae Pruritus, hyperpigmentation, spider nevi, palmar erythema, white nails, porphyria cutanea tarda, xanthomas, hair loss Pruritus, pigmentation, half and half nails Erythematous papules or urticarial plaques in distribution of striae distensae: buttocks, thighs, upper inner arms and lower backs Palpable purpura in cold-exposed areas, Raynaud's, cold urticaria, acral hemorrhagic necrosis, bleeding disorders, related to hepatitis Cinfection

Raynaud's Phenomenon DDx COLD HAND: Cryoglobulins! Cryofibrinogens Obstruction/.Occupational Lupus erythematosus, other connective tissue disease Diabetes mellitus! Drugs Hematologic problems (polycythemia, leukemia, etc) Arterial problems (atherosclerosisl Neurologic problems (vascular tonel Disease of unknown origin (idiopathic)




Acanthosis Nigricans
Renal disease Pruritic urticaria papules and plaques of pregnancy Cryoglobulinemia An asymptomatic dar'; thickened velvety hyperpigmentation of ffexural skin most commonly around the neck, Associated with diabetes, obesity and other endocrine disorders and malignancy, It is acutaneous marker of tissue insulin resistance,

D42 Dermatology

Nails and Disorders of the Nail Apparatus

Toronto Notes 2008

Nails and Disorders of the Nail Apparatus
Table 23. Nail Changes in Systemic and Dermatological Conditions
Nail Abnormality

Proximal nail plate has greater than 180 degree angle to nail fold, watch·glass nails, bulbous digits Spoon shaped nails Separation of nail plate from nail bed Hypertrophy of the nail plate and subungal hyperkeratosis Subungual hematoma Fungal infection of naille.g. dermatophyte, yeast, mouldl Often hallux with congenital malalignment, painful inflammation, granulation tissue

Associated Disease
Cyanotic heart disease, bacterial endocarditis, pulmonary disorders, GI disorders, etc. Iron deficiency, malnutrition, diabetes Psoriasis, dermatophytes, thyroid disease Poor circulation, chronic inflammation, tinea Trauma to nail bed HIV, diabetes, peripheral arterial disease Tight fitling shoes, excessive nail clipping

Koilonychia Onycholysis Onychogryphosis Onychohemia Onychomycosis Onychocryptosis (Ingrown toenailI

Pterygium inversus unguium Pitling Transverse ridging

Distal margin has v·shaped indentation Distal nail plate does not separate from underlying nail bed Punctate depressions that migrate distally with growth Transverse depressions often more in central ponion of nail plate Bands of white discolouration

Darier's disease (Follicular Dyskeratosisl Scleroderma Psoriasis, alopecia areata, eczema Serious acute illness slows nail growth (Beau's linesl, eczema, chronic paronychia, trauma Poisons, hypoalbuminemia (Muherke's lines)

Transverse white lines


Tinea, jaundice, tetracycline, pityriasis rubra pllaris, yellow nail syndrome

Green Blac'l Brown Splinter Hemorrhages Extravasation of blood from longitudinal vessels of nail bed Blood atlaches to overlying nail plate and moves distally as it grows Brown·yellow discolouration

Melanoma, hematoma Nicotine use, psoriasis, poisons Trauma, bacterial endocarditis, blood dyscrasias, psoriasis

Oil spots


LOCAL CHANGES Herpetic whitlow

HSV infection of distal phalanx Local inflammation of the nail fold around the nail bed

Genital herpes infection Acute: painful infection Chronic: constant wetling le.g. dishwashing, thumbsuc'lingl Scleroderma, SLE

Nail fold telangiectasias

Cuticular hemorrhages, roughness, capillary changes

Toronto Notes 2008

Alopecia (Hair Loss)

Dermatology D43

Alopecia (Hair Loss)
Hair Growth
• hair grows in a cyclic pattern that is defined in three stages: • growth stage =anagen phase • degenerative stage = catagen phase • resting stage = telogen phase • total duration of the growth phase reflects the type and location of hair • eyebrow, eyelash, and axillary hairs have a short anagen phase in relation to the telogen phase • growth of the hair follicles is also based on the hormonal response to testosterone and dihydrotestosterone (DHT) • this response is genetically controlled

Hair Loss: "TOP HAT"
T telogen effluvium, tinea capitis out of Fe, Zn P physical- trichotillomania, "corn-row" braiding H hormonal- hypothyroidism, androgenic A autoimmune - SLE, alopecia areata T toxins - heavy metals, anticoagulants, chemotherapy, ViI. A. SSRls


Non-Scarring (Non-Cicatricial) Alopecia
• male-pattern alopecia (androgenic alopecia)


',, - - - - - - - - - - - , }

Non-scarring alopecia alopecia


• action of testosterone on hair follicles

• early 20's-30's (female androgenic alopecia is diffuse and occurs in 40's and 50's)

Signs and Symptoms
• fronto-temporal areas progressing to vertex, entire scalp may be bald

• • • • minoxidil (RogaineT M ) lotion to reduce rate of loss/partial restoration spironolactone in women (anti-androgenic effects), cyproterone acetate (Diane-35™) finasteride (Propecia™) (5-a-reductase inhibitor) 1 mg/d in men hair transplant

• trichotillomania: impulse-control disorder characterized by compulsive hair pulling with irregular patches of hair loss, and with remaining hairs broken at varying lengths • traumatic (e.g. tight "com-row" braiding of hair)

NOll-scarring (non~icatricial) alopecia Autoimmune alopecia areata Endocrine hypothyroidism androgens Micronutrient deficiencies iron zinc Toxins heavy metals anticoagulants chemotherapy Vitamin A Trauma to the hair follicle trichotillomania 'corn-row' braiding Other severe illness childbirth Scarring (cicatricial) alopecia DevelopmentaVHereditary Disorders Aplasia cutis congenita Epidermal nevi Romberg's syndrome Generalized follicular hamartoma Primary causes Group 1: Lymphocytic Lupus erythematosus Lichen planopilaris Classic Pseudopelade Group 2: Neutrophilic Folliculitis decalvans Group 3: Mixed Acne keloidalis nuchae Secondary causes Infectious agents Bacterialli.e. post-cellUlitis) Fungal (i.e. tinea capitis) Neoplasms ILe. BCC, SCC, lymphomas, and metastatic tumours) Physical agents Medhanical trauma Burns Radiotherapy Caustic chemicals

• uniform decrease in hair density secondary to an increased number of hairs in telogen phase (resting phase) • 5% of hair normally in resting phase, about to shed (telogen)

Precipitating Factors
• post-partum, high fever, oral contraceptives, malnutrition, severe physical/mental stress, Fe deficiency

Clinical Course
• 2-4 month latent period after stimulus • regrowth occurs within few months but may not be complete

• hair loss due to insult to hair follicle impairing its mitotic activity (growing phase)

Precipitating Factors
• chemotherapeutic agents (most common), other meds (bismuth, levodopa, colchicine, cyclosporine), exposure to chemicals (thallium, boron, arsenic) • dose-dependent effect

Clinical Course
• 7-14 days after single pulse of chemotherapy; most clinically apparent after 1-2 months • reversible effect; follicles resume normal mitotic activity few weeks after agent stopped

D44 Dermatology

Alopecia (Hair Lossl/Pediatric Exanthems

Toronto Notes 2008


• autoimmune disorder characterized by patches of complete hair loss (loss of telogen hairs) localized to scalp, eyebrows, beard, eyelashes • alopecia totalis -loss of all scalp hair and eyebrows • alopecia universalis - loss of all body hair

Signs and Symptoms
• associated with dystrophic nail changes - fine stippling • "exclamation mark" pattern (hairs fractured and have tapered shafts, i.e. looks like "i") • may be associated with pernicious anemia, vitiligo, thyroid disease, Addison's disease

• • • • • generally unsatisfactory intralesional triamcinolone acetonide (corticosteroids) can be used for isolated patches wigs UV or PUVA therapy immunomodulatory (diphencyprone)

• spontaneous regrowth may occur within months of first attack (worse prognosis if young at age of onset and extensive loss) • frequent recurrence often precipitated by emotional distress

• drugs: chemotherapy, danazol, vitamin A, retinoids, anticoagulants, thallium, antithyroid drugs, OCPs, allopurinol, propanoid, salicylates, gentamicin, levodopa • toxins: heavy metals • endocrine: hypothyroidism


Scarring (Cicatricial) Alo~ecia
• irreversible loss of hair follicles with fibrosis

.... ,}-------------, ~
Scarring alopecia: absent hair follicles on exam .... biopsy required Non-scarring alopecia: intact hair follicles on exam .... biopsy not required



• physical: radiation, bums • infections: fungal, bacterial, TB, leprosy, viral (herpes zoster) • inflammatory • lichen planus (lichen planopilaris) • collagen-vascular • discoid lUpus erythematosus (treatment with topical/intralesional steroid or antimalarial); note that SLE can cause an alopecia unrelated to discoid lUpus lesions which are non-scarring • scleroderma: "coup de sabre" with involvement of centre of scalp

• biopsy from active border

Pediatric Exanthems

Itchy Eruptions in Childhood Ue-SCAB
Urticaria Contact dermatitis Scabies Chicken pox Atopic dermatitis Bites

• exanthem: an eruption on the skin occuring as a symptom of a systemic disease typically with a fever • enanthem: an eruption on a mucous membrane occuring in the context of an exanthem
Table 24. Common Pediatric Exanthems
Exanthem Chicken pox Etiology Human herpes virus IHHVI3 Incubation lO-21d, communicable l-2d pre-rash to 5d post-rash Clinicel Description Diffuse vesicular pustular eruption beginning on thorax spreading to extremities New lesions every 2-3d Enanthems Important Complicetions Necrotizing fasciitis, encephalitis, cerebellar ataxia, disseminated intravascular coagulation IDIC!. hepatitis Management Supponive therapy, Acyclovir if severe, Varicella Zoster Immunoglobulin Iwnhin 96 hrs of contactl, Varicella vaccine

Toronto Notes 2008

Pediatric ExanthemslErythema Nodosum

Dermatology D45

Table 24. Common Pediatric Exanthems (continued)
Exanthem E,teroviral Etiology Enteroviruses Most common exanthem in summer and fall Clinical Description Polymorphous rash (macules, papules, vesicles, petechiae, urticarial Slapped cheeks Ired, flushed cheeksl then 1-4 days later lacy/reticular maculo·papular rashoftrunklextremities Important Complications None Managemant Supportive care for majority Serious cases limmunosuppressedl can be treated with pleconaril No treatment: children ohen feel well NSAIDs for symptomatic arthropathy

Erythema Infectiosum Parvovirus B19 Incubation 4·14d Peaks in winter and spring G,anctl.·Crosti Synd,orne Epstein·Barr virus most common, hepatitis B, coxsackie, parvovirus Spring and early summer Coxsackie Aand Bviruses Highly contagious virus No proven viral etiology, but infectious etiology suggested Superantigen toxin-mediated bacterial process proposed late winter to early spring

STAR complex lSoreThroat, Arthritis,Rashl Fetal infection (anemia, fetal hydrops or deathl

Symmetric papular eruption of face, None buttocks, and extremities

Supportive treatment

Hand, foot and mouth disease Kawasaki disease

Vesicular eruption of palms and soles with an erosive stomatitis Fever ~5 days and 415: unilateral lymphadenopathy; puffy/red palms and soles; red, cracked lips/strawberry tongue; skin rash; non-purulent bilateral conjunctivitis Erythematous macular eruption beginning on head and spreading downwards, desquamates, no palm or sole involvement Enanthem: Koplik spots (greylwhite papules on buccal mucosa) Pink macules and papules on trunk, neel<, proximal extremities, and occasionally face Eruption aher high fever ends 1·5 days following mild prodrome (fever, headache, respiratory symptomsl, apink maculo-papular rash erupts on face spreading in a cephalocaudad direction Occipital and retroauricular nodes

Pulmonary neurological death Most common cause of vasculitis and acquired heart disease in children CNS, GI tract, kidney, eyes

Supportive treatment Aspirin, intravenous immune globulin, baseline echo and repeat in 6weeks


Paramyxovirus Incubation 10·14d, communicable 4d before and aher rash

Otitis media, pneumonia, encephalitis, SJS, glomerular nephritis, myocarditis/pericarditis

Vitamin A, immunoglobulin, measles/ mumps/rubella IMMRI vaccine


HHV 6, HHV 7 Incubation 9·10d

Neurological involvement Viral reactivation in immunosuppressed patients

Supportive treatment Antipyretics during the febrile period


RNA virus ofthe Togaviridae family Incubation 16-18d

STAR complex Congenital rubella lcataract, glaucoma, thrombocytopenia, hepatitis, deafness, congenital heartdiseasel

Supportive treatment MMRvaccine Serologic testing in rubella-€xposed pregnant women

Scarlet Fever

Generalized rash, red papules, Mastoiditis,otitis, sinusitis, "sand-paper' texture, pneumonia, meningitis, desQuamation, flexural accentuation, myocarditis, arthritis, hepatitis, enanthem Istrawberry tongue, rheumatic fever, and petechiae on palatel glomerulonephritis Pastia's lines -linear petechial streaks in axillary, inguinal. and antecubital areas Panially adapted from: Pope E. Pediatric Exanthems. lecture presentation to 200612007 University of Toronto Year 3Medical Students Group A~·hemolytic streptococci toxin typesA,B, and C latelall, winter, and early spring

11l-14 day course of penicillin

Erythema Nodosum
• acute or chronic inflammation of subcutaneous fat (panniculitis)

• infections: GAS, primary tuberculosis (TB), histoplasmosis, Yersinia • drugs: sulfonamides, oral contraceptives (also pregnancy), analgesics, trans-retinoic acid • inflammation: sarcoidosis, Crahn's > U1cerative Colitis • malignancy: acute leukemia, Hodgkin's lymphoma • 40% are idiopathic

N- NQ cause (idiopathicl in4O% Drugs (sulfortamides, OCP, etc.l Other infections (GAS+l larcoidosis Ulcerative colitis &Crohn's Malignancy (leukemia, Hodgkin's Iymphomal


• 15-30 years old, F:M =3:1 • lesions last for days and spontaneously resolve in 6 weeks

D46 Dermatology

Erythema NodosumlPmituslWounds and Ulcers

Toronto Notes 2008

Signs and Symptoms • round, red, tender, poorly demarcated nodules • sites: asymmetrically arranged on lower legs, knees, arms • associated with arthralgid, fever, maldise Investigations • chest x-ray (to rule out chest infection and sarcoidosis) • throat culture, antistreptolysin 0 (ASO) titre, purified protein derivative (PPD) skin test Treatment • symptomatic: bed rest, compressive bandages, wet dreSSings
• NSAIDs • treat underlying cause


Definition • a sensation provoking a desire to scratch Etiology • dermatologic - generalized • asteatotic dermatitis ("winter itch") • senile pruritus (may not have dry skin, any time of year) • infestations: scabies, lice • drug eruptions: ASA, antidepressants, opiates • psychogenic states • dermatologic -local • atopic and contact dermatitis, lichen planus, urticaria, insect bites, dermatitis herpetiformis • infection: varicelld, candidiasis • lichen simplex chronicus • prurigo nodularis • systemic disease - usually generalized • obstructive biliary disease, cholestatic liver disease of pregnancy • chronic renal failure, uremia secondary to hemodialysis • hematologic: Hodgkin's lymphoma, multiple myeloma, leukemia, polycythemia vera, hemochromatosis, Fe deficiency anemia • carcinoma: lung, breast, gastric • endocrine: carcinoid, OM, hypothyroid/thyrotoxicosis • infectious: HN, trichinosis, echinococcosis • psychiatric: depression Treatment • treat underlying cause • cool water compresses to relieve pruritus • topical corticosteroid and antipruritics (e.g. menthol, camphor, phenol, mirtazapine) • systemic antihistamines: Hl blockers are most effective • phototherapy with UVB or PUVA



Wounds and Ulcers
Table 25. DifferentTypes of Ulcers and Treatment
Ulcer Type Arterial
Symptoms and signs Treatment

.}------------, to 8 wound that does not heal ...

• Relentless debridement of biofilm and antimicrobials • Biopsy any wound without signs of healing after 3months!

Wound at tips of toes, cold feet with claudication, gangrene, distal hyperemia, decreased pedal pulses

1. 2. 3. 4.

Doppler study If ankle: brachial ratio <0.4, may consider amputation If gangrenous, paint w~h betadine Otherwise, dressings to promote moist interactive wound healing


Wound at malleolus, stasis change, edema, previous venous injury Wound at pressure point or secondary to unknown trauma, common at base of 1st metatarsal phalangeallMTPI Livedo reticularis, petechiae, extreme tenderness, delayed healing

Uncommon Causes of Ulcers "CHIP IN"
Cancer, cI1romosomal Hemoglobinopathy Inflammatory Pyoderma gangrenosum Infections Necrobiosis lipoidica diabeticorum

1. Local wound dressing: moist interactive healing 2. Compression: preferably four layer 3. After wound heals, support stockings for life 1. Pressure downloading by using proper shoes/seats 2. Promote moist interactive wound healing 3. Appropriate broad-spectrum antibiotic coverage 1. 2. 3. 4.
Biopsy to determine vasculitis Serum screening for vasculitis Treat vasculitis Local moist interactive wound healing

Neurotropic and Diabetic


Toronto Notes 2008

Dermatological Therapies

Dermatology D47

Common Medications
Topical Steroids
Table 26. Potency Ranking ofTopical Steroids
Relative Potency Relative Strength Generic Names Weak Moderate
xl x3 hydrocortisone 1% hydrocortisone 2% 17-valerate - 0.2% desonide mometasone furorate betamethasone - 0.1 % 17-valerate - 0.1% amcinonide betamethasone dipropionate - 0.05% f1uocinonide - 0.05% c1obetasol propionate betamethasone dipropionate ointment halobetasol propionate

Trade Names
Emo Cart'" Westcort'" Tridesilon '" Elocom'· Betnovate ," Celestoderm -V'" Cyclocort'· Diprosone'· Lidex, Topsyn gel'" Dermovate'. Diprolene'· Ultravate'·

Intertriginous areas, children, face, thin skin Arm, leg, trunk

",' ,





Body site: Il8latMt I'8rcutaneous Absorption forearm 1.0 plantar foot 0.14 palm 0.83 back 1.7 scalp 3.7 forehead 6.0 cheeks 13.0 scrotum 42.0 <calculation of strength of steroid compared to hydrocortisone on forearm: relative strength of steroid xrelative percutaneous absorption

Very Potent


Palms and sales

Extremely Potent


Palms and sales

Sunscreens and Preventative Therapy
• erythema 2-6 hours post UV exposure often associated with edema, pain and blistering with subsequent desquamation of the dermis, and hyperpigmentation • chronic UVB exposure leads to photoaging, immunosuppression, photocarcinogenesis • prevention: avoid peak UVR (10 am to 4 pm), wear appropriate clothing, wide-brimmed hat, sunglasses, and broad-spectrum sunscreen • clothing with UV protection expressed as UV protection factor (UPV) is analogous to SPF of sunscreen

'" . } - - - - - - - - - - - ,
Sunbum therapy
• symptomatic therapy • cool, wet compresses and baths • moisturizers for dryness and peeling • oral anti-inflammatory: 400 mg ibuprofen q6h to relieve pain, minimize erythema, and edema • topical corticosteroids: soothes and decreases erythema, especially with immediate application • does not reduce damage • oral steroids and antihistamines have no role


• sun protection factor (SPF): under ideal conditions a SPF of 10 means that a person who normally burns in 20 minutes will burn in 200 minutes following the application of the sunscreen, regardless of how often the sunscreen is applied • topical chemical: absorbs UV light • requires application at least 15-60 minutes prior to exposure, should be reapplied every 2 hours (more often if sweating, swimming) • UVB absorbers: PABA, salicylates, cinnamates, benzylidene camphor derivatives • UVA absorbers: benzophenones, anthranilates, dibenzoylmethanes, benzylidene camphor derivatives • topical physical: reflects and scatters UV light • titanium dioxide, zinc oxide, kaolin, talc, ferric chloride and melanin, all are effective against the UVA and UVB spectrum • less risk of sensitization than chemical sunscreens and waterproof, but may cause folliculitis or miliaria • some sunscreen ingredients may cause contact or photocontact allergic reactions, but are uncommon


'..}-----------, ,

• UVA (32().4()0 nm) • penetrates skin more eflectively than UVB or

• responsible for tanning, burning, wrinkling and premature skin aging • penetrates clouds, glass and is reflected off water, snow and cement • UVB 1290-320 nm) • absorbed by the outer dermis • is mainly responsible for burning and premature skin aging • primarily responsible for Bee, see • does not penetrate glass and is substantially absorbed by ozone

• sunburn: if significant blistering present, consider treatment in hospital; otherwise, symptomatic treatment • antioxidants, both oral and topical are being studied for their abilities to protect the skin; topical agents are limited by their ability to penetrate the skin

• uve 1200-290 nm)
• is filtered by ozone layer

D48 Dermatology

Dermatological Therapies

Toronto Notes 2008


Dermatological Therapies
Table 27. Oral therapies that are important in dermatology
Drug Name acitretin (Soriatane") Dosing Schedule 25-50 mg PO qd; maximum 75 mg/d Indications Severe psoriasis Other disorders of hyperkeratinization (ichthyosis, Oarier's diseasel Comments Monitoring strategies: Monitor lipids, lFTs at baseline and q1-2wk until stable Contra indications: Women of childbearing potential unless strict contraceptive requirements are met Drug interactions: Other systemic retinoids, methotrexate, tetracyclines, certain contraceptives May be combined with PUVA phototherapy Iknown as re-PUVAI Side effects: Headache, nausea, diarrhea, abdominal pain Reduce dose if impaired renal function


famcyclovirlfamvir"-) 250 mg PO tid x7-10 days Ifor 1" episode of genital herpesl 125 mg PO bid x5d [for recurrent genital herpes) valacyclovir IValtrex" I 1000 mg PO bid x7-10 d Ifor 1" episode of genital herpes) 500 mg PO bid x5d Ifor recurrent genital herpesl

Chickenpox HerpeslOster Genital Herpes Acute and prophylactic to reduce transmission in infected patients Herpes labialis

Side effects: Dizziness, depression, abdominal pain Reduce dose if impaired renal function Drug interactions: cimetidine Psoriasis May also be effective in: lichen Planus Dermalitis herpetiformis Erythema multiforme Recalcitrant urticaria Recalcitrant atopic dermatitis Blood pressure, renal function Contraindicalions: Abnormal renal funclion, uncontrolled hypertension, malignancy [except non-melanoma skin cancer!, uncontrolled infection, immunodeficiency (excluding autoimmune diseasel, hypersensitivity to drug long term effects preclude use of cyclosporin for >2 years; discontinue earlier if possible May consider rotating therapy with other drugs to minimize adverse effects of each drug Monitoring strategies: Obtain thio purine methyl transferase and G6PD levels before initiating; in the initial two weeks obtain methemoglobin levels and follow the blood counts carefully for the first few months Side effects: Neuropathy Hemolysis IVitamin Cand Esupplementation can help prevent this) Drug interactions: Substrate of CYP2C8I9Iminor), 2C19 Iminorl, 2E1 Iminorl, 3A4 [majorl Ohen adramatic response within hours Contraindications: Teratogenic - in females, reliable contraception is necessary Generally regarded as unsafe in lactation

cyclosporin [Neoral"I

2.5-4 mg/kg/d PO div bid Max 4mg/kg/d_ Supplied in capsules Aher 4weeks may increase by 0.5 mglkg/d q2wks Concomitant dose of magnesium may protect the kidneys


50-100-150 mg PO 00 tapering to 25-50 mg PO 00 to as low as 50 mg2x1wk

Pemphigus vulgaris Oermatitis herpetiformis

isotretinoin 0.5-1 mglkgiday given 00, IAccutane Roche") to achieve atotal dose of 120 mglkg li.e.16-20weeksl

Severe nodular and/or inflammatory acne Acne conglobata Recalcitrant acne

Night blindness, decreased tolerance to contact lenses. May transiently exacerbate acne Monitoring strategies: Baseline lipid profile and hepatic enzymes before treatment Drug interactions: Do not use at the same time as tetracycline or minocycline - both cause pseudotumour cerebri Discontinue vitamin Asupplements Drug may be discontinued at 16-20 weeks when nodule count has dropped by >70%. Asecond course may be initiated aher 2months pm Refractory cases may requ-Ife >3 courses itraconalOle (Sporanox") 100-400 mg PO 00, depending on infection treated. Supply: 100 mg tablet TCo, TCr: 200 mg PO 00 x7days, TP: 100 mg PO qd x28 days; or, 200 mg PO bid x7days, TV: 200 mg PO 00 x7days_ Toenails with or without fingernail involvement: 200 mg PO bid x7days once per month, repeated 3x_ fingernail involvement only: 200 mg bid PO x7days once per month, repeated 2x Tinea capitis Onychomycosis May also be used in: Tinea corporis Tinea cruris Tinea pedis Pityriasis versicolor If extensive or recalcitrant

Serious hepatotoxicity Contra indications: CHf Drug Interactions: Inhibits CYP 3A4. Increases concenlralion of some dru9s metabolized by this enzyme Give capsules with food, capsules must be swallowed whole

Toronto Notes 2008

Oennatological Therapies

Oennatology 049

Table 27. Oral therapies that are important in dermatology (continued)
Drug ivermectin (Mectizan", Stromettol") methotrexate ITrexall"I Dosing Schedule 200·250 ~gIkg PO qwkly x2. Take once as directed; repeat one week later Indications Onchocerciasis IUSA only)

No significant serious side effects Efficacious

Not licensed for use in C.n.da
Also effettive for: Scabies Psoriasis Atopic dermatitis Cutaneous T-ceillymphom~ Lymphomatoid papulosis May also be effective in: Cutaneous Sarcoidosis

10·25 mg qwk, PO, 1M, or IV Max:30mglwk To minimize side effects, consider folic acid supplementation: 1mg 10 5mg six days/week

Monitoring strategies: Baseline renal, liver, and hematological studies Contraindications: Pregnancy, lactation, alcohol abose, liver dysfunction, immunodeficiency syndrome, blood dyscrasias hypersensitivity to drug Restricted to severe, recalcitrant or disabling psoriasis not adequately responsive 10 other forms of therapy Especiallyefficacioos in nail psoriasis Consider combinmg with cyclosporine to allow lower doses of both drugs Contraindications: Caution if impaired renal or liver function Drug interactions: Do not use with isotretinoin (Accotane" I Side effects: Extensive; affects multiple organ systems including CNS, teeth, eyes, bones, renal, and skin Iphotosensitivity, and bloe pigmentation) Not be used as the sale treatment, or the first treatment Alternative to tetracycline Contraindications: Pregnancy, chronic or active liver disease Drug interactions: Potent inhibitor of CYP 206; use with caution when also taking ~·blockers, certain anti·arrhythmic agents, MAOI type B, andlor antipsychotics Drug concentrates rapidly in skin, hair and nails at levels associated with fungicidal activity Contraindications: Severe renal or hepatic dysfunction Pregnancy/lactation

minocycline IMinuein")

50-100 109 PO bid. Taper to 50 109 PO 00 as acne lessens.

Acne vulgaris Rosacea

terbinafine Ilamisi''')

25{) 109 PO 00 x2weeks fingernailsx6wks Toenails x12 wks Confirm diagnosis prior to treatment

Tinea capitis Onychomycosis May also be used in: Tinea corporis Tinea cruris Tinea pedis If extensive or recalcitrant Acnevolgaris Rosacea Bollous pemphigoid


250·500 109 PO daily IAcnel Taken 1hoor before or 2hours after ameal

Table 28. Topical therapies that are important in dermatology
Drug Name :alcipotriol (Dovonex"1 Dosing Schedule 0.005% cream, ointment, scalp solution, apply bid. for maintenance therapy apply qd Indications PsoriaSIS Comments Burning, itching, skin irritation, worsening of psoriasis Avoid face, mucous membranes, eyes; wash hands after application Maximum weekly dosage of cream by age: 2·5 years - 25 glwk 6-10 years - 50 glwk 11·14 years - 75 glwk >14, adults - 100glwk Avoid natural/artificial sun exposure Local skin and application site reactions; Erythema, ulceration, edema, flu·like symptoms Works best for warts on mucosal suriaces May induce inflammation and erosion Do not use in children <2 yrs old Hypersensitivity to drug, or known sensitivity to chrysanthemums Local reactions only (resolve rapidlyl; including burning, pruritis Low toxicity, excellent results Consider 2"' application after 7days Burning Lacks adverse effects of steroids May be used on all skin suriaces including head, neck, and intertriginous areas Expensive Burning Lacks adverse effects of steroids May be used on all skin suriaces including head, neck, and intertriginous areas Expensive

imiquimod IAldara"I

5% cream applied 3x1wk Apply at bedtime, leave on 6·10 hours, then wash off with mild soap and water. Max. duration 16 weeks 5% cream, applied once overnight to all skin areas from neck down

Genital Warts Cutaneous warts Actinic keratosis Superiicial basal cell carcinoma Scabi,s IKwellada·P lotion, Nix'" Dermal Cremel Pediculosis IKwellada·P Creme Rinse", Nix Creme Rinse")

permethrin (Kwellada" PLotion and Nix" Dermal cream)

pimecrolimus IElidel"l

1.0% cream bid Use for as long as lesions persist and dlc upon resolution of symptoms

Atopic dermatitis (mild to moderatel

tacrolimus topical IProtopic"I 0.03% Ichildren) or 0.1% ladoltsl ointment bid Continoe for duration of disease PLUS x1week after clearing.

Atopic dermatitis (mild to moderatel

D50 Dermatology

Summary Key Questions

Toronto Notes 2008

Summary Key Questions
Questions Answers


What are the layers of the epidermis?

Stratum corneum, Stratum lucidum, Stratum granulosum, Stratum spinosum, Stratum basale Purple, pruritic, polygonal, peripheral, papules, penis Topical corticosteroids, topical vitamin Danalogues, topical retinoids, coal tar therapy, anthralin (d~hranoll, topical salicylic acid

2. 3.

What are the 6P's of lichen planus? What are the 1st line treatments of psoriasis?


Systemic treatments of psoriasis?

(Soriatanel. Methotrexate, PUVA, oral Cyclosporin (Neora!), Sulfasalazine, Biologic therapy Lipid profile, hepatic enzymes and ~hCG (pregnancy testl


What are the baseline tests that have to be done before putting someone on Accutane? What are the causes of Stevens-Johnson syndrome (SJSJ?


50% are drug-related: NSAIDs, anticonvulsants, sulfonamides, penicillins. SJS occurs up to 1-3 weeks after drug exposure with more rapid onset upon rechallenge Salicylic acid preparations, silver nitrate stick, topical cantharone, glutaraldehyde, and occlusive methods (ducttapel A - asymmetry, B - border (irregular). C- colour varied, D- diameter (increasing or >6 mml. E- enlargement, elevation


What are the 1st line therapies for skin warts?


What is the ABCDE checklist for melanoma?


What are the causes of hair loss?

T -telogen effluvium, tinea capitis

o -out of Zn, Fe
P - physical-trichotillomania, "corn row" braiding H - hormonal - hypothyroidism, androgenic A - autoimmune - SLE, alopecia areata T - toxins - heavy metals, anticoagulants, chemotherapy, vit A, SSRls
10. What are the relative strengths of the following steroids: hydrocortisone, betamethasone, clobetasol propionate? Hydrocortisone, weak-moderate Betamethansone, potent Clobetasol propionate, extremely potent SPF (sun protection factorllO - means that a person who normally burns in 20 minutes will burn in 200 minutes following the application of the sunscreen, regardless of how often the sunscreen is applied


What does SPF 10 mean?


What colour does Tinea cap~is and erythrasma fluoresce under Wood's Light (UVA 365 nm)?

linea capitis is due to Microsporum species (canis, audouiml and will fluoresce blue-green Erythrasma caused by Corynebacterium minutissimum fluoresces coral red linea versicolor is caused by a yeast-like fungus, Pityrosporum ova/e, and diagnosis is made by examining aKOH preparation of a scale which will appear as "spaghetti &meatballs" (hyphae & sporesl
Actinic keratosis presents on sun-damaged skin, most commonly on the face, lower lip, bald scalp, ears, dorsa of hands and forearms, and appears as erythematous, slightly elevated, macules, papules or plaques covered by adherent scales Liquid nitrogen cryotherapy Topical5-fluorouracil (5%) Curettage and light electrodessication Imiquimod cream (Aldara) Photodynamic therapy Trichloracetic acid Family history of melanoma Dysplastic nevi Mu~iple normal nevi (>30, and especially>100) Sun exposure Blue eyes Red hairs Freckling


What is the cause of Tinea versicolor and how is the diagnosis made?


Presentation of actinic (solari keratosis?


Actinic (solari keratosis treatments?


Risk factors for superiicial spreading malignant melanoma?

Toronto Notes 2008

Summary Key Questions

Dermatology 051

17. Is lentigo maligna melanoma associated with pre-existing acquired nevi? Most common superficial fungal infection?

No. Superficial spreading malignant melanoma is


linea pedis - most commonly caused by Trichophyton and Epidermophyton species and affecting the 4th webspace No, it is rare in children. Dermatitis of the feet is more common Sun, hot weather, alcohol, spicy foods, exercise, hot baths, cold weather, soy, tea Topical metronidazole 0.75% IMetrogel, Metrocream; 1% Noritate, Rosasoll Systemic Antibiotics: Tetracycline, Minocin, Erythromycin, and Clonidine Retinoid: Accutane (Isotretinoin) Flaccid blisters on normal skin, mouth lesions (>80%1. painful erosions, positive Nikolsky's sign, and lesions heal with hyperpigmentation, but without scarring Pruritis, urticarial plaques and erythema may precede lesions. Lesions are tense blisters that may arise on normal or erythematous skin, and rupture less easily than in pemphigus. No Nikolsky's sign 24 hour urine for uroporphyrins (stool may also contain elevated coporphyrins1 Extremely pruritic eruption of the extensor surfaces, which is associated with gluten sensitive enteropathy in more than 90%, and thyroid disease in 30%. Presents as symmetrically grouped papulovesicles or urticarial plaques that are often excoriated

19. 20.

Is linea pedis common is children? Aggravating factors in rosacea?


Common rosacea treatments?


Presentation of pemphigus vulgaris?


Presentation of bullous pemphigoid?


Diagnosis of porphyria cutanea tarda?


What is dermatitis herpetiformis?


What causes bullous impetigo?

Staphylococcus aureus Icrusted and bullous typesI, not beta-hemolytic streptococcus lonly crusted typel

D52 Dermatology


Toronto Notes 2008

Bolognia JL, Joriuo JL, Aapini AP. Textbook of Dermatology, Vol. 1and 2, Toronto: Mosby, 2003, Fitzpatrick JE and Aeling JL. Dermatology Secrets, 2nd edition, Philadelphia: Hanley & Belfus, 2001. Johnson AA, Suurmond 0, Wolff K, eds, Color atlas and synopsis of clinical dermatology, 5th edition, NewYork: McGraw Hill, 2005, Kraft J, Ng C, Bertucci V, UniverSIty ofToronto Pharmacology Handbook: Dermatology Chapter, Toronto: 2005, Lebwohl MG, et al. Treatment of skin disease: Comprehensive therapeutic strategies, 2nd edition, Philadelphia: Mosby, 2006,

Cribier Bet al. Erythema nodosum and associated diseases. Int J Dermatol, 1998;37·667, Cummings SA et al. Approaches to the prevention and control of skin cancer. Cancer Metastatis Rev, 1997;16:309, DeShazo AD et al. Allergic reactions to drugs and biologic agents, JAMA. 1997;278:1895, Ellis C, et al. ICCAD II Faculty. International Consensus Conference on Atopic Dermatitis IIIICCAD II): Clinical update and current treatment strategies, Sr J Dermatol, 2003; 148 (suppl 63):3-10, Faergemann J, Baron A, Epidemiology, clinical presentation, and diagnosis of onychomycosis, Sr J Dermatol, 2003; 149 (suppI65!:1·4, Friedmann PS, Assessment of urticaria and angio·edema, Clin Exper Allergy, 1999;291suppl 31:109, Gordon ML et al. Care of the skin at midlife: diagnosis of pigmented lesions, Geriatrics, 1997;52:56-67, Krafchik, BA, Treatment of atopic dermatitis, J Cut Med Surg 3. 1999; 3IsuppI2):16-23 Mastrolorenzo A, Urbano FG, Salimbeni L, et al. Atypical molluscum contagiosum in an HIV·infected patient. Int J Dermatol, 1998; 27:378·380 Price VH, Treatment of hair loss, NEJM, 1999;341 :964, Aoujeau JC, Stevens·Johnson syndrome and toxic epidermal necrolysis are severe variants of the same disease which differs from erythema multi· forme, J Dermatol, 1997;274-276, Walsh SAA and Shear NH, Psoriasis and the new biologic agents: interrupting al'AP dance, CMAJ,2004;1701131:1933-1941, Whited JD et al. Does this patient have amole or amelanoma? JAMA. 1998;279-676, Wilkin J, Dahl M, Detmar M, Drake. L, Feinstein A, Odom A, Powell FStandard classification of rosacea: Aeport of the National Aosacea Society Expert Committee on the ClassificatIOn and Staging of Aosacea, JAmer Acad Dermatol, 2002;46141:584-587,
Other Sources Canadian Dermtology Association 82nd Annual Conference, June 29-July 4, 2007. Toronto, Ontario, Canada, Pope E, Pediatric Exanthems, Lecture presentation to 2006·2007 University otToronto Year 3Medical Students,


Diagnostic Medical Imaging

Bilal Ahmed and Gevork Mnatzakanian, chapter editors Deana Hathout and Ripudaman Minhas, associate editors Jai Shah, EBM editor Dr. Nasir Jaffer, Dr. Louis Wu, Dr. TaeBong Chung and Dr. Robert Bleakney, staff editors
Imaging Modalities Chest Imaging Modalities Computed Tomography (CT) Scan Thoracic Ultrasound Other Modalities in Chest Imaging Approach to the Chest X-Ray (CXR) Common CXR Signs Common CXR Abnormalities Musculoskeletal System Modalities Approach to Interpretation of Bone X-Rays Trauma Arthritis BoneTumour Infection Metabolic Bone Disease Gastrointestinal (GI) Tract Abdominal X-Ray (AXR) Radiographic Anatomy Approach to AXR Contrast Studies Abdominal Computed Tomography (CT) Solid Visceral Organ Imaging "itis" Imaging Angiography of GITract Genitourinary System Modalities Neuroradiology Modalities Selected Pathology Nuclear Medicine Thyroid Respiratory Cardiac Bone Abdomen Inflammation and Infection Brain Interventional Radiology Vascular Procedures Nonvascular Interventions Summary Key Questions References









Diagnostic Medical Imaging OM!

Toronto Notes 2008

DM2 Diagnostic Medical Imaging

Imaging Modalities

Toronto Notes 2008

Please see the Essentials of Medical Imaging software for illustrations of the content in this chapter

Imaging Modalities
X-Ray Imaging
• x-rays, or Roentgen rays, are a form of electromagnetic energy of short wavelength • as x-ray photons traverse matter, they can be absorbed (process known as "attenuation") and/or scattered • the density of a structure determines its ability to attenuate or "weaken" the x-ray beam (air < fat < water < bone < metal) • structures that have high attenuation, e.g. bone, appear white on the resulting images • two broad categories of x-ray based imaging are plain films and computed tomography (CT)

TypicIl EfIectIve Doses 110m IliapIlic MecicaI ......






Equivalent Period of Natural Background

Radiation {-2.2mSvlfeari

Plain Films
• images are produced by passing x-rays through the patient • exiting x-rays interact with a detection device to produce a 2-dimensional projection image • structures closer to the film appear sharper and less magnified • contraindications: pregnancy (relative) • advantages: inexpensive, non-invasive, readily available • disadvantages: radiation exposure, generally poor at distinguishing soft tissues

XofIY uaminIlianr.
Umbs and joints Ches\ \~ngle PA film} Skull ThoracicspiM lumbarspiM Hip <ll.5 1 3.5 <1.5 days 3days 11 days 4months 7months 7weeks 4months 6months 14 months 8months 16 months 32 years 1year 16 years 4.5 years 7weeks 6months 6months 6mont11s 1.8 years 2.7 years 2.3 years

35 65 15 Pelvis 35 Abdomen '>l IVU 125 Barium swallow 75 Barium follow through 100 Barium enema 350 CThead 115 CTdlest 400 CT abdomen or pelvis roo

Computed Tomography (CT)
• x-ray beam opposite a detector moves in a continuous 360 arc as patient is advanced through the imaging system with subsequent computer assisted reconstruction of anatomical structures in the axial plane • attenuation is quantified in Hounsfield units: +1000 (bone) > +40 (muscle and soft tissue) > 0 (water) > -120 (fat) > -1000 (air) • by adjusting the "window width" (range of Hounsfield units displayed) and "window level" (midpoint value of the window width), can maximally visualize certain anatomical structures (e.g. CT chest can be viewed using "lung", "soft tissue" and "bone" settings) • contraindications: pregnancy (relative), contraindications to contrast agents • advantages: spiral CT has fast data acquisition, CT angiography less invasive than conventional angiography, delineates surrounding soft tissues, excellent at delineating bones, excellent at identifying lung nodules/liver metastases, may be used to guide biopsies, helical CT may allow 3D reconstruction • disadvantages: high radiation exposure, IV contrast injection, anxiety of patient when going through scanner, relatively high cost, limited availability compared to plain films

RadionucrICle 1lUdieI: lung ventilation lXe-l33J 15 lung perfusjon (Tc·99m1 50 Kidrej\k~\ 00 Thyroid (Tc·99m1 00 Bone (Tc·99m1 200 l>inamic cardiac (Tc·99m) 300 PfT head (~18 FDGI 250

Source: European Commission, Radiation Protection Report 118, 'Refenal guidelines for imaging~ DirectorateGeneral for the Erwironment of the European Commission, 2000.

Contrast Agents in X-Ray Imaging
• contrast media are used to examine structures that do not have inherent contrast differences relative to their surroundings • contrast can be administered by mouth (anterograde), rectum (retrograde) or injection prior to x-ray imaging • contrast agents used include barium sulphate (Gl studies), iodine (intravenous pyelogram (IVP), endoscopic retrograde cholangio-pancreatography (ERCP), hysterosalpingography) and gas (air or CO~ used in GI double contrast exams) • contraindications: previous adverse reaction to contrast, renal failure, multiple myeloma, dehydration, diabetes, severe heart failure; barium enema is also contraindicated in toxic megacolon, acute colitis, and suspected perforation (use Hypaque™) • advantages: delineates intraluminal anatomy, may demonstrate patency, lumen integrity, or large filling defects; under fluoroscopy, may also give information on function of an organ • disadvantages: risk of contrast reaction; may cause renal failure in dehydrated patients with diabetes, myeloma patients, or patients with pre-existing renal disease

Ultrasound (UlS)
• high frequency sound waves are transmitted from a transducer and passed through tissues; reflections of the sound waves are picked up by the transducer and transformed into images • reflection occurs when the sound waves pass through tissue interfaces of different acoustic densities such that part of the wave energy is reflected as an "echo" • structures are described based on their echogenicity; hyperechoic structures appear bright whereas hypoechoic structures appear dark on brightness-modulated images • higher ultrasound frequencies result in greater resolution but greater attenuation (i.e. deeper structures more difficult to visualize) • artifacts: acoustic shadowing refers to the loss of information below an interface (e.g. gallstone) that strongly reflects sound waves; enhancement refers to the increase in reflection amplitude from structures that lie below a structure (e.g. cyst) that weakly attenuates ultrasound

Toronto Notes 2008

Imaging Modalities

Diagnostic Medical Imaging DM3

• Doppler: determines the velocity of blood flowing past the transducer based on the Doppler effect • Duplex scan: Doppler + visual images • advantages: relatively low cost, non-invasive, no radiation, real time imaging, may be used for guided biopsies, many different imaging planes (axial, sagittal), determines L)'StiC versus solid • disadvantages: highly operator-dependent, air in bowel may prevent imaging of midline structures in the abdomen, may be limited by patient habitus

Magnetic Resonance Imaging (MRI)
• non-invasive technique that does not use ionizing radiation • able to produce images in virtually any plane • patient is placed in a magnetic field; protons (H+) align themselves along the plane of magnetization due to intrinsic polarity. A pulsed radiofrequency beam is subsequently turned on which deflects all the protons off their aligned axes due to absorption of energy from the radiofrequency beam. When the radiofrequency beam is turned off, the protons return to their pre-excitation axis, giving off the energy they absorbed. It is this energy that is measured with a detector and interpreted by a computer to generate MRimages • the MR image reflects the Signal intensity as picked up by the receiver. This signal intensity is dependent on: • (1) hydrogen density: tissues with low hydrogen density (cortical bone, lung)
generate little to no MR signal and appear black. Tissues with high hydrogen
density (water) appear white on MRI
• (2) magnetic relaxation times (Tl and T2): reflect quantitative alterations in MR
signal strength due to intrinsic properties of the tissue and its surrounding
chemical and physical environment (see Table 1)

Contrast Agents in MR Imaging
• gadolinium-chelates used to highlight the blood vessels or highly vascular structures (e.g. tumours)
Table 1. MR Signal Intensities
Tissue or Body Fluid
Gas Mineral-rim tissue le.g. cortical bone, calculi) Collagenous tissue le.g. ligaments, tendons, scars) Hemosiderin Fat Protein-containing fluid (e.g. abscess, complex cystl Synovium Nucleus pulposus High bound-water tissues: Muscle, hyaline cartilage Liver, pancreas, adrenal High free-water tissues: CSF, urine, bile, edema Simple cysts GU organs, including kidney Thyroid Hemorrhage: Hyperacute 1<24 hoursl; hyperacute venous hemorrhage is slightly less bright than arterial on T2 due to deoxyhemoglobin Acute IHl days) reflects deoxyhemoglobin Chronic 1>7 daysl reflects methemoglobin • intracellular • extracellular Neuropathology: Ischemia Edema Demyelination Most malignant tumours Meningioma

T1 - weighted
Nil Nil Low High Medium

T2 -weighted
Nil Nil Low Medium to high High



Remember that WlIt8r is "white" on12 as "World War II"


Low to medium



Low Low High High Low

Low High Low High High

Medium Iisointense

Medium Iisointense

Positron Emission Tomography Scans (PET)

• non-invasive technique that involves exposure to ionizing radiation (-7mSv) • nuclear medicine imaging technique that produces images of functional processes in the body • positron-producing radioisotope, such as UHluorodeoxyglucose (I8-FDG) is
chemically incorporated into a metabolically active molecule (glucose), injected into
subject, travels to target organ, accumulates in tissues of interest, and radioactive
substance begins to decay, sending off gamma rays which are detected by PET

DM4 Diagnostic Medical Imaging

Imaging Modalities/Chest Imaging

Toronto Notes 2008

• advantages: oncologic early staging (breast, lung, brain), shows metabolism and function of tissues (not only anatomic), follow progression of cancer treatments, early signs of CAD • disadvantage: cost, ionizing radiation, lack of anatomic reference (unless used with CT/MRI) • conlraindications: pregnancy

Chest Imaging
Chest X-ray
• chest x-ray should be the initial imaging study in all patients with suspected thoracic disease • standard views: erect posterior to anterior (PA) and left lateral (minimize distortion of heart size by positioning heart closer to film) • supplemental films may include oblique, lordotic, and (left or right) lateral decubitus views • patient condition may require AP rather than PA, and supine rather than erect (i.e. bedridden) • always attempt to obtain a previous study for comparison

Computed Tomography (CT) Scan
• indications for CT in thoracic disease: • evaluation of abnormality detected on chest x-ray • staging llmg malignancies, metastatic disease • differentiation of empyema from lung abscess • detection of pulmonary embolism (PE protocol) • detection and evaluation uf aortic dissection • determine biopsy approach and may be used to guide biopsy • high-resolution CT takes fine-cut images of limited areas of the lung. Indications: • evaluation of a diffusely abnormal chest x-ray • baseline investigation for patients with diffuse lung disease • lung disease in a patient with normal CXR and abnormal pulmonary function tests • characterization of a solitary pulmonary nodule • hemoptysis

Thoracic Ultrasound
• pleural effusions may be identified and tapped, pleural lesions identified and biopsied • anterior mediastinal masses may be identified and biopsied • "real-time" imaging can evaluate diaphragmatic excursion
Approach to the Chest X·Ray


It Identification May Markers Prove = Position Quite = Quality Right = Respiration but Stop = Soft tissue And Abdomen Be = Bones Certain = Central shadow How = Hila Lungs = Lungs Appear = Absent structures

Other Modalities in Chest Imaging
• MRl: brachial plexus, pancoast tumour • nuclear medicine: V/Q scan, bone scan

Approach to the Chest X-Ray (CXR)
• • • • Identification: date of exam, patient name, sex, age, indications for the study Markers: Rand/or L Position: medial ends ot clavicles should be equidistant from spinous process at midline Quality: degree of penetration (e.g. thoracic disc spaces should be just visible through heart), lack of motion artifact • Respiration: right hemidiaphragm at 6th anterior interspace or 10th rib posteriorly on good inspiration; poor inspiration results in poor aeration, vascular crowding, compression and widening of central shadow

Toronto Notes 2008

Chest Imaging

Diagnostic Medical Imaging DM5

Approach • Soft tissues: neck, axillae, pectoral muscles, breasts/nipples, chest wall • nipple markers can help identify nipples (which may mimic lung nodules) • look for the amount of soft tissue present and presence of any soft tissue masses • look for the presence of air in the soft tissues • Abdomen (please see Abdominal Imaging): look for free air under the diaphragm • Bones: C-spine, T-spine, shoulder girdle, ribs, sternum (seen best on lateral film) • Central shadow: trachea, heart, great vessels, mediastinum, spine; look for mediastinal or tracheal shift • Hila: pulmonary vessels, mainstem and segmental bronchi, lymph nodes • Lungs: lung parenchyma, pleura, diaphragm; lungs on lateral film should become darker when going inferiorly • Absent structures: review the above, noting ribs, breasts, lung lobes


.}------------, The Portable CXR
• an x·ray where equipment is brought to the
bedridden patient (e.g. in ER, ICU, or general ward)
• resu~ing radiographs may not be as high in quality as stationary CXR • general~ poor inspiration (vascular crowding and accentuation of normal strueturesJ- shot in AP (apparent increased heart sizel • good for apatients progress le.g. trading an effusion, pulmonary edema, or line placementl


Common CXR Signs
Kerley B Lines • thickened connective tissue planes that occur most commonly in pulmonary edema and lymphangitic carcinomatosis • horizontal, <2 cm long and 1 mm thick, at periphery of lung, reach lung edge Air Bronchograms • normally bronchiole walls are not visible because they are filled with air and are surrounded by air • when surrounding alveoli are filled with fluid, dark, branching markings are visible (air bronchograms) Silhouette Sign • in normal CXR, diaphragm and mediastinum are visible because of difference in radiodensity between lung and these structures; i.e. there is an "interface" between the tissues • "silhouette sign" refers to loss of normally appearing interfaces, implying opacification due to consolidation (most common), atelectasis, mass, etc. in adjacent lung • silhouetting of different structures is associated with disease in specific parts of the lung (Table 2). Note that pleural or mediastinal disease can also produce the silhouette sign
Table 2. Localization Using the Silhouette Sign
Interface Lost Superior vena cava I right superior mediastinum Right heart border Right hemidiaphragm Aortic knob I left superior mediastinum Left heart border Left hemidiaphragm Location of Lung Pathology Right upper lobe Right middle lobe Right lower lobe Left upper lobe Lingula Left lower lobe

6 Signs of CHF on CXR

1) Vascular redistribution 2) Peribronchial cuffing 3) Kerly B line' 4) Pleural effusion, S) Batwing pattern (,ymmetrical

airspace disease in the lung

Snowball Sign • if the mass looks like a snowball just before impact, it is localized in the lungs • if the mass looks like a flattened snowball after impact, it is localized in the surrounding structures (i.e. chest wall, pleura, or mediastinum)

adjacent to the hila) 6) Cardiomegaly

c> Jodi Cross;ngham 2007

Figure 1. 6 Signs of CHF on CXR

Common CXR Abnormalities
Air Space Disease • air space disease refers to a pathological process primarily in the alveoli; it is
synonymous with consolidation
• cardinal features of airspace disease: • air bronchogram: - lucent branching bronchi visible through opacification • airspace nodules: - fluffy, patchy, poorly marginated appearance with later tendency to coalesce - may take on lobar or segmental distribution




DDx of airspace disease

(representative eumple)
• pus (pneumonia) • fluid (pulmonary edemal • blood (pulmonary hemorrhage) • cells (lung cancer, e.g. bronchioalveolar
carcinoma; Iymphomal
• protein lalveolar proteinosis)

DM6 Diagnostic Medical Imaging

Chest Imaging

Toronto Notes 2008



Interstitial Disease
• pathological process involving the interlobular cormective tissue (i.e. "scaffolding of the lung") • cardinal features ot interstitial disease: • linear densities: Kerley B lines (see above) • reticular pattern: thin, well-defined linear densities, often in net-like or "honeycomb" arrangement • nodular pattern: multiple, discrete, nodular densities, <5 mm diameter • reticulonodular: combination of reticular and nodular patterns • both air space and interstitial disease may occur simultaneously (e.g. pulmonary edema)


DDx of intemitiII diIeae
pulmonary edema
collagen disease (fibrosisl
metastatic disease
(Iymphangitic permeation)
inflammatory conditions (early viral
pneumonia, interstitial pneumonia)


.}-------------, DOl of pulmonary edemII • cardiogenic • renal failure, volume overload • non-alrdiogenic (acute respiratory
distress syndrome lARDS))


Pulmonary Edema
• look for vascular redistribution/enlargement, pleural effusion, cardiomegaly (may be present in cardiogenic edema and fluid overloaded states) • edema fluid initially collects in interstitium: • loss of definition of pulmonary vasculature • peribronchial cuffing • Kerley B lines • reticulonodular pattern • thickening of interlobar fissures • as pulmonary edema progresses, fluid begins to collect in alveoli causing diffuse air space disease often in a "bat wing" or "butterfly" pattern with tendency to spare the outermost lung fields

• loss of lung volume, ranging from subsegmental collapse to collapse of an entire lung • 5 causes ot atelectasis: 1. obstructive: most common and most important type; collapse of alveoli develops within a few hours of airway obstruction as air distal to obstruction is reabsorbed • obstructive atelectasis may occur secondary to neoplasm, foreign body, inflammation or mucus plug (seen in cystic fibrosis) 2. compressive: physical compression due to adjacent tumour, bulla, effusion, enlarged heart 3. traction (cicatrization): due to scarring, which distorts alveoli and contracts the lung 4. adhesive: due to lack of surfactant (-.!t surfactant = -.!t lung distensibility); can be congenital (ie. hyaline membrane disease) 5. passive (relaxation): a result of air or fluid in the pleural space (i.e. pleural effusion, pneumothorax) • direct signs of atelectasis: • displacement or deviation of a fissure (most important) • increased opacity • crowding of vessels • silhouette sign • indirect signs ot atelectasis (secondary to volume loss): • hilar shift toward collapse (most important) • mediastinal shift toward collapse (except in tension pneumothorax) • diaphragm elevation • compensatory hyperinflation in other areas • in the absence of a known etiology, persisting atelectasis must be investigated to rule out a bronchogenic carcinoma

Pulmonary Nodule (Table 3)
• differential diagnosis: • malignancy (primary or metastatic) • benign neoplasm: hamartoma, bronchial adenoma • granuloma • simulated: nipple, bone lesion, skin lesion, foreign body, artifact • less common causes include abscess, hematoma, infarct, loculated pleural effusion, organized pneumonia, sarcoidosis, cystic disease, vascular lesions

Differential diagnosis for cavitating lung nodule Cancer A.utoimmune Vascular Infection Trauma Youth (Congenital)

Toronto Notes 2008

Chest Imaging

Diagnostic Medical Imaging DM7

Table 3. Characteristics of Benign & Malignant Pulmonary Nodules
Malignant Margin Contour
Calcification DoublingTime
ill-defined/spiculated I"corona radiata"l lobulated eccentric or stippled 20-460 days cavitation, collapse, adenopathy, pleural effusion,
lytic bone lesions, smoking history

well·defined smooth diffuse, central, popcorn, concentric <20 days or >460 days

Other Features

• doubling time: time required for a lesion to double in volume; this corresponds to a 1.26x increase in diameter • 2-year follow-up is recommended; if no change, then 99% chance benign • CT scan excellent for determining the pattern of calcification and presence of fat
(as in hamartoma)
• clinical information and CT appearance determine level of suspicion of malignancy • if high probability, invasive testing is indicated • if low probability, repeat CXR in 1-3 months and then every 6 months for 2 years • invasive tests include fine needle aspiration under CT or fluoroscopic guidance.
This is more sensitive (>90% for malignancy) than transbronchial biopsy, but
carries increased morbidity
• generally transbronchial biopsy is better for central lesions; transthoracic better for peripheral lesions

An elevated hemidiaphragm suggests intra-abdominal process, pregnancy, diaphragmatic paralysis, atelectasis, lung resection or pneumonectomy. Pleural effu· sion also may resu~ in apparent elevation.

PLEURA Pleural Effusion
• in an uncomplicated effusion fluid is higher laterally than medially, forming a meniscus with the pleura; a horizontal fluid level is seen only in a hydropneumothorax (both fluid and air within pleural cavity) • pooling of fluid occurs first in the posterior recess, then spreads laterally and anteriorly; therefore, the lateral film is most sensitive for pleural effusion (min 75cc of fluid accumulation on lateral film compared to 200cc of fluid on PA to first detect pleural effusion) • lateral decubitus film with effusion in dependent position will show layering unless effusion is loculated • effusion may exert mass effect, shift trachea and mediastinum to opposite side or cause atelectasis of adjacent lung • ultrasound is superior to plain film for detection of small effusions and may also aid in thoracentesis



• upright chest film allows visualization of visceral pleura as curvilinear line paralleling chest wall, separating partially collapsed lung from pleural air • more obvious on expiratory (increased contrast between lung and air) or
lateral decubitus film (air collects superiorly)
• more difficult to detect on supine film; look for the "deep (costophrenic) sulcus" sign, "double diaphragm" sign (dome and anterior portions of diaphragm outlined by lung and pleural air, respectively), hyperlucent hemithorax, sharpening of adjacent mediastinal structures • mediastinal shift may occur if air is under tension ("tension pneumothorax")

•.r - - - - - - - - - - - - ,


Free air underneath diaphragm (pneumoperi· toneum)- see Abdomina/Imaging, DMl2.

• asbestos exposure may cause various pleural abnormalities including benign plaques (most cornmon) that may calcify, diffuse pleural fibrosis, effusion, and malignant mesothelioma

DM8 Diagnostic Medical Imaging

Chest Imaging

Toronto Notes 2008

MEDIASTINUM Mediastinal Mass
• radiologically, the mediastinum is divided into three compartments; this provides the approach to the differential diagnosis of a mediastinal mass • anterior (anterior line formed by anterior trachea and posterior border of heart and great vessels) • 4 T's: thyroid, thymic neoplasm (e.g. thymoma), teratoma, and "terrible" lymphoma • thymic or pericardial cyst, epicardial fat pad • foramen of Morgagni hernia • middle (extending behind anterior mediastinum to a line 1 em posterior to the anterior border of the thoracic vertebral bodies) • esophageal carcinoma, esophageal duplication cyst • metastatic disease • lymphadenopathy (all canses) • hiatus hernia • bronchogenic cyst • posterior (posterior to the line described above) • neurogenic tumour (e.g. neurofibroma, schwannoma) • multiple myeloma • pheochromocytoma • neurenteric cyst, thoracic duct cyst • lateral meningocele • Bochdalek hernia • extramedullary hematopoiesis • in addition, any compartment may give rise to lymphoma, lung cancer, aortic aneurysm or other vascular abnormality, abscess, and hematoma

The 4TI of an Anterior

Mediutinal Mell:
Thyroid Thymus Teratoma "Terrible" lymphoma

Enlarged Cardiovascular Shadow
• heart borders • on PA view, right heart border is formed by right atrium; left heart border is formed by left atrium and left ventricle • on lateral view, anterior heart border is formed by right ventricle; posterior border is formed by left atrium (superior to left ventricle) and left ventricle • cardiothoracic ratio = greatest transverse dimension of the central shadow relative to the greatest transverse dimension of the thoracic cavity • in an adult, good quality erect PA chest film, cardiothoracic ratio of >0.5 is abnormal; DDx of ratio >0.5: • cardiomegaly (myocardial dilatation or hypertrophy) • pericardial effusion • poor inspiratory effort/low lung volumes • pectus excavatum • ratio <0.5 does not exclude enlargement (e.g. cardiomegaly + concomitant hyperinflation) • pericardial effusion • globular heart • loss of indentations on left mediastinal border • peri- and epicardial fat pad separation on lateral film ("sandwich sign") • right atrial (RA) enlargement • increase in curvature of right heart border • enlargement of superior vena cava (SVC) • left atrial (LA) enlargement • straightening of left heart border • increased opacity of lower right side of cardiovascular shadow
(double heart border)
• elevation of left main bronchus (specifically, the upper lobe bronchus on the lateral film), distance between left main bronchus and "double" heart border >7 em, splayed carina (late sign) • right ventricular (RV) enlargement • elevation of cardiac apex from diaphragm • anterior enlargement leading to loss of retrosternal air space on lateral • increased contact of RV against sternum • left ventricular (LV) enlargement • displacement of cardiac apex inferiorly and posteriorly • "boot-shaped" heart • Rigler's sign: on lateral film, from junction of inferior vena cava (IVC) and heart at level of the left hemidiaphragm, measure 1.8 em posteriorly then 1.8 em superiorly -> if cardiac shadow extends beyond this point, then LV enlargement is suggested [Note: not to be confused with Rigler's sign in the abdomen]

Toronto !':otes 2008

Musculoskeletal System (MSK)

Diagnostic Medical Imaging DM9

Musculoskeletal System (MSK)
• see also Orthopaedics

• plain film • initial study used in most evaluations of bone • minimum of two films at right angles to each other (usually AP and lateral) to lUll' out a fracture • image proximal and distal joints (particularly important where there are paired bones e.g. radius/ulna) • not very effective in evaluating soft tissue injury • fast, inexpensive, readily available
• CT




Plain film first for fractures CTforCortex MRI for Marrow

• evaluation of bone cortex and type of cortical expansion • for cornrrUnuted fractures and complex structures (skull, spine, acetabulum, calcaneus, sacmm) • IV contrast may be used to determine lesion vascularity • ",valuation of soft tissue calcification/ossification • excellent for visualization of bone marrow and surrounding soft tissues (ligaments, tendons, joint capsules, menisci, cartilage) • can visualize vascular structures without need for contrast

• i\IRl

• U/S



• diagnose tendon and ligament injury (e.g. rotator cuff injury) • determine if lesions are cystic or solid • guided biopsy of soft tissue lesions • Doppler - determines vascularity of structures • nuclear medicine (skeletal scintigraphy) • determine the location and extent of bony lesions • radioisotopes localize to areas of increased bone turnover or calcification ­ growth plate in children, tumours, infections, fractures, metabolic bone disease (e.g. Paget's), sites of reactive bone formation in arthritis, and periostitis • very sensitive, not specific (trauma, infection, inflammation look the same)


Approach to Fractures 1} Look for fracture lines
(abnormal black lines)
2) Look for discontinuation/
disruption of cortex border
3} Look for joint space
4) Look for soft tissue involvement
(swelling, calcification)

Approach to Interpretation of Bone X-Rays
• identification - name, age of patient, type of study, region of investigation • soft tissues - swelling, calcification/ossification • joints - alignment, joint space, presence of effusion, osteophytes, erosions, bone
density, overall pattern and symmetry of affected joint
• bone - periosteum, cortex, medulla, trabeculae, density, articular ends, bone
destruction, bone production, appearance of the edges or borders of any lesions
(see Figure 2)

• description of fractures • patient (name, age, sex)
views (e.g. AP and lateral of right wrist)
• site of fracture • bone (e.g. tibia, scaphoid, etc.) • region of bone (e.g. proximal, distal, metaphyseal, epiphyseal, diaphyseal) • intra-articular vs. extra-articular • pattern of fracture line • simple: a single break divides bone in two pieces • comminuted: bone broken into more than two pieces displacement (described with reference to distal fragment) soft tissue involvement • calcification, gas, foreign bodies
• open (compound) vs. closed
• type of fracture - stress: fracture due to repetitive small trauma - pathologic: fracture in area of bone weakened by disease • for specific fracture descriptions and characteristics of fractures, see Orthopaedics




Types of Fractures • transverse • avulsion
• oblique • impacted
• spiral




Types of Displacements • translation • impaction • angulation • dislocation • rotation

DMlO Diagnostic Medical Imaging

Musculoskeletal System (MSK)

Toronto Notes 2008


' } - - - - - - - - - - - - , Arthritis .~
• see Rheumatology, RH4

The Radiographic Hallmarks of OA 1. joint space narrowing
2, subchondral sclerosis
3, subchondral cyst formation
4, osteophytes

• metastatic tumours to hone are much more common than primary bone tumours, particularly if age >40 years • diagnosis usually requires a biopsy if primary not located • few benign tumours/lesions have potential for malignant transformation • CT is the best way to identify the extent of a bone lesion in the cortex, or extent of cortical involvement • MRl is good for tissue delineation and preoperative assessment of surrounding soft tissues, and medullary/marrow involvement • plain film is less sensitive'than other modalities

... '. ~ - - - - - - - - - - - - , )
These lesions can safely be

• age - most common tumours by age group: • <1 year of age: metastatic neuroblastoma • 1-20 years of age: Ewing's tumour in tubular bones • 10-30 years of age: osteosarcoma and Ewing's tumour in flat bones • >40 years of age: metastases, multiple myeloma and chondrosarcoma • single or multiple lesions: multiple lesions are more suggestive of malignant process or metabolic disease • cortical thickening: new bone formation, suggestive of osteomyelitis, malignancy, or pathological fractures

left alone

• Osteoma • Bone island • Nonossifying fibroma

Characteristics of Tumours
• see Figure 2 and Table 4 • margins/zones of transition • transition area from normal bone to area of lesion, reflects aggressiveness of the lesion • well-defined lesion with narrow zone of transition (i,e, sharp cut-off between normal and abnormal) suggest a non-aggressive process • sclerosed borders are suggestive of a non-aggressive process • an ill-defined lesion with a permeative pattern is suggestive of malignancy • expansile • intact, ballooned cortex is more likely benign • destruction of cortex is more likely malignant • periosteal reaction • mature well-formed solid periosteal reaction: most likely a non-aggressive process • soft tissue • soft tissue mass: matrix tumour, osseous, cartilage

..... . ~ - - - - - - - - - - - - , ) Periosteal Reaction
• "onion skinning": Ewing's sarcoma • "sunburst'; "hair on end":
• 'codman's triangle": osteosarcoma,
Ewing's sarcoma, subperiosteal,


Margination of [esions

Patterns of
cortical distucbance

Patterns of medullary

Periosteal new bone


thin rim of

thick rim of sclerosis

sunburst teot divetb

...._ _undul.ting


©Patrick Cervini, 2002

Figure 2. Radiographic Appearance of Bone Remodelling and Destruction Processes

Toronto Notes 2008

Musculoskeletal System (MSK)

Diagnostic Medical lmaging DMll

Table 4. Characteristics of Benign and Malignant Bone Lesions
o single

o multiple


o no

bone pain area of delineation o overlying cortex intact o no or simple periosteal reaction o sclerotic margins with sharp zone of transition o no soft tissue mass
o sharp

lesions (metastatic/multiple myeloma)
(some syndromes have multiple benign lesions)
o bone pain o poor delineation of lesion - wide zone of transition
o loss of overlying cortex/bony destruction
o periosteal reaction - aggressive o wide zone of transition o soft tissue mass


Note: for specific bone tumours see Orthopaedics



Metastatic Bone Tumours
• all malignancies have potential to metastasize to bone • metastases are 20-30x more common than primary bone tumours • when a primary malignancy is first detected, a bone scan is often part of the initial
• may present with pathological fractures or pain • biopsy or determination of primary is the only way to confirm the diagnosis • metastasis can cause a lytic (decreased density) or a sclerotic (increased density)
reaction when seeding to bone

Table 5. Characteristic Bone Metastases of Common Cancers Lytic Sclerotic Expansile
breast lung thyroid kidney
multiple myeloma
prostate breast treated tumours thyroid renal

lytic =decreased density
sclerotic =increased density




Most Common Metastatic
(in order of frequency)
"Be Like People That Know" Breast Lung Prostate Thyroid Kidney

• Tc99m, followed by indium-Ill labelled white cell scan or gallium radioisotope scan is the best modality to establish the presence of bone infection • plain film • visible 8-10 days after process has begun
• osteomyelitic changes on plain film
• soft tissue swelling that is deep and extends from the bone with loss of tissue planes (because fat becomes edematous) • local simple periosteal reaction over the area of bone • pockets of air (from anaerobes) may be seen in the tissue planes • metaphysis over the area of infection may appear mottled and nonhomogeneous with a classic "moth-eaten" appearance

Bone Abscess
• classical appearance known as Brodie's abscess on plain film
• overlying cortex has periosteal new bone formation
• sharply outlined radiolucent area with variable thickness in zone of transition • variable thickness periosteal sclerosis • sequestrum: a piece of dead bone within a Brodie's abscess • a sinus tract or cloaca may communicate between the abscess through the cortex to the surface of the bone

Metabolic Bone Disease
• with increasing age, hormonal changes lead to bone resorption exceeding bone
• reduction in amount of normal bone; fewer and thinner trabeculae; diffuse process; affecting all bones • Dual X-ray Absorptiometry (DEXA) - gold standard for measuring bone mineral
density (BMD)




Diagnostic sensitivity of DEXA high­ est when BMD measured at lumbar spine and proximal femur.

DMU Diagnostic Medical Imaging

Musculoskeletal System (MSK)/Gastrointestinal Tract

Toronto Notes 2008

"'",9 ) - - - - - - - - - - - - - - , ,
Osteoporosis 'Meouceo amount of bone

• T-5core: the number of standard deviations from the young adult mean • used to diagnosis osteoporosis and is a measure of current fracture risk • most clinically valuable
• -2.5 < t < -1 = osteopenia
• t < -2.5 = osteoporosis • Z-score: the number of standard deviations from the age-matched mean • appearance on plain film: • increase in bone lucency • compression of vertebral bodies • biconcave vertebral bodies ("codfish" vertebrae) • long bones have appearance of thinned cortex and increased medullary cavity • look for complications of osteoporosis (e.g. insufficiency fractures: hip, vertebrae, sacmm, pubic rami, calcaneus most common)

Normal amount of bone, but reduced Mineralization of normal osteoid

OsteomalacialRickets • reduction in bone density due to W1ffiineralized osteoid • initial radiological appearance of both osteoporosis and osteomalacia is osteopenia (coarse and poorly defined bone texture) • seams of W1ffiineralized osteoid • "fuzzy", ill-defined trabeculae • softening and arching of long bones • Looser's zones (pseudofracture) • characteristic radiological feature • fissures or clefts at right angles to and extending through cortex of long bones • DDx: osteomalacia, chronic renal disease, fibrous dysplasia, hyperthyroidism, Paget's, osteodystrophy, x-linked hypophosphatemia Hyperparathyroidism • most common cause is renal osteodystrophy (also caused by malignancy) • skeletal manifestations of chronic renal insufficiency • chondrocalcinosis • intra-articular deposits of calcium • calcifications of the soft tissues (including arteries and peri-articular soft tissue) • resorption of bone typically in hands (subperiosteal and at tufts), 51 joints (subchondral), skull ("salt and pepper" appearance), osteoclastomas (brown tumours) • "rugger jersey spine": band-like osteosclerosis at superior/inferior margins of vertebral bodies Paget's Disease • abnormal remodelling of bone - especially skull, spine, pelvis • may involve single or multiple bones • 3 phases: 1st lytic, 2nd mixed (lytic/sclerotic), 3rd sclerotic • features: • coarsening of the trabeculae with bone expansion • bone softening/bowing • bone scan will reveal high activity, especially at bone ends • thickened cortex • complications: • pathological fractures • cardiac failure • early OA • nerve entrapment in base of skull • malignant degeneration

Gastrointestinal (GI) Tract


Abdominal X-Ray (AXR)
• acute abdomen: bowel perforation, toxic megacolon, bowel ischemia, small bowel obstruction (5BO), large bowel obstruction (LBO) • chronic symptoms: constipation, calcifications (gallstones, renal stones, urinary bladder stones, etc.)


3 Views of Abdomen 'CXR • Supine AXR • Erect/Upright AXR

Radiographic Anatomy
• AXR - 3 most common views: supine, upright and left lateral decubitus (LLD)

Toronto Notes 2008

Gastrointestinal Tract

Diagnostic Medical Imaging DM13

Table 6. Differentiating Small and large Bowel

Mucosal Folds Location Maximum diameter Maximum fold thickness Other

Small Bowel
uninterrupted valvulae conniventes lor plicae circularisl
central 3cm 3mm rarely contains solid fecal material

Large Bowel

interrupted haustra extend only partway across lumen peripherallpicture frame!
6cm 19 cm at cecum)
commonly contains solid fecal material

• bilateral flank fat stripes adjacent to ascending and descending colon • abdomen divided into 2 cavities: • peritoneal cavity - lined by peritoneum that wraps around most of the bowel, the spleen and most of the liver; forms a recess lateral to both the ascending and descending colon (paracolic gutters) • retroperitoneal cavity - contains duodenum (2nd, :lrd, and 4th parts), ascending and descending colon and the rectum, pancreas, kidneys, adrenal glands, ureters, bladder, psoas muscles, and the abdominal aorta; the contour of several of these organs can often be seen on radiographs

roacti to AXR
• • • • Mnemonic: lilT Free ABDO" I = identification: date, name, age of patient, type of study T =technical factors: good coverage, appropriate penetration, identify view Free = free fluid • assess distance between lateral fat stripes and adjacent colon for evidence of free peritoneal fluid in the paracolic gutters • pooling of the bowel to the centre of the supine film • ascites (free fluid in the peritoneal cavity) and blood (hemoperitoneum) are the same density on the radiograph, therefore, cannot be differentiated • large amounts of fluid ---+ diffuse increased opacification on supine HIm; bowel floats to centre of anterior abdominal wall • A=Air
upright film: air under diaphragm llD film: air between liver and abdominal wall supine film: gas outlines of structures
not normally seen:
• inner &outer bowel wall (Rigler's sign) • falciform ligament • peritoneal cavity I"football" sign) gas outlining retroperitoneal structures allowing increased visualization: • psoas shadows • renal shadows lucent air streaks in bowel wall, 2types: 1. linear 2. rounded Icystoides type)




Approach to AXR
Free ABDO"
Technical factors
Free fluid
Bowel wall thickening
Dens~ies (bones, calcifications)


Table 7. Abnormal Air on Abdominal X·Ray

Air Extraluminal

• intraperitoneal (pneumoperitoneum!

Common Etiologies

perforated viscus postoperative (up to 10 days to be resorbedl

... '9 ) - - - - - - - - - - - , ,
perforation of retroperitoneal segments of bowel:
duodenal ulcer, post-eolonoscopy

• retroperitoneal

What's in the Retroperitoneum?
1) Duodenum (2 nd, 3'd, 4th part)
2) Ascending, descending colon
3) Rectum
4) Kidneys, ureters, bladder, adrenals
5) Psoas, quadratus lumborum

(pneumatosis intestinalis!

linear: ischemia, necrotizing enterocolitis
• primary (idiopathic) • secondary to COPD adynamic Iparalytic) ileus, mechanical bowel
obstruction (see Table 8)
abscess (evaluate with CT)

Intraluminal Loculated Biliary
Portal venous

dilated loops of bowel, air·fluid levels

mottled, localized in abnormal position without normal bowel features
air centrally over liver cholangitis, emphysematous cholecystitis air peripherally over liver in branching pattern

sphincterotomy, gallstone ileus, erosive peptic ulcer

bowel ischemiMnfarction

DM14 Diagnostic Medical Imaging

Gastrointestinal Tract

Toronto Notes 200S

Table 8. Adynamic Ileus vs. Mechanical Obstruction

Calibre of bowel loops Air-Fluid levels (erect and LLD films only)

Adynamic Ileus normal or dilated same level in asingle loop

Mechanical Obstruction usually dilated multiple air fluid levels giving "step ladder" appearance, dynamic (indicating peristalsis presentl "string of pearls" lrow of small gas accumulations in the dilated valvulae conniventes) dilated bowel up to the point of obstruction (i.e. transition point) no air distal to obstructed segment "hairpin" 1180~ turns in bowel ileocecal valve (ICV) function in large bowel obstruction: • competent ICV: bowel distention from site of obstruction to valve; cecal distention>10 cm represents increased risk for perforation • incompetent ICV: small and large bowel distended; radiographic appearance more similar to paralytic ileus


air throughout GI tract generalized or localized • in alocalized ileus (e,g. pancreatitis, appendicitis): dilated loop "sentinel loop" remains in the same location on serial films, usually adjacent to the area of inflammation

• volvulus ("twisting of the howel upon itself") - from most to least common: • sigmoid: "coffee bean" sign (massively dilated sigmoid projects to right or mid-upper abdomen) with proximal large bowel dilation; see Table 9 • cecal: massively dilated bowel loop projecting to left or mid-upper abdomen with small bowel dilation • gastric: rare • small bowel: "corkscrew sign" (rarely diagnosed on plain films, seen best on CT) • toxic megacolon • manifestation of fulminant colitis • extreme dilatation of colon (>6.5 em) with mucosal changes including foci of edema, ulceration and pseudopolyps, loss of normal haustral pattern • B = bowel wall thickening • increased soft-tissue density in bowel wall, thumb-like indentations in bowel wall "thumb-printing", or a picket-fence appearance of the valvulae conniventes ("stacked coin" appearance) • encountered in IBD, infection, ischemia, hypoproteinemic states, and submucosal hemorrhage • D = densities • bones - look for gross abnormalities of lower ribs, vertebral column and bony pelvis • abnormal calcifications - approach by location • RUQ: renal stone, adrenal calcification, gallstone, porcelain gallbladder • RLQ: ureteral stone, appendicolith, gallstone ileus • LUQ: renal stone, adrenal calcification, tail of pancreas • LLQ: ureteral stone • central: aorta/aortic aneurysm, pancreas, lymph nodes • pelvis: phleboliths (calcified veins), uterine fibroids, bladder stones • 0 =organs • kidney, liver, gallbladder, spleen, pancreas, urinary bladder, psoas shadow • outlines can occasionally be identified because they are surrounded by more lucent fat, but all are hest visualized with other imaging modalities (CT, MRI)

Toronto Notes 2008

Gastrointestinal Tract

Diagnostic Medical Imaging DM15

Contrast Studies
Table 9. Types of Contrast Studies
Cine Esophagogram Barium Swallow

- contrast agent swallowed -recorded for later playback and analysis - contrast agent swallowed under fluoroscopy, selective images captured


cervical esophagus

aspiration, webs, Zenker's diverticulum, cricopharyngeal bar, laryngeal tumour achalasia, hiatus hernia, esophagitis, cancer esophageal tear: 11 MalioryWeiss tear (mucosall 2) Submucosal tear Isubmucosal! 31 Boerhaave's tear (transmural! ulcers, neoplasms, filling defects

dysphagia, rio GERD, post esophageal surgery

thoracic esophagus

Upper GI Series

-double contrast study

-111 barium to coat mucosa,
then (2) gas pills for distention -patient NPO after midnight Barium Enema - colon filled retrograde with barium and air or CO, -bowel prep the night before procedure

dyspepsia, investigate possible UGI bleed, weight loss/anemia, post gastric surgery

thoracic esophagus, stomach, duodenum

altered bowel habits, suspected LGI bleed, weight loss, anemia, rio large bowel obstruction, suspected perforation, check surgical anastamosis, history of polyps post operatively to assess anastomoses for leak/obstruction, perforation GI bleed with nondiagnostic upper GI series/barium enema, weight loss/anemia, diarrhea, lBO,
malabsorption, abdominal pain, post small bowel
lBO, malabsorption, weight loss/anemia, Meckel's diverticulum

large bowel rectum may be obscured by tube - therefore must do sigmoidoscopy to exclude rectal lesions large bowel entire small bowel

diverticulosis, neoplasms, lBO, intussusception lcan be reduced with barium or air enema I, VOlvulus perforation, obstruction neoplasms, lBO, malabsorption, infection

Hypaque Enema

-water soluble contrast with or without bowel prep

Small Bowel FoliowThrough -single contrast images following UGI series

Small Bowel Enema lenteroclysisl

duodenal intubation 11 bariumlmethyl cellulose infusion and fluoroscopic evaluation 2) CT enteroclysis with water infusion

entire small bowel

as above

Abdominal Computed Tomography (CT)
• plain CT: renal colic, hemorrhage • contrast CT: • portal venous phase: majority of cases • biphasic (arterial and portal venous phases): liver, pancreas, bile duct tumours

AComparison of Colonoscopy and Double­ Cordnst BaM Enema for SuMtilanca after
PoIypec1Dmy (NEMJm June 15; 342:1766-1772)

• oral: barium or water soluble (water soluble if suspected perforation) given in most cases to demarcate GI tract • rectal: given for investigation of colonic lesions • IV: given immediately before or during CT to allow identification of arteries and veins • caution: contrast allergy (give pre-medication = steroids and antihistamine) • contraindication: impaIred renal fun,tion

Sludy: Randomized, blinded clinical trial.
Patients: Part of National Polyp Study. Total of 580 patients with previous polypectomy. Inl8MlIItion: Patients received atotal of 862 paired colonoscopy and double-contrast barium enema (DC BE) studies. Endoscopist was bl"lOded to DCBE results (performed prior to colonoscopyl. Main oub:_: For either modality, detaction of polyps, size of polyps detected. ResuIIs: Positive colonoscopy studies, 242. Positive barium enema studies, 222126%1, of which 94 were coincident with colonoscopy find­ ings. Detection rate for DCBE 139%1 was signifi­ cantly related to polyp size. For polyps s~ed 0.5 cm or less on colonoscopy, 32% of DCBE studies were positive. For polyps s~ed 0.6 to 1.0 cm, 53% of polyps were detected with DCBEln the 139 paired examinations with positive DCBE results and negative colonoscopy resutts, 19 polyps of which 12 were adenomas were detected on colonoscopic re-examination.
Conclusion: Colonoscopy is amore effective
method of surveillance than DCBE No endpoints vis-a-vis patient outcome were examined in this study.

Approach to Interpretation of Axial Abdominal CT Images
1. look through all images in Gestalt fashion to identify any obvious abnormalities 2_ look at each organ/structure individually, from top to bottom evaluating size and "hape of each area of increased or decreased density 3. evaluate the following: • visible lung (bases), liver, gallbladder, spleen, pan,reas adrenals, kidneys, ureters, and bladder • stomach, duodenum, small bowel mesentery, and colon/appendix retroperitoneum: aorta, vena cava, and mesenteric vessels; look for adenopathy in vicinity of vessels peritoneal cavity for fluid or masses • vertebrae, spinal cord and bony pelvis abdominal wall and adjacent soft tissue

CT and Bowel Obstruction
• cause of bowel obstruction rarely found on plain films - CT is best choice for imaging

CT Colonography (virtual colonoscopy)
• emerging imaging technique for evaluation of intraluminal colonic masses (i.e. polyps, tumours) • CT scan of the abdomen after the instillation of air into a prepped colon • computer rendering of 2-dimensional CT images into a 3-dimensional intraluminal view of the colon in order to look for polyps • lesions seen on 3D rendering correlated with 2D axial images • indications: surveillance in low-risk patients, incomplete colonoscopy, staging of identified colonic lesions

DM16 Diagnostic Medical Imaging

Gastrointestinal (GI) Tract

Toronto Notes 2008

Solid Visceral Organ Imaging
• VIS: assessment of cysts, abscesses, tumours, biliary tree • CT with IV contrast: liver parenchyma (MRI better) • MRI: differentiation of benign hemangiomas from primary liver tumours and metastases • cirrhosis and portal hypertension, CT findings: • altered liver size, contour, density fatty infiltration: liver appears less dense than spleen (reverse true if healthy) advanced cirrhosis: liver small and irregular (fibrous scarring, segmental atrophy, regenerating nodules) • varices (caput medusa, esophageal varices, porto-systemic shunts, dilated splenic vein) • splenomegaly dl1d ascites • investigation of liver masses • require contrast to visualize certain hepatic masses • hepatic blood supply: 20% hepatic artery, 80% portal vein 3 phases of enhancement following IV contrast bolus: • arterial phase (20-30 sec) • portal venous phase (60-70 sec) - provides maximum enhancement of hepatic tissue - most tumours supplied by hepatic artery and relatively hypovascular, therefore, appear as low-attenuation masses in portal venous phase • equilibrium phase (1.5-3 min)
Table 10. Imaging of Liver Masses Mass UIS

Usually low attenuation on contrast enhanced scan Small: hypervascular enhances in arterial phase Large: low·attenuation Well·defined, low attenuation, homogenous


Multiple masses of variable echotexture Single/multiple masses, or diffuse infiltration Well·defined, anechoic, acoustic enhancement

Liver Mass DDx "5 Hs"

Hydatid cyst Hemangioma Hepatic adenoma Hyperplasia Ifocal nodularl

Simple cyst Abscess Hydatid cyst Hemangioma Focal nodular hyperplasia

Poorly defined, irregular margin, hypoechoic contents Low·attenuation lesion with an irregular enhancing wall Simple/multiloculated cyst Homogenous hyperechoic mass Well·defined mass, central scar seen in 50% Low·attenuation simple or multiloculated cyst; calcification Peripheral globular enhancement in arterial phase scans; central·filling and persistent enhancement on delayed scans Equal attenuation to liver in portal venous phase, enhancement in arterial phase Well·defined margin with heterogeneous texture due to hemorrhage or fat

Hepatic adenoma Most common in young women taking oral contraceptives, Well·defined mass with hyperechoic areas due to hemorrhage
Reviled EstimIteI aI ~Test Senativity
IIld Specffic:ity in Suspec1lld IIiaryTRIClIli.­ (Shea JA et al. ArdIives ofInternal Medicine. 154{12): 25m1, 1994 Nov 281

• U/S, CT, and/or nuclear medicine scan • primary lymphoma> splenic metastases • CT for splenic trauma (hemorrhage)

PurpoIe:To assess lhe sensitivity and specificity of
1es1S used 10 diagnose d1oIelittlias~ and acute dlole­ cystitis, including ultrasonography, OIal dlolecystogra
­ phy, radionudeotide scanning withTechnetium, MRI, CT. Study CbarIct8ristics: Meta-analysis of II studies evaluating the use of different imaging modalities in the diagno~s of biliary Iract disease.
Participants: No limits. Main Outcomes: Sensrrivity and specificity of the dif· ferent imaging modalities, using the gold standard of surgery, autopsy, or 3month dinical follow-up for dlolelithiasis, for acute dlolecystitis, pathologic find­ ings, confirmation of an allernate disease, or clinical resolulion during hospital~ation for dlolecystitis were uses as the standard, Rasutts: for evaluating cholelrrhiasis, UIS had the best unadjusted sensitivity 10.97; 95% CI, 0.95 to 0.991 and specificity 10.95, 95% CI, 0.8810 lOOI and adjusted Ifor verification biasl sensrrivity (0.84, 95% a0.7610 0,921 and specificity 10.99; 95% a, 0097 to lOOI. for evaluat· ing acute dlolecystitis, radionucleotide scanning has Ihe best sensilivity 10,97; 95% CI. 0.9610 0.981 and • specificity 10.~; 95% a, 0.8610 0.951. Conclusions: UIS ~ the test of dloice for d"Jagno~ng cholelithiasis and radionudeotide scanning is the supe­ rior lest for diagnosing acute cholecystitis


• U/S
• CT • bile ducts usually visualized only if dilated, secondary to obstruction
(e.g. choledocholithiasis, benign stricture, mass)

• dilated intrahepatic ductules seen as branching, tubular structures following pathway of portal venous system • ERCP, MRCP, PTC: further evaluation of obstruction

• tumours • U/S: mass is more echogenic than normal pancreatic tissue • CT: preterred modality for diagnosis/staging • ductal dilation secondary to stone/tumour • MRCP: imaging of ductal system using MRI cholangiography • ERCP: assessment of pancreatic and bile ducts via Ampulla of Vater; therapeutic potential (stent placement, stone retrieval); complication = acute pancreatitis occurs in 5% of diagnostic procedures and 10% of therapeutic procedures • pancreatitis and/or its complications: pseudocyst, abscess, necrosis, splenic artery aneurysm (see Uiti~" Imaging section below)

Toronto Notes 2008

Gastrointestinal (GI) Tract

Diagnostic Medical Imaging DM17

66itis" Imaging
\. Acute Cholecystitis • C/S very accurate - thick wall, pericholecystic fluid, gallstones, dilated gallbladder,
positive sonographic Murphy's sign
• nuclear medicine (HillA scan) may be helpful in equivocal cases, but is not often used; it has equivalent sensitivity and specificity to ultrasound

Acute Appendicitis • U/S very useful - thick-walled appendix, appendicolith, dilated fluid-filled appendix • U/S may also demonstrate other causes of RLQ pain (e.g. ovarian abscess, IBD,
ectopic pregnancy)
• CT: enlargement of appendix (>6 mm in outer diameter), enhancement of appendiceal wall, adjacent inflammatory stranding, appendicolith • CT: done to facilitate percutaneous abscess drainage Acute Diverticulitis • most common site is rectosigmoid (diverticula are outpouchings of colon wall) • CT is imaging modality of choice, although U/S is sometimes used
• oral and rectal contrast given before CT to opacify bowel
• cardinal signs: thickened wall, mesenteric infiltration, gas-filled diverticula, abscess • CT can be used for percutaneous abscess drainage before or in lieu of surgical intervention • sometimes difficult to distinguish from perforated cancer (therefore, send abscess fluid for cytology and follow up with colonoscopy) • if chronic, may see fistula (most common to bladder) or sinus tract (linear or branching structures) Acute Pancreatitis • clinical/biochemical diagnosis • imaging used to support diagnosis and evaluate for complications (diagnosis cannot
be excluded by imaging alone)
• U/S good for screening and follow up (although useless if ileus present as gas
obscures pancreas)
• hypoechoic enlarged pancreas • CT is useful in advanced stages of pancreatitis and in assessing for complications • enlarged pancreas, edema, stranding changes in surrounding fat with indistinct fat planes, mesenteric and Gerota's fascia thickening, pseudocyst in lesser sac, abscess (gas or thick-walled fluid collection), pancreatic necrosis (low attenuation gas-containing non-enhancing pancreatic tissue), hemorrhage • CT-guided needle aspiration and/or drainage done for abscess drainage when clinically indicated • pseudocyst may be followed by CT and drained if symptomatic

ComputedTOIIICllP'IPhY and U~lOgrIflhy to
Detect Acute Appandicitis in Adults and

[Terasawa Tet al. Annals ofInternal Meditine. 141171:
537·546,2004 Oct 51
PlIpose:To review the diagnostic accuracy of CT and
uttrasonography in the diagnosis of acute appendidtis.
Study Characteristics Meta·analysis of 22 prospec·

tive studies evaluating the use of CT or ultrasonogra·
phy, followed by surgical or clinical follow-up in
patients with suspected appendidtis.
Par1icipants: Age 14 and older with aclinical suspi·
cion of appendicitis.
Main Outcomes: Sensitivity and specificity using sur·
gery or clinical follow-up as the gold standard.
Results: CT 112 studies) had an overall sensitivity of
0.94196% D, 0.91 to 0.96) and aspedficity of 0.96196%
D, 0.93 to 0.96). Uttrasonography 114 studiesl had an
overall sensnivity of 0.86195% CI, 0.83 to 088\ and a
specificity of 0.81196% a, 0.78 to 0.841.
Conclusions: CT is more accurate for diagnosing
appendicitis in adutts and adolescents, although verifi­
cation bias and inappropriate blinding of reference
standards were noted in the included studies.

Angiography of GI Tract - - - - - - - - - - _......_.... • GI tract arterial blood supply: • celiac artery: hepatic, splenic, gastroduodenal, left/right gastric • superior mesenteric artery (SMA): jejunal, ileal, ileo-colic, right colic, middle colic • inferior mesenteric artery (IMA): left colic, superior rectal • imaging of GI tract vessels: • conventional angiogram: invasive (puncture femoral artery), catheter used • aortography: catheter injection into abdominal aorta • selective arteriography of individual vessels • CT angiogram: IV contrast (no catheterization required), computer generated images

DM18 Diagnostic Medical Imaging

Genitourinary (GU) System

Toronto Notes 2008

Genitourinary (GU) System
CT Urography • historically, intravenous urography (IVU) provided anatomical and functional information about the urogenital system; this has largely been replaced by cr urography • excretory-phase CT is new imaging technique of choice exclusively to assess the renal collecting systems. It has a high sensitivity (95%) in detecting upper urinary tract uroepithelial malignancies, and is also useful for detecting renal calculi • indications include hematuria (with negative cystoscopy and U/S studies ruling out parenchymal causes), unexplained hydronephrosis on U/S, evaluation of the renal collecting system post-trauma (e.g. post pelvic surgery) • CT features of various renal lesions are as follows: • renal cysts: fluid fil1ed lesions with smooth, well-defined borders, low density, no enhancement with contrast (smooth walled, bright lesions on non-contrast CT may suggest hyperdense cysts consisting of debris from proteinaceous material or previous hemorrhage into a benign cyst) • complex renal cysts: thick walled, may contain calcifications, some may be septated, wal1s may enhance with contrast • renal ceJJ carcinoma: less-defined borders, same density as kidney, enhancement with contrast (characterizing vascularity) ± areas of necrosis • angiomyolipoma (a henign renal neoplasm composed of fat, vascular, and smooth muscle elements): fat density seen on non-contrast CT, some enhancement with contrast (less intense than renal cell carcinoma)


Acute reaction. to IV contrast -Hot BUNS·
Hypotension Bradycardia Urticaria Nausea/vomiting Seizures

• initial study for evaluatiun of kidney size and nature of renal masses (solid vs cystic renal masses vs complicated cysts) • technique of choice fur screening patients with suspected hydronephrosis (no intravenous contrast injection, no radiation to patient, and can be used in patients in renal failure) • solid renal masses: echogenic (bright on U/S) • cystic renal masses: smooth well-defined walls with anechoic interior (dark on U/S) • complicated cysts: internal echoes within a thickened, irregular-waJJed cyst • transrectal U/S (TRUS) useful to evaluate prostate gland and guide biopsies • Doppler U/S to assess renal vasculature

Retrograde Pyelography • used to visualize the urinary col1ecting system via a cystoscope, ureteral catheterization, and retrograde injection of contrast medium • ordered when the intrarenal collecting system and ureters can't be opacified using intravenous techniques (patient with impaired renal function, high grade obstruction) • only yields information about the collecting systems (renal pelvis and associated structures); no information regarding the parenchyma of the kidney Voiding Cystourethrogram (VCUG) • bladder fil1ed with contrast to the point where voiding is triggered • real-time images via fluoroscopy (continuous x-ray imaging) to visualize bladder • contractility and evidence uf vesicoureteric reflux • indications: children with recurrent UTIs, hydronephrosis, hydroureter, suspected lower urinary tract obstruction or vesicoureteral reflux Retrograde Urethrogram • used mainly to study strictnres or trauma to the male urethra

• strengths: high spatial and tissue resolution, lack of exposure to ionizing radiation and nephrotoxic contrast agents • indicated over CT for depiction of renal masses in patients with previous nephron sparing surgery, patients requiring serial follow-ups (less radiation dosage), patients with reduced renal function and patients with solitary kidneys

Renal Scan
• 2 radionuclide tests f( II kidney - renogram and morphological scan • renogram • to assess renal function and collecting system • useful in evaluation of renal failure, workup of urinary tract obstruction and hypertension, investigatiun of renal transplant

Toronto Notes ZOOS

Genitourinary (GU) SystemiNeuroradiology

Diagnostic Medical Imaging DMI9

• intravenous injection of a radionuclide, technetium-99m pentetate (Tc99m-DTPA) or iodine-labelled hippurate, and imaged at I-second intervals with a gamma camera over 30 minutes to assess perfusion. Delayed static images over the next 30 minutes can be used to assess renal function and the collecting system • morphological • to assess renal anatomy • study done with Tc99m-DMSA and Tc99m-glucoheptonate • useful in investigation of renal mass and cortical scars

• MRI is the modality of choice for most neuropathology; even under circumstances when MRI is preferred, CT is frequently the initial study because of its speed, availability and lower cost • CT is preferred for: • acute head trauma: CT is best for visualizing "bone and blood." MRI is used in this setting only when CT fails to detect an abnormality in the presence of strong clinical suspicion • acute stroke • meningitis: rule out mass lesion (e.g. abscess) prior to lumbar puncture • tinnitus and vertigo: CT and MRl are used in combination to detect bony abnormalities and CN VIII tumours, respectively

Skull Films
• rarely performed; CT is modality of choice • indications include: • facial fracture • sinus disease • penetrating trauma • destructive bony lesions (e.g. metastases) • metabolic disease • skull anomalies • post-operative changes • generally not indicated for non-penetrating head trauma • standard views (each designed to demonstrate a particular area of the skull) • PA (frontal bones, frontal/ethmoid sinuses, nasal cavity, superior orbital rims, and mandible) • Lateral (frontal, parietal, temporal, and occipital bones, mastoid region, sella turcica, orbital roofs, and lateral aspects of facial bones) • Towne's view/occipital; "half-axial" (occipital bone, mastoid and middle ear regions, foramen magnum, and zygomatic arches) • Base view (basal structures of skull, including major foramina) • Water's view/occipitomental (facial bones and sinuses) • panoramic view (mandible)



Approach to interpretation of skull films
• • • • • • • bony vau~ sella turcica facial bones basal foramina sinuses calcifications soft tissues




bone =bright >grey matter> white matter
("fatty" myelin) >CSF >air =dark

• excellent study for evaluation of bony abnormalities • often done first without and then with intravenous contrast to show vascular structures or anomalies • vascular structures and areas of blood-brain barrier impairment are opaque (white/show enhancement) with contrast injection • when in doubt, look for circle of Willis or confluence of sinuses to determine presence of contrast enhancement • posterior fossa obscured by bone • rule out skull fracture, epidural hematoma (lenticular shape), subdural hematoma (crescentic shape), subarachnoid hemorrhage, space occupying lesion, hydrocephalus, and cerebral edema


.)-------------., Approach to head CT • soft tissues • bone • cortical parenchyma • ventricular system • symmetry • falx shift

DM20 Diagnostic Medical Imaging


Toronto Notes 2008


DOl for ring enhancing I..ion on CT with contmt: "MAGICAL DR"

• introduction of water-soluble, low-osmotic-contrast media into subarachnoid space using lumbar puncture followed by x-ray or CT scan • excellent study for disc herniations, traumatic nerve root avulsions • use has decreased due to MRl

(high glade astrocytomal
Resolving hematoma
[" by far the 3most common Ox's]

MRI (see Table 1)
• shows brain anatomy in fine detail • clearly distinguishes white from grey matter (especially TI-weighted series) • multiplanar reconstruction helpful in pre-op assessment

Cerebral Angiography
• evaluation of vascular lesions such as atherosclerotic disease, aneurysms, vascular malformations • digital subtraction angiography (DSA) commonly used to create images of vessels

Nuclear Medicine
• SPECT using HMPAO (technetium-99m labelled derivative of propylamine oxane) imaging assesses cerebral blood flow by diffusing rapidly across the blood brain barrier and becoming trapped within cells • PET imaging assesses cerebral metabolic activity

Selected Pathology

..... , ) - - - - - - - - - - - - - - ,
Transient ischemic atlacJs are not associated with radiological findings.


• see Neurosurgery, NS9 for intracranial mass lesions • see Neurosurgery, NS30 and Plastic Surgery, PL27 for head trauma • see Emergen<;y Medicine, ER8 for vertebral trauma

Cerebrovascular Disease (see Neurology, N58 and Neurosurgery, NSI4)
• carotid artery disease • evaluate with Duplex Doppler VIS • MR angiography or CT angiography if carotid angioplasty or endarterectomy is under consideration (conventional angiography reserved for inadequate MRA orCTA) • infarction • early changes • CT - usually normal within 6 hours of infarction - edema (loss of grey-white matter differentiation­ "insular ribbon" sign, effacement of sulci, mass effect) - within 24 hours, development of low-density, wedge-shaped area of infarction extending to periphery (correlating to distribution of affected artery) - in case of ischemic stroke, may see hyperattenuating (bright) artery - intravascular thrombus or embolus - in case of hemorrhagic stroke or transformation (common in basal ganglia and cortex), may see bright acute blood • MRI - edema with high signal on T2-weighted images and FLAIR (fluid-attenuated inversion - recovery) image (loss of grey-white matter differentiation, effacement of sulci, mass effect) - diffusion scan shows restricted movement of water (indicative of cytotoxic edema) • subacute changes (CT and MRI) • edema and mass effect more prominent • gyral enhancement with contrast indicative of blood-brain barrier breakdown • chronic changes (CT and MRl) • encephalomalacia (parenchymal volume loss) with dilatation of adjacent ventricles



Multiple Sclerosis (MS)
• MRI is the most sensitive diagnostic test (>90%), but not specific; ischemic demyelination can produce similar features; confluent multiple sclerosis lesions can be mistaken for a neoplasm • acute phase: plaques undergo inflammatory reaction with edema, cellular infiltration and spectrum of demyelination • chronic phase: astrocytic hypoplasia, resolution of cellular inflammation and loss of myelin • T2-weighted MRI shows round or ovoid white matter plaques with a periventricular or subcortical distribution


DDx IUIp8Ct8d MS lesion
VIICU/opIthy. isdlemia, vasculitis, hyper­
tension, migraine
demyel\nlting d.....:MS, progressive
multifocalleukoencephalpathy, age-related
intlammItory prlIC8II: sarcoid,lyme

Toronto Notes 2008

Neuroradiology/Nuclear Medicine

Diagnostic Medical Imaging DM21

• plaques are hyperintense on T2-weighted image due to breakdown of myelin • lesions tend to be confluent and >6 mm in diameter • new lesions with active demyelination may enhance with gadolinium contrast; older,
less active lesions do not
• specificity greatly improved if periventricular plaques are accompanied by lesions in
the cerebellum, cerebral peduncles, corpus callosum and spinal cord
• FLAIR imaging superior for supratentorial white matter lesions

Degenerative Spinal Abnormalities (see Nemosurgery, NS24 and Orthopaedics, 0R21)
• spondylosis • mild: slight disc space narrowing and spur formation • severe (spondylosis deformans): marked disc space narrowing, facet joint
narrowing, spur formation; may result in stenosis of the intervertebral
foramina or vertebral canal
• if symptomatic, evaluate with CT, MRI, and/or myelography • herniated disc • if symptomatic, evaluate with CT, MRI, and/or myelography

Nuclear Medicine
Radioactive Iodine Uptake (see Endocrinology, E21)
• .ill index of thyroid function (trapping and organification of iodine) • radioactive 1-131 or 1-123 PO in fasting patient • measured as a percentage of administered iodide taken up by thyroid • increased RAJU: toxic multinodular goiter, toxic adenoma, Graves' (although may be
• decreased RAill: subacute thyroiditis, late Hashimoto's disease, hormone suppression • falsely decreased in patient with recent radiographic contrast studies, high dietary
iodine (i.e. seaweed)

Thyroid Imaging (Scintiscan)
• Tc99m pertechnetate IV or radioactive iodine • provides functional anatomic detail • hot (hyperfunctioning) lesions • adenoma, toxic multinodular goiter • usually benign, cancer very unlikely (less than 1%) • cold (hypohmctioning) lesions • cancer must be considered until biopsy negative even though only 6-10% are
• cool lesions • cancer must be considered as a cool lesion may represent cold nodules
superimposed on normal tissue
• if cyst suspected, correlate with VIS • senlm thyroglobulin to detect recurrent thyroid cancer post treatment.

Radioiodine Ablation
• 1-131 for Graves, multinodular goiter, thyroid cancer

'. } - - - - - - - - - - - - - - , ,

vIa Scan
• e),.amine areas of lung in which ventilation and perfusion do not match • yen tila tion scan • patient breathes radioactive gas through a closed system, filling alveoli proportional to ventilation ventilation scan defects indicate: airway obstruction, chronic lung disease, bronchospasm, tumour mass obstruction • perfusion scan • radiotracer injected IV ---> trapped in pulmonary capillaries (l in 1500 arterioles occluded) according to blood flow • gives a map of pulmonary circulation • relatively contraindicated in severe pulmonary HTN and right-to-left shunt • PE areas of lung are well ventilated but not perfused (unmatched defect) • PE is wedge-shaped, extend to periphery, usually bilateral and multiple • reported as high probability, intermediate, low or normal • VIQ scans for PE nave been largely replaced by spiral CT scan with contrast (see Respirology, R20)

For PE Investigation: normal scan makes P£

Probablity of PE: High 80-100%, intermediate 2Q.8O%, low <20%,




ventilation scan defects indicate: Airway obstruction, chronic lung disease, bronchospasm, tumour mass obstruction.




Perfusion scan defects indicate:
reduced blood flow due to PE, COPO, asthma, br<lncl1ogenic carcinoma, inflammatory lung diseases (pneumo­ nia, sarcoidosisl, mediastinitis, mucus plug, vasculitis,

DM22 Diagnostic Medical Imaging

Nuclear Medicine

Tomnto Notes 2008



Myocardial Perfusion Scanning
• for investigation of angina, atypical chest pain, coronary artery disease (CAD), post bypass follow-up • thallium-20l (a radioactive analogue of potassium) or Tc99m MIl3I • injected at peak exercise (physical stress) or after persantine challenge (vasodilator) and again later at rest • persistent defect (at rest and stress) suggests infarction; reversible defect (only during stress) suggests ischemia • used to discriminate between reversible (ischemia) vs. irreversible (infarction) changes when other investigations are equivocal • see Cardiology, Cll for more details


Active uptake of radiolabel by myocardi· um proportional to regional blood flow.




Persistent defect (at rest and stressl sug·
gests infarction; reversible defect (only
during stress) suggests ischemia.

Radionuclide Ventriculography




MUGA scan: can be used to study the
function of the heart at aparticular stage
of contraction. Superior to ECHO only in
its reproducibility in EF measurement

• Tc99m attached to red blood cells • first pass through right ventricle (RV) .... pulmonary circulation -> left ventricle (LV) provides information about RV function • cardiac MUGA scan (MUltiple GAted acquisition scan) sums multiple cardiac cycles • evaluation of LV function • images are obtained by gating (synchronizing) the count acquisitions to the ECG signal • MUGA scan can be used to study the function of the heart at a particular stage of contraction • provides information on ejection fraction (normal = 55-65%), ventricular volume, and wall motion



Pyrophosphate Scintigraphy
• technetium pyrophosphate concentrates in bone and necrotic tissue • used to detect infarcted tissue 1-5 days post-MI when ECG and enzyme results are equivocal or unreliable • sensitivity and specificity about 90% in transmural infarct


Technetium pyrophosphate concentrates
in bone and necrotic tissue.



Bone Scan
• isotopes • technetium Tc99m: • triphasic bone scan: perfusion blood pool -> delayed bone images • uptake can distinguish bone vs. soft tissue infection and septic arthritis vs. osteomyelitis vs. peripheral cellulitis • acute osteomyelitis: increased activity in blood pool and delayed bone images, usually does not cross joint • septic arthritis & cellulitis: increased activity in blood pool and normal or slightly increased activity in delayed images, may cross joint • indium-llI WEC: tracks the active migration of the WEC - more specific for infection • gallium-67 citrate: may see uptake in some tumours, also more specific for infectiun • radioactive tracer binds to hydroxyapatite of bone matrix • increased hinding when increased blood supply to bone and/or high bone turnover (active osteoblasts) • positive bone scan • bone metastases from breast, prostate, lung, thyroid • primary bone tumour • arthritis • fracture • infection • anemia • Paget's disease • multiple myeloma: typically normal or cold (false negative); need a skeletal survey • superscan: good visualization of bone, but not kidneys, due to diffuse metastases


Indications for 8 Bone Scan • bone pain of unknown origin

• AVN • suspected malignancy • staging malignancy (cancer of breast, prostate, kidney, thyroid or lungl • follow up after treatment • detection and follow up of primary
bone disease
• assessment of skeletal trauma • detection of soft tissue calcification • renal failure

Toronto Notes 2008

Nuclear Medicine

Diagnostic Medical Imaging DM23

Liver/Spleen Scans
• IV injection of technetium-labelled sulphur colloid (usually technetium) that is
phagocytosed by reticuloendothelial (Kupffer's) cells of liver and spleen
• "cold spots": lesions displacing the normal reticuloendothelial system (RES) (tumour,
abscess, cyst, hemangioma, infarct)
• diffuse patchy reduction in uptake: diffuse parenchymal disease (e.g. cirrhosis)

HIDA (Hepatobiliary IminoDiacetic Acid) Scan
• IV injection of radiotracer (HillA) which is bound to protein, taken up, and excreted
by hepatocytes into biliary system
• can be performed in non-fasting state but prefer NPO after midnight • gallbladder visualized when cystic duct is patent, usually seen by 30 min to 1 hour • if gallbladder is not visualized, suspect obstructed cystic duct (acute or chronic
• acute cholecystitis: no visualization of gallbladder at 4-hour or after administration of
morphine at I-hour
• chronic cholecystitis: no visualization of gallbladder at I-hour but seen at 4-hour or
after morphine administration
• differential diagnosis of obstructed cystic duct: acute cholecystitis, decreased
hepatobiliary function (commonly due to alcoholism), bile duct obstruction, parenteral
nutrition, fasting less than 4 hours or more than 24 hours
• filling of gallbladder rules out cholecystitis probability) • assess bile leaks post-operatively


RBC Scan
• IV injection of radiotracer with sequential images of the abdomen (Tc99m labelled
• GIbleed • if bleeding acutely at <0.5 mL/min, the focus of activity in the images generally
indicates the site of the acute bleed, look for a change in shape and location on
sequential image
• if bleeding acutely at >0.5 mL/min, usc angiography (more specific) • RBC scan is more sensitive for lower GI bleed • liver lesion evaluation • hemangioma has characteristic appearance, cold early, fills in later

Renal Scan
• see Genitourinary System Imaging, DM18

Inflammation and Infection
• use gallium-67 citrate, or indium-Ill or Tc99m labelled WBCs • gallium accumulates in skeleton, lacrimal glands, nasopharynx, normal liver, spleen,
bone marrow, sites of inflammation, some neoplasms (lymphomas)
• labelled WBCs accumulate in normal spleen, liver, bone marrow, sites of inflammation
and infection (abscess, sarcoid, osteomyelitis)

• SPECT Tc99m-HMPAO imaging assesses cerebral blood flow, taken up in cortical and
subcortical grey matter; used for CVA, vasculitis, dementia
• PET imaging assesses metabolic activity by using l8-FDG • CSF imaging, intrathecal administration of Ill-In DTPA to evaluate CSF leak or to
differentiate normal pressure hydrocephalus from other causes of hydrocephalus

DM24 Diagnostic Medical Imaging

Interventional Radiology

Toronto Notes 2008

Interventional Radiology
.}------------, Contraindications to Intravascular


Vascular Procedures
• injection of contrast material through a catheter placed directly into an artery (or vein) to delineate vascular anatomy • catheter can be placed into a large vessel (e.g. aorta, vena cava) for a "flush" or selectively placed into a branch vessel for more detailed examination of smaller vessels and specific organs • more recently, non-invasive evaluation of vascular structures is being performed (colour Doppler DIS, CT angiography (CTA) and MR angiography (MRA» • indications: aneurysm, peripheral ischemia, coronary, carotid and cerebral vascular disease, PE, trauma, bleeding, vascular malformations • Significant complications occur in <5% of patients • complications: puncture site hematoma, infection, pseudoaneurysm, AV fistula, dissection, thrombosis, embolic occlusion of a distal vessel

Contrast Media

Anaphylactoid reaction, renal failure, multiple myeloma, dehydration, dia­ betes, severe heart failure.

Percutaneous Transluminal Angioplasty (PTA)
• introduction and inflation of a balloon into a stenosed vessel to restore distal blood supply • common alternative to surgical bypass grafting with five year patency rates similar to surgery, depending on site • renal, iliac, femoral. mesenteric, subclavian and carotid artery stenoses are amenable to treatment • vascular stents may help improve long term results by keeping the vessel wall patent after PTA • covered stents (a.k.a. stent grafts) may provide an alternative treatment for aneurysms and AV fistulas • complications: similar to angiography, but includes vessel rupture



Thrombolytic Therapy
• infusion of a fibrinolytic agent (urokinase, streptokinase, TNK, tPA - used most commonly) via a catheter inserted directly into a thrombus • can restore blood flow in a vessel obstructed with a thrombus or embolus • indications: treatment of ischemic limb (most common indication), early treatment of Ml or stroke to reduce organ damage, treatment of venous thrombosis (DVT of leg or PEl • complications: bleeding, stroke, distal embolus, reperfusion injury with myoglobinuria and renal failure if advanced ischemia present

Advanced ischemia patients should
receive surgery rather than thrombolysis.

• • • • injection of occluding material into vessels permanent agents: coils, balloons, glue temporary: gel foam, autologous blood clots indications: management of hemorrhage (epistaxis, trauma, GI bleed), treatment of AVM, pre-operative treatment of vascular tumours (bone metastases, renal cell carcinoma), varicocele embolization for infertility, symptomatic uterine fibroids • complications: • post embolization syndrome (pain, fever, leukocytosis) • unintentional embolization of a non-target organ with resultant ischemia insertion of metallic "umbrellas" to mecharucally trar emboli preventing a PE inserted via femoral vein, jugular vein, or antecubita vein placed infrarenally to avoid renal vein thrombosis indications: contraindication to anticoagulation, failure of adequate anticoagulation (i.e. recurrent PE despite therapeutic anticoagulant levels), complication of

Inferior Vena Cava Filter
• • • •

Indications for Central Venous ACce88 -FAT (taxi! CAB" Fluids Antibiotics

Central Venous Access
• variety of devices available • pt'ripherally inserted ct'ntral cathett'r (PlCC), external tunneJled catheter (Hickmann), subLUtaneous port (portacath™) • indications: chemotherapy, TPN, long-term antibiotics, administration of fluids and blood products, blood sampling • complications: venous thrombosis, infection, pneumothorax

TPN Chemotherapy Adminstration of blood Blood sampling

Toronto Notes 2008

Interventional Radiology/Summary Key Questions

Diagnostic Medical Imaging DM25

Nonvascular Interventions
Percutaneous Biopsy
• replaces an open surgical procedure • many sites are amenable to biopsy using VIS, fluoroscopy or CT guidance • complications: • false negative biopsies due to sampling error or tissue necrosis • pneumothorax in 30% of lung biopsies, chest tube required in approximately 5% pancreatic biopsies are associated with risk of inducin~ pancreatitis • transjugular liver biopsies can be performed to minirruze bleeding complications in patients with uncorrectable coagulopathies or ascites




ERCP is the primary modality for distal
common bile duct obstructions.

Abscess Drainage
• • • • placement of a drainage catheter into an infected fluid collection administer broad spectnun N antibiotics prior to procedure routes: percutaneous (most common), transvaginal transrectal complications: • bacteremia with sepsis • hemorrhage, injury to intervening structures (e.g. bowel)

Percutaneous Biliary Drainage (PBD)/Cholecystostomy
• placement of drainage catheter ± metallic stent into obstructed biliary system (PBD) or
gallbladder (cholecystostomy) for relief of jaundice or infection
• percutaneous access can be used to crush or remove stones • mdications: • cholecystostomY,: acute acalculous cholescytitis • percutaneous biliary drainage: biliary obstruction secondary to stone or tumour • comphcations: • acute: sepsis, hemorrhage • long-term: tumour overgrowth and stent occlusion

Percutaneous Nephrostomy
• placement of catheter into renal collecting system • mdications: hydronephrosis (urinary obstruction as a result of a stone or tumour) • complications: hematuria, pseudoaneurysm, AV fistulas

• percutaneous placement of catheter directly into either stomach (gastrostomy)
or through stomach into small bowel (gastrojejunostomy)
• indications: • feeding: inability to eat (most commonly eNS lesion, e.g. stroke) or esophageal
• decompression: gastric outlet obstruction • complications: gastroesophageal reflux with aspiration, peritonitis, hemorrhage, bowel injury

Radiofrequency (RF) Ablation
• VIS or CT guided probe is inserted into tumour, Rf energy delivered through probe
causes heat deposition and tissue destruction
• indications: most commonly used for hepatic tumours (hepatocellular carcinoma and
• complications: destruction of neighbouring tissues and structures

Summary Key Questions
Questions 1. What are 5indications for thoracic CT? Answers
evaluation of abnormality detected on chest x-ray
staging lung malignancies, metastatic disease
differentiation of empyema from lung abscess
detection of pulmonary embolism (PE protocol)
detection and evaluation of aortic dissection
determine biopsy approach and may be used to guide biOpsy


2. What number is used to define an abnormal cardiothoracic ratio?
3. What does the term "silhouette sign" refer to?

loss of normally appearing interfaces, implying opacification in adjacent lung pus, fluid, blood, cells, protein linear densities, reticular, nodular, and reticuJonoduJar pattern thickened connective tissue planes that occur most commonly in pulmonary
edema and lymphatic carcinomatosis

4. What is the differential diagnosis for airspace disease of the lung? 5. What are the cardinal features of interstitial lung disease? 6. What is a Kerley 8 Line?

DM26 Diagnostic Medical Imaging

Summary Key Questions/References

Toronto Notes 2008

Questions 7. What are the 5causes of atelectasis?

Answers obstructive, compressive, passive, traction, adhesive cancer, autoimmune, vascular, infection, trauma, congenital thyroid, thymus, teratoma, terrible lymphoma decreased joint space, subchondral sclerosis, marginal osteophytes, subchondral cysts breast, lung, thyroid, kidney, multiple myeloma if the patient cannot sit or stand to detect pneumoperitoneum to detect air-fluid levels mucosal folds: SB > uninterrupted valvulae conniventes; LB >interrupted haustra extending only partway across lumen location: SB, central; LB > peripheral (picture frame) maximum diameter: SB >3cm; > 6cm 19 cm at cecum) air under the diaphragm, Rigler's sign (inner and outer bowel wall visible) perforated viscus, postoperative ileus> bowel normal caliber or dilated, air throughout GI tract in ileus obstruction> bowel usually dilated, multiple air-fluid levels within a loop of bowel ("step-ladder" appearance I, dilated bowel up to the point of obstruction with no air distal to obstructed segment colonoscopy hepatocellular carcinoma (HCCl. hydatid cyst, hemangioma, hepatic adenoma, hyperplasia Ifocal nodular) acute pancreatitis complicates 5% of diagnostic and 10% of therapeutic procedures CT blood = white on CT epidural hematoma = lenticular shape subdural hematoma = crescentic shape metastasis, abscess, primary brain tumour (glioblastomal. infarct, aneurysm, TB, radiation necrosis duplex doppler U/S MR angiography or CT angiography if carotid angioplasty or endarterectomy are under consideration toxic multinodular goiter, toxic adenoma, Graves' (may also be normal) used to examine areas of lung in which there is a mismatch between ventilation and perfusion in the case of pulmonary embolism, there are areas of lung which are' ventilated, but not perfused (i.e. an unmatched defect) bone metastases from breast, prostate, lung, thyroid, primary bone tumour, arthritis, fracture, infection, anemia, Paget's disease anaphylactoid reaction, renal failure, mu~iple myeloma, dehydration, diabetes, severe heart failure

8. What is the differential diagnosis for a cavitating lung nodule?

9. What are the 4T's of an anterior mediastinal mass?
10. What are the signs of osteoarthritis on plain film? 11. Which metastases to bone are lytic in nature?

12. When is an abdominal lateral film indicated?

13. What features on AXR allow for the differentiation of small and large bowel?

14. Name 2radiographic signs associated with intraperitoneal air. What are 2 causes of this?
15. What radiographic findings allow for the differentiation of an adynamic ileus from mechanical bowel obstruction?

16. What is the gold standard for detection of colonic polyps?
17. Differential diagnosis for liver mass -list 5.

18. What is acommon, potentially serious complication of an ERCP? What is its incidence?
19. What is the most accurate imaging study for the diagnosis of acute appendicitis? 20. How do you differentiate between epidural and subdural hematomas on aCT of the head?

21. What is the differential diagnosis for ring enhancing lesions?
22. What imaging modalities are used for the investigation of suspected carotid artery disease? 23. List 3 causes of increased radioactive iodine uptake by the thyroid? 24. What is aVlQ scan used to identify? What is seen in the case of a pulmonary embolism?

25. List the causes of a positive bone scan. 26. What are contra indications to IV contrast?

Gay S, Woodcock Jr RJ (20001. Radiolo~y Recall. Baltimore: lippincott Williams & Wilkins. Brant WE, Helms CA (1999). Fundamentals 01 diagnostic radiology. Philadelphia. Lippincott Williams and Wilkins. Chen MYM, Pope, Tl, Ott DJ. (2004) Basic Radiology. New York. lange Medical Books/McGraw Hill. Daffner RH 11993). Clinical radiology: the essentials. Baltimore: Williams & Wilkins. Erkonen WE, Smith Wl. (2005) Radiology 101. Philadelphia: Lippincott Williams & Wilkins. Fleckenstein p,Tranun-Jensen J (2001). Anatomy in Diagnostic Imaging. 2nd ed. Copenhagen: Blackwell Publishing. Goodman lR 12007). Felson's Principles 01 Chest Roentgenology: A Programmed Text. 3rd ed. Philadelphia: Saunders. Joffe SA, Servaes S, Okon S, Horowitz M. Multi-detector row CT urography in the evaluation 01 hematuria. Radiographies. 2003, 23(6):1441-55. Juhl JH, Crummy AB, Kuhlman JE (1998). Paul and Juhl's Essentials 01 Radiologic Imaging. Phildelphia: lippincott-Raven. Katz DS, Math KR, Groskin SA (1998). Radiology secrets. Philadelphia: Hanley and Bellus. Novelline RA (2004). Squire's Fundamentals 01 Radiology. 6th ed. Cambridge:Harvard. Ouellette H, Tetreault P. (20021. Clinical Radiology made ridiculously simple. Miami: MedMaster. Sam PM, Curtin HD (1996). Head and neck imaging. 3rd ed.. St. louis: Mosby. Weissleder R, Rieumont MJ, Wittenberg J. (19971 Primer 01 Diagnostic Imaging, 2nd ed. Philadelphia: Mosby.


Emergency Medicine
Alun Ackery and Michelle Strasberg, chapter editors Deana Hathout and Ripudaman Minhas, associate editors Jai Shah, EBM editor Dr. Dan Cass, Dr. Margaret Thompson and Dr. Jeffrey Tyberg, staff editors

Initial Patient Assessment and Management Rapid Primary Survey Resuscitation Detailed Secondary Survey Definitive Care Ethical Considerations Traumatology Epidemiology Considerations forTraumatic Injury HeadTrauma Spine and Spinal Cord Trauma ChestTrauma AbdominalTrauma GenitourinaryTract Injuries Orthopaedic Injuries A. Life and Limb Threatening Injuries B. Upper Extremity Injuries C. Lower Extremity Injuries SoftTissue Injuries/Emergency Wound Management Pediatric Trauma Trauma in Pregnancy



Common Pediatric ER Presentations .......41
Modified Coma Score for Infants The Febrile Infant Febrile Seizures Common Childhood Infections Concerning Rashes Respiratory Distress Abdominal Pain Child Abuse and Neglect Common Psychiatric ER Presentations ...45 Approach to Common Psychiatric Presentations Acute Psychosis Suicidal Patient Violent Patient Toxicology 46 Approach to the Overdose Patient ABCs ofToxicology Disposition from the Emergency Department Procedural Sedation Commonly Used Medications Summary Key Questions References 52


Approach to Common ER Presentations 22 Abdominal Pain Acute Pelvic Pain Alcohol Related Emergencies Altered Level of Consciousness (LOC) Anaphylaxis and Allergic Reactions Asthma Chest Pain Chronic Obstructive Pulmonary Disease (COPD) Congestive Heart Failure Diabetic Emergencies Headache Hypertensive Emergencies Ophthalmologic Foreign Body and Corneal Abrasion Sexual Assault Seizures Syncope Stroke Vaginal Bleed Environmental Injuries Heat Exhaustion and Heat Stroke Hypothermia Frostbite Inhalation Injury Near Drowning



Toronto Notes 2008

Emergency Medicine ERI

ER2 Emergency Medicine

Initial Patient Assessment and Management

Toronto Notes 200S

Initial Patient Assessment and Management
1. Rapid Primary Surve (RPS)
• Airway maintenance with cervical spine (C-spine) control • Breathing and ventilation • Circulation (pulses, hemorrhage control) • Disability (neurological status) • Exposure (complete) and Environment (temperature control) • restart sequence from beginning if patient deteriorates
IMPORTANT: always watch for signs of shock while doing primary survey (see Table 1)


• • • • first priority is to secure airway assume a cervical injury in every trauma patient and immobilize with collar assess ability to breathe and speak signs of obstruction • agitation, confusion, "universal choking sign" • respiratory distress • failure to speak, dysphOnia • cyanosis • think about ability to maintain patency in future • can change rapidly, therefore reassess frequently • goals • permit adequate oxygenation and ventilation • facilitate ongoing patient management • give drugs via endotracheal tube (ETT) if IV not available • N.B. start with basic management techniques before progressing to advanced (see below) 1. Basic Airway Management (Temporizing Measures)
• protect the C-spine
• head-tilt or jaw thrust if C-spine injury suspected to open the airway
• sweep and suction to clear mouth of foreign material
• nasopharyngeal airway
• oropharyngeal airway (not if gag present)
• "rescue" airway devices (e.g. laryngeal mask airway (LMA); combitube)
• transtracheal jet ventilation through cricothyroid membrane
• used as last resort to ventilate

Approach to the Critically III
1. Rapid Primary Survey (RPSl 2. Resuscitation (often concurrent
with RPSl
3. Detailed Secondary Survey 4. Definitive Care

.... ~ ,}-----------,
Noisy breathing is obstructed breath­ ing until proven otherwise.


Airway Management

If IV access is not available, the
following drugs can be given
down an ETI ("NAVEL"):
Naloxone (Narcanl
Ventolin (Salbutamoll

2. Definitive Airway Management

• ETT intubation with inline stabilization of spine (see Figure 1) • orotracheal ± Rapid Sequence Intubation (RSI) • nasotracheal - may be better tolerated in conscious patient • relatively contraindicated with basal skull fracture • does not provide 100% protection against aspiration • indications for intubation • unable to protect airway (e.g. Glasgow Coma Scale (GCS) $8; airway trauma) • inadequate oxygenation with spontaneous respiration (02 saturation <90% with 100% O2 or rising pC0 2 ) • profOlmd shock • anticipate in trauma, overdose, congestive heart failure (CHF), asthma, chronic obstructive pulmonary disease (COPD) and smoke inhalation injury • anticipated transfer of critically ill patients • rescue airway devices (used to obtain/maintain airway if intubation not possible) • laryngeal mask airway • intubate LMA • combination esophageal/tracheal devices • surgical airway (if unable to intubate using oral/nasal route and unable to ventilate) • cricothyroidotomy

Toronto Notes 2008

Initial Patient Assessment and Management

Emergency Medicine ER3

trauma requiring intubation no immediate need immediate need apneic

t C -spine x-ray




fiberoptic En or nasal En or RSI


oral En RSlj



s~acial smash
nasal ( ± RSI)




rescue deVices or cricothyroidotomy



oral En

or1En Ino RSI)

E~ or oral En

unable rescue devices or cricothyroidotomy


~ ,.
rescue deVices or cricothyroidotomy

• note: clearing the C-spine also requires clinical assessment (cannot rely on x-ray alone) En lendotracheal tube intubation). RSI (rapid sequence intubationl

Figure 1. Approach to Endotracheal Intubation in an Injured Patient

• LOOK • LISTEN • FEEL mental status (anxiety, agitation, decreased LOC), colour, chest movement (bilateral or asymmetrical), respiratory rate/effort, nasal flaring sounds of obstruction (e.g. stridor), breath sounds, symmetry of air entry, air escaping flow of air, tracheal shift, chest wall for crepitus, flail segments, sucking chest wounds, subcutaneous emphysema

Breathing Assessment
• measurement of respiratory function: rate, pulse oximetry, arterial blood gas (ABC), A-a gradient

Management of Breathing
• treatment modalities: nasal prongs simple face mask -+ oxygen reservoir • Venturi mask: used to precisely control O 2 delivery • Bag-Valve mask and CPAP to supplement ventilation


.... .l------------,
Shock in a trauma patient is hemorrhagic until proven otherwise.


Definition of Shock
• inadequate organ and tissue perfusion with oxygenated blood (brain, kidney, extremities) • not a level of blood pressure
Table 1. Estimation of Degree of Hemorrhagic Shock
Class Blood Loss (% of blood volume) Pulse Blood pressure Respiratory rate Capillary refill Urinary output Fluid replacement

<750 cc «15%) <100 Normal 20 Normal 30 cc!hr Crystalloid

750-1500 cc 115-30%) >100 Normal 30 Decreased 20 cc!hr Crystalloid

1500-2000 cc (30-40%1 >120 Decreased 35 Decreased 10 cc!hr Crystalloid +blood

>2000 cc 1>40%1 >140 Decreased >45 Decreased None Crystalloid +blood


CaUIleI of Shock (SHOCKE):

SpinaVneurogenic, Septic H· Hemorrhagic o· Obstructive (e.g. tension pneumothorax, cardiac tamponade, pulmonary
embolism) C· Cardiogenic (e.g. blunt myocardial injury, arrhythmia, Mil K· anaphyiactiK E • Endocrine le.g. Addison's, myxedema\ coma)

Table 2. MajorTypes of Shock
Hypovolemic Cardiogenic Distributive Obstructive

- Hemorrhage (External and Internal) - Severe burns - High output fistulas

- Myocardial Ischemia - Arrhythmias - Congestive Heart Failure - Cardiomyopathies - Cardiac valve problems

- Septic - Anaphylactic - Neurogenic ISpinal cord injury)

- Cardiac tamponade -Tension pneumothorax - Pulmonary embolism - Aortic stenosis - Constrictive pericarditis

ER4 Emergency Medicine

Initial Patient Assessment and Management

Toronto Notes 2008

",' ,


Clinical Evaluation
• rapidly assess for cause of shock • clinical features of acute hemorrhage • early: tachypnea, tachycardia, narrow pulse pressure, reduced urine output, reduced capillary refill, cool extremities and reduced central venous pressure (CVP) • late: hypotension and altered mental status

Estimated Systolic Blood Pressure Based on Position of Most Distal Palpable Pulse


Radial Femoral



Management of Hemorrhagic Shock
• secure airway and supply O 2 • TREAT THE CAUSE OF THE SHOCK • conb'ol external bleeding • direct pressure • elevate extremities if no obvious unstable fracture • consider vascular pressure points (brachial, axillary, femoral) • do not remove impaled objects as they tamponade bleeding • tourniquet only as last resort • prompt surgical consultation for active internal bleeding • infusion of 1-2 L of NS/RL as rapidly as possible -> 2 large bore (14 gauge) Ns wide open • warm bloodlTY fluids, especially for massive transfusions • replace lost bloud volume at ratio of 3:1 • if inadequate responsE', consider ongoing blood loss (e.g. chest, abdomen, pelvis, extremities) > operative intervention required • indications for blood transfusion • severe hyputension on arrival • shock persists following crystalloid infusion • rapid bleeding • transfusion options with packed red blood cells (PRBCs) • cross matched if possible • type-specific (provided by most blood banks within 10 minutes) • preferred to a-negative uncross-matched blood if both available • a-negative (children and women of child-bearing age) • a-positive if nu time for cwssmatch (males/postmenopausal women) • anticipate complications with massive transfusions • transfusion with fresh frozen plasma (FFP) • used for clinical C'vidence of impaired hemostasis • ongoing hemorrhage, PT >1.5x normal range

Hemorrhage Management: RED Rest Elevate the bleeding area above the level ofthe heart Direct pressure on the bleeding site

'" .J-------------,
Since only 30% of infused isotonic crystalloids remains in intravascular space, you must give 3x estimated blood loss,


Signs and Symptoms of Shock (TV SPARC CUBE): Thirst Vomiting Cyanotic Unconscious BPlow Eyes blank

Sweating Pulse weak Anxious Respirations - shallow, r a p i d , Cool

• assess level of consciousness by AVPU method (see sidebar) or GCS

Glasgow Coma Scale (GCS)
• for use in trauma patients with decreased LaC; good indicator of severity of injury and neurosurgical prognosis • often used for metabolic coma, but less meaningful • most useful if repeated and used for monitoring of trend • change in GCS with time is more relevant than the absolute number • patient with deteriorating GCS needs immediate attention
Table 3. Glasgow Coma Scale

The "AVPU" method of assessing level of consciousness: A-Alert V - responds to Verbal stimuli P - responds to Painful stimuli U - Unresponsive

Eyes Open Spontaneously To voice To pain No response

Best Verbal Response

Best Motor Response

4 3
2 1

Answers questions appropriately Confused, disoriented Inappropriate words Incomprehensible sounds No verbal response

5 4
3 2 1

Obeys commands Localizes to pain Withdraws from pain Decorticate (flexion) Decerebrate (extension) No response

6 5 4 3 2

• best reported as a 3 part score: Eyes + Verbal + Motor = Total • provides indication of degree of injury • 13-15 = mild injury • 9-12 = moderate injury • $8 = severe injury • if patient intubated, GCS score reported out of 10 + T (T= tubed, i.e. no verbal component)

Toronto Notes 2008

Initial Patient Assessment and Management

Emergency Medicine ERS

• • • • undress patient completely; logroll to examine back essential to assess entire body for possible injury keep patient warm with a blanket ± radiant heaters; avoid hypothermia warm IV fluids/blood
Unproven or Hannful Treatments for Hemorrhage Shock • Trendelenberg position • steroids (used only in spinal cord injury) • MAST garments • vasopressors

2. Resuscitation
• • • • • • • done simultaneously with primary survey attend to ABCs manage life-threatening problems as they are identified vital signs q5-15 minutes ECG, BP and O2 monitors Foley catheter and nasogastric (NG) tube if indicated tests and investigations: CBC, electrolytes, BUN, Cr, glucose, amylase, INRjPTT, ~-hCG, toxicology screen, cross & type

3. Detailed Secondary Survey
• done after rapid primary survey problems have been addressed • identifies major injuries or areas of concern • full physical exam and X-rays (C-spine, chest, pelvis - required in blunt trauma, consider T-spine and L-spine)
Foley contraindications: • blood at urethral meatus • scrotal hematoma • high-riding prostate on DRE

• "SAMPLE": Signs and Symptoms, Allergies, Medications, Past medical history, Last meal, Events related to injury
NG tube contraindications: • significant mid-face trauma • basal skull fracture

Head and Neck
• pupils • assess equality, size, symmetry, reactivity to light • inequality suggests local eye problem or lateralizing CNS lesion • reactivity/level of consciousness (LaC) • reactive pupils + decreased LaC ---+ metabolic or structural cause • non-reactive pupils + decreased LaC ---+ structural cause (especially if asymmetric) • extraocular movements and nystagmus • fundoscopy (papilledema, hemorrhages) • palpation of facial bones, scalp • tympanic membranes, fluid in ear canal, hemotympanum, Battle's sign, neck tenderness

• inspect for flail segment, contusion • palpate for subcutaneous emphysema • auscultate lung fields

• assess for peritonitis, abdominal distention, and evidence of intra-abdominal bleeding • FAST (Focused Abdominal Sonogram in Trauma), diagnostic peritoneal lavage (DPL) orCT • rectal exam for gastrointestinal (GI) bleed, high riding prostate and anal tone (best to do during the log roU) • bimanual exam in females




Musculoskeletal (MSK)
• examine all extremities for swelling, deformity, contusion, tenderness • log roll and palpate thoracic and lumbar spines • palpate iliac crests and pubic symphysis, pelvic stability (lateral, AP, vertical)

• GCS • alterations of rate and rhythm of breathing are signs of structural or metabolic abnormalities • progressive deterioration of breathing pattern implies a failing CNS • full cranial nerve exam • assessment of spinal cord integrio/ • conscious patient: assess dIstal sensation and motor ability • unconscious patient: response to painful or noxious stimulus applied to extremities

Signs of increased intracranial pressure UCP) • deteriorating LOC (hallmark of increasing ICP) • deteriorating respiratory pattern • Cushing reflex (high Bp, low heart rate, irregular respirations) 'Iateralizing CNS signs (e.g. cranial nerve palsies, hemiparesis) • seizures • papilledema (occurs late) 'NN and HlA

ER6 Emergency Medicine

Initial Patient Assessment and Managementffraumatology

Toronto Notes 2008

4. Definitive Care
• • • • continue therapy continue patient evaluations and special investigations specialty consultations including OR as needed disposition: home, admission, or transfer to another setting (e.g. OR, ICU)



Ethical Considerations
Consent to Treatment: Adults
• emergency rule: consent not needed when patient is at imminent risk from a serious injury (e.g. severe suffering, loss of limb, vital organ or life) AND obtaining consent is either: a) not possible (e.g. patient is comatose); OR b) would increase risk to the patient (e.g. time delay) • the emergency rule assumes that most people would want to be saved in an emergency • any capable and informed patient can refuse any treatment or part of treatment, even if it is life-saving • consider: is the patient truly capable? does pain, stress, or psychological distress impair their judgment? • exceptions to the Emergencv Rule: treatment cannot be initiated if: ]. a competent patient has previously refused the same or similar treatment and there is no evidence to suggest the patient's wishes have changed 2. an advance directive is available - e.g. do not resuscitate (DNR) order • refusal of help in a suicide situation is not an exception; care must be given • if in doubt, initiate treatment, care can be withdrawn if appropriate at a later time or if wishes clarified by family


JehovlIh's Witnesses • capable adults have the right to refuse medical treatment • may refuse whole blood, PRBCs, platelets, plasma andWBCs even if life-saving • should be questioned directly about the use of albumin, immunoglobulins, hemophilic preparations • do not allow for autologous transfusion unless there is uninterrupted extra corporeal circulation • usually ask for the highest possible quality of care without the use of the above interventions (e.g. CIyslalioids for volume expansion, attempts at bloodless surgelY) • patient will generally sign hosp~al
forms releasing medical staff from liability • most Ieqal cases involve children of Jehovah's Witnesses; if life-saving treatment is refused CAS is contacted

Consent to Treatment: Children
• treat immediately if patient is at imminent risk • parents/guardians have right to make treatment decisions • if parents refuse treatment that is life-saving or will potentially alter the child's quality of life, Children's Aid Society (CAS) must be contacted - consent of CAS is needed to treat

Other Issues of Consent
• need consent for HIV testing of patient and for administration of blood products

Duty to Report
• law may vary depending on province and/or state • gunshot wounds, potential dnmken drivers, suspected child abuse, various communicable diseases

• statistics • leading cause of death in patients <45 yrs • 4th highest cause of death in North America • causes more deaths in children/adolescents than all diseases combined • trimodal distribution of death • minutes: lethal injuries, death usually at the scene • early: this period includes the "golden hour" (death within 4-6 hours), decreased mortality with trauma care • days-weeks: death from multiple organ dysfunction, sepsis, etc. • injuries generally fall into two categories • blunt (most common): motor vehicle collision (MVC), pedestrian-automobile impact, motorcycle collision, fall, assault, sports, etc. • penetrating (increasing in incidence): gunshot wound, stabbing, impalement • high risk injuries: • MVC at high speed, resulting in ejection from vehicle • motorcycle collisions • vehicle vs. pedestrian crashes • fall from height>12 ft

Toronto Notes 2008


Emergency Medicine ER7

Considerations forTraumatic Injury
• important to know the mechanism of injury in order to anticipate traumatic injuries • always look for an underlying cause (alcohol, medications, illicit substances, seizure, suicide attempt, medical problem) • always inquire about head injury, loss of consciousness, amnesia, vomiting, headache and seizure activity

Motor Vehicle Collision (MVC)
• vehicle(s) involved: weight, size, speed, amount of damage • type of crash (to assess location of possible injuries) • lateralfT-bone or head-on: head, cervical spine, thoracic, abdominal, pelvic and lower extremity • rear-end: hyper-extension of cervical spine (whiplash injury to neck) • roll over: energy dissipated, less likely severe injury if victim restrained by seatbelt, however still significant potential morbidity • location of patient in vehicle • use and type of seatbelt • lap belt: spine and abdominal injury • shoulder belt: look for major vessel injury • ejection of patient from vehicle/entrapment of patient under vehicle • airbag deployment • use of helmet in motorcycle or bicycle collisions

Pedestrian-Automobile Impact
• high morbidity and mortality • vehicle speed is an important factor • site of impact on car • children tend to be run over • adults tend to be struck in lower legs, impact again on car (truncal injury) and thrown to the ground (head injury)

"',..}-----------, ,
Vehicle vs. Pedestrian Crash In adults look for triad of injuries: 1. tibia-fibula or femur fracture 2. truncal injury 3. craniofacial injury

• • • • 1 storey = 12 feet distance of fall: 50% mortality at 4 stories and 95% mortality at 7 stories position in which patient landed and type of surface assess for shock, lower extremity, spine and pelvic fractures

Gunshot Wounds (GsW)
• type of gun • handgun injuries: medium or high velocity, extent of injury may be limited to a small area • hunting and rifle injuries: high velocity, widespread injury • shot gun: wide spread tissue destruction • type of ammunition (e.g. hollow point bullets) • range of shot • close range: massive tissue destruction, deposition of wadding into wound • characterize route of entry and site of exit wound (if any) • GSW with hypotension: immediate transport to OR • hypotension indicates severe blood loss (>2 L blood loss in 70 kg patient is required to produce hypotension)

Stab Wounds
• route/direction of entry, length of blade • type of penetration (stab, slash, impalement) • victim recollection and witness reports are often inaccurate and may not correlate with depth/severity of wound • if blade in-situ, DO NOT REMOVE - it may be tamponading on bleeding vessel

ER8 Emergency Medicine


Toronto Notes 2008


Head Trauma
• see also Neurosurgery, NS29 • 60% of trauma admissions have head injuries • 60% of MVC-related deaths are due to head injury

Specific Injuries
Signs of basal skull fracture
• Battle's sign (bruised mastoid processl • Hemotympanum • Raccoon eyes (periorbital bruisingl • CSF otorrhea/rhinorrhea

• fractures (diagnosed by CT of head, often not visible on x-ray) A) skull fractures: • vault fractures: • linear, non-depressed - most common - typically occur over temporal bone, in area of middle meningeal artery (commonest cause of epidural hematoma) • depressed - open (associated overlying scalp laceration, tom dura) vs. closed • basal skull • typically occur through floor of anterior cranial fossa (longitudinal more common than transverse) • clinical diagnosis superior (Battle's sign, raccoon eyes, CSF otorrhea/rhinorrhea, hemotympanum) B) facial fractures (see Plastic Surgery, PS27) • neuronal injury A) diffuse: • concussion • mild: temporary disturbance of neurological function, complete recovery • classical: temporary, reversible neurological disturbance, with temporary «6 hrs) LOC, complete recovery • diffuse axonal injury • mild: coma 6-24 ms, possibly lasting deficit • moderate: coma >24hrs, little or no signs of brainstem dysfunction • severe: coma >24hrs, frequent signs of brainstem dysfunction B) focal injuries • contusions • intracranial hemorrhage (epidural, subdural, intracerebral)

Canadian CT Head Rule
CT Head is only IIlqUiIlld for patients with minor head injuries with any one of the foUowing:
High risk (for neurological interventionI • GCS soore <15 at 2hafter injury •Suspected open or depressed skull fracture •Any sign of basal skull fracture Ihemotympanum, 'raccoon' eyes, cerebrospinal fluid otorrhea/rhinorrhoea, Battle's sign) 'Vomiting ~2 episodes

• pre-hospital status • mechanism of injury

Physical Examination
• assume C-spine injury until ruled out • vital signs • shock (not due to isolated brain injury, except in infants) • Cushing's response to increasing ICP (bradycardia, hypertension, irregular respirations) • severity of injury determined by: 1) level of consciousness • Glasgow Coma Scale (GCS): GCS ~ intubate, any change in score of 3 or more = serious injury 2) pupils: size, anisocoria >1 mm (in patient with altered LOC), response to light 3) lateralizing signs (motor/sensory), may become more subtle with increasing severity of injury • re-assess frequently

Medium risk Ifor brain injury on CT) •Amnesia before impact >30 min •Dangerous mechanism lpedestrian struck by motor vehicle, occupant ejected from motor vehicle, fall from height >3 feet or five stairs) Minor head injury is defined as witnessed loss of oonsciousness, definite amnesia, or wit· nessed disorientation in apatient with aGCS score of 13-15.
I.G. SlilIII, GJI.WolIs, \(.Vandenkeen, C. Clemen~ et al. The Lancet May 5, 2001. 357: 9266; 1391·1396.

• labs: CBC, electrolytes, coags, glucose, tox screen • CT scan • skull X-rays - little value in the early management of obvious blunt head injury • for diagnosis of calvarium fractures (not brain injury) • may help localize foreign body after penetrating head injury • C-spine imaging, often with cr neck and head CT

... '. , - - - - - - - - - - - - , l
Treatment of Increased ICP • Elevate head of bed • Mannitol • Hyperventilate • Paralyzing agents

• general • ABCs • treat other injuries, must treat hypotension, hypoxia (both contribute significantly to mortality)

Toronto Notes 2008


Emergency Medicine ER9

• early neurosurgical consultation for acute and subsequent patient management • medical • seizure treatment/prophylaxis • benzodiazepines, phenytoin, phenobarbital • steroids are of no proven value • treat suspected raised ICP ---t consider the following: • raise head of stretcher 20° if patient hemodynamically stable • intubate and hyperventilate (100% O2 ) to a pC02 of 30-35 mmHg • mannitol1g1kg infused as rapidly as possible (reserved for head-injured patients with signs of increased ICP) • consider paralysing meds if agitated/high airway pressures • maintenance of cerebral perfusion pressure is critical • surgical

Disposition • neurosurgical ICU admission for severe head injuries (HI) • in hemodynamically unstable patient with other injuries, prioritize most life­ threatening injuries and try to maintain cerebral perfusion • for minor head injury not requiring admission, provide 24-hour HI protocol to competent caregiver, follow-up with neurology as even seemingly minor HI may cause lasting deficits

Spine and Spinal Cord Trauma
• assume cord injury with significant falls (>12 ft), deceleration injuries, blunt trauma to head, neck or back • spinal immobilization (cervical collar, spine board during patient transport only) must be maintained until spinal injury has been ruled out (see Figure 2) • vertebral injuries may be present without spinal cord injury; normal neurologic exam does not exclude spinal injury • spine may be unstable despite normal C-spine X-ray (SOWARA =spinal cord injury without radiologic abnormality) • injuries can include: complete/incomplete transection, cord edema, spinal shock


..... . ~ - - - - - - - - - - - - , }


Collar everyone with at least one

of the following criteria:

• midline tenderness • neurological symptoms or signs • significant distracting injuries • head injury • intoxication • dangerous mechanism • history of LOC

History • mechanism of injury, previous deficits, SAMPLE • neck pain, paralysis/weakness, parasthesia Physical Exam • ABCs • abdo: ecchymosis, tenderness • neuro: complete exam, including mental status • spine: maintain neutral position, palpate C-spine for tenderness, step-off; log-roll, then palpate thoracic and lumbar spine; assess rectal tone • extremities: check cap refill, suspect thoracolumbar injury with calcaneal fractures Investigations • labs: CBC electrolytes, creatinine, glucose, coags, cross and type, tox screen • imaging: • full C-spine X-ray series for trauma (AP, lateral, odontoid) • thoracolumbar X-rays • AP and lateral views • indicated in: • patients with C-spine injury • unconscious patients (with appropriate mechanism of injury) • patients with symptoms or neurological findings • patients with deformities that are palpable when patient log-rolled • patients with back pain • patients with suggestive injuries, e.g. bilateral calcaneal fractures • consider CT (for subtle bony injuries), MRl (for soft tissue injuries) if appropriate




If afracture is found, be suspi­ cious, look for another fracture.

..... .}--------------, ~
Note: Patients with penetrating trauma (especially gunshot and knife wounds) can also have spinal cord injury.

..... .'}--------------, ~


Of the investigations, the lateral C-spine X-ray is the single most important film. 95% of all abnor­ malities are found on this film.

ERIO Emergency Medicine


Toronto Notes 2008

Suspected C-spine Injury •• based on mechanism of injury le.g. MVC, fall, sports)


History: midline neck pain, numbness or parasthesia, presence of distracting pain, patient head-injured, patient intoxicated, loss of consciousness or past history of spinal mobility disorder Physical exam: posterior neck spasm, tenderness or crepitus, any neurologic deficit or autonomic dysfunction, altered mental state




C-spine cleared

(-spine cleared]

/ Abr Remain immobilized, consult spine service

extension films . - - Neck pain




1. Plain x-rays, 3views 2. CT scan if: • inadequate plain film survey • suspicious plain film findings •to better delineate injuries seen on plain films • any clinical suspicion of atlanto-axial dislocation • high clinical suspicion of injury despite normal x-ray • to include C1-C3 when head CT is indicated in head trauma

ormal films

Abnormal films

Remain immobilized, consult spine service






The Canadian CSpine IkIIe
For Alert IGIoogow Como ScaIo 15} and Stable Trauma Patients . . . CenIcaI Spino ICSpineI injul'f
1. Artj HigIHlioll FtctorThat Mandalas RacIiotnPl'Y? Agel 65Years

Figure 2. Approach to clearing the C-spine



Management of Cord Injury
• • • • • • • • • immobilize evaluate ABCs treat shock (maintain sBP >100 mmHg) insert NG and Foley catheter high dose steroids: methylprednisolone 30 mglkg bolus, then 5.4 mglkglhr drip, start within 6-8 hrs of injury (controversial and recently has less support) complete imaging of spine spine consult continually reassess high cord injuries as edema can travel up cord if cervical cord lesion, watch for respiratory insufficiency • low cervical transection (C5-Tl) produces abdominal breathing
(phrenic innervation of diaphragm still intact)
• high cervical cord injury (above C4) may require intubation and ventilation beware hypotension (neurogenic shock) • treabnent: warm blanket, Trendelenberg position (occasionally), volume infusion, consider vasopressors

Dangerous Med1anisml



Not 2. Any lDiHisk FtctorThat AJIows Salt Asaesament 01 Range 01 Motion?
Simple Rear-end MVCt

Siffiny Position In ED


------. /



line C-SpineTenderness

3. Ah/e 10 Acliw/y Ilolalo WI UnaIlIe >5'lebandRight

NoIlacliogr' Ah/e' l'l1Y
tDangeroos Mechanism:
tfall from 2: 1rneterl5stairs 'axialloadloheade.g.diving •MVC high speed I> 100 knvM rober. ejection tmotorized reaeational vehicles tbicydecollision
tSim~e rear~nd MVC exdulles: •pushed into oncoming traflk 'hnbybufJ1argetrud< -rollover 'hitbyh~h-speedvehK:le

• 3-view C-spine series is the screening modality of choice • lateral Cl-Tl ± swimmer's view (see Figure 3 and Table 2 for interpretation) • lateral view is BEST, identifies 90-95% of injuries

lOeiayed: Not immedl~e ot>et ned< pain LG. Stief!" el al. JAMA Oct 17. 2001. 2I6:lt51; 1841-1848.


Toronto Notes 2008


Emergency Medicine ERll

Table 4. Interpretation of Lateral View: The ABCS A • Adequacy and Alignment • must see C1 to C7·T1 junction; if not, downward traction of shoulders, swimmer's
view, bilateral supine obliques, or CT scan needed
• lines of contour (in children <8 years of age: can see physiologic subluxation of
C2 on C3, and C3 on C4, but the spinolaminal line is maintained)
• fanning of spinous processes - suggests posterior ligamentous disruption • widening of facet joints • check atlanto-occipital joint: • line extending inferiorly from clivus should transect odontoid • atlanto-axial articulation - widening of predental space (normal: <3 mm in adults, <5 mm in children) indicates injury of C1 or C2
B - Bones • height, width and shape of each vertebral body • pedicles, facets, and laminae should appear as one - doubling suggests rotation
1. anterior vertebral line 2. posterior vertebral line ." [anterior margin of spinal canall ~ 3. posterior border of facets -£ 4. laminar fusion line (posterior margin of spinal canall ~ 5. posterior spinous line .~ (aln"g tips of spinous processesl ~

C - Cartilage • intervertebral disc spaces - wedging anteriorly or posteriorly suggests vertebral

5 - Soft Tissues • widening of retropharyngeal (normal: <7 mm at C1-4, may be wide in children <2 yrs
on expiration) or retrotracheal spaces (normal: <22 mm at C6-T1, <14 mm in children
<5 yrs)

Figure 3. Lines of Contour on a
Lateral C-Spine X-Ray

• odontoid view (open mouth or oblique submental view) (see Figure 4) • examine the dens for fractures - beware of artifact (horizontal or vertical) caused by the radiological shadow of the teeth overlying the dens - if unable to rule out fracture, repeat view or consider CT or plain film tomography • examine lateral aspects of Cl and spacing relative to C2 • AP view • alignment of spinous processes in the midline • spacing of spinous processes should be equal • check vertebral bodies

1. Dens 2. Cl Lateral Mass 3. C2 To clear the x-ray ensure that:
AI the dens is centred between the lateral c
masses of Cl !g B) Cl and C2 are aligned laterally ~ CI the lateral masses of Cl are :g symmetrical in size @

Supine Oblique Views
• • • • rarely used detects some injuries not visible on the usual 3 views but CT is best better visualization of posterior element fractures (lamina, pedicle, facet joint) can be used to visualize the C7-T1 junction

Figure 4. C-Spine X-Ray: Odontoid

Sequelae of C-spine Fractures
• decreased descending sympathetic tone (neurogenic/spinal shock) responsible for
most sequelae
• cardiac • no autoregulation, falling BP, decreasing HR, vasodilation • management: give IV fluids ± vasopressors • respiratory • no cough reflex (risk of aspiration pneumonia) • no intercostal muscles ± diaphragm • management: intubate and maintain vital capacity • gastrointestinal • ileus, vasodilation, bile and pancreatic secretion continues (>lL/day), risk of aspiration, GI stress ulcers • management: NG tube may be required for suctioning, feeding, etc. • renal • hypoperfusion ..... give IV fluids • kidney still producing urine (bladder can rupture if patient not urinating) • management: Foley catheter may be required (measure urine output) • skin • vasodilation, heat loss, no thermoregulation, atrophy (risk of skin ulcers) • muscle • flaccidity, atrophy, decreased venous return • penis • priapism



•.r - - - - - - - - - - - - - ,

20% of C-spine fractures are accompa­
nied by other spinal fractures, so ensure
thoracic and lumbar spine x-rays are nor­
mal before proceeding to OR.

ER12 Emergency Medicine


Toronto Notes 2008


Chest Trauma
• two types: A. found and managed in 1 survey B. found and managed in 20 survey



Trauma to the chest accounts
for, or contributes to 50% of
trauma deaths.

• see Table 5 below
Table 5. Life-Threatening Chest Injuries Found in 1· Survey
Physical Exam Airway Obstruction 'anxiety, stridor, hoarseness, altered mental status 'apnea, cyanosis Investigations 'do not wait for ABG to intubate Management 'definitive airway management • intubate early , remove FB if visible with lal'{ngoscope prior to intubation 'needle thoracostomy­ large bore needle, 2"' ICS mid clavicular line, followed by chest tube in 5-ICS, anterior axillaI'{ line


BO% of all chest injuries can be managed non·surgically with simple measures such as intubation, chest tubes, and pain control.




3WlIy seal for open pneumothorax ft.e.

sucking chest wound)
Allows air to escape during the expiratory
phase (so that you don't get atension pneu·
mothoraxl but seals itsen to allow adequate
breaths during the inspiratory phase.

Tension Pneumothorax 'clinical diagnosis 'one·way valve causing accumulation of air in pleural space

'respiratory distress, tachycardia, 'non-radiographic diagnosis distended neck veins, cyanosis, asymmetl'{ of chest wall motion 'tracheal deviation away from pneumothorax
, percussion hyperresonance
'unilateral absence of hreath sounds

Open Pneumothorax 'air entering chest from wound rather than trachea

'gunshot or other wound (hole >213 tracheal diameter) ±exit wound , unequal breath sounds

'ABG: decreased pO,

• air-tight dressing sealed on 3sides • chest tube 'surgery


DDx of LifeThreatening Chest Injuries
Open pneumothorax
Tension pneumothorax
Rail chest
Airway obstruction
Contusion: pulmonary, myocardial
Hernia: traumatic, diaphragmatic
ESophageal perforation
Tracheobronchial disruption!
Traumatic injury

Massive Hemothorax ' pallor, flat neck veins, shock '>1500 cc blood loss in chest cavity 'unilateral dullness 'absent breath sounds, hypotension

• usually only able to do supine , restore blood volume CXR·· entire lung appears • chest tube radioopaque as blood spreads 'thoracotomy if: out over posterior thoracic cavity • >1500 cc total blood loss • ~200 cclhr continued drainage •ABG: decreased pO" • 0, +fluid therapy +pain control increased pCO, 'judicious fluid therapy in absence of 'CXR: rib fractures, lung contusion systemic hypotension • positive pressure ventilation , ± intubation and ventilation

Flail Chest 'paradoxical movement of flail 'free·floating segment of chest segment wall due to >2 rib fractures, each 'palpable crepitus of ribs at 2sites • decreased air entl'{ on affected side • underlying lung contusion (cause of morbidity and mortality) CardiacTamponade • clinical diagnosis • pericardial fluid accumulation impairing ventricular function • penetrating wound (usuallyl , Beck's triad: hypotension, distended neck veins, muffled heart sounds , tachycardia, tachypnea
, pulsus paradoxus
, Kussmaul's sign


'IVfluids • pericardiocentesis • open thoracotomy

Toronto Notes 2008


Emergency Medicine ER13


• need to have high index of suspicion, usually dependent on mechanism of injury • see Table 6 below

Table 6. Potentially Life-Threatening Chest Injuries Found in 2° Survey

Physical Exam Pulmonary Contusion
• blunt trauma to chest • interstitial edema impairs compliance and gas exchange

• CXR: areas of opacification of lung within 6hours of trauma


• maintain adequate ventilation • monitor with ABG, pulse oximeter and ECG • chest physiotherapy • positive pressure ventilation if severe




Ruptured Diaphragm

• blunt trauma to chest or • CXR: abnormality of diaphragm! • laparotomy for diaphragm repair and
abdomen le.g. high lap belt in MVC) lower lung fieldsiNG tube placement because of associated intra·abdominal
• CT scan and endoscopy· sometimes injuries helpful for diagnosis • usually penetrating trauma Ipain out of proportion to degree of injUlvl • CXR: mediastinal air Inot alwaysl • esophagram IGastrograffin) • flexible esophagoscopy
• early repair Iwithin 24 hrs.1 improves
outcome but all require repair

Ruptured diaphragm is more ohen diagnosed on the left side. as liver conceals right side defect.

Esophageal Injury

• 90% tear at subclavian Inear ligamentum arteriosuml, most die at scene • sawageable if diagnosis made rapidly

• sudden high speed • CXR, CT scan, transesophageal echo deceleration le.g. MVC, fall, airplane ITEE), aortography Igold standard) crash), complaints of chest pain, • see sidebar for CXR features
dyspnea, hoarseness
!frequently absent)
• decreased femoral pulses,
differential arm BP larch tearl
• blunt trauma to chest (usually in setting of multi·system trauma and therefore difficult to diagnosel • physical examination: overlying
injury, i.e. fractures, chest wall
• ECG: arrhythmias, ST changes • patients with anormal ECG and normal hemodynamics never get dysrhythmias

• thoracotomy Imay treat other severe injuries firstl

Blunt Myocardial Injury

• antiarrhythmic agents

X-ray features of Aortic tear IABC WHITE): • depressed left mainstem Bronchus • pleural Cap •Wide mediastinum (most consistent) • Hemothorax • Indistinct aortic knuckle •Tracheal deviation to right side • Esophagus (NG tubel deviated to right


1. Penetrating NeckTrauma
• includes all penetrating trauma to the three zones of the neck (Figure 5) • management: injuries deep to platysma require further evaluation by angiography
or surgery
• do not explore penetrating neck wounds except in the OR

'.}--------------, ,

If penetnrting neck trauma present,
• clamp structures (can damage nerves) • probe • insert NG tube (leads to bleeding) • remove weaponlimpaled object

2. Airway Injuries
• always maintain a high index of suspicion • larynx • history: strangulation, clothes line, direct blow, blunt trauma, any penetrating injury involving platysma • triad: hoarseness, subcutaneous emphysema, palpable fracture crepitus • other symptoms: hemoptysis, dyspnea, dysphonia • investigations: CXR, CT scan, arteriography (if penetrating) • management • airway - manage early because of edema • C-spine may also be injured, consider mechanism of injury • surgical - tracheotomy vs. repair • trachea/bronchus • frequently missed • history: deceleration, penetration, increased intra-thoracic pressure; complaints of dyspnea, hemoptysis • examination: subcutaneous air, Hamman's sign (crunching sound synchronous with heart beat) • CXR: mediastinal air, persistent pneumothorax or persistent air leak after chest tube inserted for pneumothorax • management: surgical repair if >1/3 circumference







loop I







o Adrian Yell (10061

Zone III: superior aspect of neck Zone II: midportion of neck Icricoid to the angle of mandible) Zone I: base of neck (thoracic inlet to cricoid cartilage)

Figure 5. Zones of the Neck in

ER14 Emergency Medicine


Toronto Notes 200S

o ~

Abdominal Trauma

;OW. . . . . .::OO"

~_ _....._ _._J



• two mechanisms: • blunt trauma: usually causes solid organ injury (spleen injury is most common) • penetrating trauma: usually causes hollow organ injury or liver injury (most common)

•.1 - - - - - - - - - - - - - ,

Seatbelt injuries may cause • retroperitoneal duodenal trauma • intraperitoneal bowel transection • mesenteric injury
'l:spine injury

• results in two types of hemorrhage • intra-abdominal bleed • retroperitoneal bleed • adopt high clinical suspicion of bleeding in multi-system trauma


, .}------------,

History • mechanism of injury, SAMPLE history Physical Exam • often unreliable in multi-system trauma • slow blood loss not immediately apparent
• other injuries may mask symptoms
• serial examinations are required • abdomen: • inspect: contusions, abrasions, seatbelt sign, distention
auscultate: bruits, bowel sounds
• palpate: tenderness, rebound tenderness, rigidity, guarding DRE: rectal tone, blood, bone fragments, prostate location placement of NC, foley catheter should be considered part of the abdo exam • other systems to assess: CVS, respiratory (possibility of diaphragm rupture), pelvis, back, neuro as it pertains to abdo sensation, CU Investigations • labs: CBC, electrolytes, coags, cross & type, glucose, creatinine, CK, lipase, amylase, liver enzymes, ABC, blood EtOH, ~-hCC, VIA, tox screen • imaging: see Table 7
,...Ta_b-,l,---e_'o_lm_a_9 9 :..i_n--:::i"_A_bd--,-o_m_i_"_al_li_ra_u_m_a_-----'-----:-;--;---,.-------------'tIII­
Imaging Strengths Limitations

Indications for Folay & NG tube in abdotrauma FoIay catheter: unconscious or mul­ tiply injured patient who cannot void spontaneously. Contraindications: blood at the meatus, an ecchymotic scrotum, or a·high-riding" prostate on DRE (retrograde cystourethrogram is indicated to rule out a urethral tear or ruptured bladder) NG tube: used to decompress the stomach and proxi­ mal small bowel Contraindications: facial fractures or basal skull fractures suspected.



•.1 - - - - - - - - - - - - - ,

Criteria for Positive Lavage • >10 cc gross blood • bile, bacteria, foreign material • RBC count>100,000 x 1()6!L • WBe >500 x 1Q6!L, amylase>175 IU



Chest 1I00king for free air under diaphragm, diaphragmatic hernia, air fluid levels), pelvis, cervical, thoracic, lumbar spines Most specific test Most sensitive test Tests for intra-peritoneal bleed

No soft tissue

CT scan Diagnostic Peritoneal Lavage IDPLI

Radiation exposure 20x more than xray Cannot use if hemodynamic instability Cannot test for retroperitoneal bleed or diaphragmatic rupture Cannot distinguish lethal from trivial bleed Results can take up to 1hr NOT used to identify specific organ injuries If patient has ascites, FAST will be falsely positive

Ultrasound: FAST (focused abdominal sonogram for trauma)

Identifies presenceJabsence of free fluid in peritoneal cavity RAPID exam: less than 5 minutes Can also examine pericardium and pleural cavities



• imaging must be done if: • equivocal abdominal examination, suspected intra-abdominal injury or distracting injuries • multiple trauma patient resulting in unreliable physical exam (altered sensorium, i.e. secondary to drugs, alcohol, head trauma, or distracting injury; spinal cord injury resulting in abdominal anesthesia) • unexplained shock/hypotension multiple trauma patients who must undergo general anesthesia for orthopaedic, neurosurgical, or other injuries • fractures of lower ribs, pelvis, spine


Laparotomy is mandatory if
penetrating trauma and:

• shock • peritonitis • evisceration • free air in abdomen • blood in NG tube, Foley catheter, or on
rectal exam

Management • general: ABCs, fluid resuscitation and stabilization • surgical: watchful wait vs. laparotomy • solid organ injuries: decision based on hemodynamic stability, not the specific injuries • hemodynamically unstable or persistently high transfusion requirements -> laparotomy • hollow organ injuries: laparotomy • even if low suspicion on injury: admit and observe for 24 hours

• high risk of gastrointestinal perforation and sepsis • history: size of blade, calibre/distance from gun, route of entry

Toronto Notes 2008


Emergency Medicine ER15

• local wound exploration (not reliable) with the following exceptions: • thoracoabdominal region (may cause pneumothorax) • back or flanks (muscles too thick)

.... . ~ - - - - - - - - - - - - , }
'Rule ofThirds' for stab wounds:
·113 do not penetrate peritoneal cavity
·113 penetrate but are harmless
·113 cause injury requiring surgery


• general: ABCs, fluid resuscitation and stabilization • gunshot wounds ---+ always require laparotomy • stab wounds ---+ "rule of thirds" (see sidebar)

• see also Urology, U32

Tract Injuries


• blunt trauma - often associated with pelvic fractures • renal contusions (minor injury - parenchymal ecchymoses with intact renal capsule) • renal parenchymal tears/laceration: non-communicating (hematoma) vs. communicating (urine extravasation, hematuria) • extraperitoneal rupture of bladder from pelvic fracture fragI!lents • intraperitoneal rupture of bladder from trauma and full bladder
anterior (bulbous) urethral damage with pelvic fractures
• ureter: rare, at uretero-pelvic junction • penetrating trauma • damage to: kidney, bladder, ureter (rare) • acceleration/deceleration injury • renal pedicle injury - high mortality rate (laceration and thrombosis of renal artery, renal vern, and ttieir branches) • iatrogenic • ureter (from instrumentation)

.... .~ - - - - - - - - - - , )
Gross hematuria suggests bladder


• • • • mechanism of injury hematuria (microscopic or gross), blood on underwear dysuria, urinary retention history of hypotension

Physical Examination
• abdominal pain, flank )Jain, costovertebral angle (CVA) tenderness, upper quadrant mass, perineal lacerations • ORE: sphincter tone, position of prostate, presence of blood • scrotum: ecchymoses, lacerations, testicular disruption, hematomas • bimanual exam, speculum exam • extraperitoneal bladder rupture: pelvic instability, suprapUbic tenderness from mass of urine or extravasated blood • intraperitoneal bladder rupture: acute abdomen




In the case of gross hematuria, the GU system is investigated from dis­ tal to proximal (i.e. urethrogram, cystogram, etc.l

• plain film: look for fractures (lower rib, lower thoracic, upper lumbar vertebrae, pelvis) • renal: CT scan (best, if hemodynamically stable), intravenous pyelogram (IVP) during lap'arotomy, renal arteriography (If renal artery injury suspected) • ureter: retrograde ureterogram • bladder: urinalysis, CT scarl, urethrogram, ± retrograde cystoscopy, ± cystogram (distended bladder + post-void) • urethra: retrograde urethrography

• urology consult • renal • minor injuries - conservative management • bedrest, hydration, analgesia, antibiotics • major injuries - admit • conservative management with frequent reassessments, serial urinalysis, ± reimaging • surgicafrepair (exploration, nephrectomy) (e.g. hemodynamically unstable or continuing to bleed >48h, major urine extravasation, renal pedicle injury, all penetrating wounds and major lacerations, infections, renal artery thrombosis) • ureter • uretero-uretostomy • bladder • extraperitoneal: minor rupture: Foley drainage x 10-14 days
major rupture: surgical repan
• intraperitoneal: drain abdomen ana surgical repair • urethra • anterior: conservative, if carmot void ---> Foley or suprapubic cystostomy and antibiotics • posterior: suprapubic cystostomy (avoid catheterization) ± surgical repair

ER16 Emergency Medicine


Toronto Notes 2008


Orthopaedic Injuries
• see also Orthopaedics. ORlO, ORIS, 0R29, OR34

Goals of ED Treatment
• identify injuries accurately and address potentially life/limb threatening problems appropriately • reduce immobilize frac.tures (cast/splint) as appropriate • provide adequate pain relief • arrange proper follow-up if necessary


Description of Fractures ISOlARTAn: Site
Open vs. closed Length
Articular Rotation Translation Alignment/angulation Type (i.e. Salter-Harris, etc.)


• mechanism of injury may be very important

Physical Examination

• Look (inspection): "SEADS" Swelling, Erythema, Atrophy, Deformity, Skin changes
(e.g. bruises)
• Feel (palpation): all joints/bones -local tenderness, swelling, warmth, crepitus, joint
effusions, subtle deformity
• Move: joints affected plus above and below injury - active ROM preferred to passive • Neurovascular status: distal to injury (BEFORE and AFTER reduction)

... '. ) - - - - - - - - - - - - , ~
Reasons for Emergent Orthopaedic

• threat to life is usually due to blood loss (e.g. up to 3 L in pelvic fractures, 1.5 L per long bone fracture) • threat to limb is usually due to interruption of blood supply to distal part of limb or to susceptible part of bone
Table 8. Life and Limb Threatening Orthopedic Injuries
Life Threatening Injuries Limb Threatening Injuries

-compartment syndrome - irreducible dislocation
- circulatory compromise
•open fracture •injury requiring surgical repair

• Major pelvic fractures 'Traumatic amputations • Massive long bone injuries (beware fat emboli) 'Vascular injury proximal to knee/elbow

• Fracture/dislocation of ankle (talar AVN) • Crush injuries • Compartment syndrome • Open fractures • Dislocations of knee/hip • Fractures above knee/elbow


Open Fractures
• communication between fracture site and external surface of skin - risk of osteomyelitis • remove gross debris, irrigate, cover with sterile dressing - formal irrigation and debridement often done in the OR • control bleeding with pressure (no clamping) • splint • antibiotics (15' generation cephalosporin and aminoglycoside) and tetanus prophylaxis • must secure definitive surgical care within 6-S hours

Vascular injury/compartment syndrome is suggested by "The 6 Ps": Pulse discrepancies Pallor Paresthesia/hypoesthesia Paralysis Pain (especially when refractory to
usual analgesics)
Polar (cold)

Vascular Injuries
• realign limb/apply longitudinal traction and reassess pulses (e.g. Doppler probe) • surgical consult

Compartment Syndrome
• increased interstitial pressure in an anatomical "compartment" (forearm, calf) with little room for expansion, resulting in -.J...perfusion and potential muscle/nerve necrosis • excessive pain which is worse with passive stretching and refractory to analgesia is the hallmark sign early on; also look for "the 6 Ps" (see sidebar) • requires prompt decompression - remove constrictive casts, dressings; fasciotomy may be needed ASAP

lateral view

• anterior shoulder dislocation • axillary nerve (lateral aspect of shoulder) and musculocutaneous nerve (extensor aspect of forearm) at risk
• seen on lateral view: humeral head anterior to glenoid
• reduce (traction, leverage of scapular manipulation), immobilize in internal rotation, re-X-ray, out-patient appointment with ortho • with forceful injury, look for fracture • Colles' fracture (Figure 6) • distal radius fracture with dorsal displacement • from fall on an outstretched hand (FOOSH) • AP film: shortening, radial deviation, radial displacement • lateral film: dorsal displacement, volar angulation

A- Pview
1. 2. 3. 4. 5. 6.

dorsal tilt dorsal displacement ulnar stylOid fracture radial displacement radial tilt shortening

Figure 6. Colles' fracture

Toronto Notes 2008


Emergency Medicine ER17

• reduce, immobilize with splint, out-patient with ortho or immediate ortho
referral if complicated fracture
• if involvement of articular surface, emergent ortho referral • scaphoid fracture tenderness in anatomical snuff box, pain on scaphoid tubercle, pain on axial loading of thumb • negative X-ray: thumb spica splint, re-X-ray in 1 week ± bone scan • positive X-ray: thumb spica splint x 6-8 weeks • risk of avascular necrosis (AVN) of scaphoid if not immobilized
• outpatient ortho appointment



,r;, "-,,,.,.., ,~~aPitate



• ankle and foot fractures • see Ottawa Ankle and Foot rules (Figure 8) • knee injuries • see Ottawa Knee rules (Figure 9) • avulsion of the base of 5th metatarsal • occurs with inversion injury • supportive tensor or below knee walking cast for 3 weeks • calcaneal fracture • associated with fall from height • associated injuries may involve ankles, knees, hips, pelvis, lumbar spine

Figure 7. Carpal Bones

bones (1-5) ~



Reasons for Splinting
- reduces pain - reduces further damage to vessels and nerves - reduces risk of inadvertently converting aclosed fracture into an open fracture - facilitates patient transport


o Posterior
edge or tip of lateral

____ €)
+-1 •

Posterior edge or lip of medial


G Base ol51h



An ankle radiographic series is required only if there is any pain in malleolar zone and any of these findings:
1. bone tenderness at A
2, bone tenderness at B
3, inability to bear weight both immediately and in emergency department
Afoot radiographic series is required only if there is any pain in midfoot zone and any of these findings:
1. bone tenderness at C
2, bone tenderness at D
or 3, inability to bear weight both immediately and in emergency department

Figure 8. Ottawa Ankle Rules

Reprinted with permission from Stiell et. al. (1994) JAMA 271(11):827-832, copyright © (1994), American Medical Association,
A knee x-ray examination is required only for acute injury patients with one or more of: • age 55 years or older • tenderness at head of fibula • • isolated tenderness of patella* inability to bear weight both immediately and in the emergency department (four steps)" • inability to flex to 90'

*no bony tenderness of knee other than patella "unable to transfer weight twice onto each lower limb regardless of limping

Figure 9. Ottawa Knee Rules

Reprinted with permission from: Stiell et. al.I19971 JAMA 278(23):611·5, copyright © 11997), American Medical Association,

ER18 Emergency Medicine


Toronto Notes 2008

SoftTissue InjuriesIEmergency Wound Mana ement
Goals of ED Treatment
• • • • • identify injuries and stop any active bleeding - direct pressure manage pain wound examination and exploration (history and physical) cleansing, ± antibiotic and tetanus prophylaxis repair and dressing

Tetanus Prophylaxis
• both tetanus toxoid (Td) and immunoglobulin (TIC) are safe (and indicated) in pregnancy

Table 9. Guidelines forTetanus Prophylaxis for Wounds
Immunization History Uncertain or <3 doses
3or more, none for>10 years 3or more, >5 but <10 years ago 3or more, <4years ago

A.cute treatment of conlus;ons IRlCEI: Rest Ice Compression Elevation

Non Tetanus Prone Wounds T1G3 TeF Yes Yes No No No No No No

Tetanus Prone Wounds1 Td T1G Yes Yes Yes Yes Yes No No No

... '.:}-----------, ,
Not Joint

Clallwilhnwlaaorlllhlr A,palllnlian !dIyll
IIOIIIilloIWIItlUl1ft 5

1 wounds >6 hours old, >1 em deep, puncture wounds, avulsions, wounds resuning from missiles, crush wounds. burns, frostbite, wounds contaminated with dirt. feces, soil. or saliva '0.5 mllM Ietanus and diphtheria toxoids ITdl. adsorbed I telanus immune globulin ITIGI, 250 units deep 1M Source: MMWR 2001; 5O{201; 418, 427. MMWR 1991; 401RR121; 1·52.

• tender swelling (hematoma) following blunt trauma • is patient on anticoagulants? do they have a coagulopathy (e.g. liver disease)?




Joint Scalp


Mucous absorbable Iv~ryll Membrane
for Ioriger periods of tinne


• partial to full thickness break in skin • management • dean thoroughly, :±. local anesthetic, with brush to prevent
foreign body impregnation (tattooing)
• antiseptic ointment (Polysporin™ or Vaseline™) for 7 days for facial and complex abrasions • tetanus prophylaxis - see Table 9 above

N.B. Patients on steroid therapy may need sutures in




• see also Plastic Surgery, PL9 • consider every structure deep to a laceration injured until proven otherwise • in hand injury patient, include following in history: handedness, occupation, mechanism of injury, previous history of injury • physical exam • think about underlying anatomy • examine tendon function actively against resistance and neurovascular status distally • clean and explore under local anesthetic; look for partial tendon injuries • x-ray wounds if a foreign body is suspected (e.g. shattered glass) and not found when exploring wound (remember: not all foreign bodies are radiopaque), or if suspect intra-articular involvement • management • disinfect skin/use sterile techniques • irrigate copiously with normal saline • analgesia ± anesthesia • maximum dose of lidocaine: • 7 mglkg with epinephrine • 5 mglkg without epinephrine • in children, topical anesthetics such as LET (lidocaine, epinephrine and tetracaine) and in selected cases a short-acting benzodiazepine (midazolam or other agents) for sedation and amnesia are useful • secure hemostasis • evacuate hematomas, debride non-viable tissue, remove hair and remove foreign
• ± prophylactic antibiotics • suture unless delayed presentation, a puncture wound, or mammalian bite • take into account patient and wound factors when considering suturing • advise patient when to have sutures removed

Alternatives to Sutures

otissue glue
o Steristrips1M o staples


Where not to use local anesthetic with
Ears, Nose, Fingers, Toes and Hose

Toronto Notes 2008


Emergency Medicine ER19


palmar digital nerves

• see also Plastic Surgery, PL24 • localized infection of the dermis • bacterial (5. aureus, GAS, H. injluenzae, rarely pseudomonas, MRSA) infection of skin and subcutaneous tissues • look for "rubor, calor, dolor, tumor" (erythema, warmth, pain, swelling) • have high index of suspicion in patients who are immunocompromised (e.g. HIV, OM), vasculopaths, IV drug users • treat with immobilization and elevation of infected area, antibiotics, analgesics, and close follow-up • antibiotics for common cellulitis: cefazolin IV then cephalexin PO (alt: c1indamycin PO, vancomycin IV then linezolid PO); consider MRSA




Differential Diagnosis of cellulitis
Necrotizing Fasciitis
Gas gangrene
Cutaneous anthrax
Vaccinia vaccination
Insect bite (hypersensitivity)
Acute gout

Fixed drug reaction
Pyoderma gangrenosum

• may be associated with a retained foreign body • look for warm, swollen, painful, erythematous fluctuant masses • ensure absence of systemic symptoms and presence of subcutaneous air in simple abscesses • anesthetize locally • treat with incision and drainage ± antibiotics - apply warm compress, give analgesics




Which Abscesses Need Antibiotics?
•evidence of systemic illness le,g. cellulitisl •immunocompromised patient •patient at risk for endocard~is

Mammalian Bites
• see also Plastic Surgery, PLIO • history • time and circumstances of bite, symptoms, allergies, tetanus immunization status, comorbid conditions, rabies risks, HIV/hepatitis risk (human bite) • high morbidity associated with clenched fist injuries (CFIs), "fight bites" • physical examination • assess type of wound: abrasion, laceration, puncture, crush injury • assess for direct tissue damage: skin, bone, tendon, neurovascular status • investigations • if bony injury or infection suspected check for fracture and gas in tissue with X-rays • ALWAYS get skull films in children with scalp bite wounds, ± CT to rule out cranial perforation • initial management • wound cleansing and copious irrigation as soon as possible • irrigate/debride puncture wounds if feasible, but not if sealed or very small openings; avoid hydrodissection along tissue planes • debridement is important in crush injuries to reduce infection and optimize cosmetic and functional repair • culture wound if signs of infection (erythema, necrosis or pus); obtain anaerobic cultures if wound foul smelling, necrotizing, or abscess; notify lab that sample is from bite wound • prophylactic antibiotics • types of infections resulting from bites: cellulitis, lymphangitis, abscesses, tenosynovitis, osteomyelitis, septic arthritis, sepsis, endocarditis, meningitis • a 3-5 day course of antibiotics is recommended for all bite wounds to the hand and should be considered in other bites if any high-risk factors present (efficacy not proven) • dog and cat bites (pathogens: Pasteurella multocida, 5. aureus, 5. l'iridans) • 80% of cat bites, 5% of dog bites become infected • 1st line: amoxicillin + clavulinic acid • human bites (pathogens: Eikenella cnrrodens, S. aureus, S. viridans, oral anaerobes) • 1st line: amoxicillin + c1avulinic acid '"



Early wound irrigation and debridement
are the most important factors in
decreasing infection.

ER20 Emergency Medicine


Toronto Notes 2008


• additional management issues • rabies (see Infectious Diseases, ID9) • reservoirs: warm-blooded animals except rodents, lagomorphs (e.g. rabbits) • post-exposure vaccine is effective; treatment depends on local prevalence (contact public health) • to suture or not to suture? • vascular structures (i.e. face and scalp) are less likely to get infected, therefore consider suturing • avascular structures (i.e. pretibial regions, hands and feet) by secondary intention

Snake Bites
• history, physical exam, investigations and initial management similar to mammalian bites • additional management issues • snake bites are rarely fatal but proper precautions must be taken • supportive management, observe for compartment syndrome, analgesia, tetanus prophylaxis • contact regional Poison Control Centre for consultation • constriction band should be placed proximal to bite • observe for signs and symptoms of envenomation 15min-2hrs after bite (pain, sweating, edema, chills, weakness, numbness, tingling, HR changes, faintness, ecchymosis, N/V); if no envenomation then remove band and monitor closely for 24hrs • if envenomation present, administer antivenom


Insect Bites
Posterior • Bee Stings • 5 types of reactions to stings (local, large local, systemic, toxic, unusual) • history and physical exam KEY to diagnosis; no lab test will confirm • investigations: CBC, electrolytes, BUN, creatinine, glucose, ABGs, ECG • ABC management, epinephrine O.lmg N over 5 minutes if shock, antihistamines, cimetidine 300mg N /IM/PO, steroids, ~-agonists for SOB/wheezing 3mg in 5mL NS via nebulizer, local site management • West Nile Virus (see Infectious Diseases, ID28) • severity: asymptomatic 80%, flu-like symptoms 20%, encephalitis <1% • clues: aseptic meningitis/encephalitis in late summer in prevalent area • incubation 3-14 days, symptoms last 3-6 days • general symptoms: fever, malaise, anorexia, headache, altered mental status, motor weakness, ataxia, extrapyramidal signs, GI signs, myalgias, lymphadenopathy, rash, myocarditis, optic neuritis • diagnosis: CSF and serum for serology investigations: CBC, electrolytes, CSF; CT/MRI management: ABCs, N fluids for dehydration, antibiotics if signs of meningitis (based on CSF analYSiS), analgesia, antipyretics, Interferon-alpha2b, ribavirin

Burns (see also Plastic Sur~ery, PSI9)
Figure 11. Rule of 9's forTotal Body Su rface Area

Use palm of the patient's hand to estimate 1%of BSA affected.





High Risk Factors for Infec:tion: • puncture wounds • crush injuries • wounds greater than 12 hours old • hand or foot wounds, wounds near joints • immunocompromised patient • patient age greater than 50 years • prosthetic joints or valves
(risk of endocarditisl

• immediate management ~ome can be done before arrival to hospital) • remove noxious agent/stop burning process establish airway ifneeded (indicated with bums >40% BSA or smoke inhalation injury) • resuscitation for 2nd and 3rd degree bums • Parkland Formula: Ringer's lactate 4cc/kg/%BSA burned; give 1/2 in first 8 hours, 1/2 in next 16 hours • urine output is best measure of resuscitation, should be 40-50 cc/hr or 0.5 cc/kg/hr; avoid diuretics • pain relief - continuous morphine infusion at 2 mglhr with breakthrough bolus • bum wound care - prevent infection, clean with mild soap and water, sterile dressings • physical examination • Bum size: • rule of nines (see Figure 11); does not include 1st degree bums • Bum depth: • 1st degree: epidermis only (e.g. sunburn) • 2nd degree: superficial partial thickness - into superficial dermis deep partial thickness - intonair follicles, sweat glands • 3rd degree: all layers of the skin • 4th degree: to fat, muscle, even bone

Toronto Notes 2008


Emergency Medicine ER21

• further management • escharotomy or fasciotomy for circumferential bums (chest, extremities) • topical antibiotics • systemic antibiotics infrequently indicated • guidelines for hospitaHzation • 2nd degree bums to >10% BSA; any significant 3rd degree bums • 2nd degree on face, hands, feet, perineum or across major joints • electrical, chemical bums and inhalation injury • bum victims with underlying medical problems or immunosuppressed patients

Pediatric Trauma
• priorities remain the same (Airway, Breathing, Circulation)

• • • • • "smffing position" short trachea (5 em in infants, 7.5 em at 18 months) uncuffed ETI under age 8 surgical cricothyroidotomy NOT indicated needle cricothyroidotomy with jet ventilation if unable to intubate



Pediatric OrotrachealTube Diametar: diameter =~ +4

• noting tachypnea is important • stethoscope not as useful for diagnosing problems

• norma] blood volume = 80 ml/kg • fluid resuscitation • bolus crystalloid 20 ml/kg • repeat x 1 if necessary • blood replacement if no response to second bolus of crystalloid • venous access • intraosseous infusion if unable to estabHsh N access in <30 seconds • venous cutdown (medial cephalic, external jugular, great saphenous)

• children prone to hypothermia • blankets/external warming/cover scalp
Table 10. Normal Vitals in Pediatric Patients



Systolic BP

Weight (kg)

30-50 30-40 20-30 14-20 12-20 12-16

120-160 120-140 100-110 90-100 80-100 60-90

>60 70-80 80-95 90-100 100-110 100-120

3-4 8-10 12-16 18-26 26-50 >50

6mo-lyr 2-4yr 5-8yr g-l2vr >12\'r

Trauma in Pregnancy
• priorities the same (Airway, Breathing, Circulation)

Hemodynamic Considerations
• near term, inferior vena caval compression in the supine position can decrease cardiac output by 30-40% • use left lateral decubitus (LLD) positioning or hip bolster to alleviate compression and increase blood return • BP drops 5-15 mmHg systolic in 2nd trimester, increases to normal by term • HR increases 15-20 beats per minute by 3rd trimester


Blood Considerations
• physiologic macrocytic anemia of pregnancy (Hb 100-120) • WBC increases to high of 20,000

ER22 Emergency Medicine

Approach to Common ER Presentations

Toronto Notes 2008



• pregnant patients may lose 35% of blood volume without typical signs of shock (i.e. tachycardia, hypotension) • the fetus may be in "shock" due to contraction of the uteroplacental circulation • fetal HR changes an> an indication of maternal circulatory compromise

All pregnant patients should be posi­ tioned in left-lateral decubitus.

Management Differences
• • • • • place bolster under right hip to stop inferior vena cava compression fetal monitoring (Doppler) early obstetrical consult do not avoid necessary x-rays, but shield as much as posssible consider need for RhoGAM if mother Rh-

Approach to Common ER Presentations

Abdominal Pain
Rule Out Life-Threatening Causes
• Gl: perforated viscus, hepatic/spleruc injury, ischemic bowel (diffuse pain) • GU: ectopic pregnancy • CVS: Ml, aortic dissection, ruptured AAA (tearing pain)

Additional Differential Diagnosis
• Gl: appendicitis, diverticulitis, bowel obstruction, hepatitis, cholecystitis, pancreatitis • urinary: cystitis, pyelonephritis, ureteral calculi • gerutal • female: pelvic inflammatory disease (PID), endometriosis,
salpingitis/tubo-ovarian abscess, ovarian torsion/cyst
• male: testicular torsion, epididymitis • other: diabetic ketoacidosis (DKA), Herpes Zoster Virus (HZV), intra-abdominal abscess, pneumorua, lead poisoning, porphyria, sickle cell crisis


Abdominal Assessment

Assess in all 4 quadrants for Distention Rigidity Guarding Eviceration/Ecchymosis Rebound tenderness Masses

History and Physical Examination
• • • • • • • • determine onset, course, location and character of pain: PQRST associated GU, Gl, respiratory, CV symptoms abdominal trauma/surgeries general appearance, vitals respiratory, CVS back: CVA ter,demess, ecchymoses extremities: differential pulses, psoas/obturator sign abdomen, including DRE, pelvic exam (females), gerutal exam (males)

Unstable patients should not be sent for imaging.

• do not delay consultation if patient unstable • CBC electrolytes, glucose, LFTs, amylase, BUN/creat, V/A, + others if indicated: ~-hCG, lactate, ECG • AXR: look for calcifications, free air, gas pattern, air fluid levels • CXR upright: look for pneumoperitoneum (free air under diaphragm) • U/S: biliary tract ectopic pregnancy, AAA • CT: trauma, AAA, pancreatitis

• NPO, IV, NG tube, analgesics • growing evidence that small amounts of narcotic analgesics improve diagnostic accuracy of physical exam of surgical abdomen • consult as necessary: general surgery, vascular, gynecology, etc.

Acute Pelvic Pain
..... ~




All women of childbearing age assumed to be pregnant until proven otherwise.

• gynecological • ruptured ovarian cysts - most common cause of pelvic pain, follicular cyst most common type
• ovarian torsion - rare, 50% will have ovarian tumour
• leiomyomas (uterine fibroids) - especially with torsion of a pedunculated fibroid or in pregnant patient (degeneration)

Toronto Notes 2008

Approach to Common ER Presentations

Emergency Medicine ER23

• ectopic pregnancy - ruptured/expanding/leaking • spontaneous abortion - threatened or incomplete • infection - endometritis, PID, tuboovarian abscess • dysmenorrhea and endometriosis - rarely cause new onset acute pelvic pain • non-gynecological • GI - gastroenteritis, appendicitis, bowel obstruction, diverticulitis, illD, illS • GD - cystitis, pyelonephritis, ureteral stone
• other - porphyria, abdominal angina, aneurysm, hernia, zoster

History and Physical Exam
• • • • • determine onset, course, location and character of the pain associated symptoms: vaginal bleeding, bowel or bladder symptoms, radiation vitals gynecological exam abdominal exam

• I3--hCG for all women of childbearing age • CBC and differential, P'IT, INR • pelvic and abdominal US - evaluate adnexa, look for free fluid in the pelvis or masses, evaluate thickness of endometrium

• general: analgesia, determine if admission and consults needed • gynecology consult if history and physical suggestive of serious cause • other consults as indicated - general surgery, urology, etc. • specific:
• ovarian cysts
• unruptured or ruptured and hemodynamically stable - analgesia and follow-up • ruptured with significant hemoperitoneum - may require surgery • ovarian torsion - surgical detorsion or removal of ovary • uncomplicated leiomyomas, endometriosis and secondary dysmenorrhea can usually be treated on an outpatient basis, discharge with gynecology follow-up

Alcohol Related Emergencies
• see also Psychiatry. PS20

Acute Intoxication
• • • • slurred speech, CNS depression, disinhibition, lack of coordination nystagmus, diplopia, dysarthria, ataxia-~ may progress to coma frank hypotension (peripheral vasodilation) if obtunded rule out: • head trauma/intracranial hemorrhage • associated depressant/street drugs • synergistic ---> respiratory/cardiac depression
hypoglycemia (screen with bedside glucometer)
• hepatic encephalopathy • precipitating factors: GI bleed, infection, sedation, electrolyte abnormalities, protein meal • Wernicke's encephalopathy ("WACO")
post-ictal state, basilar stroke

EtOH levels correlate poorly with





EtOH intoxication may invalidate
informed consent.


• beware withdrawal signs - see Table 11
Table 11. Alcohol Withdrawal Signs
Time since last drink 6-8 hr Syndrome Description

Wernicke's encephalopathy (WACO):
Ocular findings: nystagmus, eN VI

mild withdrawal alcoholic hallucinations withdrawal seizures delirium tremens lOT)

• generalized tremor, anxiety, agitation, but no delirium • autonomic hyperactivity (sinus tachycardia), insomnia, nausea, vomiting • visual (most common), auditory and tactile hallucinations • vitals often normal • typically brief generalized tonic-clonic seizures • may have several within a few hours • 5% of untreated withdrawal patients • severely confused state, fluctuating levels of consciousness • agitation, insomnia, hallucinations/delusions, tremor • tachycardia, hyperpyrexia, diaphoresis • high mortality rate

Withdrawal Symptoms
Nausea and vomiting
Paroxysmal sweats
Visualltactilelauditory disturbances

1-2 days 8 hl'-2 days 3-5 days


ER24 Emergency Medicine

Approach to Common ER Presentations

Toronto Notes 2008

• treatment • diazepam 10-20 mg IV or PO OR lorazepam 2-4 mg IV or PO qlhr until calm • thiamine 100 mg IM then 50-100 mg/day and fluid resus with D5NS • magnesium sulfate 4 g IV over 1-211 (if hypomagnesemic) • admit patients with delerium tremens (0'1')

Seizures (also see ER35)
• associated with ingestion and withdrawal • withdrawal seizures • occur 8-48 hrs after last drink (typically brief generalized tonic-clonic seizures) • if >48 hrs, think of DT (see Table 11) • prophylaxis: diazepam 20 mg PO qlh x 3 minimum • CT head if focal seIzures have occurred

Cardiovascular Complications
• hypertenSion (HTN) • cardiomyopathy: SOB, edema • arrhythmias ("holiday heart") • atrial fibrillation (most common), atrial flutter, PVC, PAC, SVT, VT (especially torsade if hypomagnesemic/hypokalemic)

Metabolic Abnormalities
• alcoholic ketoacidosis • history of chronic alcohol intake with abrupt decrease/cessation • malnourished, abdominal pain with nausea and vomiting • anion gap (AG) metabolic acidosis, urine ketones, low glucose and normal osmolality • treatment: dextrose, thiamine (50-100 mg prior to dextrose), volume repletion (with NS) • generally resolves in 12-24 hr • abnormal alcohols (see also Toxicology, ER46) • ethylene glycol CNS, CVS, renal findings • methanol • early: lethargy, confusion • late: headacne, visual changes, NN, abdominal pain, tachypnea • both produce severe metabolic acidosis with AG and osmolar gap EtOH co-ingestion is protective • treatment • IV 10% EtOH holus and drip to achieve blood level of 20 mmol/L • alcohol loading may be done PO • fomepizole if available • urgent hemodialysis relJuired • other abnormalities associated with alcohol: hypomagnesemia, hypophosphatemia, hypocalcemia, hypoglycemia

Gastrointestinal Abnormalities
• gastritis • common cause of abJominal pain and GI bleed in chronic alcohol users • pancreatitis • serum amylasf' very unreliable in patients with chronic pancreatitis, may need serum lipase • hemorrhagic form (15%) associated with increased mortality
fluid resuscitation very in1portant
• hepatitis • AST/ALT ratio >2 suggests alcohol as the cause as well as elevated GGT with acute ingestion • peritonitis/spontaneous bacterial peritonitis • occasionally accompanies cirrhosis • leukocytosis, fever, genf'ralized abdominal pain/tenderness • paracentesis for diagnosis (common pathogens: E. coli, Klebsiella, Strep) • GI bleeds • most commonly gastritis or ulcers, even if patient known to have varices • consider Mallory-Weiss tear secondary to retching
• often complicated by underlying coagulopathies

Miscellaneous Problems
• rhabdomyolysis • presents as acute weakness associated with muscle tenderness • usually occurs after prolonged in1mohilization • increased creatinine kinase (CK), hyperkalemia • myoglobinuria - may lead to acute renal failure • treatment: IV fluids, forced diuresis (mannitol 20% 15 mglkg IV over 30 min) • increased infections - due to impaired host defences, comprorrused immunity, poor living conditions • atypical pneumonias (Gram negatives, anaerobes, TB)

Toronto Notes 2008

Approach to Cornmon ER Presentations

Emergency Medicine ER25

• • • •

meningitis peritonitis with ascites bacteremia - after urinary tract infection (UTI), soft tissue infections treatment usually requires admission and N antibiotics

Altered Level of Consciousness (LOC)
Definitions • altered mental status - collective, non-specific term referring to change in mental content or attentiveness • delirium - acute, transient, fluctuating, potentially reversible organic brain disorder presenting as altered LOC or attentiveness • dementia - insidious, progressive, organic brain disorder with change in memory, judgment, personality and cortical function • lethargy - state of decreased awareness and mental status (patient may appear wakeful) • stupor - unresponsiveness from which the patient can be aroused • coma - a sleep-like state, non arousable to consciousness
Use the GCS to evaluate LOC (see ER4)
Coma (GCS :>8)





Primary CNS DiseaselTrauma



M • Major organ failure E • Electrolyte/Endocri ne T •ToxinslTemperature , ,
Bilateral Cerebral Brainstem
A • Acid disorders B· Base disorders Hemispheres (affecting cognition) (affecting Recticular
o . decreased Oxygen level /~ Activitating System (RASll L - Lactate .......------------.. I· Insulin (diabetes)/Infection (sepsis) Compression Direct C • Cardiac/hyperCalcemia • supra/infratentorial o brainstem Diffuse lesion Diffuse trauma/ischemia tumour infarct o sub/epidural 0 brainstem hematoma hemorrhage




Poasible Causes of Coma
Trauma (especially head)
Insulin (too little or too much)
Psychotic episode




Figure 12. Etiology of Coma

GCS under 8, intubate!

History • obtained from family, friends, police, paramedics, old chart, etc. • onset and progression • abrupt onset suggests CNS hemorrhage/ischemia or cardiac cause • progression over hours to days suggests progressive CNS lesion or toxic/metabolic cause • preceding events • it is essential to determine patient's baseline LOC preceding deterioration • antecedent trauma, seizure activity, fever • past medical history (e.g. similar episode, depression) Physical Examination • vitals including temperature, cardiac, chest, respiratory, abdominal exam, and the "five Ns" (see sidebar) • complete neuro exam, particular examination of the eyes Investigations • rapid blood sugar, CBC, electrolytes, Cr, BUN, LFTs, glucose, serum osmolality, ABGs, coags, troponins, U/A • ECG, CXR, Head CT • drug levels of specific toxins if indicated Diagnosis • distinguish between structural and toxic-metabolic coma • structural coma • pupils, extraocular movements and motor findings are asymmetric or absent

Universal Antidotes (DON'T):



Evaluation of comatose patient: (Five Nsl Noggin - e.g. raccoon eyes and Battle's
sign (bruising of the mastoid
process) appears about
8hours after trauma
Neck - C·spine, neurogenic shock,
nuchal rigidity
ENT - otorrhea, rhinorrhea, tongue
biting, odour on breath,
Needles - track marks Neurological- concentrate on GCS,
respiration, \lOsture,
movement, pupils,

ER26 Emergency Medicine

Approach to Common ER Presentations

Toronto Notes 2008

• toxic-metabolic coma • dysfunction at lower levels of the brainstem (e.g. caloric unresponsiveness) • respiratory depression in association with an intact upper brainstern (e.g. equal and reactive pupils; see exceptions in Table 1) • extraocular movements and motor findings are symmetric or absent
Table 12. Toxic· Metabolic Causes of Fixed Pupils
Dilated • anoxia • anticholinergic agents (e.g, atropine,TeAs) • methanollrarel Dilated to Normal • hypothermia • barbiturates Constricted • cholinergic agents (e.g. organophosphates) • opiates (e,g. heroin), except meperidine

• essential to re-examine frequently - status can change rapidly • diagnosis may become apparent only with the passage of time • delayed deficit after head trauma suggestive of epidural hematoma (characteristic "lucid interval")

• readily reversible alteration of LOC: discharge if adequate follow-up care available • ongoing decreased LOC: admit to service based on tentative diagnosis • transfer patimt if appropriate level of care not available

Anaphylaxis and Allergic Reactions

,,' ,

• exaggerated immune response mediated by histamine, leukotriene C4, prostaglandin 02, and tryptase • classic anaphylaxis: IgE mediated, sensitization then re-exposure • anaphylactoid reaction: non-lgE mediated, direct trigger, may occur with first exposure (e.g. radiocontrast dyes); presentation and treatment same as for anaphylaxis


Most common triggers for


• penicillin • stings • nuts • shellfish

History and Physical Examination
• general- marked anxiety, apprehension, tremor, cold sensation • skin - generalized urticaria, edema, erythema, pruritus • respiratory - nasal congestion, sneezing, coryza, cough, hoarseness, sensation of throat tightness, dyspnea, stridor, wheeze • eyes - itch, tearing, conjunctival injection • cardiovascular - hypotension, tachycardia, weakness, dizziness, syncope, chest pain, arrhythmia, Ml • GI - abdominal pain, nausea, vomiting, diarrhea

• remove causative agent; secure ABCs • epinephrine: • on scene - epi-pen (injectable epinephrine) if available • moderate signs and symptoms (minimal airway edema, mild bronchospasm, cutaneous reactions) • adult: 0.3-0.5 mL of 1:1000 solution 1M epinephrine • child: 0.Q1 mL/kg/dose up to 0.4 mL/dose 1:1000 epinephrine • severe signs and symptoms (laryngeal edema, severe bronchospasm and shock) • epinephrine via IV or EIT starting at 1 ml of 1:10,000 (0.1 mg) in adults; O.Q1 mLlkg in drildren • cardiac monitoring, ECC • diphenhydramine (BenadryI'M) 50 mg 1M or IV q4-6h • methylprednisolone 50-100 mg IV dose depending on severity • salbutamol (Ventolin rM ) via nebulizer if bronchospasm present • glucagon (for those on ~-blockers with resistant hypotension) 5-15 f.lg qlmin N

• cutaneous IgE-mediated reaction • treatment: epinephrine, antihistamines, steroids (may not work) and airway management

Beware of the silent asthmatic! This is amedical emergency and may require emergency intubation.

• see also Rcspirology, R6 • chronic inflammatory airway disease with episodes of bronchospasm and inflammation resulting ill airflow obstruction

Toronto Notes 2008

Approach to Common ER Presentations

Emergency Medicine ER27

Differential Diagnosis of Wheezing
• • • • • • • • foreign body aspiration/upper airway obstruction bronchiolitis pneumonia cystic fibrosis (CF) congestive heart failure (CHF) Hodgkin's lymphoma anaphylaxis croup

• O 2 sat • peak flow meter
• ±ABG

Treatment of Asthma ASTHMA: Adrenergics (P agonist) STeroids Hydration Mask (0 2) Antibiotics (if concurrent infection)

• CXR if diagnosis in doubt or concerns of pneumonia, pneumothorax, etc.
Table 13. Asthma Assessment and Management
Respiratory arrest imminent

History and Physical Examination
• exhausted, confused, diaphoretic, cyanotic • silent chest, ineffective respiratory effort • decreased HR • O sat <90% despite supplemental O 2 2

'100% O , cardiac monitor, IV access
2 • intubate
• p-agonist: MDI4-8 puffs OR nebulizer 5mg continually • anticholinergics: MDI4-8 puffs q20 min x 3 OR nebulizer 0.5 mg q20 min x3 'IV steroids: methylprednisolone 125 mg, hydrocortisone 500 mg • anticipate need for intubation • similar to above management Ip-agonist may be less frequent; q15-20 min)

Severe Asthma

• agitated, diaphoretic, laboured respirations • difficulty speaking in full sentences • no relief from p-agonist • O sat <90%, FEV, <50% 2 • SOB at rest, cough, congestion, chest tightness • nocturnal symptoms • inadequate relief from p-agonist • FEV, 50-80% • exertional SOB/cough with some nocturnal symptoms • good response to !l-agonist • FEV, >80%

Moderate Asthma

• O to achieve 02-sat >90% 2 • p-agonist - puffer of neb q1 h • steroids: prednisone 40-60 mg PO • anticholinergics • p-agonist
• monitor FEV,
• consider steroids (nebulized or PO)

Mild Asthma

Chest Pain

Rule Out Life-Threatening Causes
• CYS: acute coronary syndrome/acute MI, pericarditis/cardiac tamponade, aortic dissection • respiratory: pulmonary embolism (PE)/tension pneumothorax • GI: esophageal rupture/pneumomediastinum
LifeThreatIlning causes of Chest JIlin "PET MAP" PE
Esophageal rupture Tamponade MVangina Aortic dissection Pneumothorax

Additional Differential Diagnosis
• • • • • cardiac: stable angina respiratory: pneumonia, spontaneous pneumothorax (young, thin, tall) GI: peptic ulcer disease (POO), pancreatitis, cholecystitis, esophagitis, reflux MSK: rib fractures, costochondritis, zoster, etc. psychogenic/anxiety (diagnosis of exclusion)

Initial Resuscitation and Management
• O;u N, cardiac monitoring, CXR (portable if unstable), ECG

• must evaluate cardiac risk factors (DM, HTN, hyperlipidemia, smoking, 151 degree
relative with CAD <50 yo)
• classic presentations (but presentation seldom classic) • aortic dissection: sudden severe tearing pain, often radiating to back • pulmonary embolism: pleuritic chest pain (75%), dyspnea, anxiety, tachycardia • pericarditis: anterior precordial pain, pleuritic, relieved by sitting up and leaning forward acute coronary artery disease (CAD): retrosternal squeezing/pressure pain, radiation to arm/neck, dyspnea, nausea/vomiting, syncope • esophageal: frequent heartburn, acid reflux, dysphagia, relief with antacids • more likely to be atypical in females, diabetics, and >80 years

ER28 Emergency Medicine

Approach to Common ER Presentations

Toronto Notes 2008


Physical Examamination
• vitals • BP in BOTH arms: >20 mmHg difference suggests thoracic aortic dissection • palpate chest wall for tender points, but be aware that 25% of patients with acute MI have chest wall tenderness • consider a diagnosis of MSK disease only if palpation fully reproduces pain and symptoms and more serious causes excluded • cardiac exam, respiratory exam, peripheral vascular exam

Signs and Symptoms of MI

Persistent chest pain
Upset stomach
Shortness of breath
Excessive sweating


Signs of PE on CXR Westennark's sign: abrupt tapering of avessel on chest film. Hampton's hump: awedge-shaped infiltrate that abuts the pleura.

I \ . 9 ' ) - - - - - - - - - - - ,
Wells' Score for PE Previous Hx of OVT/emboli +1.5 HR >100: +1.5 Recent immobility or Sx: +1.5 Clinical signs of OVT: +3 Alternate Ox less likely than PE: +3 Hemoptysis: +1 Cancer: +1 Low probability =0-2
Intermediate probability = 2-6
High probability =>6



Every Acute MI patient in the ER

• CBC, electrolytes • serial cardiac enzymes • normal CK does NOT rule out MI • troponin [ more sensitive (but positive later than CK-MB; can have false positives in renal failure, must follow for 8 hrs post onset of symptoms) • ECG • always compare with previous • PE and acute MI may have normal ECG in up to 50% of cases • consider IS-lead ECG if hypotensive or if ECG shows inferior MI or AV node involvement ·CXR • always compare with previous • PE • 50% completely normal • atelectasis, elevated hemidiaphragm, pleural effusion • aortic dissection • mediastinal widening, bulging aortic arch, separation of intima calcification from edge of aortic shadow, depressed left main bronchus • change from previous CXR is the most accurate finding • CXR is normal in 20% of thoracic dissections • pneumothorax • may need inspiration and expiration views • ABGs - normal in 20% of patients with PE • D-dimer, V/0 scan or helical CT, venous leg Doppler, if PE suspected (see Wells' Score) • negative D-dimer rules out PE in low probability patients • patients with intermediate or high probability Wells' score require imaging

must be greeted by BMONA right

• see also Cardiology, C25


• immediate stabilization • oxygen 4L/min • IV access • cardiac monitors • "STAT" ECG • cardiac enzymes (CK, Troponins) • ASA I60-325mg chewed • nitroglycerin 0.3 mg SL q5min x 3 (IV for CHF, HTN, unresolved pain) • morphine 2-5 mg IV q5-30min if unresponsive to NTG • metoprolol 5 mg slow IV q5min x 3 if no contraindication (beware in inferior wall AMI) • thrombolytics or primary percutaneous coronary intervention (PCI) • agents include t-PA, r-PA, Streptokinase, and TNK • evaluate indications and contraindications prior to use • enoxaparin (Low Molecular Weight Heparin) Imglkg SC bid (30mg IV STAT post TNK infusion) • other - antiarrythmics, cardioversion, defibrillation, transthoracic pacing, angioplasty • cardiology consult

Addition of Clot*fognI to AitJirin and Fibrinolyllc Therapy lot MyocaIliaIInfarction with ST-Segment Elevation ISabalne Metal. NEJM. 352{121: 1179-1191,2005 Marl Purpose: To assess the benefit of addil19 clopiOOgrei fo aspinn and fibrinol\1ic tl1erapy in Sfelevation MI. SIlIdy Characteristics; Dooble-blind, IlCT. following inten­ tion-ta-treat anaiy5is, with 3491 patients and clinical follow-up at:lldays. Participenls: Indi~duals presenting within 12 hours of onset of Sfelevation Mllmeatl iI1Je 57, 11).3% male, 50.3% smokers, 9.1% previous Mil. Those presenting after 12 hours, age >75, or with prev~us CABG were excluded. Inlenenlion: CIopKlograllllO mg Ioadng dose folWwed by 75 mg od untU day of ang~raml or placebo, in addition to aspinn, afibrinolytic agent and hepann wilen appropriate. Prinrt 0utQmle: ComJ)JSite of occluded infarct-related artery on angiography (Thrombos~ in Myocard~llnfa~n flow grade 0or 11. or death or rectJrrentMI prior to al19~ra­ phy. Results: Rates of pnmary end point were 21.7% in the ~are­ bo group and 15.0% in the clo~rel groop 195% CI, 24­ 41'IMmol\\j the individual components of the pnmary end point do~rngrel had asignificant eflect on the rate of an occluded infarct-related artery and the rate of rectJrrent MI, Ixrt no effect on the rate of death from any cause. At 30 days clinical follow-up, there was no difference in rate of death from cardiovascular causes, as~nificant reduction in the odds of rectJrrent MI, and anon-s~nfficant reduet~n in recur­ rent isdlernia with need for urgent revascularization. The rates of ma~r bleeding and intracranial hemorrhage were similar between the two groups. Conclusion: Addft~n of dopidogrel improves the petenty rate of infarct-related arterifs and reduces isdlemk com~ka­ tions, both of wIIidl are assocated with improved long·tenn survival after MI.Thetrial was not powered to detect asur· vival bernifit and none was seen.

Chronic Obstructive Pulmonary Disease (COPO)
• see also Respirology. R8


• emphysema: destruction of alveoli can lead to tachypnea and dyspnea • chronic bronchitis: chronic cough and sputum production • usuall y co-exist

History and Physical Examination
• • • • worsening dyspnea or tachypnea acute change in frequency, quantity and colour of sputum production premorbid nealth status trigger: pneumonia, urinary tract infection, PE, CHF, drugs

Toronto Notes 2008

Approach to Common ER Presentations

Emergency Medicine ER29

Investigations • CBC, electrolytes, ABG, CXR, ECG, PFTs Management • keep O 2 sat 88-92% (BEWARE OF CO2 RETAINERS, but do not withhold O 2 if hypoxic) • bronchodilators + anticholinergics • steroids: methylprenisolone 125 mg IV or prednisone 40 mg PO (tapered over 3 weeks) • antibiotics: TMP-SMX, cephalosporins, qumolones (if signs of infection) • ventilation (chance of ventilation dependency) • admit if co-morbid illness • discharge on antibiotics, bronchodilators and short course of steroids (taper if necessary)

Congestive Heart Failure
• also see Cardiology. C33


Etiology • decreased myocardial contractility: ischemia, infarction, cardiomyopathy, myocarditis • pressure overload states: hypertension, valvular abnormalities, congenital heart disease • restricted cardiac output: myocardial infiltrative disease, cardiac tamponade • volume overload: idiopathic Causes of Exacerbation or Precipitants • cardiac: acute myocardial infarction or ischemia, cardiac tachyarrhythrnias (e.g, atrial fibrillation), uncontrolled hypertension • medications: discontinuation of, non-compliance with or change in prescribed cardiac medications, NSAIDS, steroids • dietary: increased sodium intake • increased cardiac output demand - infection, anemia, hyperthyroidism, pregnancy • other: pulmonary embolus, physical overexertion, renal failure HistorylPresentation • left-sided heart failure • dyspnea, decreased exercise tolerance, paroxysmal nocturnal dyspnea,
orthopnea, nocturia, fatigue, possibly altered mental status
• in severe cases pulmonary edema: severe respiratory distress, pink frothy or
white sputum, rales, S3 or 54
• right-sided heart failure • dependant edema, jugular venous elevation/distention, hepatic enlargement,
• patients often present with a combination of right-Sided and left-sided symptoms Physical Examination • vitals: tachypnea, tachycardia, hypo- or hypertension, hypoxia • respiratory: crackles, wheezes • cardiac: laterally displaced apex, S3 or 54, jugular venous distention, hepato-jugular reflex • abdominal: hepatomegaly, ascites • peripheral vascular: peripheral or sacra] edema, weak peripheral pulses, pulsus alternans (alternating weak and strong pulse), cool extremities Investigations • labs: CBC, electrolytes, AST, ALT, bilirubin, creatinine, BUN, cardiac enzymes • chest X-ray: very important! • Grade 1 - pulmonary vascular redistribution 1/// • Grade 2 - perihilar infiltrates )f-'" • Grade 3 - interstitial edema, Kerley B lines • Grade 4 - alveolar edema, bilateral infiltrates (= pulmonary edema) • also may see cardiomegaly and in severe cases pleural effusions • ECG: look for MI, ischemia • in CHF: LVH, atrial enlargement, conduction abnormalities • ABG: if severe or refractory to treatment • hypoxemia, hypercapnia and acidosis are signs of severe CHF • echocardiogram: not usually used in emergency evaluation, previous results may aid in diagnosis


Causes of CHF Exacerbation (FAILURE): Forgot medication Arrhythmia/anemia Ischemia/infaretion/infection Lifestyle (i.e. too much salt) Upregulation of cardiac output (pregnancy, hyperthyroidism) Renal failure Embolism (pulmonary)


Hospital management required if: • acute MI • pulmonary edema or severe respiratory distress • severe complicating medical illness (e.g. pneumonial • anasarca • symptomatic hypotension or syncope • refractory to outpatient therapy • thromboembolic complications requiring interventions • clinically significant arrhythmias • inadequate social support for safe outpatient management • persistant hypoxia requiring supplemental oxygen

ER30 Emergency Medicine

Approach to Common ER Presentations

Toronto Notes 2008


AcuteTreatment of CHF (LMNOP): Lasix lfurosemide)
Position (sit upright)

Management (acute) • ABC, may require intubation if severe hypoxia • sit upright, cardiac monitoring and continuous pulse oximetry • IV TKYO only, Foley catheter (to follow effectiveness of diuresis) • 100% O 2 by mask • if poor response may require CPAP, BiPAP, or intubation • 0.3 mg nitro SL q5min PRN ± topical nitro patch (0.2-0.8 mglhr) • if not responding or ischemia: 10-200 i-!g/min IV, titrate • diuretic if volume overloaded (e.g. furosemide 40-80 mg IV) • morphine 1-2 mg IV - may need to repeat • if hypotensive may require dobutamine (2.5 i-!g!kg/min IV) or dopamine (5-10 i-!g/kg/min IV), titratE' up to sBP 90-100 • ASA 160 mg chew and swallow • treat precipitating factor (e.g. treat pneumonia) • cardiology or medicine consult

Diabetic Emergencies
• see also Endocrinology, E7

Precipitating Factors in DKA

(the 5 Ie):

Insulin missed

..... . l - - - - - - - - - - - - - ,
4criteria for DKA Ox: hyperglycemia, metabolic acidosis, hyperketonemia, ketonuria.


Diabetic Ketoacidosis (DKA) • severe insulin deficiency resulting in dehydration and electrolyte abnormalities • history and physical examination - often young, type 1 DM, may be first presentation of undiagnosed DM (may occur in small percentage of type 2 patients) • early symptoms: • polyuria, polydipsia, malaise
late signs and symptoms:
• anorexia, nausea, vomiting, dyspnea (often due to acidosis), fatigue • abdominal pain • drowsiness, stupor, coma • Kussmaul's respiration • fruity acetone breath • investigations • CBC, glucose, electrolytes, BUN/creatinine, Ca, Mg, phosphate • calculation of Anion Cap [Na - (Cl + HC03 )] • urine glucose and ketones, ~-hCC (to rule out ectopic pregnancy)
• ECG (M! possible precipitant of DKA; electrolyte disturbances may predispose to arrhyilimia) • management • treat for SHOCK: ABCs • rehydration - bolus of NS, then high rate NS infusion (but beware of overhydration and cerebral edema, especially in pediatric patients) • insulin - initial bolus of 5-10 U short-acting/regular insulin (or 0.2 U/kg) IV in adults - followed by continuous infusion at 5-10 U (or 0.1 U/kg) per hour add D5W when blood glucose <15 mM (goal is to stop ketogenesis, which requires more insulin than inhibition of gluconeogenesis .... :.msulin + glucose are given until resolution of acidosis, ketonemia) • potassium - essential to avoid hypokalemia: replace KCl (20 mEq/T ' if adequate renal function and initial K <5.5 mmol/L) - use cardiac monitoring if potassium levels normal or low • note: bicarbonate is not given unless patient is at risk of death or shock Hyperosmolar Nonketotic Hyperglycemic Syndrome (HONK) • state of extreme hyperglycemia (due to relative insulin deficiency, increased counter­ regulatory hormones, gluconeugenesis) and dehydration (due to osmotic diuresis) in type 2 DM, high mortality • history and pfiysical examination • mental disturbances, coma, delirium, seizures • polyuria • nausea, vumiting • investigations • CBC, electrolytes, creatinine, BUN, glucose, Mg, phosphate, urine glucose and ketones • anion gap

Cerebral edema may occur if hyperos­ molality treated too aggressively.

• ECG • management • rehydration with NS (total water deficit estimated at average 100 cc/kg body weight)

Toronto Notes 2008

Approach to Common ER Presentations

Emergency Medicine ER31

• O2and cardiac monitoring, frequent electrolytes and glucose monitoring • insulin as required • identify and treat cause

Hypoglycemia • very common ED presentation • management focus: 1. treatment of hypoglycemia 2. investigation of cause (most often due to exogenous insulin, EtOH, sulfonylureas) • neuroglycopenic symptoms: dizziness, H/A, confusion, fatigue, decreased
concentration, paralysis, seizures, coma
• autonomic symptoms: diaphoresis, trembling, warmth, anxiety, nausea • history and physical examination • last meal, known diabetes, prior similar episodes, drug therapy • liver / renal/endocrine / neoplastic disease • depression, EtOH or drug use • management: • IV access and rapid BG • D50W 50 mL rv push, glucose PO if mental status permits • if rv access not possible, glucagon 1-2 mg IM, repeat x 1 in 10-20 min. • O~ cardiac, frequent BG monitoring • thiamine 100 mg IM • full meal as soon as mental status permits • if episode due to long acting insulin, suJfonylureas, watch for prolonged hypoglycemia due to long t1/2 • search for cause

'" . } - - - - - - - - - - - - ,
Insulin Sulfonylureas Ethanol Salicylates Acetaminophen NSAIDS (l-adrenergic agonists Lithium Calcium MAOI Coumadin Sulfa abx Cotrimazole Ampicillin Tetracycline Amphetamines. oocaine Pyridoxine ACE-I Theophylline Quinine


• see also Neurology. N54

Etiology • the common • common migraine (no aural/classic migraine (involves aura) • gradual onset, unilateral/bilateral, throbbing • nausea/vomiting, photo/phonophobia • treatment: analgesics, neuroleptics, vasoactive meds • tension/muscular headache • never during sleep, gradual over 24 hours • posterior/occipital • increased with stressors • treatment: modify stressor, local measures, NSAIDs • the deadly • subarachnoid hemorrhage (SAH) - see also Neurosurgery, NS15 • sudden onset, increased with exertion • "worst" headache, nausea and vomiting, meningeal signs • diagnosis: CT, LP (5-10% of patients with SAH have negative initial CT) - sensitivity of CT decreases with time and is much less sensitive by
48-72 hr

Note: up to 5% of patients with subarach­ noid hemorrhage have anormal CT scan; if suspect SAH with anegative Cl; perlorm alumbar puncture.

BEWARE: every headache is serious until proven otherwise.


• management: urgent neurosurgery consult • increased ICP • worst in morning, supine, or bending down • physical exam: neurological deficits, cranial nerve palsies, papilledema • diagnosis: CT scan • management: consult neurosurgery • meningitis (see Infectious Diseases, ID7) • fever, nausea/vomiting, meningeal signs, purpuric rash • altered level of consciousness • perform CT to rule out SAH then do LP for diagnosis • treatment: early empiric antibiotics (depending on age group), steroid therapy • temporal arteritis (not immediately deadly but causes great morbidity) (see Ophthalmology, OP41) • one-sided scalp tenderness, jaw claudication, visual disturbances • labs: elevated ESR • temporal artery biopsy is gold standard for diagnosis • treatment: high-dose steroids immediately if TA suspected

DDx Subarachnoid Hemorrhage: BATS Berry aneurysm Arteriovenous malformation! Adult polycystic kidney disease Trauma Stroke

Do not delay IV antibiotics for LP

ER32 Emergency Medicine

Approach to Common ER Presentations

Toronto Notes 2008


Hypertensive Emergencies
Etiology Hypertensive Emergency (Hypertensive Crisis) • definition: acute elevation of systolic and diastolic BP associated with end-organ damage (CNS, eyes, heart. or kidneys) • immediate goal of IV lherapy is to reduce the dBP by 10-15% (to approx. 110 mmHg) in 30-60 min (5-10 min tor aortic dissection) • treatment may be initiated in the ED followed by prompt admission to ICU for continuous BP monitoring • BP should NOT be lowered rapidly in patients with major cerebrovascular event • BP lowering attempted if dBP >120 to 130 mmHg; aim to reduce dSP by 20% in the first 24h • 1'BP is an attempt to maintain cerebral perfusion pressure; decreasing BP too fast may extend or worsen stroke Hypertensive Urgency • definition: severely elevated blood pressure (usually dBP >115) with no evidence of end-organ damage • most commonly due to non-compliance with medications • treatment: gradually reduce pressure over 24-48 hours to a level appropriate for the patient • goal is to differentiate hypertensive emergencies from hypertensive urgencies History and Physical Examination • prior hypertensive crises • antihypertensive medications prescribed and BP control • monoamine oxidase inhibitors (MAOls) • street drugs (cocaine, amphetamines, phencyclidine, etc.) • blood pressure measurement in all limbs • fundoscopic exam (hemorrhages, papilledema, etc.) Investigations • CBC, electrolytes, BUN, creatinine, urinalysis • peripheral blood smear - to detect microangiopathic hemolytic anemia • CXR - if SOB or chest pain • ECG, troponins, CK if chest pain • CT head - if neurological firidings or severe headache Treatment of Hypertensive Emergencies (see Table 14)



HYPERTENSIVE EMERGENCIES Hypertensive Encephalopathy • pathophysiology: cerebral hyperperfusion due to blood pressure in excess of the capacity for cerebral autoregulation • signs and symptoms: headache, nausea, vomiting, mental status changes (lethargy to coma), fundoscopic changes (hemorrhage, exudates, cotton wool spots, papilledema, sausage linking), over hours can lead to coma and death Pregnancy Induced Hypertension (PIH) • see Obstetrics. 01314 • watch for HTN, seizures, proteinuria, thrombocytopenia, increased AST, clonus, and hyperreflexia • initial treatment = magnesium sulfate IV; often lowers BP sufficiently without other agents Cardiovascular Emergencies • left ventricular failure (LVF) • pathophysiology: decreased LV function due to increased afterload, increased oxygen demana and decreased coronary blood flow may cause angina, MI, or pulmonary edema • signs and symptoms: chest pain, SOB • avoid diazoxide, hydralazine, minoxidil as these drugs increase oxygen demand • thoracic aortic dissection (see Cardiology. C48) Hypertensive Renal Emergencies • renal failure can be either the cause l'r effect of a hypertensive emergency • hypertension associated with deteriorating renal fuilction is considered an emergency • hypertension in the setting of chronic renal failure is due to sodium and water retention by the diseased kidney and increased activation of the renin-angiotensin system • diagnosis: proteinuria, RBC and R13C casts in urine, elevated BUN and creatinine • treatment: IV calcium channel blockers. ± emergent ultrafiltration


Wrth CNS manifestations of severe hypertension, it is often difficu~ to differ­ entiate causal relationships ILe. hyperten­ sion could be secondary to primary cere­ bral everrt [Cushing effectll.

Toronto Notes 2008

Approach to Common ER Presentations

Emergency Medicine ER33

Catecholamine Induced Hypertensive Emergencies
• etiology • discontinuation of short-acting sympathetic blocker (e.g. clonidine, propranolol) • pheochromocytoma • sympathomimetic drugs (cocaine, amphetamines, phencyclidine) • MAOI in combination with sympathomimetics or tyramine-containing foods (cheese, red wine) • treatment: re-administer sympathetic blocker if due to withdrawal (e.g. clonidine,
Table 14. Most commonly used agents for the treatment of hypertensive crisis

... '., - - - - - - - - - - - , )
Catecholamine Induced Hypertensive Emergencies Avoid use of non-selective 13-block­ ers as they inhibit 13-mediated vasodilation and leave a-adrenergic vasoconstriction unopposed.


Onset of Action Duration of Action

Advene Effects


'Sodium Nitroprusside [vascular smooth muscle dilator) 1st line 0.25 -10 pglkglmin Immediate 3-5 min NN,muscletwitching, sweating, cyanide intoxication,coronary steal syndrome Most hypertensive
emergencies lesp CHF,
Use in combination with Il-iJlodters
lie. esmololl in aortic dissection
Caution with high ICP and azotemia Most hypertensive emergencies
Caution with acute CHF

... '. , - - - - - - - - - - - - - , }
Most commonly used agents are labetalol and nitroprusside.

'Nicardipine ICCBI

2mg Wbolus, then 4mglkglhr W

15-30 min

40 min

Tachycardia, headache, flushing, local phlebnis lie. encephalopathy, RF, eclampsia, sympathetic crisis)
Tachycardia, headache, Ii.e. acuteRF)

'Fenoldopam Mesylate 0_05-0.t pmglkglmin IV <5 min Idopamine receptor antagonistl

8-10 min nausea, flushing

Most hypertensive
Caution with glaucoma
Acute LVlailure

'Enalapril (ACEII
, Nitroglywh

0.625-1.25 mg IV q6h 15-30 min

12-24 hr Theoretical fall in pressure in high renin states not Avoid in acute MI,
seen in studies pregnancy, acute RF
3-5 min

5-20pg/min IV


Hypotension, bradycardia, M~ Pulmonary edema
headache, lightheadedness, dizziness
Dizziness, drowsiness, headache, tachycardia, Na retention


5-10mg IV/1M q20min 5-20 min Imax20mgl

2-6 nrs

ADRENERGIC INHIBITORS •Labetalol 20 mg IV bolus ql0 min or 0.5-2mg/min 5-10 min 3-6hr Vomiting, scalp tingling, burning in throat, Avoid in acute CHF, HB >1st degree diuiness, nausea, heart
block,orthostatlc hypotension 10-20 min bronchospasm Most hypertensive
emergencies lesp. eclampsial


250 - 500 uglkg/min forI min, then 50uglkglmin for 4min; repeat

1-2 min

Hypotension, nausea, Aortic dissection, acute MI
SVT dysrythmias, perioperative HTN
Avoid in acute CHF, HB >1st degree

, Phentolamine 5-15 mg q5-15 min 1-2 min 'Hypotension may occur with all of these agents

3-10 min

Tachycardia, headache, flushing

Catecholamine excess lie. pheol

Ophthalmologic Foreign Body and Corneal Abrasion
• see also Ophthalmology. OP19


• patient may complain of pain, tearing, itching, redness, photophobia, foreign body
• elicit history of potential trauma to eye • mechanism of foreign body insertion - if high velocity injury suspected (welding, metal grinding, metal striking metal), must obtain orbital x-rays to exclude presence of intraocular metallic foreign body

Physical Examination
• • • • • visual acuity with best corrected vision pupils, extraocular movement, external ocular structures fundoscopy tonometry - measurement of intraocular pressure (normal pressure: 10-20 mmHg) slit lamp exam • systematic examination of anterior segment structures and vitreous • proparacaine anaesthetic drops may ease examination
ALWAYS assess visual acuity in both
eyes when apatient presents to the ER
with an ophthalmologic complaint.

ER34 Emergency Medicine

Approach to Common ER Presentations

Toronto Notes 2008



• look for rust ring with metallic foreign body, corneal edema, anterior chamber cells/flare • may use fluoroscein dye which stains de-epithelialized cornea green when viewing with cobalt blue filter


Contraindications to pupil dilation: - shallow anterior chamber -iris-supported lens implant -potential neurological abnormality requiring pupillary evaluation - caution with DJ disease - mydriatics can cause tachycardia

• • • • • • • copious irrigation with saline for any foreign body remove foreign body under slit lamp exam with cotton swab or sterile needle antibiotic drops qid until healed patching may not improve healing or comfort - do not patch contact lens wearers limit use of topical anesthetic to examination only consider tetanus prophylaxis ophtho consult if globe penetration suspected


.... , } - - - - - - - - - - - ,
Legally required to report sexual
assault if victim is <16 years of age.


Sexual Assault ~---~--~---~-~-~-----'
• 1 in 4 women and 1 in 10 men will be sexually assaulted in their lifetime

General Approach
• • • • • • • • ABCs, treat acute, serious injuries ensure patient is not left alone and provide ongoing emotional support set aside adequate time for exam (usually 1.5 hours) obtain consent for medical exam and treatment, collection of evidence, disclosure to police (notify police as soon as consent obtained) Sexual Assault Kit (document injuries, collect evidence) if <72hrs since assault label samples immediately and pass directly to police offer community crisis resources (e.g. shelter, hotline) do not report unless victim requests (legally required if <16 years old)

• who? how many? when? where did penetration occur? what happened? any weapons or physical assault? • post-assault activities (urination, defecation, change of clothes, shower, douche, etc.) • gynecologic history • gravity, parity, last menstrual period • contraception • last voluntary intercourse (sperm motile 6-12 hours in vagina, 5 days in cervix)

Physical Examination
• evidence collection is always secondary to treatment of serious injuries • never re-traumatize a patient with the examination • general examination • mental status • sexual maturity • patient should remove clothes and place in paper bag • document abrasions, bruises, lacerations, tom frenulum/broken teeth (indicates oral penetration) • pelvic exam and specimen collection • ideally before urination or defecation • examine for seminal stains, hymen, signs of trauma • collect moistened swabs of dried seminal stains • pubic hair combings and cuttings • speculum exam • lubricate with water only • vaginal lacerations, foreign bodies • Pap smear • oral/cervical/rectal culture for gonorrhea and chlamydia • posterior fornix secretions if present or aspiration of saline irrigation • immediate wet smear for motile sperm • air-dried slides for immotile sperm, acid phosphatase, ABO group • others • fingernail scrapings • saliva sample from victim

• VDRL - repeat in 3 months if negative • serum ~-hCG • blood for ABO group, Rh type, baseline serology (e.g. hepatitis, HIV)

Toronto Notes 2008

Approach to Common ER Presentations

Emergency Medicine ER35

• involve local/regional sexual assault team • medical • suture lacerations • tetanus prophylaxis
gynecology consult for foreign body, complex lacerations
assumed positive for gonorrhea and chlamydia
• management: azithromycin 1 g PO x 1 dose
(all: doxycycline 100 mg PO bid x 7 days)
and cefixime 400 mg PO x 1 dose
• may start prophylaxis for hepatitis B and HN
pre and post counselling for HN testing
pregnancy prophylaxis offered
• levonorgestrel 0.75 mg STAT, repeat in 12 hours (Plan BTM) • psychological • high incidence of psychological sequelae • have victim change and shower after exam completed • follow-up with MD in rape crisis centre within 24 hours • best if patient does not leave ED alone

• identify the problem (need high index of suspicion) • suggestive injuries • somatic symptoms (chronic and vague complaints) • psychosocial symptoms • if disclosed, be supportive and assess danger

• • • • • treat injuries ask about sexual assault and children at home document findings plan safety follow-up: family doctor/social worker

• see also Neurology, N8

• generalized seizure (consciousness always lost): tonic/clonic, absence, myoclonic, atonic • partial seizure (focal): simple partial, complex partial • causes: trauma, intracranial hemorrhage, structural abnormality, infection, toxins/drugs, metabolic disturbance (hypo/hyperglycemia, hypo/hypematremia, hypocalcemia, hypomagnesemia); primary seizure disorder • differential diagnosis: syncope, pseudoseizures, migraines, movement disorder, narcolepsy/cataplexy

• from patient and bystander: flaccid and unconscious, often with deep rapid breathing • preceding aura, rapid onset, loss of bladder/bowel control, tongue-biting

Physical Examination
• injuries to head and spine, tongue laceration, aspiration

• known seizure disorder: anticonvulsant levels • Accucheck • first time seizure: CBC, serum glucose, electrolytes, BUN, creatinine, Ca, Mg; consider prolactin, ~-hCG, tox screen • consider CT, MRI, C-spine X-ray, EEG


• O2

• medications to stop seizure - continue to next step if seizure continues: • lorazepam 2-4 mg (0.1 mglkg) N/IM or diazepam 5-10 mg N q2-3 min until seizure stops • phenytoin 20 mglkg N at 50 mg/min • consult neurology
phenobarbital 20 mglkg N at 50-75 mg/min
• if the above steps fail, RSl • emergency EEG if no response after 15-20 minutes • lCU admission

ER36 Emergency Medicine

Approach to Common ER Presentations

Toronto Notes 2008

• definition: sudden, transient loss of consciousness and postural tone with spontaneous recovery • usually caused by generalized cerebral hypoperfusion

CaulII of Syncope by SYltem (HEAD. HEART, VeSSELS): HypoxialHypoglycemia Epilepsy Anxiety Dysfunctional brainstem

• cardiogenic: arrhythmia, outflow obstruction (e.g. PE, tamponade, tension pneumo, pulmonary HTN), MI, valvular disease • non-cardiogenic: peripheral vascular (hypovolemia), vaso-vagal,
cerebrovascular tfisoraers, eNS, metabolic disturbances


Heart attack
Embolism (PE) Aortic obstruction ftll'ftllm disturbance Tachycardia Vasovagal Situational Subclavian steal ENT (glossopharyngeal neuralgia) Low systemic vascular resistance Sensitive carotid Sinus

• gather details from witnesses • distinguish between syncope and seizure (see Neurology. N8) • signs and symptums during presyncope, syncope and postsyncope • past medical history, drugs

Physical Examination
• postural BP and HR • cardiovascular, respiratory and npuro exam

• ECG, bedside glucose • as indicated: CBC, electrolytes, BUN, creatinine, ABGs, Troponin, Mg, Ca, (tailor to clinical presentation and patient's premorbid condition)

• • • • ABCs, N, 0 20 monitor examine for signs of trauma caused by syncopal episode cardiogenic syncope: admit to medicine/cardlOlogy non-cardiogenic syncope: discharge with follow-up as indicated by cause


-9 ­

• see also Neurology. N57

Differentiation of UMN ~
VIImII LMN Di.....

lMN . . .

Types of Stroke
• ischemic stroke (80% of all strokes) • hemorrhagic stroke

Muscular deficit Musde groops Reflexes Incrvased Tone Increased Fasciculalions Absent

Individual muscles

• consider acute stroke if acute neurological deficit (focal or global) or altered LaC • more likely to be hemorrhagic if: nausea, vomiting, headache, change in LaC, sei.zure • common symptoms of stroKe: abrupt onset of hemiparesis/monoparesis, visual loss/ field deficits, diplopia, dysarthria, ataxia, vertigo, aphasia, sudden decrease in LOC • determine time of sYIIlptom onset for consideration of thrombolytic therapy • N.B. if patient is candidate for thrombolysis, very brief assessment and 5TAT cr head


AbrertJ minimal Present

IWardJaw ..... delloPIIo G;fdmagoolfJ; Berge E.
Cod1rane ~ 01 ~ PMv.s 2005; Issue 31 P\IpaIt:To re'oiewthe eIficlr;y and safety Iithromboly­

~forAl:ull"'" S1nIIII

Physical Examination
• • • • vitals if decreased IDC: assess for ability to protect airway rule out trauma, infection, meningeal mitation search for cardiovascular causes of stroke • ocular fundi (retinopathy, emboli, hemorrhage) • CV5 (irregular heartbeat, murmurs, gallops) • PVS (carotid, radial and femoral pulses; auscultate for carotid bruits) • neuro: • mental status, LOC, cranial nerves, motor function, sensory function, cerebellar function, gait, deep tendon reflexes • confirm presence uf stroke syndrome, and distinguish from stroke rnirnics (seizure, systemic infection, brain tumour, positional vertigo, Bell's palsy) • establish neurological baseline should patient improve/deteriorate

116 doutje.bIjnd) with 5W patients.
~ Patients with acute isd1em~ stroke con·
firmedbyct ........:kIy thrombolitic agent, artf dose, intra­ venously or inlra-arterial. fIlilwy lhBomet: Earty outcomes 17 to 10 daysl include dealhs from aU causes or so,mptomatic inttiK:fa­ niaI /iemonIlages.late ootoomes \l and 6monthsl include dea1hs fr«n all causes. Of poor funcliona out· CO/l'j! at foIlow.lJp (dBath or dependencyl as measured by Rankin or 8aIthel scores. . . .ThromboIytic therapy ~ associatad with an excess of eatIy dea1hs I~ 1.81; 95% a, 1.46-2.241 aoo ~ inIracraniaI hemoot1age lOR 137; 95% a, 2.68-4.221. Use of athromboIylic agent within three houn of stroke is ~ in redOOng death or depend­ MY:{ at 310 6months (~0.66, ~% a0.5310 0.831 with­ out aslatisticaI~ significant increase in dealhs I~ 1.13, 95% l.86 kllASl. When given wiIlin six haws, throm· boIytic thet'apy signfficantIy reduaid the proportion of palienIs dead 01 dependent at three kl six months lOR 0.84, $% a0.75 kl D.95I, but aiso significantly increased the cxtds of death (OR 1.33, 95% 15 to 1.53\. Noo-tan­ dom IXIIllpIIisons of n.fA suggest Kmay be associated with slightly less hazanl and IOOre benefit than other ~ Canr:IuIionI:Thrombolytic 1herarI increases immedi­ ate hazanl in patients, but _ used within three hours of isd1emic stroke decreases death or dependency with­ out significant increase ~ mortality.

SlIld¥ QInclIriIlica: ~ revieN of 18 RCTs

sis in acute isdIemic strtte.

Table 15. Stroke Syndromes
Region of Stroke
Anterior Cerebral Mery

Stroke Syndrome
'Primarily frontal lobe function affected 'Altered mental status, impaired judgement, contralateral lower extremity weakness and hypoeslhesia, gait apraxia • Contralateral hemiparesis [arm &face weakness> leg weakness) and hypoesthesia, ipsilateral hemianopsia, gaze preference to side of lesion " agnosia, receptive/expressive aphasia •Affects vision and thought 'Homonymous hemianopsia, cortical blindness, visual agnosia, altered mental status, impaired memory 'Wide variety of CN, cerebellar and brainstem deficits: vertigo, nystagmus, diplopia, visual field deficits, dysphagia, dysarthria. facial hypoesthesia, syncope, ataxia 'Loss of pain and temperature sensation ipsilateral face and contralateral body


Middie Cerebral Artery


Posterior Cerebral Artery

Vertebrobasilar Artery

Toronto Notes 2008

Approach to Common ER PresentationslEnvironmental Injuries

Emergency Medicine ER37

Investigations • CBC, electrolytes, blood glucose, coagulation studies, ± cardiac biomarkers,
± toxicology screen
• CT scan, non-contrast: look for hemorrhage, ischemia • ECG: rule out atrial fibrillation, acute MI as source of emboli Management • ABC's with RSI if GCS :<:;8/rapidly decreasing GCS/inadequate
airway protection reflexes
• IV ± cardiac monitoring • judge fluid rate carefully to avoid overhydration (cerebral edema) as well
as underhydration (underperfusion of the ischemic penumbra)
• BP control: only treat severe hypertension (sBP >200, dBP >100, mean arterial BP
>140) or hypertension associated with hemorrhagic stroke transformation, cardiac
ischemia, aortic dissection, or renal damage; use IV nitroprusside or labetalol
• cerebral edema control: hyperventilation, mannitol to decrease ICP if necessary • consult neurosurgery, neurology as indicated Medications • acute ischemic stroke: thrombolytics (rt-PA, e.g. alteplase) if within 3 hours of
symptom onset with no evidence of hemorrhage by CT scan
• antiplatelet agents: prevent recurrent stroke or stroke after TIAs (e.g. aspirin (1st line);
clopidogrel, ticlopidine (2nd line)

Vaginal Bleed
• see also Gynecology. GY6 and Obstetrics. OB22

L o

Etiology • pregnant patient • 1st/2nd trimester pregnancy: ectopic pregnancy, abortion (threatened, incomplete,
complete, missed, inevitable, septic), morar pregnancy
• 2nd/3rd trimester pregnancy: placenta previa, placental abruption, premature
rupture of membranes, preterm labour
• either: trauma, bleeding cervical polyp • postpartum • postpartum hemorrhage, uterine inversion, retained placental tissue,
• non-pregnant patients • dysfunctional uterine bleeding, uterine fibroids , pelvic tumors, trauma,
endometriosis, Pill
History • last menstrual period, sexual activity, contraception, history of Pill • pregnancy details • determine amount of blood • urinary, GI symptoms Physical Examination • look for signs of hypovolemia • pelvic examination - NOT if suspected placenta previa (ultrasound first) • speculum exam • if rregnant use sterile speculum • bimanua examination • sterile gloves if pregnant • if patient is near term with possible rupture of membranes and without
other indications defer bimanual examination
Investigations • p-hCG test for all patients with child-bearing potential • CBC, blood and Rh type, quantitative p-hCG, PTT, INR • type and cross if signilicant blood loss • 1st/2nd trimester/non-pregnant: • ultrasound (D/S) - intrauterine pregnancy, ectopic pregnancy, traumatic injury,
foreign body
• must correlate D/S findings with p-hCG if D/S is non-diagnostic • 2nd/3rd trimester pregnancy: • D/S if no fetal heart tones, no documented intrauterine pregnancy or
unknown lie of placenta
• DIC panel if placental abruption - platelets, PTT, INR, fibrinogen

ER38 Emergency Medicine

Approach to Common ER PresentationslEnvironmental Injuries

Toronto Notes 2008

• postpartum: • U/S for retained prodllct~ • ~-hCG if concerned ahuut retained tissue

Management • ABCs • pulse oximeter and cardiac monitors if unstable • Rh immune globulin for vaginal bleeding in pregnancy and Rh-negative mofher • 1st/2nd trimester pregnancy: • ectopic pregnancy: definitive treatment wifh surgery or methotrexate • intrauterine pregnancy, no concerns of coexistent ectopic: discharge patient wifh obstetrics follow up • U/S indeterminate or ~-hCG > 1000-2000 ill for furfher work-up and/or gynecology consult • abortions: if complete, discharge if stable, for all ofhers get gynecology consult • 2nd/3rd trimester pregnancy: • placenta previa ur placental abruption: obstetrics consult for possible adlnissioll • postpartum: • uterine inversion: replace utems immediately, may require operative management • postpartum hemorrhage: extraction of placenta if retained, hysterectomy if unconlrolle(i blet'ding • retained tissue: D&C • endometritis: IV antibiotics • non-pregnant • dysfunctional uterine hleeding • <35-40 years of age: Provera™ 10 mg PO x 10 days, warn patient of a wifhdrawal bleed, discharge if stable • if unstable, admit for IV hormonal fherapy, possible D&C • >35-40 years of age: uterine sampling necessary prior to initiation of hormonal treatment to mle out endometrial cancer, U/S for any masses felt on exam • structural abnormalities: fibroids or uterine tumors may require D&C for diagnosis/treatment, U/S for workup of ofher pelvic masses, Pap smear/biopsy for cervical lesions

Environmental Injuries
Heat Exhaustion and Heat Stroke
Heat Exhaustion • clinical features relate to loss of circulating volume caused by exposure to heat stress • "water depletion": heat exhaustion (HE) occurs if lost fluid not adequately replaced • "salt depletion": HE occurs when losses replaced wifh hypotonic fluid Heat Stroke • life-threatening emergency resulting from failure of normal compensatory heat-shedding mechanisms • divided into dassicdl and exertional subtypes (see Table 16 below)
Table 16. Heat Exhaustion vs. Heat Stroke
Heat Exhaustion
Clinical Features •non·specific malaise, headache, fatigue •body temp (<W.5'C lusually normall

Classical Heat Stroke
• occurs in sening of high ambient temperatures le.g. heat wave. poor ventilation) •often patients are older, poor. and sedentary or immobile • dry. hot skin •temp usually >40.5"(; •altered mental status, seizures. delirium, coma •may have elevated AST. AlT

Exertional Heat Stroke
•occurs with high endogenous heat production le.g. exercise} and overwhelmed homeostatit mechanisms •patients often younger, more active •skin often diaphoretic •other symptoms as for classical HS. but may also have Die. acute renal failure, rhabdomyolysis. marked lactit acidosis

•no coma or seizures

•dehydration It HR, orthostatic hypotensionI


•rest in a0001 environment •normal saline IV if orthostatic hypotension; otherwise replace losses slowly PO

•cool down body temperature with lVater mist le.g. spray bonlel and standing fans •ice water immersion also effettive; monitor body temp closely to avoid hypothermic overshoot •seture airway because of risk of seizures and aspiration •give fluid resuscitation if still hypolensive after above therapy •avoid Q·agonists [epinephrine, etc.! peripheral vasoconstriction and antipyretics IASA. etc.!

• if patient does not respond relatively quickly to cooling treatments, consider ofher possible etiologies of hyperpyrexia (e.g. meningitis, thyroid storm, anticholinergic poisoning, delirium tremens, ofher infections, etc.)

Toronto Notes 2008

Environmental Injuries

Emergency Medicine ER39

• predisposing factors: extremes of age, lack of housing. drug overdose, EtOH ingestion, trauma (incapacitating), cold water immersion, outdoor sports • treatment based on: (a) re-warming and (b) supporting cardiorespiratory function • complications: coagulopathy, acidosis, ventricular arrhythmias (Vfib), asystole, volume/electrolytes depletion • labs: CBC electrolytes, ABC, serum glucose, creatinine/BUN, Mg. Ca, amylase, coags • imaging: CXR (aspiration pneumonia, pulmonary edema are common) • monitors: ECC, rectal thermistor, Foley catheter, NC tube, monitor metabolic status frequently
Table 17. Classification of Hypothermia
Class Mild Temp Symptoms/Signs

32-34.9°C Tachypnea, tachycardia, ataxia, dysarthria, shivering Loss of shivering, arrythmias, Osborne (Jl waves on ECG, decreased LOC, combative behaviour, muscle rigidity, dilated pupils Coma, hypotension, acidemia, ventricular fibrillation, asystole, flaccidity, apnea

Moderate 28-31.9°C



Re-warming Options • gentle fluid and electrolyte replacement in all (due to cold diuresis) • Passive External Re-warming (PER): • suitable for most stable patients with core temperature >32.2°C • involves covering patient with insulating blanket; body generates heat and re-warms through metabolic process, shivering • Active External Re-warming (AER) • involves use of warming blankets • beware "afterdrop" phenomenon (warming of extremities causes vasodilation and movement of cool pooled blood from extremities to core, resulting in a DROP in core temperature --+ cardiac arrest) • safer when done in conjunction with active core re-warming (below) • Active Core Re-warming (ACR) • generally for patients with core temperature <32.2°C, and/or with
cardiovascular instability
• avoids "afterdrop" seen with AER alone • re-warm core by using: • warmed humidified oxygen, IV fluids • peritoneal dialysis with warm fluids • gastric/colonic/pleural irrigation with warm fluids • external circulation (cardiopulmonary bypass machine) Cardiac Arrest in the Hypothermic Patient • do all procedures gently or may precipitate ventricular fibrillation (VF) • check pulse and rhythm for at least 1 minute; may have profound bradycardia • if any pulse at all (even very slow) do NOT do CPR • if in VF try to defibrillate up to max 3 shocks if Te <30°C • intubate gently if required, ventilate with warmed, humidified O 2 • medications (vasopressors; antiarrhythmics) may not be effective at low temperatures • controversial; may try one dose • focus of treatment is re-warming!


Classification • ice crystals form between cells • classified according to depth - similar to burns (1st to 3rd degree) • 1st degree • symptoms: initial paresthesia, pruritus • signs: erythema, edema, hyperemia, no blisters • 2nd degree • symptoms: numbness • signs: blistering (clear), erythema, edema • 3rd degree • symptoms: pain, burning. throbbing (on thawing); may be painless if severe • signs: hemorrhagic blisters, skin necrosis, edema, no movement

ER40 Emergency Medicine

Environmental Injuries

Toronto Notes 2008

• treat for hypothermia: Oz. IV fluids, maintenance of body warmth • remove wet and constrictive clothing • immerse in 40-42°C agitated water for 10-30 minutes (very painful; administer adequate analgesia) • clean injured area, leave injured region open to air • consider aspiration/debridement of blisters (controversial) • debride skin gently with daily whirlpool immersion (topical ointments not required) • tetanus prophylaxis • consider penicillin C as frost bite injury at high risk of infection • surgical intervention may be required to release restrictive eschars • never allow a thawed area to re-chill/freeze


Inhalation Injury



• carbon monoxide (CO) poisoning (see Toxicology section, ER46) • direct thermal injury - limited to upper airway • smoke causes bronchospasm and edema from particulate matter and toxic inhalants (tissue asphyxiates, pulmonary irritants, systemic toxins)

Biological Weapons Microbes (anthrax, Qfever, viruses), bacterial toxins Iricin, botulinum}, mycotoxins and others are usually spread by droplets (aerosols).
Diluted household bleach (1 :19 with water) is good for most biohazard materials for decontamination. Use contact isolation protocols, and treat for the specific agent.

• risk factors: closed spacE' fires, decreased mentation (overdose, alcohol intoxication, head injury, etc.)

• cherry red skin/blood (usually a post-mortem finding, generally unreliable) • facial bums, intraoral bums, singed nasal hairs, soot in mouth/nose, hoarseness, carbonaceous sputum, wheezing • headache, nausea, confusion • POz normal but O 2 sat low

• true Oz sat must be measured (not pulse oximeter nor calculated value based on a blood gas) • measure carboxyhemoglobin levels • ABC • CXR ± bronchoscopy

• CO poisoning: 100% O 2 ± hyperbaric O 2 (controversial) • direct thermal injury: humidified oxygen, early intubation, pulmonary toilet, bronchodilators


Near Drowning
• most common in children <4 yrs and teenagers • must also assess for shock, C-spine injuries, hypothermia, SCUBA-related injuries (barotrauma, air emboli, lung re-expansion injury) • complications: volume shifts, electrolyte abnormalities, hemolysis, rhabdomyolysis, ATN, DIC

Physical Examination
• • • • • ABC's, vitals - watch closely for hypotension lungs: rales (ARDS, pulmonary edema), decreased breath sounds (pneumothorax) CVS: murmurs, arrhythmias, JVP (CHF, pneumothorax) H&N: assess for C-spine injuries neuro: GCS or AVPU, pupils, focal deficits

• labs: CBC, electrolytes, ABGs, Cr, BUN, urinalysis • imaging: CXR (pulmonary edema, pneumothorax) • ECG

Toronto Notes 2008

Environmental Injuries/Common Pediatric ER Presentations

Emergency Medicine ER41

Management • ABCs, treat for trauma, shock, hypothermia • intensive respiratory care: • ventilatory assistance if decreased respirations, pCOz >50 mmHg, or pOz <60 mmHg on max Oz • hypoxia: maintain pOz at 60-80 mmHg • respiratory acidosis: ventilate • metabolic acidosis: improve perfusion, .J...pCOz • arrhythmias: usually respond to corrections of hypoxemia, hypothermia, acidosis • pulmonary edema: Oz, CPAP/BiPAP/positive pressure ventilation • vomiting: very common, insert NG suction to avoid aspiration • convulsions: usually respond to 0z; if not, diazepam 5-10 mg IV slowly • bronchospasm: bronchodilators • bacterial pneumonia: not necessary to prophylax with antibiotics unless contaminated
water or hot-tub (Pseudomonas)
• must observe for 24 hours as non-cardiogenic pulmonary edema may develop

Common Pediatric ER Presentations
Modified Coma Score for Children
Table 18. Modified GCS
Modified GCS for Children <4 yr Eye opening 4- spontaneously 3- to speech 2- to pain 1- no response Verbal Response 5- oriented, social, speaks, interacts 4- confused speech, disoriented, consolable 3- inappropriate words, not consolable/aware 2- incomprehensible, agitated, restless, not aware 1- no response Motor Response 6- normal, spontaneous movement
5-localizes pain
4- withdraws to pain
3- decorticate flexion
2- decerebrate extension 1- no response

Any infant <1 year of age with a large, baggy scalp hematoma requires skull x-rays:t CT.

Modified GCS for infants Eye opening 4- spontaneously 3- to speech 2- to pain 1- no response Verbal Response 5- coos, babbles 4- irritable cry 3- cries to pain 2- moans to pain 1- no response Motor Response 6- normal, spontaneous movement
5- withdraws to touch
4- withdraws to pain
3- decorticate fiexion
2- decerebrate extension 1- no response

The Febrile Infant o -------~~~--~--~~-~~~-~• see also Pediatrics, PSI • for fever >38°C without obvious focus: • <28 days • admit • full septic work up (CBC & diff, blood C&S, urine C&S, CSF, CXR if indicated) • treat empirically with broad spectrum IV antibiotics • 28-90 days • as above unless infant meets Rochester criteria (see below) • >90 days • toxic: admit, treat, full septic workup • non-toxic and no focus: investigate as indicated by history and physical

ER42 Emergency Medicine

Common Pediatric ER Presentations

Toronto Notes 2008

• Rochester Criteria for Febrile Infants age 28-90 days old: • febrile infants with temperature >38"C • non toxic - looking • previously well (>37 weeks GA, home with mother, no hyperbilirubinemia, no prior antibiotics or hospitalizations, no chronic/underlying illness) • no skin, soft j-issue, bone, joint, or ear infection on physical exam • WBC 5000-15,000, bands <1500; urine <10 WBC/HPF, stool <5WBC/HPF • serious bacterial infections occur in 7-9% of well-appearing infants 28-90 days old BUT if all of the above Rochester criteria are present, incidence of serious bacterial infection is <1%

Febrile Seizures
Etiology • children aged 6 months to 5 years with fever or history of recent fever • simple vs complex febrile seizures
Table 19. Simple vs Complex Febrile Seizures
Characteristic Duration Type of seizure Frequency Simple <15 min Generalized 1 in 24 hours Complex >15 min Focal features >1 in 24 hours

• normal neurological exam afterward • no evidence of intracranial infection or history of previous non-febrile seizures • often positive family history of febrile seizures

Investigations and Management • if it is a febrile seizure: treat fever AND look for source of fever • if not a febrile seizure: treat seizure AND look for source of seizure • note: may also have fever but may not meet criteria for febrile seizure

Common Childhood Infections
• see also Pediatrics. P50
Table 20. Antibiotic Treatment of Pediatric Bacterial Infections
Infection Meningitis
Neonatal GBS, fco/i, listeria, S. aureus, Gram negative bacilli same pathogens as above and below
S. pneumococcus, H. influenzae type b(>5 yrsl. meningococcus



'·3 months
>3 mos

•ampicillin +aminoglycoside (gentamicinI or •ampicillin +cefotaxime ±cloxacillin if risk of S. aureus •ampicillin +cefotaxime ±cloxacillin if risk of S. aureus •cefuroxime •ceftriaxone or cefotaxime, if risk of meningitis •vancomycin, if penicillin/cephalosporin- resistant pneumococci 'amoxicillin • high dose amoxicillin or clavulin • high dose c1avulin or cefuroxime or ceftriaxone

Otitis Media 1st line 2nd line Treatment failure Strep Pharyngitis group AIl-hemolytic Streptococcus UTI • penicillinlamoxicillin or erythromycin Ipencillin allergy) •amoxicillin/ampicillin or •trimethoprim-sulfamethoxalOle •cefuroxime ±macrolide (erythromycinl or •ampicillin ±macrolide •ampicillinlamoxicillin or cefuroxime •ampicillin/amoxicillin +macrolide or cefuroxime +macrolide

S. pneumoniae, H. influenzae type b, M. Catarrhalis

E. Coli, Proteus, H. Influenzae, Pseudomonas, S. saprophyticus, Enterococcus, GBS Pneumonia
'-3mos viral, S. pneumoniae, C. trachomatis, B. pertussis, S. aureus, H. influenzae viral, S. pneumoniae, S. aureus, H. influenzae, Mycoplasma pneumoniae as above

>5 years

Toronto Notes 2008

Common Pediatric ER Presentations

Emergency Medicine ER43

Concerning Rashes
• see also Pediatrics. P50 and Dermatology. D44

• see also Pediatrics. P58 • maculopapular rash starting at hairline, spreading to face/trunk + 3 Cs (cough, coryza, conjW1ctivitis) • complications: pneumonia, OM, encephalitis • management: Vit A if hospitalized and/or immW1compromised; respiratory isolation, treat contacts with immune globulin

Erythema Infectiosum
• • • • • • • • see also Pediatrics. P60 'slapped cheeks', maculopapular lacy-like rash on trunk/limbs complications: STAR (sore throat, arthritis, rash), aplastic crisis management: supportive, respiratory isolation x 7d

VZVlChicken Pox
see also Pediatrics. P57 itchy, vesicular, maculo-papular rash at multiple stages complications: GAS, acute encephalitis, acute cerebellar ataxia, hepatitis, DIC management: symptomatic, acyclovir only for complicated cases, respiratory + contact isolation • prevention: VZIG within 96 hrs of exposure, Varicella vaccine (Varivax TM)

Kawasaki Disease
• leading cause of acquired cardiac disease in children; can cause coronary artery aneurysms • fever >5 d plus 4 of 5 of the following: • unilateral lymphadenopathy • bilateral, non-purulent conjW1ctivitis • cracked lips, strawberry tongue • rash • puffy, red palms and soles • management: • acute phase: NIG 2g1kg and ASA 100 mglkg/day W1til fever resolves • subacute: ASA 3-5 mg/kg/day W1til platelets normalize, or indefinitely in case of cardiac disease • ECG and echocardiography with echocardiography follow-up at 2, 6, 12 months

Respiratory Distress
• see also Pediatrics. P86


History and Physical Examination
• • • • • infants not able to feed, older children not able to speak in full sentences anxious, irritable, lethargic - may indicate hypoxia tachypnea >60, retractions pulsus paradoxus wheezing, grunting, vomiting

Table 21. Stridorous Upper Airway Diseases: Diagnosis
Feature Age range (yrs) Prodrome Temperature Radiography Etiology Barky Cough Drooling Croup Bacterial Tracheitis Epiglottitis1

Appear Toxic
Intubation? ICU? Antibiotics

0.5-4 Days Low grade Steeple sign Parainfluenza Yes Yes No No No

5-10 Hrs to days High Exudates in trachea S. aureusiGAS Yes No Yes Yes Yes

'rare now with Hib vaccine in common use

2-8 Minutes to hrs High Thumb sign H flu type b No Yes Yes Yes Yes No oral exam

ER44 Emergency Medicine

Common Pediatric ER Presentations/Common Psychiatric ER Presentations

Toronto Notes 2008

• management of croup • humidified O 2 • racemic t'pinephrine glh x 3 doses, observe for 'rebound effects' • dexamethasone x 1 dos0 • consider bacterial tracheitis/epiglottitis if unresponsive to croup therapy • management of bacterial tracheitis • start croup therapy • usually require intubation, ENT consult, ICU • start abx (e.g. cloxacillin), pending C&S • management of epiglottitis • 4 D's: droolin8t dyspnea, dysphagia, dysphonia + tripod sitting • do NOT EXAMINE OROPHARYNX or AGITATE patient • immediate anaesthesia, ENT call - intubate • then IV fluids, Abx, blood cultures • management of asthma • supplemental 00 if sats <90% or Pa02 <60% • bronchodilator therapy: salbutamol (Ventolin™) 0.15 mglkg by masks g20 min x3 • add 250-500 I-lg ipratropium (Atrovent™) to first 3 doses salbutamol • give corticosteroid therapy as soon as possible after arrival (prednisolone 2 mg/k8t dexamethasone 0.3 mg/kg) • MgS04 if critically ill, not responding to inhaled bronchodilators, steroids; give IV bolus, then infusion • IV ~2-agonistsif critically ill and not responding to above

[. o

Abdominal Pain
• see also Pediatrics, P40

History • nature of pain, associated fever • associated GI, GU symptoms • anorexia, decreased fluid intake Physical Exammination • HEENT, respiratory, abdominal exam including ORE, testicular/genital exam
Table 22. Differential Diagnosis of Abdominal Pain in Infants/Children/Adolescents
Colic UTI Constipation Gastroenteritis Sepsis HSP (Henoch Schonlein purpura) Inflammatory Bowel Disease HUS (Hemolytic Uremic Syndrome) Pneumonia Strep Throat SCD crisis DKA Functional

Malrotation with volvulus Hirschprung's Necrotizing enterocolitis Incarcerated hernia Intussusception Duodenal atresia Appendicitis Cholecystitis Pancreatitis Testicular torsion Ectopic pregnancy Trauma Pyloric stenosis

'remember to keep an index of suspicion for child abuse

Ctiild JA6use and Neglect
• see also Pediatrics, P15 • obligation to report ANY suspected/known case of child abuse or neglect to CAS yourself (DO NOT DELEGATE) • document injuries • consider skeletal survey X-rays, ophtho consult, CT head • injury patterns associated with child abuse: • head injuries: tom frenulum, dental injuries, bilateral black eyes, traumatic hair loss, diffuse severe CNS injury, retinal hemorrhage • Shaken Baby Syndrome: diffuse brain injury, subdural/subarachnoid hemorrhage, retinal hemorrhage, minimal/no evidence of external trauma, associated bony fractures • skin injuries: bites, bruises/burns in shape of an object, glove/stocking distribution of bums, bruises of various ages, bruises in protected areas

Toronto Notes 2008

Common Pediatric ER Presentations/Common Psychiatric ER Presentations

Emergency Medicine ER45

• bone injuries: rib fractures without major trauma, femur fractures age <1 year
of age, spiral fractures of long bones in non-ambulatory children, metaphyseal
fractures in infants, multiple fractures of various ages, complex/multiple skull
• genitourinary/gastrointestinal injuries: chronic abdominal/perineal pain,
injury to genitals/rectum, STI/pregnancy, recurrent vomiting or diarrhea

Common Psychiatric ER Presentations
Approach to Common Psychiatric Presentations
• see Psychiatry, PS2 • before seeing patient, ensure your own safety; have security/police available if

• safety • assess suicidality: suicidal ideation, intent, plan, lethal means, past attempts, future planning • assess homicidality: access to weapons, intended victim, history of violence • command hallucinations • mood symptoms • psychotic symptoms: delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, negative symptoms (affective flattening, alogia, avolition) • substance use history: most recent use, amount, previous withdrawal reactions • past psychiatric history, medications, compliance with medications • medical history: obtain collateral if available



Key functions of emergency psychiatric: aaaesament: lis the patient medically stable?
2. Rule out medical cause
3. Is psychiatric consult needed? 4. Are there safety issues (51, HII? 5. Is patient certifiable?

• complete physical exam focusing on: vitals, neurological exam, signs of head trauma,
signs of drug toxicity, signs of metabolic disorder
• mental status exam: general appearance, speech, mood and affect, thought content and
form, perceptions, cognition including MMSE, judgment, insight, reliability

• investigations vary with: patient's age, established psychiatric diagnosis vs. first
presentation, history and physical suggestive of organic cause
• as indicated: blood glucose, urine and serum toxicology screen, pregnancy test,
electrolytes, TSH, AST/ALT, bilirubin, serum creatinine, BUN, osmolality
• blood levels of psychiatric medications • CT head if suspect neurological etiology • LP if indicated

Acute Psychosis
Differential Diagnosis
• primary psychotic disorder (e.g. schizophrenia) • secondary to medical condition (e.g. delerium) • drugs: substance intoxication or withdrawal, medications (e.g. steroids, anticholinergics) • infectious (CNS) • metabolic (hypoglycemic, hepatic, renal, thyroid) • structural (hemorrhage, neoplasm)


• violence prevention • remain calm, empathetic and reassuring • ensure safety of staff and patients, have extra staff and/or security on hand • patients demonstrating escalating agitation or overt violent behavior may require physical restraint and/or chemicaltranquilization (see VioLent Patient,

• treat agitation: whenever possible, offer medication to patients as opposed to administering with force (helps calm and engage patient) • benzodiazepines - lorazepam 2 mg PO or IM • antipsychotics - oJanzapine 5 mg PO, haloperidol 5 mg PO/IM • treat underlying medical condition • psychiatry or Crisis Intervention Team consult

Features that suggest organic etiology: A age >40 years old B babbling (incoherent speech or speech difficuttiesl C concerning vital signs
D disorientation
E emotional lability
F fluctuating course G global impairment of cognitive function H headaches I immodesty J just started (sudden onsetl K
L loss of consciousness
M movement abnormalities (tremor,

ata'kia, ~l:lIornotor retardationl


neurological findings (focal! other abnormalities on physical exam perceptions (visual hallucinations)

ER46 Emergency Medicine

Common Psychiatric ER Presentationsrroxicology

Toronto Notes 2008



Epidemiology • attempted suicide F>M, completed suicide M>F • second leading cause of death in people <24 yo Management • ensure patient safety: close observation, remove potentially dangerous objects from person and room • assess thoughts (ideation), means, action (preparatory, practice attempts), previous attempts • admit if there is evidence of intent and organized plan, access to lethal means, psychiatric disorder, intoxication (suicidal ideation may resolve with few days of abstinence) • patient may require certification if unwilling to stay voluntarily • do not start long-term medications in the emergency department • psychiatry or crisis team consult

High risk patients
"SAD PERSONS" Sex = male Age >45 years old Depression Previous attempts Ethanol use Rational thinking lost Suicide in family Organized plan No spouse, no support system Serious illness Total number of risk factors >7 hospitalize, consider hospitalization if 5-6

Violent Patient
Differential Diagnosis • rule out lethal organic cause (see Acute Psychosis, ER45) • leading organic causes are EtOH, drugs, and head injuries Prevention • be aware and look for prodromal signs of violence: anxiety, restlessness, defensiveness, verbal attacks • try to de-escalate the situation: address the patient's anger, empathize Restraints • pharmacological • often necessary - may mask clinical findings and impair exam • haloperidol 5-10 mg IM (be prepared for dystonic reactions, especially with multiple doses of neuroleptics over a short period) + lorazepam 2 mg IM/IV • look for signs of anticholinergic 00 first (see Toxicology, ER46) • physical • present option to patient in firm but non-hostile manner • sufficient people to carry it out safely • restrain supine or on side; preferably 4-point restraints, never less than 2-points (opposite arm and leg) • suction and airway support available in case of vomiting • once restrained, search person/clothing for drugs and weapons

Approach to the OVemose PitieiitJToxic EXposure
History • who? age, weight, underlying medical problems, medications • what? substance and how much • when? time since exposure determines prognosis and need for contamination, symptoms since • how? route • why? intention, suicidality

.... . } - - - - - - - - - - - - - ,
Suspect overdose when: • a~ered level of consciousness/coma • young patient with life-threatening
• trauma patient • bizarre or puzzling clinical presentation


Physical Examination • focus on: ABCs, LOC/GCS, vitals, pupils Principles of Toxicology • 5 principles to consider with all ingestions i. resuscitation (ABCs) II. screening (toxidrome? clinical clues?) iii. decrease absorption of drug IV. increase elimination of drug v. antidote available?

Toronto Notes 2008


Emergency Medicine ER47

ABCs ofToxicolo y
• basic axiom of care is symptomatic and supportive treatment • address underlying problem only once patient is stable
A Airway (consider stabilizing the C-spine)
B Breathing
C Circulation
Dl Drugs
• ACLS as necessary to resuscitate the patient • universal antidotes
D2 Draw bloods
D3 Decontamination (decrease absorption)
E Expose (look for specific toxidromes)/Examine the Patient
F Full vitals, ECG monitor, Foley, X-rays, etc.
G Give specific antidotes, treatments
Go back and reassess
Call Poison information
Obtain corroborative history from family, bystanders

D1 - Universal Antidotes
• treatments that will not harm patients and may be essential

• do not deprive a hypoxic patient of oxygen no matter what the antecedent medical
history (Le. even COPD with CO2 retention)
• if depression of hypoxic drive, intubate and ventilate • exception: paraquat or diquat (herbicides) inhalation or ingestion (oxygen radicals
increase morbidity)

• • • • give to any patient presenting with altered LOC measure blood glucose prior to glucose administration if possible adults: 0.5-1.0 glkg (1-2 mL/kg) IV ofD50W children: 0.25 glkg (2-4 mL/kg) IV of D50W

Thiamine (Vitamin 8 1 )
• 100 mg IV/IM to all patients with IV/PO glucose • a necessary cofactor for glucose metabolism, but do not delay glucose if thiamine
• to prevent Wemicke-Korsakoff syndrome • Wernicke's encephalopathy - Ataxia, Confusion, Ophthalmoplegia (WACO) • untreated, may progress to Korsakoff's psychosis (disorder in learning and processing of new information), usually irreversible • prophylaxis: thiamine (100 mg/day x 3 days) • must assume all undifferentiated comatose patients are at risk



Populations at risk for thiamine

• alcoholics • anorexics • hyperemesis of pregnancy • malnutrition states

• antidote for opioids: administration is both diagnostic and therapeutic (1 min onset of action) • used for the undifferentiated comatose patient • loading dose • adults • 2 mg initial bolus IV/IM/SL/SC or via EIT (EIT dose = 2-2.5x IV dose) • if no response after 2-3 minutes, increase dose by 2 mg increments until a response or to max 10 mg • known chronic user, suspicious history, or evidence of track marks, give om mglkg • child
• om mglkg initial bolus IV/IO/EIT
• 0.1 mglkg if no response and narcotic still suspected • maintenance dose • may be required because half-life of naloxone much shorter than many narcotics (half-life of naloxone is 30-80 minutes) • hourly infusion rate at 2/3 of initial dose that produced patient arousal

ER48 Emergency Medicine


Toronto Notes 2008

02 - Draw Bloods
• essential bloods (see Table 24 for interpretation) • CBC, electrolytes, BUN/creat, glucose, INR/PTT, osmolality • ABGs, measure O 2 sat • acetylsalicylic acid (ASA), acetaminophen, EtOH levels • potentially useful bloods • drug levels - NOT serum drug screen • Ca, Mg, P04 • protein, albumin, lactate, ketones, liver enzymes, CK - depending on drug and clinical presentation

Serum Drug Levels • treat the patient, not the drug level • negative tox screen signifies only that the specific drugs tested were not detectable in the specimen at the time it was obtained (i.e. does not rule out a toxic ingestion) • specific drugs available on general screen vary by institution; check before ordering • urine screens also availahle (qualitative only) Table 23. Toxic Gaps (see also Nephrology, NPl7)
Anion Gap lAG) = Na' - P + HeO,'! • normal range 10·14 mmolfL Metabolic Acidosis Increased AG: "MUDPILES CAT" (' = toxic) Methanol Uremia Diabetic ketoacidosIs/Starvation ketoacldusis Phenformin'lParaldehyde' Isoniazid, iron, ibupr01er Lactate (anything that causes seizures or shockl Ethylene glycol' Salicylates' Cyanide, carbon monoxide' Alcoholic Ketoacidosis' Toluene, theophylline' Increased POG: "MAE DIE" lif it ends in "-01; it will likely .,. the POG) Methanol Acetone Ethanol Diuretics (glycerol, mannitol, sorbitoll Isopropanol Ethylene Glycol Note: normal osmolar gap does not rule out toxic alcohol; only an elevated gap is helpful Oxygen saturation gap = measured - calculated 0, sat • measured by absorption spectrophotometry Ipulse oximetry) • calculated from HbfO, saturation curve Increased O2 saturation gap • carboxyhemoglobin • methemoglobin • sulfhemoglobin Plasma Osmolar Gap (POGI = measured - calculated osmoles • normally POG <10 mOsmiL • calculated osmolality =2Na + BUN + blood glucose (mmoIlL)

Decreased AG

• electrolyte imbalance (increased Na'fK'/Mg"j • hypoalbuminemia (50% fall in albumin -5.5 mmolfL decrease in the AG! • Li, Br elevation • paraproteins (multiple myelomal

NormalAG • high K: pyelonephritis, obstructive nephropathy, renal tubular acidosis (RTAI. IV,TPN • low K: small bowel losses, acetazolamide, RTA I, II

Table 24. Use of the Clinical Laboratory in the Initial Diagnosis of Poisoning
Test ABG Electrolytes Finding 'hypoventilation 11' pCO,) • hyperventilation I.. pCO,1 '1' anion-gap metabolic acidosis • hyperkalemia • hypokalemia • hypoglycemia • elevated osmolar gap • wide QRS complex • prolonged QT interval • atrioventricular block • radiopaque pills or objects • elevated level 1>140 mgIL or 1000 ~moliL 4hours after ingestion! Selected Causes • CNS depressants (opioids, sedative-hypnotic agents, phenothiazines, EtOH) • salicylates, CO, other asphyxiants • "MUDPILES CAT": see "Metabolic Acidosis' above • digitalis glycosides, fluoride, potassium • theophylline, caffeine, Il-adrenergic agents, soluble barium saks, diuretics • oral hypoglycemia agents, insulin, EtOH, ASA • "MAE DIE"; see "Toxic Gaps' above 'TCAs, quinidine, other class la and Ic antiarrhythmic agents • quinidine and related antiarrhythmics, terienadine, astemizole • Ca" antogonists, digitalis glycosides, phenylpropanolamine • "CHIPES": Calcium, Chloral hydrate, CCI" Heavy metals, Iron, Potassium, Enteric coated Salicylates, and some foreign bodies • may be only sign of acetaminophen poisoning

Glucose Osmolality and Osmolar Gap ECG

Abdominal X-Ray Serum Acetaminophen

Toronto Notes 2008


Emergency Medicine ER49

D3 - Decontamination and Enhanced Elimination
Ocular Decontamination
• saline irrigation to neutralize pH; alkali exposure requires ophthalmology consult



Dermal Decontamination (wear protective gear)
• remove clothing, brush off toxic agents, irrigate all external surfaces


Gastrointestinal Decontamination
• single dose activated charcoal (SDAC) • absorption of drug/toxin to AC prevents availability • contraindications: caustics, SBO, perforation • dose: 10g/g drug ingested or 19!kg body weight • odourless, tasteless, prepared as slurry with H2 0
• whole bowel irrigation • 500 mL (child) to 2000 mL (adult) of balanced electrolyte solution/hour by
mouth until clear effluent per rectum
• indications • awake, alert patient who can be nursed upright • delayed release product • drug/toxin not bound to charcoal • drug packages (if any evidence of breakage --+ emergency surgery) • recent toxin ingestion • contraindications • evidence of ileus, perforation, or obstruction • surgical removal in extreme cases • indicated for drugs that are toxic, form concretions, or cannot be removed by
conventional means

Substances NOT Absorbed by
Activated Charcoal
'li • Fe •Alcohols • Lead •Caustics

• weakly acidic substances can be trapped in alkali urine (pH >7.5) to increase
elimination (e.g. ASA, methotrexate, 2,4-D, Phenobarb)

Multidose Activated Charcoal (MDAC)
• for toxins which undergo enterohepatic or enteroenteric recirculation including
phenobarbitol and theophylene
• removes drug that has already been absorbed by drawing them back into GI tract • various regimens: 12.5g (1/4 bottle) PO qlh or 25g (1/2 bottle) PO q2h until non-toxic
and charcoal stool

Criteria for Hemodialysis
• toxins that have: • high water solubility, low protein binding, low molecular weight, adequate
concentration gradient, small volume of distribution (Vd) or rapid plasma
• removal of toxin will cause clinical improvement • advantage is shown over other modes of therapy • predicted that drug or metabolite will have toxic effects • impairment of normal routes of elimination (cardiac, renal, or hepatic) • clinical deterioration despite maximal medical support • useful for the following toxin blood levels: • methanol • ethylene glycol • salicylates • lithium • bromine: >15 mmol/L • phenobarbital: 430-650 mmol/L • chloral hydrate (-+ trichloroethano1\: >200 mg/kg
• others include theophylline, carbamazepine, valproate, methotrexate

ERSO Emergency Medicine


Toronto Notes 2008

E - Examine the Patient
• vital signs (including temperature), skin (needle tracks, colour), mucous membranes, pupils, odours and CNS • head-to-toe survey including: • C-spine • signs of trauma, seizures (incontinence, "tongue biting", etc.), infection (meningismus), chronic alcohol/drug abuse (track marks, nasal septum erosion) • mental status
Table 25. SpecificToxidromes
Toxidrome Anticholinergics Overdose Signs and Symptoms
Hyperthermia Dilated pupils Dry skin Vasodilation Agitation/hallucinations Ileus Urinary retention Tachycardia "Hot as ahare" "Blind as abat" "Dry as abone" "Red as abeet" "Mad as ahatter' "The bowel and bladder lose their tone and the heart goes on alone"

Examples of Drugs
Antidepressants (e.g. TCAs) Cyclobenzaprine (FlexeriPM I Carbamazepine Antihistamines (e.g. diphenhydraminel Antiparkinsonians Antipsychotics Antispasmotics Belladonna alkaloids le.g. atropine) Natural plants mushrooms, trumpet flower Anticholinesterases physostigmine insecticides lorganophosphate, carbonatesl nerve gas




Anticholinergics "Hot and Dry" Sympathomimetics "Hot and Wet"

"DUMBELS' Diaphoresis, Diarrhea, Decreased blood pressure Urination Miosis Bronchospasm, Bronchorrhea, Bradycardia Emesis, Excitation of skeletal muscle Lacrimation Salivation, Seizures Dysphonia, dysphagia Rigidity and tremor Motor restlessness, crawling sensation (akathisial Constant movements (dyskinesia) Dystonia (muscle spasms, laryngospasm, trismus, oculogyric Crisis, torticollisl Increased respiratory rate Decreased level of consciousness Seizures Cyanosis unresponsive to 0, Lactic acidosis Hypothermia Hypotension Respiratory depression Dilated or constrictied pupils (pinpoint in opiate 001 CNS depression Increased temperature CNS excitation (including seizuresl Tachycardia, hypertension Nausea and vomiting Diaphoresis Dilated pupils Mental status changes, autoomic hyperactivity, neuromuscular abnormalities, hyperthermia, diarrhea, HTN


Major tranquilizers Antipsychotics

Hemoglobin Derangements

Carbon monoxide poisoning (carboxyhemoglobinl Drug ingestion (methemoglobin, sulfhemoglobinl

Narcotics, Sedatives! Hypnotics. EtDH

EtOH Benzodiazepines Opiates (morphine, heroin, etc.) Barbiturates GHB Amphetamines caffeine Cocaine, LSD, PCP Ephedrine &other decongestants Thyroid hormone Sedatives, EtOH withdrawal MAOI, TCA, SSRI, opiate analgesics, Cough medicine, weight reduction medications


Serotonin Syndrome

Note: ASA poisoning and hypoglycemia mimic sympathomimetic toxidrome

Toronto Notes 2008


Emergency Medicine ER51

G - Give
<5.0' 5.1-9.0'

S~ecific Antidotes

and Treatments

Table 26. Protocol for Warfarin Overdose
Cessation of warfarin administration, observation, seriallNRJPT If no risk factors for bleeding, hold warfarin x 1-2 days and reduce maintenance dose
Vitamin K1-2 mg PO if patient at increased risk of bleeding
Hold warfarin, Vitamin K2-4 mg PO, seriallNRJPT, additional Vitamin Kif necessary Fresh frozen plasma (FFP) 10-15 mL, Vitamin K10 mg IV over 10 min, increase Vitamin Kdosing
(q4h) if needed, phenobarbitol (little evidence)

9,1-20.0' >20.0 or

Urine Alkalinization Treatment for ASA Overdose
• urine pH >7.5 • fluid resuscitate first, then 3 amps NaHCOJlitre of DSW @ 1.5 x maintenance • add 20-40 mEq kcal/litre if patient is able to urinate
Table 27. Specific Antidotes and Treatments ­ call local poison information centre for specific doses and treatment recommendations

Toxin Acetaminophen Treatment Decontaminate (charcoall N-acetylcysteine Considerations Often clinically silent; evidence of liver/renal damage delayed >24 hrs Toxic dose >200 mglkg 1>7.59 adult)
Monitor drug level immediately and @4hrs post-ingestion; also liver
Enzymes, INR, PIT. BUN, Cr
Hypoglycemia, metabolic acidosis, encephalopathy • poor prognosis
Monitor serum pH and drug levels closely
Monitor K+ level; may require supplement for urine alkalinization
Hemodialysis may be needed if intractable metabolic acidosis, very
high levels, or end-organ damage (i.e, unable to diuresel Special antidotes available. Consult PIC


Decontaminate (activated charcoal) Alkalinize urine (see Table 23); want urine pH >7,5


Decontaminate lactivated charcoal) Supportive care
Decontaminate (activated charcoall
Supportive care
Decontaminate (activated charcoal) CaCI1-4 g of 10% sol'n IV if hypotensive atropine or isoproterenol if severe
other; high-dose insulin, inotropes or
aggressive supportive therapy
Cyanide antidote kit or hydroxycobalamin
Nitrate, then Na Nitrite; Na thiosulfate
Decontaminate (charcoal) Digoxin-specific Ab fragments 10-20 vials IV if acute; 3-6 if chronic 1vial 140 mg) neutralizes 0.6 mg of toxin


Il-blockers calcium Channel Blockers

Special antidotes considered. Consul! PIC Order ECG, Iytes lespecially Ca, Mg, Na, K)



Use for life·threatening arrhythmias unresponsive to
Conventional therapy, 6hr serum digoxin>19 nmoVL, initial K+
>5 mM, ingestion >10 mg (adul!)/ >4 mg Ichild)
Common arrhythmias include V-fib, V-tach, and conduction blocl<s

Acute Dystonic Axn Benztropine: 1-2 mg IMIIV then 2mg PO x3days OR Benztropine (Cogentin to Ihas euphoric effect and potential for abuse
Diphenhydramine 1-2 mg/kg IV,
Then 25 mg PO qid x3days
Heparin Insulin! oral hypoglycemic Protamine sulfate 25-50 mg IV Glucose IV/POING tube Glucagon: '·2 mg 1M lif no access to glucose) Glyburide carries highest risk of hypoglycemia among oral agents;
Consider octreotide 150-100 ug SC q6hl in these cases consult local PIC

ER52 Emergency Medicine

ToxicologylProcedural Sedation

Toronto Notes 2008

Table 27. Specific Antidotes and Treatments ­ call local poision information centre for specific doses and treatment recommendations (continued)
Toxin Ethanol Treatment Gastric decontamination if ingestion <1 hr Thiamine 100 mg IM/IV Manage airway and circulatory suppon Consider hemodialysis if serum EtOH >500 mgldL Ethanol (10%110 mVkg over 30 min, then 1.5 n1l/h Or fomepizole (4·mp.thylpyrazole!15 mg/kg IV load Over 30 min, then 10 mg/kg q12h See ER40 See ER47 Aggressive supportive care NaHCO, bolus for wide DRS/seizures Flumazenil antidote contraindicated in combinedTCAIbenzodiazepine Overdose Also consider cardiac and Hypotension suppon, gastric Decontamination, seizure control Monitor CK; treat rhabdomyolysis with high flow fluids Considerations Hypoglycemia very common in children Mouthwash =70% EtOH; perfumes and colognes = 40·60% EtOH Order serum EtOH level and glucose level; treat glucose level Appropriately CBC, lyles, glocose, ethanol level Consider hemodialysis

Ethylene glycoV Methanol

CO Poisoning Opioids TCAs


Decontaminate (charcoal), supportive care, Decontaminate (charcoal) if oral Aggressive supportive care

Disposition from the Emergency Department
• methanol, ethylene glycol • delayed onset, admit and watch clinical and biochemical markers • TCAs • prolonged/delayed cardiotoxicity warrants admission to monitored (rCU) bed • if asymptomatic and no clinical signs of intoxication: 6 hour ED observation adequate with proper decontamination • sinus tachycardia alone (most common finding) with history of OD warrants observation in ED • hydrocarbons/smoke inhalation • pneumonitis may lag 6-8 hours • consider observation for repeated clinical and radiographic examination • ASA, acetaminophen • if borderline leveL get second level 2-4 hours after first • oral hypoglycemics • admit all patients for minimum 24 hours if hypoglycemic
• observe asymptomatic patient for at least 8 hours

Psychiatric Consultation • once patient medically cleared, arrange psychiatric intervention if required • beware - suicidal ideation may not be expressed

Procedural Sedation
• procedural sedation: the technique of sedative or dissociative agent administration with or without analgesics to induce a state that allows a patient to tolerate an unpleasant or painful procedure while maintaining all protective cardiorespiratory functions (i.e. a depressed level of consciousness without loss of a patient's protective airway reflexes) • must weigh degree of pain and expected relief versus risk/complications of sedation and procedure

Requirements for Safe Procedural Sedation in the Emergency Department • airway suitable for safe intubation and wntilation • appropriate equipment/personnel available • intact and functioning cdrdiorespiratory and neurological system • ideally, NPO for minimum 4-6 hours • anesthetic history and drug allergies, include manifestations • appropriate IV access, monitoring (oxygen saturation, BP, HR, etc.) • informed consent obtained Common Procedural Sedation Medications (titrate to effect) • see Commonly Used Medications section, RR53

Toronto Notes 2008

Commonly Used Medications

Emergency Medicine ER53

Commonly Used Medications
Drug fentanyl midazolam Dosing Schedule 0.5-1.0

Indications Procedural sedation Procedural sedation

Comments Very short acting narcotic Icom pIi cation=a pne aI Short acting benzodlazepine (complication=apnea when used with narcoticl fentanyl and midazolam often used together for procedural sedation Short acting Anesthetic/sedative (complic8t1on=apnea, decreased BPI Benzodiazepine antagonist NB don't use in chronic benzo Not to be used in fingers, nose, toes, penis, ears


50 ~g/kg IV

propofol flumazenil lidocaine with epi lidocaine w/o epi Polysporin® morphine (MS ContinI Percocet 1O/325® acetaminophen Tylenol #3® Ibuprofen thiamine

0.25-05 mg/kg IV 0.3 mg IV bolus q5min x 3doses max 7 mg/kg SC max 5 mg/kg SC apply to affected area bid-tid 15-30 mg PO q8-12h 0.1-0.2mg/kg max 15 mg IV q4h 1-2 tabs PO q6h pm 325-650mg PO q4-6h pm 1-2 tabs q4-6h pm 200-800 mg PO tid pm max 1200 mg/d Wernicke's encephalopathy: 100 mg IV/1M initially then 50-100 mg 1M/IV OD/PO x 3d anxiety: 2-10 mg PO tid/qid alcohol withdrawal: 10-20 mg PO/W qlh titrated to signs/symptoms anxiety: 0.5-2 mg PO/1M/IV q6-8h status epileptic us; 4 mg IV repeat up to q5min status epilepticus: Load 20 mg/kg IV
@ less then 50 mg/min then 5-10 mg/kg IV @ less then 50 mg/min

Procedural sedation Reversal of procedural sedation Local anesthetic Local anesthetic Superficial infections Mild to moderate acute/chronic pain Prescribed in combination with NSAIOs or acetaminophen Moderate pain control Pain control Pain control Mild to moderate acute pain Analgesia and anti-inflammatory properties To treat/prevent Wernicke's encephalopathy Anxiety Alcohol withdrawal Anxiety Status epilepticus Status epilepticus

GI and constipation side effects DO NOT CRUSH, CUT or CHEW Oxycodone + acetaminophen Max 4 9 acetaminophen 00 Max 4 g 00 Max 4 9 acetaminophen DO

Caution use in pregnancy




Begin maintenance dose -12hr after loading dose Continuous ECG, BP monitoring recommended Max 1mg/dose Caution with cardiac abnormalities Contraindicated with peanut/soy allergy Caution with narrow-angle glaucoma Not to be used with other anti-hypertensives

epinephrine salbutamol Ipratropium bromide nitroglycerin

anaphalaxis: 0.1-0.5 mg 1M; can repeat ql0-15min 2 puffs inhaled q4-6h (4yrsl max 12 puffs/day 2-3 puffs tid-qid, max 12 puffs/day acute angina: 0.3-0.6 mg SL q5min, OR 5 ~g/min IV increasing by 5-20 ~g/min q3-5min 325-650 mg PO q4h max 4g/day stroke/MI risk: 81-325 mg PO 00 5 mg slow IV q5min x 3 if no contraindications 1 mg/kg SC BID bolus 5-10U (0.2 U/kg) then 5-10 U (0.1 U/kgl per hour 0.5-1.0 g/kg (1-2mllkg) IV of 050W CHF: 40-80 mg IV HTN: 10-40 mg PO BID 2.5-5.0 mg PO/1M initial effective dose 6-20 mg/day 0.5-2 mg or 0.01-0.02 mg/kg initial bolus IV/IM/SUSC or via m 12-2.5x IV dosel, increase dose by 2 mg until response/max 10 mg 30-100 g PO in 250 ml H2 0

Anaphalaxis Asthma Asthma Angina Acute MI Pain control Cardiac prevention Acute MI Acute MI Hyperglycemia

ASA P-blockers (metoprololl enoxaparin insulin R

Monitor blood glucose levels Consider K replacement also measure blood glucose levels before administration

glucose furosemide (Lasix) haloperidol naloxone

Hypoglycemia/DKA CHF HTN Psychosis Comatose patient Opioid overdose Reversal in procedural sedation Poisoning/overdose Monitor for electrolyte imbalances Monitor with Parkinsuns; results in CNS depression


ER54 Emergency Medicine

Summary Key QuestionslReferences

Toronto Notes 2008

Summary Key Questions

Questions Answers Airway/C-spine, Breathing, Circulation, Disability, Environment/Exposure. Restart when conditions deteriorates.


How do you assess a patientthat presents to the ED? When do you restart this assessment? How does consent change in the context of Emergency Medicine IEM)? What is the Cushing's reflex? What are the universal antidotes in EM? What should every patient with an MI receive?


Consent is not needed when patient is at imminent risk from serious injury AND obtaining consent is not possible. Sign of increased ICP: high Bp, low HR, irregular respirations Oxygen, glucose, naloxone, thiamine. "BEMOAN": Beta-blockers, Enoxaparin, Morphine, Oxygen, ASA, Nitroglycerin Battle sign, hemotympanum, racoon eyes, CSF otorrhea/rhinorrhea Hemorrhagic


4. 5.

6. What are the signs of a basal skull fracture?


Shock in atrauma patient is _ proven otherwise?



Level of consciousness is assessed using what scale? At what GCS should you intubate?



8or less C-spine X-rays

10. What investigation is KEY for a potential spinal cord trauma patient? 11. What is the management of atension pneumothorax?
12. What imaging modalities should be considered in abdominal trauma? 13. For penetrating trauma, when is laparotomy mandatory? 14. What are the contra indications to a Foley catheter? 15. What nerves are at risk with an anterior shoulder dislocation? 16. When is an X-ray series olthe ankle required?

Large bore IV needle inserted into 2nd ICS mid-clavicular line, followed by chest tube in 5th ICS ant-axillary line FAST, DPL, X-ray, CT

Shock, peritonitis, evisceration, free air, gunshot, blood in NG, Foley, or on ORE Blood at the urethral meatus, ecchymosis of the scrotum, "high riding" prostate Axillary nerve lIateral), and musculocutaneous nerve (extensor aspect of forearm) Any pain in the malleolar zone AND tenderness in either malleolar zone OR inability to weight bear Any pain in the midfoot zone AND Tenderness at the navicular or 5th metatarsal OR inability to weight bear 7mg/kg with epinephrine, 5mg/kg without epinephrine

17. When is an X-ray series of the foot

18. What is the maximum dose of subcutaneous lidocaine that can be given with and without epinephrine? 19. Where should lidocaine with epinephrine NOT be used? 20. What is the most commonly used antibiotic for cellulitis? 21. What is the first line antibiotic for human bites?

Ears, nose, fingers, toes, and hose Ipenisl

Cefazolin/Ancef (IV) and Ceohalexin/Keflex (PO)

Amoxicillin +clavulinic acid

Toronto Notes 2008

Summary Key Questions

Emergency Medicine ER55

22. What is the resuscitation formula for someone with 2nd or 3rd degree burns? 23. What volume of fluid should be given in pediatrics as resuscitation? 24. What investigation must your order for afemale with abdominal pain? 25. How do you manage a patient with EtOH withdrawal? 26. If you suspect a patient is experiencing delirium tremens lOTI. approx. when was their last drink? 27. How you manage an asthma exacerbation in the ER? 28. What are the principles of management of DKA? 29. What is the acute treatment of CHF? 30. What are the headache (H/AI red flags?

Parkland formula: RL 4cc/kg/%BSA; give 1/2 in 1st 8 hours, 1/2 in next 16 hrs NS or RL 20cc/kg IV


Diazepam 20 mg IV/PO qlh until calm, thiamine 100 mg IV/IM/PO 00 x3d 3-5 days ago

Oxygen, beta-agonist If severe; anticholinergics, steriods, & prepare to intubate Rehydration wiNS IV, insulin RIV w/ D5W, potassium replacement Lasix, morphine, nitroglycerine, oxygen, and sitting upright Worst H/A of your life, new H/A after age 50, morning H/A, NN meningeal signs, visual changes, scalp tenderness, jaw claudication, worse w/bending or Valsalva Within 3 hours and NO evidence of hemorrhagic stroke

31. Within what window of time must thrombolytics be administered for stroke? 32. What is the risk of performing any cardiac procedures in the hypothermic patient? 33. What is asign of hypothermia, sometimes found on ECG? 34. For an infant <28 days with afever >38'C, what workup must be ordered? 35. A "slapcheek" distribution of a rash in a child is suggestive of what virus? 36. What is the role of the ED physician in management of the suicidal patient?

Ventricular fibrillation

Osborne IJ) waves

Full septic workup (CBC diff, blood C&S, urine C&S, CSF, CXR if indicatedl BEFORE antibiotics are administered Parvovirus

Assessing intent and organized plan, access to lethal means, patient safety; completion of Form 1when appropriate (Ontario onlyl

37. How long is aform 1valid? 38. What are the five principles of toxicology?

72 hours
Resuscitation, screening (draw blood), decrease drug absorption, increase drug elimination, administer available antidote "Mad as aHatter" - agitation/hallucinations "Hot as a hare" - hyperthermia "Blind as a bat" - dilated pupils "Dry as a bone" - dry skin "Red as a beet" - vasodilatation "The bowel and bladder lose their tone and the heart goes on alone" - urinary retention, tachycardia Alcoholics, anorexics, hyperemesis of pregnancy, malnutrition states Increased temp, CNS excitation, tachycardia, hypertension, resp, depression, pupil changes, CNS depression 4g Decontaminate Icharcoall, N-acetylcysteine

39. What are the signs and symptoms of an anticholinergic overdose?

40. What popluations are at risk for thiamine deficiency? 41. What are the signs and symptoms of an amphetamine overdose (sympathomimetics)?

42. Wnat is maximum daily dose of acetaminophen?
43.. What is the acute management of acetaminophen overdose?

ER56 Emergency Medicine


Toronto Notes 2008

Barash PG, Cullen BF, Stoelting RK (2001) 4th ed. Clinical Anesthesia. Lippincott, Philadelphia, USA. Collins VJ (1996). Physiologic and Pharmacologic Bases of Anesthesia. Williams &Wilkins, Pennsylvania, USA. ElliottWJ. (2001). Hypertensive emergencies. Crit Care Clin, 17(21:435-51. Epstein M. (1999). Diagnosis and management of hypertensive emergencies. Clin Cornerstone, 211):41-54. Ferri F(ed) 12001). Practical Guide to the Care of the Medical Patient. 5th ed. Mosby Kalant H, Roschlau WH (19981. Principles of Medical Pharmacology. Oxford University Press, NewYork, USA. Keim, Setal (20041. Emergency Medicine On Call. McGraw Hill.Marx (ed) (2002). Rosen's Emergency Medicine: Concepts and Clinical Practice. 5th ed. Mosby Roberts JR and Hedges JR (ed) (1998). Clinical procedures in emergency medicine. 3rd ed. WB Saunders Co. Tintinalli JE and Kelen GE (ed) 11999). Emergency medicine: A comprehensive study guide. 5th ed. McGraw-Hili Professional Publishing. Varon J, Marik P(2000).The DiagnosIs and management of hypertensive crises. Chest 2000;118(11:214-27 Vidt DG. (2001). Emergency room management of hypertensive urgencies and emergencies. J Clin Hypertens, 3(3):158-64. Wells PS, Anderson DR, Rodger M, et al. (2000). Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the simpliRED d-dimer. Thromb Haemost. 83: 416-20. Wells PS, Anderson DR, Rodger M, et al. (20001. Excluding pulmonary embolism at the beside without diagnostic imaging: Management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model. Ann Int Med. 135: 98-107. Woods, WA et al (ed) (2000).Emergency Medicine Recall. LippincottWilliams and Wilkins. Dargan p. Wallace C, Jones AL. An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg. Med J. 2002;19;206-209 Munro P. Management of eclampsia in the accident and emergency department. Emerg. Med. J. 2000;17;7-11 Frampton A. Reporting of gunshot wounds by doctors in emergency departments: A duty or a right? Some legal and ethical issues surrounding breaking patient confidentiality. Emerg. Med. J. 2005;22;84-86 Warden Cet al. Evaluation and management of febrile seizures in the out-of-hospital and errergency department settings. Ann Emerg Med.2003;41;215-222 American college of emergency physicians: clinical policy for the initial approach to patients presenting with altered mental status. Ann Emerg Med Feb 1999; 33: 251 - 280 Chu, P. Blunt AbdominalTrauma: current concepts. Current Orthopedics (2003) 17, 254-259.


Therese Kozminski, Maayan Seitelbach and Ferhan Siddiqi, chapter editors Lawrence Aoun and Sam Silver, associate editors Jeremy Adams, EBM editor Dr. Alice Cheng, staff editor
Basic Anatomy Review Major Endocrine Organs Glucose Regulation Disorders of Glucose Metabolism Pre-Diabetes Diabetes Mellitus (DM). Treatment of Diabetes Acute Complications Chronic Complications Macrovascular Complications Microvascular Complications Other Complications Hypoglycemia Metabolic Syndrome Dyslipidemias Overview of Lipid Transport Hypercholesterolemia Hypertriglyceridemia Combined Hyperlipidemia Dyslipidemia and the Risk for CAD Treatment of Dyslipidemias Obesity Pituitary Gland Pituitary Hormones Growth Hormone (GH) Prolactin (PRL) Leutinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Antidiuretic Hormone (ADH) Pituitary Pathology Thyroid Thyroid Hormones Tests ofThyroid Function and Structure Hyperthyroidism Graves' Disease Subacute Thyroiditis (Thyrotoxic Phase) Postpa rtu m Thyro iditis Toxic Adenomarroxic Multinodular Goitre Thyrotoxic Crisisrrhyroid Storm Hypothyroidism Hashimoto'sThyroiditis Riedel's StrumalWoodyThryoiditis Myxedema Coma Sick Euthyroid Syndrome (SES) Non-Toxic Goitre Thyroid Nodules Thyroid Malignancies



Adrenal Cortex Adrenocorticotropin Hormone (ACTH) Adrenocortical Hormones Tests of Adrenocortical Function Hyperaldosteronism Cushing's Syndrome Congenital Adrenal Hyperplasia (CAH) Hyperandrogenism Adrenocortical Insufficiency Adrenal Medulla Catecholamine Metabolism Pheochromocytoma Multiple Endocrine Neoplasm (MEN) Calcium Homeostasis Hypercalcemia Hypocalcemia Hyperphosphatemia Hypophosphatemia Hypermagnesemia Hypomagnesemia Metabolic Bone Disease Osteoporosis Osteomalacia and Ricketts Renal Osteodystrophy Paget's Disease of Bone






16 17


Male Reproductive Endocrinology .....49 Androgen Regulation Tests ofTesticular Function Hypogonadism Infertility Erectile Dysfunction Gynecomastia Common Medications Diabetes Medications Dyslipidemia Medications Thyroid Medications Metabolic Bone Disease Medications Summary Key Questions References




Toronto Notes 2008

Endocrinology El

E2 Endocrinology

Basic Anatomy Review

Toronto Notes 2008

Basic Anatomy Review
Major Endocrine Organs
Corticotropin-RH (CRH),
Gonadotropin-RH (GnRH),
Thyrotropin-RH (TRH),
Growth hormone-RH (GHRHj, Antidiuretic hormone (ADH), Oxytocin Note; RH = releasing hormone

Pituitary gland:
Anterior pituitary
Growth hormone (GH), Prolactin (PRU, Thyroid-stimulating hormone (TSH), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), Adrenocorticotropic hormone (AGH)

Thyroid gland:
Triiodothyronine (T3), Thyroxine (T4)

Parathyroid glands:
Adrenal cortex:

androgens, aldosterone Parathyroid hormome (PTH)



estrogen, progesterone

Figure 1. Endocrine System

Glucose Regulation


FFA release



Circulatory system



. . IPromotes ITZD = thiazolidinedione

FFA = free fatty acid


0< -

glucosidase inhibitor

Major target orgrans and actions of oraily administered antihyperglycemic agents in type 2 diabetes mellitus

Figure 2. Antihyperglycemic Agents
(Oral antihyperglycemic therapy for type 2 diabetes mellitus, Reprinted from CMAJ 18 January 2005; 172(21; 213-226 by permission of the publisher)

Toronto Notes 2008

Disorders of Glucose Metabolism

Endocrinology E3

Disorders of Glucose Metabolism
• • • • • 1-5% .rer year develop diabetes mellitus 50-80 Yo revert to normal glucose tolerance weight loss may improve glucose tolerance increased risk of developing macrovascular complications lifestyle modifications -.j.,progression to DM by 51%

Diagnostic Criteria
• impaired fasting glucose (IFG): fasting blood glucose (FBG) 6.1-6.9 mmol/L (110-125 mgJdL) • impaired gfucose tolerance (lGT): 2h 75 g oral glucose tolerance test (OGTT) 7.8-11.0 mmol/L (140-200 mgldL)

Diabetes Mellitus (OM)
• syndrome of disordered metabolism and inappropriate hyperglycemia secondary to an absolute/relative deficiency of insulin, or a reduction in biological effectiveness of insulin, or both

Diagnostic Criteria
• anyone of the following are considered diagnostic of diabetes: • presence of classic symptoms of DM (polyuria, polydipsia, polyphagia, weight loss, blurry vision, nocturia, ketonuria) PLUS random blood glucose (BG) ~11.l mmol/L (200 mgldL) • FBG ~7.0 mmol/L (126 mgldL) • 2h 75 g OGTT ~11.l mmol/L (200 mgldL)

Etiology and Pathophysiology
Table 1. Etiologic Classification of Diabetes Mellitus
Type 1diabetes (Immune-mediated ~ cell destruction, usually leading to absolute insulin deficiency) II. III. Type 2diabetes (ranges from predominantly insulin resistance with relative insulin deficiency to apredominantly insulin secretory defect with insulin resistance 2' to ~ cell dysfunction) Other specific causes of diabetes: a. Genetic defects of ~ cell function (e.g. MODY - Maturity-Onset Diabetes of theYoung) or insulin action b. Diseases of the exocrine pancreas: • pancreatitis, pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis c. Endocrinopathies: • acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma, hyperthyroidism
d, Drug-induced:
• Glucocorticoids, thyroid hormone, I)-adrenergic agonists, thiazides, phenytoin, c10zapine e, Infections: • congenital rubella, CMV, coxsackie
Genetic syndromes associated with diabetes:
• Down's syndrome, Klinefelter's syndrome,Tumer's syndrome Gestational Diabetes Mellitus


E4 Endocrinology

Disorders of Glucose Metabolism

Toronto Notes 2008

Table 2. Comparison ofType 1 and Type 2 Diabetes Mellitus

Onset Epidemiology

•usually <30 years of age •more common in Caucasians •rare in Asians, Hispanics, Aboriginals, and Blad<s •accounts for 5-10% of all OM •autoimmune •MZ twin concordance is 30-40% •associated with HLA dass II oR3 and oR4, with either being present in up to 95% of Type 1OM •certain oQ alleles also confer arisk •synergistic effects of genetic, immune, and environmental factors that result in pcell destruction resulting in impaired insulin secretion •autoimmune process is believed to be triggered by environmental factors (?viruses, bovine milk protein, nitrosurea compounds) •pancreatic cells are infiltrated with lymphocytes resulting in islet cell destruction •80% of Pcell mass is destroyed before features of diabetes present

•usually >40 years of age •increasing incidence in pediatric population secondary to obesity •more common in Blad<s, Hispanics, Aboriginals, Asians •accounts for >90% of all OM •complex &multifactorial •greater heritability than Type 1OM •MZ twin concordance is 70-90% •polygenic •non-HLA associated •impaired insulin secretion, peripheral insulin resistance (likely due to receptor and post receptor abnormalityl, and excess hepatic glucose production




Natural history


honeymoon period

'cell defect

'cell decompens.tion





after initial presentation, honeymoon period often occurs where glycemic control can be achieved with little or no insulin treatment as residual cells are still able to produce insulin •as those cells are destroyed, there is complete insulin deficiency

• early on, glucose tolerance remains normal despite insulin resistance as pcells compensate with increased insulin production • as insulin resistance & compensatory hyperinsulinism continue, the pcells are unable to maintain the hyperinsulinemic state which results in glucose intolerance and diabetes

Circulating autoantibodies

•islet cell Ab present in up to 60-85% I most common islet cell Ab is against glutamic acid decarboxylase (GAOl •up to 60% have Ab against insulin •personal history of other autoimmune diseases including Graves', myasthenia gravis, autoimmune thyroid disease, and pernicious anemia


Risk Factors

•fatty liver •age 240 y •abdominal obesity/overweight •hyperuricemia •first-degree relative with OM •raceJethnicity IBlad<, Aboriginal, Hispanic, Asian-American, Pacific Islander) •history of IGT or IFG 'HTN • dyslipidemia



Body Habitus Treatment

•normal to wasted •insulin

•typically overweight with increased central obesity •lifestyle modifications •oral antihyperglycemic agents •insulin therapy •hyperosmolar nonketotic hyperglycemic state •screen individuals with risk factors [see above)

Acute Complication Screening

•diabetic ketoacidosis

subclinical prodrome can be detected in first and second-degree relatives of those with Type 1OM by the presence of pancreatic islet autoantibodies

Toronto Notes 2008

Disorders of Glucose Metabolism

Endocrinology E5

Treatment of Diabetes
Diet • daily carbohydrate intake 50-55% of energy, protein 15-20% of energy and fat <30% of energy • maintain intake of both saturated and polyunsaturated fats <10% of total calories each • limit sodium, alcohol and caffeine • Type 1: carbohydrate counting is used to titrate insulin regimen • Type 2: weight reduction Lifestyle • regular physical exercise can improve insulin sensitivity, and lower lipid concentrations and blood pressure • smoking cessation Medical Treatment - Oral Antihyperglycemic Agents (Type 2 OM) • initiate oral antihyperglycemic therapy within 2-3 months if lifestyle management does not result in glycemic control • initiate immediately if HbAlC >9.0% • for details on each oral antihyperglycemic agent, please see Common Medications
Clinical assessment and initiation of nutrition therapy and physical activity

Intensive illlUlin therapy foI'Type 1 OM
(NfJM 1993;329 (14):9n-861

Study. Randomized controlled triallmean follow
­ up 6.5 years).
I'IItientI: 1441 patients with Type 1OM (mean
age 27 y; 53% men; 96% white), stratified accord
­ ing to retinopathy and nephropathy at baseline
(mild vs. nonel. Exclusions included hypenension,
hypercholesterolemia, severe complications of
OM, and severe medical conditions.
1rIIetwJnlion: Conventional therapy (1-2 insulin
injections per day, daily se~-monitoring of blood
glucosel vs.lntensive therapy (3+ insulin injec­
tions per day, se~-monitoring of blood glucose 4+
times per day, with dosage adjusted to meet tar­

gets). /IIIJin ~ retinopathy lfundus photo­
graphs), nephropathy (urinary albumin excretion >40 mg/24hr), neuropathy (abnormal neuro exam). 1IeIuIlI: Patients in the intensive therapy group had lower mean HbA1C levels (p<O.OO1). ~ RRR %195%C1l Retinopathy 63152-711 Nephropathy 39121-521 Neuropathy 60 (38-741 Concllllion: Intensive blood glucose control delayed the onset and reduced the progression of microvascular complications in type 1diabetes.

Mild 10 moderate hyperglycemia (HbA1C < 9.0%)

Marked hyperglycemia (HbA1C':: 9.0%)


Blood gIucoIe control in Type 2 OM - UKPDS

33 (Lancet 1998;352:837·531
Study. Randomized controlled triallmean follow­
up 10 years).
Patients: 3867 patients with newly diagnosed
Type 2OM (mean age 53 y, 61% men, 81% white,
mean fasting plasma glucose IFPGI6.1-15.0
mmolll). Exclusions included severe cardiovascu·
lar disease, renal disease, retinopathy, and others,
1ntBIwntion: Intensive treatment with asu~ony·
lurea or insulin Itarget FPG <6 mmolill vs. con
­ ventional treatment with diet alone (target FPG
<15 mmolll without hyperglycemic symptomsl.
lIIIlIin ~ Diabetes-related endpoints IMI,
angina, hean failure, stroke, renal failure, amputa
­ tion, retinopathy, blindness, death from hyper­
glycemia or hypoglycemia), diabetes-related
death, and all-cause monality.
1IeIuIlI: Patients allocated to intensive treatment
had lower median HbA1C levels (p<O.001),
~ RRR %Ip valuel
Diabetes-related endpoint 12 (0.0291
Diabetes-related death 10 10.34)
AII-cause monality 6(0.441
Patients allocated to intensive therapy had more
hypoglycemic episodes and greater weight gain.
ConcIIIIion: Intensive blood glucose control
reduces microvascular, but not macrovascular
complications inType 2OM.


Overweight (BMI


Non-overweight (BMI <2S Kglm 2)

Biguanide (e.g. metformln) alone or in combination with 1 of: -insulin sensitizer (e.g. TZD) -insulin secretagogue (e.g. sulfonylurea) -insulin -alpha-glucosidase inhibitor (e.g. acarbose)

IF NOT AT TARGET: Add a drug from a different class or Use Insulin alone or in combination with: ·biguanide (e.g. metformin) -insulin sensitizer (e.g. thiazolidinediones (TZO)) -insulin secretagogue (e.g. sulfonylurea) -aloha-<llucosidase inhibitor le.a. acarbose)

1 or 2 antihyperglycemic agents from different classes: -biguanide (e.g. metforrmn) -insulin sensitizer (e.g. TZO) -insulin secretagogue (e.g
-alpha-glucosidase inhibitor
(e.~. acarbosel


2 antihyperglycemlc agents from different classes:

Basal and/or preprandial

·biguanide (e.g. metformin) -insulin sensitizer (e,g. TZD)
-insulin secretagogue (e.g.

-alpha-glucosidase inhibitor
(e.g. acarnose)

IF NOT ATTARGET: Add an oral antlhyperglycemlc agent from a different class or insulin

Do not use combination of insulin and insulin sensitizers (e.g. TZO) because of increased risk of edema or CHF Do not add an insulin secretagogue if using preprandial insulin

Intensify Insulin regimen or
-biguanide (e.g. metformin)
-insulin secretagogue (e.g.
su~on~urea) ..
-insulin sensitizer (e.g. TZO)
·alpha-glucosidase inhibitor (e.g. acartlose)

Timely adjustment to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target HbA 1C within 6 to 12 months

Figure 3. Approach to Treatment of Hyperglycemia in Type 2 DM

(used with permission from Can J Diabetes. 2003; 27(suppI2): 539)

Insulin (see Figure 4) • used for Type 10M, may be used in Type 2 OM at any point in treatment • doses adjusted based on individual patient needs to meet target glycemic control • administration: subcutaneous injections, continuous subcutaneous insulin infusion
pump, IV infusion (regular insulin only)
• preparations given as bolus: ultra rapid, rapid • preparations given as basal: intermediate, long-acting, long-acting analogues • insulin mixtures (%R and %NPH): 10/90, 20/80, 30/70, 40/60, 50/50 • premixed analogues: Humalog Mix 25®, Novemax 30® • estimated total daily insulin requirement: 0.5-0.7 units!kg Dosing Schedule 1. Oral agent + basal insulin (NPH, glargine, detemir) (Type 2 only) • starting with 10 units qhs, titratE' up until FBG <7.0 mmol/L
2. Twice daily injection with insulin mixture • insulin mixture used depends on the distribution of carbohydrates in meals but usually start with 30/70 • estimate total daily insulin requirement then split dose into 2/3 in AM and 1/3 before supper • AM bolus targets pre-lunch BG and AM basal targets pre-supper BG • PM bolus targets bedtime BG and PM basal targets FBG

Ilosiglitazone IIld Adwne Cardiac Evena
(N Engl J Med2007; 356(241:2457·71)
Study. Meta-analysis of 42 RCTsthat included a
group of patients taking rosiglitazone and agroup
that did not.The trials had to be 24 weeks long
and include data about myocardial infarction and
death from cardiovascular events.
1181u1fJ: There was asignificant increase in
myocardial infarctions in the group receiving
rosiglitazone lodds ratio 1.43 95% CI1.03-1.98,
p:O.031. The rosiglitazone group had ahigher rate of death from cardiovascular causes that was of borderline significance (odds ratio 7.64 CI 0.98­ 2.74, p:O.06I. ~:There was asignificantly higher rate of MI in the rosiglitazone group and an increase in death from cardiovascular causes that was of bor­ derline significance. Funher RCTsare needed to precisely define the cardiovascular risks of rosigli. lazone. Authors suggest that patients and physi­ cians •consider' the potential risks of rosiglita­ zone in the treatment of diabetes mellitus type 2.

E6 Endocrinology

Disorders of Glucose Metabolism

Toronto Notes 2008

Canadlan DiabeteI Guidelinel 2003

HbA1C Fasting plasma glucose <0.07


• disadvantages: requires rigid meal timing and carbohydrate content; limited ability to respond to increased or decreased BG 3. MDI (multiple daily injections of insulin) • estimate total daily insulin requirement then take 20% of this daily dose before breakfast, lunch, and dinner using regular, lispro or aspart (total 60%) • the remaining 40% is given as NPH, glargine or detemir at bedtime • advantages: flexible meal timing and carbohydrate content; ability to respond to increased or decreased Be, or planned exercise • disadvantages: multiple injections, requires motivation

4-7mmoVL 4-6mmoVL

2hpost 5-10mmoVL 5-8mmoVL prandial glucose


as per high or moderate risk group <130180

Table 3. Kinetics of Different Insulin Preparations
Insulin Bolus Lispro, Aspart Brand Names Humalog® Novolog® Humulin® Novolin Toronto® Duration Very rapid Rapid Onset lh) 5-10 min 1/2 -1 Peak (h) 30-40 min 1-3 Duration of action (h) 2-3 5-7

Blood pressure

Blood ~ control inType 2 OM­ UKPDS38 IBMJ 1998;317:703-13) Study. Randomized controlled triallmean follow­ up 8.4 yearsl. PItilInII: 1148 hypertensive patients withType 2 OM (mean age 56 y; 55% men; 87% white, mean BP at entry 100'34 mm Hg). Exclusions included severe cardiovascular disease, renal disease, retinopathy, and others 1ntemnlIon: Tight control of BP (target BP <150185 using captopril or atenolol, plus other drugs as neededl, vs. less tight controlltarget BP <1501105 using drugs as needed). III.m ~ As for UKPDS 33.

Regular IRI. Toronto Basal NPH/(Nj Ultralente lUI Glargine Detemir

Humulin N® Novolin NPH(Rj Humulin U® Novolin Ultralente@ Lantus®

Intermediate Long Long Long

2-4 4-5 2-4 2-4


14-18 18-28 18-20 16-20

RRR %10 valuel
Diabetes-related endpoint 2410.0046)
Diabetes-related death 3210.0191
Stroke 4410.013)
Microvascular endpoints 37 (0.00921
Condus/on:Tigtlt BP control reduces diabetes­
related morbidity and mortality in hypertensive






T,plc.Bnsulin dosing


Figure 4. Duration of Activity of Different Insulins

Glucose Monitoring
• frequent self-monitoring and recording of BG is now standard management • HbA1C reflects glycemic control over 3 months and is a measure of patient's long-term diabetes control • HbA1C 2:10% indicates poor control • American Diabetes Association (ADA) suggests HbA1C <7.0%, American Association of Clinical Endocrinologists (AACE) <6.5% • Canadian Diabetes Association (CDA) guidelines: target <7.0%, optimal <6.0%




36 Uld of3/Jl70
(_"""Rand 709b NPH InKJllnj

[m~~"H] [,n~_I] (24UlnAM) ~~)
Insulin dosing regimen


Variable Insulin Dose Schedule ("Sliding/Supplemental/Correction Scale")
• patient takes usual doses of basal insulin but varies doses of bolus insulin based on BG reading at time of dose • use baseline bolus insulin dose when within BG target range; add or subtract units when above or below target • commonly used in hospital or in perioperative management of diabetes • allows acute corrections but poor control overall ---+ reactive correction after the period of hypo or hyperglycemia rather than anticipating the BG level

Conversion Chart for percentage HbA,c to average blood sugar control
Average blood Hemoglobin Ale

sugar level Immolitl

1% HbA,cI

17.12% \~ 11% 14 12
10 8

Insulin Pump Therapy
• external battery-operated pump continuously delivers basal dose of lispro or aspart through small subcutaneous catheter • at meals, patient programs pump to deliver extra insulin bolus • basal dose may be increased or decreased based on activity, sleep, etc. • advantages: flexibility in meals and activity • disadvantages: very expensive, increased risk of DKA if pump inadvertently disconnected, frequent BG testing required


1 .......... ,8%

0plimIl -



Conversion mart adapted from Nathan DM et al. The clinical information value of' glycosyiMed hemoglobin ,"'v. NEJM 1984;310:34H.

Toronto Notes 2008

Disorders of Glucose Metabolism

Endocrinology E7


Table 4. Acute Complications of Diabetes Mellitus: Hyperglycemic Comatose States
Diabetic Ketoacidosis IDKA) • usually occurs in Type 1 DM • insulin deficiency with l' counterregulatory hormones (glucagon, cortisol, catecholamines, GH) • can occur with insulin lack (noncompliance, peor dosage, 1st presentation) or increased stress (surgery, infection, exercisel • unrestricted hepatic glucose production -> hyperglycemia -> osmotic diuresis· dehydration and electrolyte disturbance -> ,j. Na Ipseudohypenatremial • fat mobilization -> l' FFA • ketoacids -> metabolic acidosis • severe hyperglycemia results in exceeding the renal threshold for glucose and ketone reabsorption -> glucosuria and ketonuria • total body Kdepletion but serum Kmay be normal or elevated 2' to shift from ICF to ECF due to insulin lack, l' plasma osmolality • total body PO, depletion
• • • • • • • preceding polyuria, po~dipsia, pelyphagia with marked fatigue, nausea, vomiting dehydration LOC may be ,j. with high serum osmolality losm >330 mmoULI dehydration lorthostatic changesl abdominal pain fruity smelling breath Kussmaul's respiration

Com~lications -------~--


Hyperglycemic Hyperosmolar Nonketotic State IHONKj
• occurs in Type 2DM • often precipitated by sepsis, stroke, MI, CHF, renal failure, trauma, drugs (glucocorticoids, immunosupressants, phenytoin, diureticsl, dialysis, recent surgery, burns • partial or relative insulin deficiency decreases glucose utilization in muscle, fat, and liver while inducing hyperglucagonemia and hepatic glucose production • presence of asmall amount of insulin prevents the development of ketosis by inhibiting lipelysis • characterized by hyperglycemia, hyperosmolality, and dehydration without ketosis • more severe dehydration compared to DKA secondary to more gradual onset and l' duration of metabolic decompensation plus the impaired fluid intake which is common in bedridden or elderly • volume contraction -> renal insufficiency -> l' hyperglycemia, l' osmolality-> shift of fluid from neurons to ECF -> mental obtundation and coma • onset is insidious -> preceded by weakness, pelyuria, pe~dipsia • history of decreased fluid intake • history of ingesting large amounts of glucose containing fluids • dehydration lorthostatic changesl • ,j. LOC -> lethargy, confusion, comatose • Kussmaul's respiration is absent unless the underlying precipitant has also caused ametabolic acidosis

Clinical Features


• l' BG (11-55 mmollL, 198-990 mgldLI.,j. Na [spurious 2'to hyperglycemia -> for every l' in BG by 10 mmoUL (180 mg/dL) there is a,j. in Na by 3mmollL) • normal or l' K, ,j. HCO~ l' BUN, l' Cr, ketonemia,,j. PO, • 1'osmolality

• l' BG (44,4-1332 mmol/L, 800-2400 mgldLI
• in mild dehydration, may have hypenatremia (spurious 2' to hyperglycemia -> for every in BG by 10 mmol/L 1180 mgldLlthere is a,j. in Na by 3mmoUL) • if dehydration progresses, hypernatremia • ketosis usually absent or mild if starvation occurs • l' osmolality • metabolic acidosis absent unless underlying precipitant leads to acidosis (e,g, lactic acidosis in Mil • -ve for ketones unless there is starvation ketosis • glycosuria • same resuscitation and emergency measures as DKA • rehydration: IV fluids: 1Uh NS initially evaluate corrected serum Na if serum Na high or normal, swhch to 0,45% NS 14-14 mllkglhl if serum Na low, maintain NS 14-14 mllkglhl when serum BG reaches 13,9 mmolJ1125O mgldLI switch to D5W • Kreplacement: less severe Kdepletion compared to DKA if serum K<3.3 mmoVL, hold insulin and give 40 mEq K replacement if K· is 3,3-5.4, give KC120-30 mEq/L IV fluid if serum K?5,5 mmoVL, check Kevery 2h • search for precipitating event • insulin therapy: use only regular insulin IRI initially load 0,15 UI kg body weight insulin Rbolus maintenance 0,1 Ulkglh insulin Rinfusion or 1M check serum glucose hourly in general lower insulin requirement compared to DKA

ABG Urine Treatment

• metabolic acidosis with l' AG plus possible 2' respiratory alkalosis • if severe vomitingl dehydration there may be ametabolic alkalosis • +Ve for glucose and ketones • immediate resuscitation and emergency measures if patient is stuperous or comatose • monitor degree of ketoacidosis with AG not BG or serum ketone level • rehydration: 1Uh NS in first 2hrs after 1st 2L, 300-400 mllh 0,45% NS once BG reaches 13,9 mmoVL 1250 mgldLI then switch to D5W to maintain BG in the range of 139 -16,6 mmollL 1250-300 mg/dLi • insulin therapy: critical to resolve acidosis, not hyperglycemia use only regular insulin (RI initially load 0,15 UI kg body weight insulin Rbolus maintenance 0,1 Ulkglh insulin Rinfusion check serum glucose hourly • Kreplacement: as acidosis is corrected, hypekalemia may develop when K3,5- 5.5 mmoUL add KCL 3O-4OmEq/L IV fluid to keep Kin the range of 3,5-5 mEq/L • HC03, if pH <10 or if hypotension, arrhythmia, or coma is present with apH of <7.1 give HC03 in 0,45% NS do not give if pH >7,1Irisk of metabolic alkalosis !I can give in case of life-threatening hyperkalemia • ±mannitol (for cerebral edemaI • 2-5% mortality in developed countries • serious morbidity from sepsis, respiratory complications, thromboembolic complications, and cerebral edema


• overall mortality approaches 50% primarily because of the older patient population and underlying etiology


The 61's Precipitating DKA: Infection
Ischemia or Infarction
Iatrogenic (glucocorticoids)
Insulin missed
Intra-abdominal process
(e,g. pancreatitis, cholecystitis)

Average fluid loss runs at 3-6 L in DKA, and 8-10 L in HONK.

E8 Endocrinology

Disorders of Glucose Metabolism

Toronto Notes 2008

Chronic Complications Macrovascular Complications
• increased risk of coronary ilrtery disease (CAD), ischemic stroke, and peripheral vascular disease (PVO) secondary to accelerated atherosclerosis • coronary artery disease • risk of myocardial (MI) is 3-')x higher in diabetes compared to age matched controls • CAD is the leading cause of death in Type 2 OM • patients with OM are considered as "high risk" under the risk stratification for CAD (see Dyslipidemias, E12) • ischemic stroke • risk of stroke is approximately 2.5" higher in diabetes • level of glycemia is either a risk factor of stroke or a predictor of a poorer outcome in patients who suffer a stroke • HbAIC level is a significant and independent predictor of the risk of stroke • peripheral vascular disease • manifested by intermittent claudication in lower extremities, intestinal angina, foot ulceration • gangrene in the feet is 30x higher in DM compared to age matched controls • diabetics have a 15x higher risk of lower extremity amputation • treatment • reduction of comorhid risk factors (e.g. hypertension, smoking cessation) • tight glycemic control • tight low density lipoprotein (LDL) cholesterol control • low-dose ASA in patients with ("VD or increased likelihood of CV events • ACE inhibitor in high-risk vatients

Microvascular Complications
DIABETIC RETINOPATHY (see also Ophthalmology, OP38)
• • • • Type 1 OM - 25% affected at 5 years, 100% at 20 years Type 2 OM - 25% affected at Dx, 60% at 20 years leading cause of blindness in North America between the ages of 20-74 most important factor is disease duration
------..... Altered vascular penneabilicy,
--. 1'Glucose -~ Loss of capillary pericyte. basement membrane thickening, retinal vessel closure
breakdown of blood retinal barrier~


Microaneurysms"'------ Retinal hemo;hage .. (dot and blot)
Retmal vascular leakage


Macular edema

• •



----... Hard exudates



R...:tJIlal traC(]OIl

vascularfibrosis~ Iris neovascularization .. .. Floaters NeovascuJar

h factors


Nerve fibre layer infarcts (cotton wool spots), venous cbanges (shunts and beading), capillary non perfusion.

Retinal delachmfnt

Figure 5. Pathophysiology of Diabetic Retinopathy

Clinical Features
• nonproliferative • asymptomatic but with macular involvement may impair vision • microaneurysms. hard exudates, dot and blot hemorrhages • preproliferative • 10-40% progress to proliferative within 1 year • macular edema, cotton wool spots, venous shlmts and beading, intra retinal microvascular abnormalities (IRMA)

Toronto Notes 2008

Disorders of Glucose Metabolism

Endocrinology £9

• proliferative • neovascularization, fibrous scarring, vitreous hemorrhage, retinal detachment • great risk for loss of vision secondary to vitreous hemorrhage (floaters) and/or
retinal detachment

Treatment and Prevention
• • • • • tight glycemic control (delays onset, decreases progression) if hypertension is present, treat aggressively panretinallaser photocoagulation for treatment of neovascularization vitrectomy annual follow-up visits with an eye specialist (optometrist or ophthalmologist);
examination through dilated pupils whether they are symptomatic or not (immediate
referral after diagnosis of Type 2 DM; 5 years after diagnosis of Type 1 DM)
• interval for follow-up should be tailored to severity of retinopathy

DIABETIC NEPHROPATHY (see Nephrology. NP35) Epidemiology
• diabetes-induced renal failure is the most common cause of renal failure in North
• 20-40% of persons with Type 1 DM (after 5-10 years) and 4-20% with Type 2 DM have
progressive nephropathy

• thickening of capillary basement membrane and glomerular mesangium resulting in
glomerulosclerosis and renal insufficiency
• diffuse glomerulosclerosis is more common than nodular intercapillary
glomerulosclerosis (Kimmelstiel-Wilson lesions)

• random urine test for albumin to creatinine ratio (ACR) plus urine dipstick test for all
Type 2 DM patients at diagnosis, then annually, and for postpubertal Type 1 DM
patients with ~5 years duration of DM

Clinical Features
• initial changes include microalbuminuria, increased GFR (up to 140%), enlarged
• microalbuminuria: ACR of >2.0 mglmmol (men) or >2.8 mg/mmol (women) • macroalbuminuria: ACR of >20.0 mglmmol (men) or >28.0 mglmmol (women) • over 15 years progresses to cause hypertension, persistent proteinuria
(macroalbuminuria), nephrotic syndrome, and renal failure
• a high HbAlC is an independent risk factor for progression to microalbuminuria

Treatment and Prevention
• tight glycemic control • tight blood pressure control <130/80; angiotensin converting enzyme (ACE)
inhibitors (shown to reduce nephropathic complications) and calcium channel blockers
• numerous studies have shown that ACE inhibitors reduce the level of albuminuria and
reduce the rate of progression of renal disease in normotensive and hypertensive
patients with Type 1 or Type 2 DM
• use of ACE inhibitors in this setting appears to be a class effect and thus the
choice of agent will depend upon cost and compliance issues; dose varies
according to agent chosen
• there is good evidence that angiotensin receptor blockers (ARBs) also provide a
comparable reno-protective effect, though there have not been many trials that
compare ARBs and ACE inhibitors head-to-head in delaying or reducing albuminuria
• Type 1 DM if normotensive or hypertensive and patient has microalbuminuria or
macroalbuminuria -> ACE inhibitors 1st line
• Type 2 DM -> if normotensive or hypertensive and patient has microalbuminuria or
macroalbuminuria -> ARBs 1st line or ACE inhibitors if creatinine clearance (CrCl)
>60 ml/min; ARB if CrCl ::;60 ml/min
• limit use of nephrotoxic drugs and dyes • protein restriction (controversial) • renal failure may necessitate hemodialysis and renal transplant

HI) £ndocrinology

Disorders of Glucose Metabolism

Toronto Notes 2008

DIABETIC NEUROPATHY (see Neurology. N42) Epidemiology
• approximately 50% of patients within 10 years of onset of Type 1 DM and Type 2 DM

• mechanism poorly understood • acute cranial nerve palsies and diabetic amyotrophy are thought to be due to ischemic infarction of involved peripheral nerve • the more common motor and sensory neuropathies are thought to be related to metabolic or osmotic toxicity secondary to increased sorbitol and/or decreased myoinositol (possible mechanisms include accumulation of advanced glycation end (AGE) products, oxidative stress, protein kinase C, nerve growth factor deficiency) • can have peripheral sensory neuropathy, motor neuropathy, or autonomic neuropathy

• 128 Hz tuning fork or 10 g monofilament at diagnosis and annually in people with Type 2 DM and after 5 years duration of Type 1 DM

Clinical Features
Table 5. Clinical Presentation of Diabetic Neuropathies
Peripheral Sensory Neuropathy
• paresthesias (tingling, itching!, neuropathic pain, radicular pain, numbness, decreased tactile sensation • bilateral and symmetric with decreased perception of vibration and painltemperature; especially true in the lower extremities but may also be present in the hands • decreased ankle reflex • symptoms may first occur in entrapment syndromes e.g. carpal tunnel • neuropathic ulceration of foot

Motor Neuropathy

Autonomic Neuropathy

• less common than sensory • postural hypotension. resting fixed neuropathy tachycardia, decreased response to Valsalva maneuver • delayed motor nerve conduction and muscle • gastroparesis and alternating weakness/atrophy diarrhea and constipation • urinary retention and erectile dysfunction • may involve one nerve trunk (mononeuropathy! or more (mononeuritis multiplex) • some of the motor neuropathies spontaneously resolve after 6-8 wks • reversible eN palsies: III (ptosis/ophthalmoplegia), Vllinability to laterally deviate eye!, and VII (Bell's palsyl • diabetic amyotrophy: refers to pain, weakness, and wasting of hip flexors or extensors

Treatment and Management
• tight glycemic control • tricyclic antidepressants (e.g. amitriptyline), pregabalin, anti-epileptics (e.g. carbamazepine, gabapentin), and capsaicin for neuropathic pain syndromes • foot care education • Jobst fitted stocking and tilting of head of bed may decrease symptoms of orthostatic hypotension • treat gastroparesis with domperidone and metoclopramide (dopamine antagonists), erythfomycin (stimulates motilin receptors) • medical, mechanical and surgicaltrealrnent for erectile dysfunction: PDE-5 inhibitors (e.g. sildenafil, tadelafil, vardenafil), intracorporeal injections of vasoactive drugs, vacuum therapy

other Complications
• diabetic dermopathy: atrophic brown spots commonly in pretibial region known as "shin spots" secondary to increased glycosylation of tissue proteins or vasculopathy • eruptive xanthomas secondary to increased triglycerides (TG) • necrobiosis lipoidica diabeticorum: rare complication characterized by thinning skin over the shins allowing visualization of subcutaneous vessels

Bone and Joint Disease
• juvenile cheiroarthropathy: chronic stiffness of hand secondary to contracture of skin over joints secondary to glycosylated collagen and other connective tissue proteins • Dupuytren's contracture • bone demineralization: bone density 10-20% below normal • frozen shoulder

Toronto Notes 2008

Disorders of Glucose Metabolism

Endocrinology Ell

• subcapsular and senile cataracts secondary to glycosylated lens protein or increased
sorbitol causing osmotic change and fibrosis

• see Infectious Diseases

• characterized by Whipple's Triad: 1. serum glucose below 2.5 mmol/L (45 mg/dL) in males and 2.2 mmol/L (40 mg/dL) in females 2. neuroglycopenic symptoms or adrenergic symptoms (autonomic response) 3. relief provided by administration of glucose



Treatment of Acute Hypoglycemic Epiaode (Blood Glucose <4.0 mmolll) in the Awake

Patient Ie.g. able to self·treat)

Etiology and Pathophysiology
Table 6. Common causes of Hypoglycemia
Fasting Hyperinsulinism
• exogenous insulin • sulfonylurea reaction • autoimmune hypoglycemia (autoantibodies to insulin or insulin receptorl • pentamidine • pancreatic pcell tumour - insulinoma

11 Eat 15 gof carbohydrates (CHOI
(e.g. 3 x5gglucose tablets: 3packets sugar dis­
solved in water; 3/4 cup of juicel


Nonfasting (Reactive) Without hyperinsulinism
• • • • • • severe hepatic dysfunction chronic renal insufficiency hypocortisolism alcohol use non-pancreatic tumours inborn error of carbohydrate metabolism, glycogen storage disease, gluconeogenic enzyme deficiency • alimentary • functional • noninsulinoma pancreatogenous hypoglycemic syndrome • occult diabetes • leucine sensitivity • hereditary fructose intolerance
• galactosemia
• newborn infant of diabetic mother

21 Wait 15 minutes

3) Retest Blood Glucose IBG)

41 Repeat steps 1-3 until BG >5 mmoVL

51 Eat next scheduled meal. If next meal is>1hour away, eat snack including 15 gof CHO and protein




Clinical Features
• adrenergic symptoms (typically occur first; caused by autonomic nervous system
• palpitations, sweating, anxiety, tremor, tachycardia, hunger • neuroglycopenic symptoms (caused by .J.-activity of CNS) • dizziness, headache, clouding of vision, mental dullness, fatigue, confusion, seizures, coma

Hypoglycemia Unawareness: (Type 1OM »>Type 2OM) patient remains asymptomatic until severe­ ly hypoglycemic levels are reached
• ~Iucagonlepinephrine response • hx of repeated hypoglycemia or low HbA1C • autonomic dysfunction


• Electrolytes, BUN/creatinine, LFTs, drugs/toxins




• • • • for fasting hypoglycemia, must treat underlying cause for reactive hypoglycemia, frequent small feeds see Emergency Medicine. ER30 bloodwork to be drawn when patient is hypoglycemic (i.e. during hospitalized 72-hour fast): serum ketones, insulin, proinsulin, C-peptide, cortisol, and GH • treatment of hypoglycemic episode in the unconscious patient or patient NPO • D50W 50 mL (1 ampule) IV or 1 mg glucagon SC (if no IV available) • may need ongoing glucose infusion once BG >5mmol/L

Use C-peptide levels to distinguish
between exogenous and endogenous
source of hyperinsulinemia

l' =endogenous

-.v or normal =exogenous

Metabolic Syndrome
• defined by having three or more risk factors (see Table 7) • postulated syndrome related to insulin resistance associated with hyperglycemia, hyperinsulinemia, hypertension, central obesity, and dyslipidemia
• obesity aggravates extent of insulin resistance
• complications include atherosclerosis, CAD, Ml, and stroke • not to be confused with syndrome X related to angina pectoris with normal coronary arteries (Prinzmetal angina)

E12 Endocrinology

Disorders of Glucose MetabolismIDyslipidemias

Toronto Notes 2008

Table 7. Identification criteria for Metabolic Syndrome (NECP ATP 111*)
Risk Factor Defining level
Abdominal Obesity Men Waist Circumference>102 cm (40.2 inches) Women Waist Circumference >88 cm (34.6 inches) Triglyceride level ~1.7 mmol/L (150.4 mg/dL) HDL-C level Men <1.0 mmoliL Women <1.3 mmol/L Blood pressure ~130/85 mm Hg Fasting glucose level 5.7-7.0 mmol/L 1104.4-126.1 mg/dL)
'National Cholesterol Education Program AdultTreatment Panel III.
Note: ethnospecific waist circumference values also available linternational Diabetes Federation)

Definition • metabolic disorders characterized by elevations of fasting plasma cholesterol, and/or TG, and/or low HOL

Overview of Lipid Transport
• lipoproteins are spherical complexes that consist of a lipid core surrounded by a shell of water-soluble proteins and phospholipids • lipoproteins transport lipids within the body
Table 8. Lipoproteins
Lipoprotein Exogenous pathway Chylomicron Endogenous Pathway VLDL

• B·48, C, E, A·I, A·II, A·IV • B·100, C, E • B·100, E • B·100

• transport of dietaryTG from gut to adipose tissue and muscle • transports hepatic synthesizedTG from liver to adipose tissue and muscle • product of hydrolysis ofVLDL by lipoprotein lipase resulting in depletion ofTG core but enriched in cholesterol esters • formed by further removal of residualTG from IDL core by hepatic lipase resulting in greater enriched particles with cholesterol esters • transports cholesterol from liver to peripheral tissues • transports cholesterol from peripheral tissues to liver • acts as areservoir for apolipoproteins


• A-I, A-II, C, E

Figure 6. Exogenous and Endogenous Biosynthetic Lipid Pathways

Toronto Notes 2008


Endocrinology E13

Table 9. The Primary Hypercholesterolemias
Hypercholesterolemia Epidemiology Etiology! Labs



Familial Hypercl1olesterolemia !Fre{ierickson Type lIal

heterozygote: 1/500 in US population

•autosomal dominant with high penetrance •deficiency in Ihe normal LDL receptor on cell membranes


•tendinous xanthomatosis (acl1illes, patellar, and extensor tendons of handl •arcus corneae •xanthelasma •heterozygotes: premature CAD, 50% nsk of MI in men by age 30 •homozygotes: manifest CAD and other vascular disease early in cI1ildhood and can be fatal (<20 yl if untreated •asymptomatic until vascular disease develops

•heterozygotes: improvement of LDL with dual combination of HMG CoA reductase inhibitors, niacin, or bile acid sequestrants •homozygotes: partial control with portacaval shuntorLDLapheresis in conjunction with niacin; large dose atorvastatin is modestly effective

Polygenic Hypercholesterolemia IFre{ieridson Type lIal

•Most common •Few mild inhented defects in cI1olesterol


•HMG CoA reductase inhibtors, bile acid sequestrant, niacin

• • • • • • • diet anorexia nervosa hypothyroidism cholestatic liver disease (primary biliary cirrhosis) nephrotic disease monoclonal gammopathy drugs (cyclosporin, diuretics, carbamazepine)



Table 10. The Primary Hypertriglyceridemias
Hypertriglyceridemia Etiology! Pathophysiology Labs



Familial Lipoprotein Lipase deficiency IFrederickson Type II

• autosomal recessive deficiency in the lipoprotein lipase or its cofactor

l' cI1ylomicrons, moderate l' in

• dietary to -J, fat intake to <10% of • hepatosplenomegaly • splenic infarct total calories •anemia, granulocytopenia, thrombo­ cytopenia 2' to hypersplenism • pancreatitis • lipemia retinalis •eruptive xanthomata • eruptive xanthomata • lipemia retinalis • recurrent epigastric pain • premature CAD • early adulthood develop syndrome of obesity, hypertriglyceridemia, hyperinsulinemia &hyperuricemia
.,j, dietary fat intake

FaMilial Hypertriglyceridemia (Frederickson Type IVI

• several genetic defects resulting in l' hepatic VLDL synthe­ sis or ,j, removal of VLDL


•abstain from EtOH 'fibrate or niacin

obesity/metabolic syndrome alcohol diabetes mellitus drugs (corticosteroids, estrogen, hydrochlorothiazide, retinoic acid, ~ blockers without intrinsic sympathomimetic action (ISA), anti-retroviral drugs) • chronic liver failure • hepatitis • hypothyroidism • • • •

E14 Endocrinology


Toronto Notes 2008

• polyclonal and monoclonal hypergarnmaglobulinemia • glycogen storage disease • hypopituitarism and acromegaly


Combined Hyperlipidemia
Table 11. Primary Combined Hvperlipidemias
Hyperlipidemia Familial Combined Hyperlipidemia (Frederickson Type lib) Epidemiology • most common form of hyperlipidemia EtiologylPathogenesis Labs Clinical Presentation Treatment • xanthelasma • CAD and other vascular disease • dietary • niacin, fibrates • HMG CoA reductase inhibitors • weight reduction • ,j, fat, cholesterol, and EtOH in diet • fibrate, HMG CoA reductase inhibitors. niacin

'over,population ofVLDL and 1'LDL associated l' LDL 2' to excess hepatic 1'VLDL synthesis of apolipoprotein B • autosomal dominant • abnormal apoprotein F , IDL , VLDL

Dysbetalipoproteinemia (Frederickson Type III)

• tuberous, eruptive, planar xanthomata "GT • CAD and PVD

Dyslipidemia and the Risk for CAD
Intenlive lipid lowering in CAD: TNT
(NEJM 2005;352(141:1425-35!
Study Multicentre, randomized, double
blinded trial with median follow·up of 4,9
",lienk 10,001 patients with CAD and LDI,


• • • •

l' LDL is a major risk factor for atherosclerosis and CAD l' LDL is associated with l' risk of cardiovascular disease and mortality l' HDL is associated with wcardiovascular disease and mortality hypertriglyceridemia is an independent risk factor for CAD in people with DM and postmenopausal women


Intlrvenliotr. 80 mg versus 10 mg atorvas·

tatin daily.

• screening is recommended for: • men over 40 years of age • women who are postmenopausal or over 50 years of age • those with CAD • those with family history of hyperlipidemia or premature CAD • those with other risk factors (DM, smoking, abdominal obesity, hypertension) • those with manifestations of hyperlipidemia (e.g. xanthelasma, xanthoma or arcus corneae) • those with evidence of symptomatic or asymptomatic atherosclerosis • in order to stratify risk for CAD and determine target lipid levels for treatment, establish: • presence of CAD, PVD, and cerebrovasc.ular disease • risk factors for CAD • presence ot hyperlipidemia and clinical symptoms (tendon xanthoma, xanthelasma, eruptive xanthoma, lipemia retinalis, arcus corneae)
Table 12. Risk Factors for CAD

(modified from National Cholesterol Education Program)
Positive Risk Factors • age: males >45 years, females >55 years; prematore menopause • family history of CAD: MI or sodden death in first-degree male relative <45 or in first-degree female relative <55 • current smoker • hypertension (HTN): BP >140/90 mmHg or currently on antihypertensive medications • -.l-HDL cholesterol <0.90 mmollL 1<35 mg/dL! • DM orlGT • hypertriglyceridemia TG >2.3 mmol/L (>205 mg/dU • abdominal obesity (BMI ~27: waist hip ratio <0.9 in males, ~0.8 in females! Negative Risk Factors • high HDL cholesterol Non-traditional Positive Risk Factors
• • • • • • • • • • tApo B (apolipoprotein B) -.l-Apo A-1 lapolipoprotein A-1) small dense LDL tfibrinogen tPAI-1 1'11,6 (interleukin 6) tTNF (tumour necrosis factor) tCRP Ie-reactive protein! -.l-adiponectin '1'homocysteine

"-in outcomes: Death from CAD, MI, car·

diac arrest, or stroke.
R_ItB: A primary event occurred in 8.7% of
the patients receiving intensive therapy, com·
pared to 10.9% of patients receiving standard
therapy IRR 0.78, p<O.OOl). There was no dif·
ference in overall mortality. Incidence of per·
sistent transaminase elevations was higher in
the intensive therapy group 11.2% versus
0.2%, ",,0.0011.
Conclulion: Intensive statin therapy is asso·
ciated with lower rates of CAD events than
standard therapy, but also a higher rate of
transaminase elevation.

Toronto Notes 2008


Endocrinology E15

Factors Affecting Risk Assessment • metabolic syndrome (clustering of cardiovascular risk factors) • apolipoprotein B (apoB): • each atherogenic particle (VLDL IDL, LDL and lipoprotein(a)) contains one molecule of apoB • the serum concentration of apoB reflects the total number of particles and may be useful in assessing cardiovascular risk and adequacy of treatment in high risk patients and those with metabolic syndrome
Table 13. Optimal Target Levels of Apolipoprotein B by Risk Group
High Moderate Low

Target apoS levels (giL)




• C-reactive protein (CRP) levels: • highly sensitive and may be clinically useful in identifying those at a higher risk of cardiovascular disease than predicted by the global risk assessment

SimVllltatin 10 lower CAD risIt •TIle Heart Protection Study (Lam;et2002;360:7-221 Study. Randomired, double-blind, placebo-eontrolled triallmedian follow-up 5.0 years). I'ItientJ: 20,536 patients with coronary disease, other oo:lu~ve a~eoal disease, or diabetes (aged M yearsl who had atotal dlolesterollevel of 3.5mmoL'L Int8n8ntion: Simvastatin 40 mg/day or ~acebo. AWn Outcomes: Mo~ality, fatal or non·fatal vascular events. ~ The use of ~mvastatin ~gnificanlly decreased total mortality (12.9 vs. 14.7, j)'O.OOO31 and the first event rate of any cardiovascular event by 25% Ip<O.OOO1I. Conclusion:Treatment with ~mvastatin improved sur­ vival and cardiovascular outcomes in high-os!< CAD patients.

Statins and CHD in dyslipidemia - 4S trial

Treatment of Dyslipidemias
Approach to Treatment
For clinical guidelines see Can J Cardiol2006; 22(111:913-27.

• establish treatment targets (see Table 14)

Table 14. Initiation and Target LDL by Risk Group
Level of Risk

Moderate Low

>20% 10-20% <10%

Target LOL (mmolll) <2.0 <3.5 <5.0

(mgldL) <78 <136.5 <195



Treatment of Hypercholesterolemia • conservative: 4-6 month trial unless in high risk group in which case medical treatment should start immediately • diet
• -J,- fat: <30% calories
• -J,- saturated fat: <10% calories
• -J,- cholesterol: <300 mglday
• l' fiber: >25-35 glday
• -J,- EtOH
• smoking cessation • aerobic exercise: 30-60 minutes/day, 4-7 times/week • weight loss: target BM! <25 kglm2 • medical • HMG-CoA reductase inhibitors, ezetimibe, bile add sequestrants, niacin (see Common Medications, E52 for further details) Treatment of Hypertriglyceridemia • conservative: 4-6 month trial • diet
• -J,- fat and simple carbohydrates
• l' omega-3 fatly adds
• -J,- EtOH
• medical: fibrates, niacin (see Common Medications, E52 for further details) • failed conservative measures • TG >10 mmol/L (885 mg/dL) to prevent pancreatitis • combined hyperlipidemia

(Lancet 1994; 344:1383-891 Study: Randomized, double-blind, placebo-oon
­ trolled triallmedian follow-up 5.4 yearsl.
Patients: 4444 patients with angina or previous
M1152% ~ 60 yrs; 82% menl with serum choles­
terol of 5.5-8.0 mmoliL, triglycerides S 2.5 mmoliL.
Intervention: Simvastatin 20 mg/day or placebo,
vvith dosage titrated to reach target cholesterol
level of 3.0-5.2 mmoliL.
Main outcomes:Total mortality, major coronary
Results: In the simvastatin group, the mean
changes in total, lOl, and HOL cliolesterol, and
triglycerides, were ·25%, -35%, +8%, and ·10%
respectively, with little change observed in the
placebo group. Simvastatin significantly reduced
the risks of death IRRR 0.70, p=O.00031, and major
coronary events IRRR 0.66, p<O.OOOOli.
(;{lnclusion: long-term treatment with simvas­
tatin lowered dlolesterol and improved survival in
CHO patients.

..... ' •.r - - - - - - - - - - - - , !

For Stalin Follow-Up • lipids and liver enzymes every 4-6 months or if patient complains of jaundice, RUQ pain, dark urine • CK at baseline and if patient complains of myalgia •dlc statin if CK >10 xupper limit of normal

Stalins and ezetimibe in dysIipidemia

IMayoClin Proc 2005; May; 80/51:585-6.1 Study. Multi-eentered double-blind RCT of 3,030 patients vvith lOGC levels above ttheir target value as determined by the National Cholesterol Education Program AduhTreatment Panel III who were randomized to receive their regular statin therapy and placebo or their statin therapy plus eletimibe 110 g/dayl. Results: Significantly more patients treated with ezetimibe plus statin 171.0%1 attained their lOl level goals compared to statin plus placebo 120.6%1. Ezetimibe was well tolerated with no sig­ nificant differences in safety profile between the two groups. Conclusion: Ezetimibe is effective in providing fu~her reduction of lOGC levels for patients treat­ ed with statins.

E16 Endocrinology


Toronto Notes 2008



Underweight Normal Overweight Obese -Class I •Class II . Class III


ClaIIiflcetion of Weight In Adults:
<18.5 18.5-24.9 25-29.9

• presence of abnormal absolute amount or relative proportion of body fat • Body Mass Index (BMl) • weightlheight2 (kglm 2; in US, Ibs/inches2 x 703) • BMl >27 leads to increased health risk • obesity: 20% or greater above ideal body weight (IBW) orBMI>30 • morbid obesity: 170% of IBW or BMl >40

30·34.9 35-39.9

• 15-25% of North American adults

Etiology and Pathophysiology
• • • • • • positive energy balance: energy input> energy output multifactorial increasing age is a risk factor genetic variations in energy expenditure behaviourllifestyle - diet and exercise secondary causes • endocrine: Cushing's syndrome, pcas, hypothyroidism • drugs: antidepressants, antiepileptics, antipsychotics, high dose glucocorticoids • hypothalamic injury: trauma, surgicaL lesions in ventromedial or
paraventricular median nucleus

• treatment should be based on medical risk • comprehensive approach including caloric restriction, increased physical activity and behaviour modification • diet • caloric restriction with a balanced diet with reduced fat, sugar and alcohol • exercise • behaviour modification • individual or group therapy, self-monitoring, stimulus control, stress management, cognitive change, crisis intervention • drug therapy • pancreatic lipase inhibitor: orlistat (XenicaITM) found to be mildly to moderately effective • sibutramine (Meridia™) • surgical therapy • gastroplasty ("stomach stapling") • laparoscopic banding of stomach (effective but costly) • liposuction • weight loss is regained by fat accumulation at the same site or elsewhere • not advocated if patient has significant medical comorbidities • does not reduce metabolic risks

• cardiovascular • hypertension, CAD, congestive heart failure (CHF), varicose veins, sudden death from arrhythmia • respiratory • dyspnea, sleep apnea, pulmonary embolus, infections • gastrointestinal • gallbladder disease, gastroesophageal reflux disease (GERD), fatty liver • musculoskeletal • osteoarthritis • endocrine/metabolic • lGT -+ Type 2 DM, hyperuricemia, hyperlipidemia, pcas, hirsutism, irregular menses, infertility • increased risk of neoplastic diseases • endometriaL post-menopausal breast, prostate, and colorectal cancers

Toronto Notes 2008

Pituitary Gland

Endocrinology E17

Pituitary Gland
Pituitary Hormones

opamlne GHIH





0 a.


prolactin TSH





2~ c: ­



thyroid gland

adrenal cortex

liver somatomedins (IGF)



c: u Q.l u_


"'c: c: '" WCi> c:


T3,T4 breast



endocrine cells of gonads


o '" E ~ c: 0 w-'='
- Q.l </) c:

u 0




2'''' "'2' 1-0

multiple target organs

gonadal germ cells

CRH =corticotrophin-releasing hormone; GnRH =gonadotropin-releasing hormone; GHIH =growth hormone-inhibiting hormone;
GHRH =growth hormone-releasing hormone; PRH =prolactin-releasing hormone;TRH =thyrotropin-releasing hormone

Figure 7. Hypothalamo-pituitary hormonal axes

Hypothalamic Control of Pituitary • trophic and inhibitory factors control the release of pituitary hormones • most hormones are primarily under trophic stimulation except prolactin which is
primarily under inhibitory control with dopamine
• transection of the pituitary stalk (Le. dissoaation of hypothalamus and pituitary) leads
to pituitary hypersecretion of prolactin and hyposecretion of all remairung hormones
Anterior Pituitary Hormones • growth hormone (GH), luteinizing hormone (LH), follicle stimulating hormone (FSH),
thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and
prolactin (PRL)
Hypothalamic Hormones • antidiuretic hormone (ADH) and oxytocin • peptides synthesized in the supraoptic and paraventricular nuclei of the hypothalamus
Table 15. The Physiology and Action of Pituitary Hormones
Hormone Inhibitory Stimulus
• glucose challenge • glucocortiooids • hypothyroidism • somatostatin • dopamine agonists ·IGF·ll1ong·loop)

Secretory Stimulus
• insulin induced hypoglycemia

• polypeptide • acts indirectly through serum factors synthesized in the liver: IGFlsomatomedinsl • serum GH undetectable for most of the day and is sup­ pressed after meals that are high in glucose • sustained rise during sleep • polypeptide • episodic secretion




'REM sleep • arginine, c1onidine, propranalol, "dopa 'GHRH

• needed for linear growth ·IGF stimulates growth of bone and cartilage

The Pituitary Honnon.. "GOAT FLAP" GH Oxytocin


• promotes milk production • inhibits GnRH secretion


• tonically by dopamine • 0, receptor agonists

• sleep

• stress
• pregnancy • hypoglycemia • mid-menstrual cycle • breast feeding
• sexual activity • dopamine antagonists • drugs: psychotropics, anti
­ hypertensives, opiates, high
dose estrogen

Antiiliuretic hormone (ADH) Prolactin

E18 Endocrinology

Pituitary Gland

Toronto Notes 2008

Table 15. The Physiology and Action of Pituitary Honnones (continued)
Hormone LHIFSH Inhibitory Stimulus
• estrogen • progesterone • testosterone ·inhibin • continuous GnRH infusion

Secretory Stimulus
• pulsatile GnRH

• polypeptide • glycoproteins (similar a subunitTSH and hCG) • secreted in pulsatile fashion

• stimulate gonads via cAMP • ovary: ·LH stimulates theca cells to produce androgens which are subsequently converted to estrogens in granulosa cells -LH induces luteinization in follicles -FSH stimulates growth of granulosa cells in ovarian follicle and :ontrols estrogen formation • testes: ·LH stimulates testosterone from Leydig cells ·FSH stimulates Sertoli cells to produce spermatozoa


• dexamethasone • cortisol

'CRH • metyrapone • insulin induced hypoglycemia • fever, pain, stress ·TRH • epinephrine • prostaglandins • hypovolemia or .j, effective circulatory volume • l' serum osmolality • stress, pain, fever, paraneoplastic

• polypeptide • pulsatile and diurnal variation Ipeaks at 2-4 am; lowest at 6pm·12 ami

• stimulates growth of adrenal cortex and secretion of its hormones


• circulating thyroid hormones iT" T,) • opiates, dopamine
• .j, serum osmolality

• glycoprotein

• stimulates growth of thyroid and secretion ofT, andT, via cAMP • acts at renal collecting ducts to stimulate insertion of aquaporin channels to increase water reabsorption thereby concentrating urine


• octapeptide • osmoreceptors in hypothalamus detect serum osmolality • contracted plasma volume is amore potent stimulus than osmolality • nonapeptide


• EtOH

• suckling and distention of female genital tract

• causes uterine contraction • physiologic importance is unknown • breast milk secretion


Growtti Hormone (GH)


• cause of short stature in children (see Pediatrics, P33) • insignificant in adults

Gigantism • excess GH secretion before epiphyseal fusion


Acromegaly • excess GH secretion in adults (after epiphyseal fusion)

• pituitary adenoma secreting GH, carcinoid or pancreatic islet tumours secreting ectopic GHRH resulting in excess GH

• secretion remains pulsatile, but the nocturnal surge, glucose suppressibility, and hypoglycemic stimulation are lost • proliferation of bone, cartilage, soft tissues, organomegaly • insulin resistance and IGT

Clinical Features


Signs and Symptoms of

Acromegaly "A8CDEF" Arthralgia/Arthritis Blood pressure raised Carpal tunnel syndrome Diabetes Enlarged organs
Field defect (visual)

• enlargement of hands and feet, coarsening of facial features, thickening of calvarium,
prognathism, infraorbital puffiness, thickening of skin, 1'oiIiness, sweating, acne,
sebaceous cysts, fibromata mollusca, acanthosis nigricans, arthralgia, degenerative osteoarthritis (OA), thvromegaly, renal calculi, hypertension, cardiomyopathy, and DM

• glucose suppression test is the most specific test ... 1'GH in OGrr • insulin-like growth factor-l (IGF-l)


• surgery, octreotide (somatostatin analogue), growth hormone receptor antagonist, bromocriptine, radiation

Toronto Notes 2008

Pituitary Gland

Endocrinology E19

Prolactin (PRL)
• prolactinoma is the most common pituitary adenoma (prolactin secreting tumours may be induced by estrogens and grow during pregnancy) • pituitary stalk lesions • primary hypothyroidism (l'TRH) • chronic renal failure resulting in decreased clearance, biliary cirrhosis

Clinical Features
• galactorrhea, infertility, hypogonadism

• serum PRL, TSH, liver enzyme tests, creatinine • MRl

• long acting dopamine agonist: bromocriptine, cabergoline or quinagolide (Norprolac™) • surgery ± radiation (rare) • these tumours are very slow-growing and sometimes require no treatment

Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)
• hypogonadism, amenorrhea, erectile dysfunction (ED), loss of body hair, fine skin, testicular atrophy, failure of pubertal development


• pergonal, hCG, or GnRH analogue if fertility desired • symptomatic treatment with estrogen/testosterone

• 2° hypersecretion in gonadal failure

Antidiuretic Hormone (ADH)
• disorder resulting from deficient AOH action resulting in the passage of large volumes of dilute urine

Diagnostic Criteria
• fluid deprivation will differentiate true OI (high urine output persists, urine osmolality < plasma osmolality) from psychogenic 01 (psychogenic polydipsia) • response to exogenous AOH will distinguish central from nephrogenic 01

Diagnosing Subtypes of OJ After DDAVP: Concentrated urine =Central No effect =Nephrogenic

Etiology and Pathophysiology
• central OI: insufficient AOH due to post-pituitary surgery, tumours, stalk lesion, hydrocephalus, histiocytosis, trauma, familial central OI • nephrogenic OI: collecting tubules in kidneys resistant to AOH (drugs including litflium, hypercalcemia, hypokalemia, chronic renal disease, hereditary nephrogemc 01) • psychogenic polydipsia must be ruled out

Clinical Features
• passage of large volumes of dilute urine, polydipsia, dehydration

• OOAVP/vasopressin for total 01 • OOAVP, chlorpropamide, clofibrate, or carbamazepine for partial 01 • nephrogenic 01 treated with solute restriction and thiazide aiuretics

• hyponatremia with corresponding plasma hypo-osmolality', urine sodium concentration above 40 mEq/L, unne less than maximally ailuted (>100mosm!kg), euvolernia (edema absent), and absence of adrenal, renal or thyroid insufficiency


E20 Endocrinology

Pituitary Gland

Toronto Notes 2008

... .)------------, ~
SIADH no CenbrIl SlIt WatilIg lcsw) CSW can occur in cases of subaradlOoid hem­ orrhage. Na is excreted by malfunctioning renal tubules, mimiding findings of SIADH.


Etiology and Pathophysiology
• • • • malignancy (lung, pancreas, lymphoma) CNS disease (inflammatory, nemorrhage, tumour, Guillain-Barre syndrome) respiratory disease (TB, pneumonia, empyema) drugs (vincristine, chlorpropamide, cyclophosphamide, carbamazepine, nicotine, morphine, DDAVP, oxytoon) • stress (post-surgical) • treat underlying cause, fluid restriction, and demeclocycline (antibiotic with anti-ADH properties)




PITUITARY ADENOMA (see also Neurosurgery. NSll) Clinical Features
• related to size and location • visual field defects (usually bitemporal hemianopsia), oculomotor palsies, increased lCP (mal have neadaches) • skull radiograph: double floor" (large sella or erosion), calcification • CI and MRI far more sensitive for dIagnosis • related to destruction of gland • hypopituitarism • related to increased hormone secretion • PRL (galactorrhea), GH (acromegaly in adults, gigantism in children), ACTH (Cushlng's disease = Cushing's syndrome causedoy a pituitary tumour), tumours secreting LH, FSH and ISH are rare


"Go Look For The Adenoma Please" GH, LH, FSH,TSH, ACTH, PAL : Acompressive adenoma in the pitu­ itary will impair hormone production in this order (i.e. GH-secreting cells are most sensitive to compression)


• occurs when subarachnoid space extends into sella turcica, partially filling it with CSF resulting in remodeling and enlargement of sella turcica and flattening ofthe pituitary gland • usuallyeupituitary • may have headaches • MRI: herniation of diaphragm sellae and the presence of CSF in the sella turcica • no treatment necessary


• acute hemorrhage/infarction of pituitary tumour • sudden severe headache, altered level of consciousness • ocular symptoms: ophthalmoplegia with pituitary tumour likely indicates apoplexy since tumour rarely gets big enough to encroach on cranial nerves • neurosurgical emergency: acute decompression of pituitary via trans-sphenoidal route

• the eight "I"s: • Invasive: generally primary tumours • Infarction: e.g. Sheehan's syndrome • Infiltrative disease: e.g. sarcoidosis, hemochromatosis, histiocytosis Iatrogenic: following .surgery or radiation Infectious: e.g. syphilIs, TB • Injury: severe head trauma
Immunologic: autoimmune destruction
• Idiopathic: familial forms, congenital midline defects

Clinical Features
• typical clinical progression in panhypopituitarism (GH (most common def) -> [R/FSH ->ACTH -. ISH) • fall in GH is clinically not apparent • fall in PRL is variable, but may present as decreased lactation • gonadotropin insufficiency causes erectile dysfunction in men and amenorrhea or infertility in women ISH deficiency produces clinical hypothyroidism • ACTH deficiency leads to adrenal msufficiency

• Triple Bolus Test • stimulates release of all anterior pituitary hormones in normal individuals • rapid sequence N infusion of insulin, gonadotropin releasing hormone (GnRH) and thyroid releasing hormone (TRH) insulin (usual dose 0.15 units/kg of human regular insulin) hypoglycemia -> increased GH and ACTH • GnRH (100 flg N push) -> increased LH and FSH • TRH (200 I-lg N push over 60 sec) -> increased TSH and PRL

Toronto Notes 2008


Endocrinology E21



Thyroid Hormone Synthesis
• the synthesis of T4 (thyroxine) and T3 (triiodothyronine) by the thyroid gland involves trapping and oxidation of iodide, iodination of thyroglobulin, and release of T4 and T3 • free T4 (0.03%) and free T3 (0.3%) represent the honnonally active fraction of thyroid honnones • the remaining fraction is bound to thyroxine binding globulin (TBG) and albumin and is hence biologically inactive • T3 is more biologically active (3-8x more potent) than Tv but T4 a has longer half-life • 85% ofT4 is converted to T3 or reverse T3 (RT3 ) in the periphery by 5' or 5 deiodinase, respectively • RT3 is metabolically inactive but produced in times of stress to decrease metabolic activity • most of the plasma T3 pool is derived from the peripheral conversion of T4

Regulation of Thyroid Function
• extrathyroid • stimulation of thyroid by TSH, epinephrine, prostaglandins (cAMP stimulators) • T3 negatively feeds back on anterior pituitary to inhibit TSH and on hypothalamus to inhibit TRH • intrathyroid (autoregulation) • increasing iodide supply inhibits iodide organification, thus decreasing T3 and T4 synthesis (Wolff-01aikoff effect) • varying thyroid sensitivity to TSH in response to iodide availability • increased ratio of T3 to T4 in iodide deficiency • increased activity of peripheralS' deiodinase in hypothyroidism to increase T3 production despite low T4 levels

Tests ofTh roid Function and Structure
• sensitive TSH (sTSH) is the single best test for assessing thyroid function • hyperthyroidism • primary: TSH is low and does not rise in response to TRH because of negative feedback from increased levels of circulating T3 and T4 • secondary: increased TSH which results in increased T3 and T4 • hypothyroidism • primary: increased TSH (most sensitive test) because of less negative feedback from T3 and T4 • secondary: TSH is low with variable response to TRH depending on the site of the lesion (pituitary or hypothalamic)




Thyroid Assesment
1. Serum thyroid hormones
2. AntibQdies 3. Thyroglobulin, calcitonin 4. Thyroid imaging/scans 5. Biopsy (FNA)

Free T3 and Free T4
• total T3 and T4 levels depend on amount of TBG • TBG increases with pregnancy, oral contraceptive (OCP) use, acute infectious hepatitis, biliary cirrhosis • TBG decreases with androgens, glucocorticoids, cirrhosis, hyponatremia, phenytoin, ASA, NSAIDS, nephrotic syndrome, severe systemic illness • free T3 and T4 are mdeyendent of TBG and measure biological activity • standard assessment 0 thyroid function measures TSH and if necessary free
T4 and free T3

Thyroid Autoantibodies
• thyroglobulin antibodies (TgAb), thyroid peroxidase (microsomal antibodies), TSH
receptor inhibiting antibodies
• increased in Hashimoto's disease • thyroid stimulating immunoglobulin (TSI) • increased in Graves' disease

Plasma Thyroglobulin
• used to monitor residual thyroid activity post-thyroid ablation, e.g. for thyroid
cancer recurrence
• undetectable levels =remission • nonnal or elevated levels = probable persistent, recurrent, or metastatic disease

En Endocrinology


Toronto Notes 2008

Serum Calcitonin
Does this Pltient have 8 Goitre? IJAMA 1995; 273:813-171

Clinical diagnosis was based on degree of
lateral prominence, visibility, and palpa
­ bility of the thyroid gland. Most primary
studies did not report the specifics of thy
­ roid examination technique, and therefore
no evidence exists to support the superi·
ority of anyone method.
The combined results of 9studies detail
the accuracy of the clinical examination
for the presence of goiter (using ultra­
sound or autopsy as the gold standard
Sensitivity 70% (68%-73%)
Specificity 82% 179%-85%1
LR+ 3.8 (3.3 to 4.5)
LR0.37 (0.33 to 0.40)
The combined results of 4studies detail
the predictive utility of assessing grades
of thyroid gland weight: Weight Reference LR+ 95%CI 0-20 g normal 0.15 10.10-0.211 20-40 g 1-2x 1.9 11.1-3.0) >40 9 >2x 25.0 (2.6-1751

• not routinely done to investigate most thyroid nodules • ordered if suspicious of medullary thyroid carcinoma or family history of MEN ITa or IIb syndromes

Thyroid ImaginglScans
• normal gland size 15-20 g (estimated by palpation) • thyroid DIS • to detect size of gland, solid vs. cystic nodule • thyroid scan (Technetium-99) • differentiates between hot (functioning) and cold (non-functioning) nodules • to distinguish between three major types of high-uptake hyperthyroidism • Graves' disease (diffuse uptake) • toxic multinodular goiter (multiple discrete areas) • solid toxic adenoma (sin~le intense area of uptake) • test of structure - order if there IS a thyroid nodule and patient is hyperthyroid • radioactive iodine uptake (RAID) • RAID measures the turnover of iodine by thyroid gland in vivo in areas of low iodine intake and endemic goitre, 24 h RAID may be as high as 60-90% • in areas of high iodine intake, normal 24 h RAIU will be 8-30% • RAIU is high in Graves' disease or toxic nodular goitre and low in subacute thyroiditis, active phast' of Hashimoto's thyroiditis, and excess iodine intake (e.g. amiodarone) • test of function - order if patient is hyperthyroid

Thyroid Biopsy
• fine needle aspiration (PNA) for cytology • differentiates between benign arid malignant disease



• excess production of thyroid hormone • thyrotoxicosis: denotes clinical, physiological, and biochemical findings in response to elevated thyroid hormone

• 1% of general population (4-5% of elderly women) • F:M=5:1

Etiology and Pathophysiology
Table 16. Differential Diagnosis of Hyperthyroidism
Disorder Graves' disease Toxic Nodular Goitre Toxic Nodule Thyroiditis 'Subacute TSH T4 andTa Thyroid Antibodies

l' l' l'


..t. ..t. ..t. ..t.

l' l' l' l' l'


Up to 50% of cases


'Silent , Postpartum McCune-Albright syndrome ..t.

In classical subacute thyroiditis, ESR l' At least 2of Ilolyostotic fibrous dysplasia, cafe au lait spots, and autonomous endocrine hyperfunction iodine induced

Jod Basedow Extrathyroidal sources
ofthyroid hormone:
, Endogenous:
(struma ovariae, ovarian teratoma, metastatic
follicular cal
, Exogenous
txcessive Thyroid
, Pituitary thyrotrophoma • Pituitary thyroid hormone receptor resistance '1' hCG le.g. pregnancy)









Toronto Notes 2008


Endocrinology E23

Clinical Features
Table 17. Clinical Features of Hyperthyroidism
General Cardiovascular • fatigue, heat intolerance, irritability, fine tremor • tachycardia, atrial fibrillation, palpitations • elderly patients may have only cardiovascular symptoms, commonly new onset atrial fibrillation


• weight loss with l' appetite, thirst, increased frequency of bowel movements (hyperdefecationl • proximal muscle weakness, hypokalemic periodic paralysis (common in Orientals) • scant menses, -J.. fertility • fine hair, skin moist and warm, vitiligo, soft nails with onycholysis (Plummer's nails)

Dermatology MSK Hematology

• -It bone mass, proximal muscle weakness
• leukopenia, lymphocytosis, splenomegaly, lymphadenopathy (occasionally in Graves' disease)

Signs and Symptoms of hyperTHYROIDISM: Tremor Heart rate up Yawning (fatigued) Restlessness Oligomenorrhea/amenorrhea Intolerance to heat Diarrhea Irritability Sweating Muscle wasting/Weight loss

• • • • antithyroid drugs (thionamides: propylthiouracil (PTU) or methimazole (MMI»

radioactive iodine thyroid ablation surgery

Graves' Disease
• syndrome characterized by hyperthyroidism with anyone of the following features
including diffuse goiter, ophthalmopathy, dermopathy (need not appear together)

most common cause of thyrotoxicosis
occurs at any age with peak in 3rd and 4th decade
F> M = 7:1,1.5-2% of U.s. women familial predisposition: 15% of patients have a close family member with Graves'
disease and 50% have family members with positive circulating antibodies
• association with HLA B8 and DR3 • may be associated with other autoimmune disorders in family (e.g. pernicious anemia, Hashimoto's disease) • • • •

Etiology and Pathophysiology
• autoimmune disorder due to a defect in T-suppressor cells • B-Iymphocytes produce TSI that bind the TSH receptor and stimulate the thyroid • immune response can be triggered by pregnancy (especially postpartum), iodine
excess, lithium therapy, viral or bacterial infections, glucocorticoid withdrawal
• cause of ophthalmopathy uncertain (can occur even when euthyroid) • antibodies against extraocular muscle antigens (fibroblasts implicated) with lymphocytic infiltration • glycosaminoglycan deposition • dermopathy may be related to cutaneous glycosaminoglycan deposition

Clinical Features
• diffuse goiter ± bruit • ophthalmopathy: proptosis, lid lag, lid retraction, diplopia, characteristic stare,
conjunctival injection
• dermopathy (rare): pretibial myxedema (thickening of dermis) • acropachy: clubbing and thickening of distal phalanges

• increased free T4 (and/or increased T3 ) • positive for TSI • TRH stimulation test (with a flat TSH response) is diagnostic, if sTSH and free T4 are inconclusive

• thionamides • propylthiouracil (PTU) or methimazole (MMI) • inhibit thyroid hormone synthesis by inhibiting the peroxidase catalyzed reactions, thereby inhibiting organification of iodide, blocking the coupling of iodotyrosines, and inhibiting peripheral deiodination of T4 to T3

E24 Endocrinology


Toronto Notes 2008

• •

• •

• most useful in young patients with small glands and mild disease • continue treatment until remission occurs (20-40% of patients achieve spontaneous remission at 6-18 mos of treatment) • small goitre and recent onset are good indicators for long-term remission with medical therapy • MMI contraindicated in pregnancy • major side effects: hepatitis and agranulocytosis • minor side effects: rash, fever and arthralgias • iodinated contrast agents: sodium ipodate and iapanoic acid can inhibit conversion ofT4 to T3 and is especially effective in combination with MMI symptomatic treatment with ~-blockers thyroid ablation with radioactive 131 1if ITO or MMI trial does not produce disease remission • high incidence of hypothyroidism after 1311, requiring lifelong thyroid hormone replacement • contraindicated in pregnancy subtotal thyroidectomy (indicated rarely for large goitres) • risks include hypoparathyroidism and vocal cord palsy ophthalmopathy • prevent drying • high dose prednisone in severe cases
• orbital radiation, surgical decompression

• course involves remissions and exacerbations unless gland is destroyed by radioactive iodine or surgery • some patients remain euthyroid after treatment however many develop hypothyroidism • lifetime follow-up care needed • risk of relapse is 37%, 21 %, 6% in thionamindes, radioiodine ablation, and surgery groups respectively


Subacute Thyroiditis (Th rotoxic Phase)
• acute inflammatory disorder of the thyroid gland characterized by an initial thyrotoxic state followed by hypothyroidism

Etiology and Pathophysiology
• acute inflammation of the thyroid, probably viral in origin, characterized by giant cells and lymphocytes • often preceded by upper respiratory tract infection (URTI) • disruption of thyroia follicles by inflammatory process results in the release of stored hormone

Clinical Features
• initially presents with fever, malaise, and soreness in neck • thyroid gland enlarges • two forms • painful ("DeQuervain's") thyroid, ears, jaw and occiput • painless ("Silent") • usually transient thyrotoxicosis with a subsequent hypothyroidism phase due to depletion of stored hormone, finally resolving in a euthyroid state over a period of months

Laboratory Investigation
• • • • elevated free T'V T3' low TSH, RAID markedly reduced marked elevation of ESR in painful variety only as disease progresses, values consistent with hypothyroidism may appear rise in RAID reflects gland recowry

• high-dose anti-inflammatories (e.g. ASA) can be used for painful form (increases peripheral T. l conversion) • prednisone may be required for severe pain, fever, or malaise • !:i-adrenergic blockade is usually effective in reversing most of the hypermetabolic and cardiac symptoms • if symptomatically hypothyroid may treat short-term with thyroxine

• full recovery in most cases, but permanent hypothyroidism in 10% of painless thyroiditis

Toronto Notes 2008


Endocrinology E25

Postpartum Thyroiditis
Definition • painless thyroiditis occurring in the postpartum period Epidemiology • occurs in 5-10% of postpartum mothers and is symptomatic in 1/3 of patients Etiology and Pathophysiology • autoimmune-mediated Clinical Features • thyrotoxicosis 2-3 months postpartum with a subsequent hypothyroid phase
at 4-8 months postpartum
• may be mistakenly diagnosed as postpartum depression Treatment • same as silent thyroiditis Prognosis • most resolve spontaneously without need for supplementation • may recur with subsequent pregnancies


Toxic AdenomaIToxic Multinodular Goitre
Etiology and Pathophysiology • autonomous thyroid hormone production from a functioning adenoma that is
hypersecreting T3 and T4
• may be singular (toxic adenoma) or multiple (toxic multinodular goitre, aka
Plummer's disease)
Clinical Features • goitre with adenomatous changes
• occurs more frequently in elderly people
• tachycardia, heart failure, arrhythmia, weight loss, nervousness, weakness, tremor, and
• atrial fibrillation is a common presentation in the elderly Investigations • low TSH, high T3 and T4 (with a larger increase in T3 ) • thyroid scan with increased uptake in nodule(s), and suppression of the remainder of
the gland
Treatment • initiate therapy with PTU or MMI to attain euthyroid state in order to avoid
radiation thyroiditis
• then use high dose radioactive iodine to ablate tissue over weeks • propranolol often necessary for symptomatic treatment prior to definitive therapy • surgery may be used as 2nd line treatment


Thyrotoxic Crisislfhyroid Storm -'!"""._---~---~---'
Definition • acute exacerbation of all of the symptoms of thyrotoxicosis presenting in a life
threatening state secondary to uncontrolled hyperthyroidism
Etiology and Pathophysiology • often precipitated by infection, trauma, or surgery in a hyperthyroid patient Differential Diagnosis • sepsis, pheochromocytoma, malignant hyperthermia, drugs Clinical Features • hyperthyroidism • extreme fever (hyperthermia), tachycardia, vomiting, diarrhea, vascular collapse,
hepatic failure with jaundice, and confusion
• arrhythmia --> congestive heart failure, pulmonary edema • mental status changes ranging from delirium to coma

£16 Endocrinology


Toronto Notes 2008

Laboratory Investigations • increased free T3' T4 , undetectable TSH • ± anemia, leukocytosis, hypercalcemia, elevated LFTs Treatment • principles are the same as in hyperthyroidism except use higher doses and frequencies • initiate prompt therapy; do not wait for confirmation from lab • propranolol (IV) for tachycardia and to wperipheral conversion of T4 to T3 (watch for CHF) • supportive: fluid and electrolytes, diuresis, vasopressors, cooling blanket, acetaminophen for pyrexia • high dose PTU • iodide (Nal, KI, Lugol's solution) to inhibit release of thyroid hormone • lithium to inhibit release of thyroid hormone • dexamethasone to block peripheral conversion, to lower body temperature, and to treat possible underlying autoimmune condition • if extreme, plasmapheresis or dialysis to remove high circulating thyroid hormone • treat precipitant Prognosis • 50% mortality rate





Definition • clinical syndrome caused by cellular responses to insufficient thyroid hormone production Epidemiology • 2-3% of general population • F:M= 10:1 • 10-20% of women over age 50 have subclinical hypothyroidism (normal T,y TSH mildly elevated) Etiology and Pathophysiology • primary hypothyroidism (90%) • inadequate thyroid hormone production secondary to intrinsic thyroid defect • iatrogenic: post-ablative (131 1or surgical thyroidectomy) • autoimmune: Hashimoto's thyroiditis, chronic thyroiditis, idiopathic, burnt out Graves' • hypothyroid phase of subacute thyroiditis • drugs: goitrogens (iodine), PTU, MMI, lithium • infiltrative disease (progressive systemic sclerosis, amyloid) • iodine deficiency • congenital (1/4,000 births) • neoplasia • secondary hypothyroidism: pituitary hypothyroidism • insufficiency of pituitary TSH • tertiary hypothyroidism: hypothalamic hypothyroidism • decreased TRH from hypothalamus (rare) • peripheral tissue resistance to thyroid hormone (Refetoff syndrome)
Table 18. Interpretation of SeRlmTSH and FreeT4 in Hypothyroidism Serum TSH
Overt Primary Hypothyroidism Subclinical Primary Hypothyroidism Secondary Hypothyroidism

Free T4

t t


wor not appropriately elevated

Toronto Notes 200S


Endocrinology E27

Clinical Features
Table 19. Clinical Features of Hypothyroidism

• fatigue, cold intolerance, slowing of mental and physical performance, hoarseness, macroglossia • slow pulse, pericardial effusion, bradycardia, hypertension, worsening CHF +angina, hypercholes
­ terolemia, hyperhomocysteinemia, myxedema heart
• weight gain with poor appetite, constipation • paresthesia, slow speech, muscle cramps, delay in relaxation phase of deep tendon reflexes ("hung reflexes"), Carpal Tunnel syndrome, asymptomatic increase in CK • menorrhagia, amenorrhea, impotence • puffiness of face, periorbital edema, cool and pale, dry and rough skin, hair dry and coarse, eyebrows thinned lIateral1131, discoloration (carotenemia) • anemia: 10% pernicious due to presence of anti-parietal cell antibodies • decreased exercise capacity, hypoventilation secondary to weak muscles, decreased pulmonary
responses to hypoxia, sleep apnea due to macroglossia


Signs and Symptoms of hypothyroidism-HIS ARM CAP-:
Hypoventilation Intolerance to cold SlowHR Fatigue Impotence Renal impairment Menorrhagia/amenorrhea Constipation Anemia Paresthesia

Dermatology Hematology Respiratory

• L-thyroxine (dose range: 0.05 to 0.2 mg/day) • elderly patients and those with CAD: start at 0.025 mg daily and increase gradually (start low, go slow) • after initiating L-thyroxine, serum T4 & TSH need to be evaluated in 6 weeks; doses adjusted until TSH returns to normal reference range
• once maintenance dose achieved, follow-up with patient annually
• secondary/tertiary hypothyroidism: • need to rio and/or treat adrenal insufficiency • monitor via measuring free T4 level NOT ONLY TSH

(see Pediatrics, P29)

Hashimoto's Thyroiditis ---• chronic autoimmune thyroiditis characterized by both cellular and humoral factors in the destruction of thyroid tissue • two major forms: goitrous and atrophic; two forms share same pathophysiology but differ in the extent of lymphocytic infiltration, fibrosis, and thyroid follicular cell hyperplasia • goitrous variant usually presents with a rubbery goiter and euthyroidism, then
hypothyroidism becomes evident
• is associated with fibrosis • atrophic variant patients are hypothyroid from the start • is associated with thyroid lymphoma


Etiology and Pathophysiology
• defect in clone of T-suppressors leads to cell-mediated destruction of thyroid follicles • B-Iymphocytes produce antibodies against thyroid components including:
thyroglobulin, thyroid peroxidase, TSH receptor, Na/I symporter

Risk Factors
• gender: female • genetic susceptibility: increased frequency in patients with Down's syndrome,
Turner's syndrome, certain HLAs, cytotoxic T-Iymphocyte-associated protein 4
• family Hx or personal Hx of other autoimmune diseases • cigarette smoking • high iodine intake • stress and infection

• high TSH, low T3 , low T4 • presence of thyroid peroxidase and thyroglobulin antibodies in serum

E28 Endocrinology


Toronto Notes 2008

• if hypothyroid, replace with L-thyroxine (analog of T 4 ) • if euthyroid, also treat with L-thyroxine if significant anti-thyroid antibody present


Riedel's StrumaIWoodyThyroiditis
• rare type of chronic thyroiditis • fibrotic inflammatory process that extends from the thyroid into surrounding tissues

Clinical Features
• i1l-defined, firm mass with "woody" consistency on palpation • possible compressive symptoms of dysphagia, stridor, hoarseness, pain

• surgical wedge resection of the isthmus (to prevent tracheal compression) • tamoxifen, prednisone


Myxedema Coma
• severe hypothyroidism complicated by trauma, sepsis, cold exposure, MI, inadvertent administration of hypnotics or narcotics, and other stressful events • rare but serious mortality of up to 60% despite therapy

Clinical Features
• hypothermia, hyponatremia, hypoglycemia, hypotension, bradycardia, hypoventilation, unresponsiveness

• decreased free T3 and T~ increased TSH, decreased glucose • check ACTH and cortisol for evidence of adrenal insUfficiency

• aggressive treatment required • A13Cs - patient should be in ICU setting • corticosteroids (due to the possibility of concomitant adrenal insufficiency): hydrocortisone 100 mg q8h • L-thyroxine 0.2-0.5 mg IV loading dose, then 0.1 mg IV OD until oral therapy tolerated • supportive measures: mechanical ventilation, fluids, vasopressor drugs, passive rewarming, IV dextrose • monitor for arrhythmia


Sick Euthyroid Syndrome (SES)


• denotes the changes in circulating thyroid hormones in patients with serious illness, trauma, or stress. It is not due to intrinsic thyroid or pituitary disease.

• the abnormalities in SES include alterations in • peripheral transport and metabolism of thyroid hormone
regulation of TSH secretion
• thyroid function itself

• initially decreased free T3 followed by decreased TSH and finally decreased free T4

Table 20. Etiology of SES
Types of SES Features

normal-T, variant low-T, variant

olow freeT 3, normal freeT" normalTSH oproposed mechanism: inhibition of peripheral 5' monodeiodination ofT, to T3 olow freeT 3, low freeT" normal or 10wTSH olowT,likely due to inhibitedT, binding to serum proteins and accelerated metabolic clearance opoorer prognosis

Toronto Notes 2008


Endocrinology E29

• treat the underlying disease; thyroid honnone replacement worsens the outcome

Non-Toxic Goitre
• generalized enlargement of the thyroid gland in a euthyroid individual that does not
result from inflammatory or neoplastic processes


• the appearance of a goitre is more likely during adolescence, pregnancy, and lactation
because of increased thyroid honnone requirements
• early stages: goitre is usually diffuse • later stages: multinodular non-toxic goitre with nodule, cyst fonnation and
areas of ischemia, hemorrhage, and fibrosis

• • • • • iodine deficiency or excess goitrogens: brassica vegetables (turnip, cassava) drugs: iodine, lithium, para-aminosalicylic acid any disorder of hormone synthesis with compensatory growth peripheral resistance to thyroid honnone

• remove goitrogens • suppression with L-thyroxine (rarely used) • surgery may be necessary for severe compressive symptoms

• compression of neck structures causing stridor, dysphagia, pain, and hoarseness • multinodular goitre may become autonomous leading to toxic multinodular goitre and

Thyroid Nodules
• clearly defined discrete mass, separated from the thyroid parenchyma • palpable nodules are found in approximately 4% of the population • M:F = 1:4

• • • • benign tumours (e.g. follicular adenoma) thyroid malignancy hyperplastic area in a multinodular goiter cyst: true thyroid cyst, area of cystic degeneration in a multinodular goiter

• F:--JA: for all nodules >1-1.5 cm • thyroid function tests • thyroid scan: 15-20% of cold nodules (rninirnal 131 1uptake into nodule) are malignant,
very low malignant potential if hot (significant 1311uptake into nodule)

Thyroid Malignancies
(see Otolaryngology. OT37)

E30 Endocrinology

Adrenal Cortex

Toronto Notes 2008

Adrenal Cortex
Adrenocorticotropin Hormone (ACTH)- - - - • a polypeptide secreted in a pulsatile fashion from the anterior pituitary with diurnal variability (peak: 0200-0400; trough: 1800-2400) • part of a prohormone (pro-opiomelanocorticotropin, POMC) which contains u, ~ and 'Y MSH, ~-endorphin and lipotropin as well as ACTH • stimulates growth of adrenal cortex and secretion of its hormones via cAMP • stimulates release of glucocorticoids, androgens and, to a limited extent, mineralocorticoids • some melanocyte stimulating activity
·Hlood glucose, trauma, infection, emotion, circadian rhythm



";"~h';"' (
.... ."\------------, ~
Layers of the Adrenal Cortex



Adrenal gland

Figure 8. Regulation of CRH-ACTH-Adrenal Gland Axis


Adrenocortical Hormones __--.,.__----~-_--.J
• all derived from cholesterol (see Figure 9) • mineralocorticoids (aldosterone) from zona glomerulosa • glucocorticoids (cortisol) from zona fasciculata • androgens from zona reticularis

GJomeruIosa produces aldostetone


F8IcicuIata produces cortiaoI

• a mineralcorticoid, which regulates extracellular fluid (ECF) volume through Na retention and K excretion (by stimulation of distal tubule NarK ATPase) • regulated by the renin-angiotensin-aldosterone system (see Figure 10) • negative feedback to juxtaglomerular apparatus OGA) by long loop (aldosterone via volume expansion) and short loop (angiotensin II via peripheral vasoconstriction)

Reticularis produces sex steroids




CD 17-hydroxylase CD 3-p-dehydrogenase ® 21-hydroxylase 4 11Qoxylase

CD 17-p-dehydrogenase CD aromatase (j) Son-reductase ® la-hydroxylase
------.. DHEA-$ , - - - - - - - - - - - ,

J~moo ..m~~ 17J,~,,".
aldosterone Mineralocorticoids Izona glomerulosal





moo oom~",_ ''''',



cortisol Glucocorticoids (zona fasciculatal





Sex Steroids
Izona reticularisl

Figure 9. Pathways of Major Steroid Synthesis in the Adrenal Gland and Their Enzymes

Toronlo Noles 2008

Adrenal Cortex

Endocrinology E31

-J, volume -J, arterial pressure -J, Na delivery to macula densa PGs sympathetic stimulation

l' arterial pressure
renal Na retention

stimulation of JGA R1in Angiotensinogen ACE Angiotensin IL

inhibition of JGA



Angiotensin II (with negative feedback to inhibit JGAI

Aldosterone release - - - - - J~ renal Na retention, Kexcretion .. Arteriolar vasoconstriction Promotion of ADH release JGA -juxtaglomerular apparatus ACE -angiotensin converting enzyme


Figure 10. Renin-Angiotensin-Aldosterone Axis, see Nephrology, NP4

Table 21. Physiological Effects of Glucocorticoids
Stimulatory Effects • stimulate hepatic glucose production (gluconeogenesisl • increase insulin resistance in peripheral tissues • increase protein catabolism • stimulate leukocytosis and
Inhibitory Effects • inhibit bone formation; stimulate bone resorption
• inhibit fibroblasts, causing collagen and
connective tissue loss
• suppress inflammation; impair cell-mediated

• sex steroids regulated by ACTH; primarily responsible for adrenarche (growth of axillary and pubic hair) • principal adrenal androgens are dihydroepiandrosterone (DHEA), androstenedione and ll-hydroxyandrostenedione • proportion of tOlal androgens (adrenal to gonadal) increases in old age

Tests of Adrenocortical Function -----------"
Table 22. Markers of Adrenocortical Function
Plasma cortisol 24 hour urinary free cortisol Serum ACTH Serum DHEA-S diurnal variation response to stimulation or suppression more informative correlates well with secretory rates good screening test for adrenal hyperfunction high in primary adrenal insufficiency low in secondary adrenal insufficiency the main adrenal androgen

Dexamethasone (DXM) Suppression Tests (DSn
• gold standard to determine presence and etiology of hypercortisolism • principle: DXM suppresses pituitary ACTH, so plasma cortisol should be lowered by negative feedback if HPA axis were normal • single dose DST: simple and reasonably accurate screening test • DXM 1 mg given at 2300 hrs would suppress pituitary ACTH production in healthy individuals, so that the normal 0800 hrs peak of plasma cortisol would fail to develop • 95% of Cushing's syndrome patients would fail to suppress • <20% false +ve results due to simple obesity, depression, alcohol, other medications • cmmImatQry tests • low dose DST: 0.5 mg DXM q6h for 48 hours, then 24 hour urinary free cortisol (UFC) twice -+ normally the UFC level would be reduced to < 54 nrnol/day

E32 Endocrinology

Adrenal Cortex

Toronto Notes 2008

• high dose DST (8mglday): 70-80% of those with adrenal cortex hyperplasia due to hypersecretion of pituitary ACTH would show suppression, whereas adrenal cortisol-producing adenoma/carcinoma and ectopic ACfH would show no changes in UFC levels or serum cortisol • however, 30-40% of ectopic ACTH tumours may partially suppress • plasma ACTH assay supplements DST for differentiation of the various etiologies of Cushing's

Short Cosyntropin Stimulation Test
• for diagnosing adrenal insufficiency, note: dexamethasone treatment does not interfere with this assay • cosyntropin is an ACTH analogue • 250 f-lg of cosyntropin 1M or IV, measure serum cortisol and ACfH at baseline (0), and cortisol at 30 and 60 minutes • physiological response: increase in plasma cortisol level by >250-500 f-lill0l/L or doubling of baseline and an absolute level of >550 f-lmol/L (rules out primary adrenal insufficiency) • inappropriate response: inability to stimulate plasma cortisol rise


• diastolic hypertension without edema; decreased renin and increased aldosterone secretion both of which are unresponsive to increases in volume

• aldosterone-producing adrenal adenoma (Conn's syndrome) (75%) • adrenal hyperplasia (25%): (a) idiopathic (b) glucocorticoid-remediable aldosteronism • adrenal carcinoma (1%) • adrenal enzyme defect (see Pediatrics, P30)

Clinical Features
• • • • hypertension refractory to standard treatment polyuria, polydipsia, nocturia fatigue, weakness, paresthesia, headache severe cases: tetany, intermittent paralysis

• electrolytes: -j,K, -j,Mg, tNa • high 24 hour urinary or plasma aldosterone + low random plasma renin

• medical: spironolactone or amiloride; hydrochlorothiazide (HCTZ) or ACE inhibitor might be added for better blood pressure control • surgical: removal of adenoma


• increase in aldosterone in response to activation of renin-angiotensin system

Etiology and Pathophysiology
Table 23. Etiology and Pathophysiology of Hyperreninism
(a) primary hyperreninism (b) secondary hyperreninism


• renin-producing tumour • renal artery stenosis • CHF, cirrhosis, nephrosis • diuretics/laxative abuse • Bartler's syndrome • hypoperfusion of kidneys • decreased effective circulating volume • JGA hyperplasia

Toronto Notes 2008

Adrenal Cortex

Endocrinology £33


_--';Zoo_ _011-_


• results from chronic glucocorticoid excess (endogenous or exogenous sources)

• ACTH-dependent (85%): bilateral adrenal hyperplasia and hypersecretion due to: • ACTH-secreting pituitary adenoma (Cushing's disease - 80% of ACTH-dependent) • ectopic ACTH-secreting tumour (e.g. small cell lung carcinoma, bronchial, carcinoid, pancreatic, adrenal or thyroid tumours) • ACTH-independent (15%) • long-term use of exogenous glucocorticoids • primary adrenocortical tumours: adenoma and carcinoma (uncommon) • bilateral adrenal nodular hyperplasia

Clinical Features

red cheeks, acne, moon face

purple striae

large abdomen

thin arms and legs



Figure 11. Features of Cushing's Syndrome
clinical features suspicious for hypercortisolism
~ 24 hour urinary free cortisol ~





<4X itease low dte DST to confirm diagnosis

measure ACTH

>4X increase

Cushing's syndrome

diaglis of Cushing's syndrome established



ACTH increased



ACTH decreased


MRI pituitary, inferior petrosal sinus sampling with CRF stimulation test • DST =DXM suppression test

CT adrenal, confirmatory high-dose DST

Figure 12. Hypercortisolism: Algorithm for Diagnosis

EM Endocrinology

Adrenal Cortex

Toronto Notes 2008

Treatment • pituitary • transsphenoidal resection, with glucocorticoid supplement peri- and post-operatively • irradiation: only 50% effective, with significant risk of hypopituitarism • adrenal • adenoma: unilateral adrenalectomy (curative) • carcinoma: palliative (frequent metastases, poor prognosis); adjunctive chemotherapy often not useful • ectopic ACTH tumour - usually bronchogenic cancer (a paraneoplastic syndrome) • chemotherapy/radiation for primary tumour • agents blocking adrenal steroid synthesis: metyrapone or ketoconazole • poor prognosis


Congenital Adrenal Hyperplasia
(see Pediatrics, P30)



-----~~------_ Definition • state of having excessive secretion of androgens
Etiology and Pathophysiology


Table 24. Etiology of Hyperandrogenism
Constitutional/Familial Medications androgen-mediated Ovarian tve family history, predisposing ethnic background

anabolic steroids, ACTH, androgens, progestational agents PCOS (see Gynecology, GY24) ovarian hyperthecosis theca cell tumours congenital hyperplasia (CAH, late-onset CAH) tumours Cushing's disease - high ACTH



Clinical Features
Hirsutism • male pattern growth of androgen-dependent terminal body hair in women: back, chest, upper abdomen, face, linea alba Virilization • masculinization: hirsutism, temporal balding, clitoral enlargement, deepening of voice, acne • increase in musculature Defeminization • loss of female secondary sex characteristics (i.e. amenorrhea, decreased breast size)

1Wo conditiORl that do NOT repr8I8IIt true hinutism
1. androgen-independent hair (e.g. lanugo hair) 2. drug-induced hypertrichosis (e.g.phenytoin,diazoxide, cyclosporine, minoxidill

Investigations • increased testosterone • increased LH/FSH, seen commonly in PCOS as ratio >2.5 • DHEA-S as measure of adrenal androgen production • 17-0H progesterone is elevated in CAH due to 21-0H deficiency Treatment • discontinue causative medications • oral contraceptives (e.g. cyproterone acetate - blocks androgen receptor; found in Diane 35™) • spironolactone - acts as peripheral androgen antagonist • cosmetic therapy • low dose glucocorticoid if CAB suspected

Toronto Notes 2008

Adrenal Cortex

Endocrinology E35

Adrenocortical Insufficiency


Table 25. Etiology of Primary Adrenocortical Insufficiency
Autoimmune (70·90%) Isolated adrenal insufficiency (most common in developed world) Polyglandular autoimmune syndrome type I & II (60-75% of pts have antibodies against adrenal enzymes and 3zones of the cortex1 Infection T8 (7·20%1 (most common in developing world) Fungal: histoplasmosis, paracoccidioidomycosis

Syphilis African trypanosomiasis Metastatic Ca Adrenal hemorrhage or infection Drugs Others Lung, breast, stomach, colon, lymphoma Coagulopathy in adults or Waterhouse-Friderichsen syndrome in children (meningococcal or Pseudomonas septicemia), heparin, coumadin Ketoconazole, rifampin, phenytoin, barbituates, megestrol acetate Adrenoleukodystrophy Congenital adrenal hypoplasia Familial glucocorticoid deficiency or resistance

• inadequate pituitary ACTH secretion • multiple etiologies (see Hypopituitarism, E20), including withdrawal of exogenous steroids that have suppressed pituitary ACrn production

Clinical Features
Table 26. Clinical Features of Adrenocortical Insufficiency
Acute Adrenal Crisis Clinical Features
Weight loss Weakness Dehydration Hypotension Vitiligo Hyperpigmentation (buccal mucosa, flexor/palmar creases) NxNx +Hx of wt loss +anorexia Acute abdomen Unexplained hypoglycemia Unexplained fever Other autoimmune endocrine deficiencies (e.g. hypothyroidism, gonadal failure)

Chronic Addison's disease 2° adrenal insufficiency
Weight loss Weakness Fatigue Hypotension Vitiligo Hyperpigmentation Anorexia GI: NxNx, constipation, abdo pain, diarrhea Salt craving Postural dizziness Myalgia Arthralgia Many of the signs and symptoms seen in primary adrenal insufficiency are also present here. EXCEPT: Hyperpigmentation GI: less common


Hyponatremia Hyperkalemia Hypercalcemia Azotemia Eosinophilia Anemia Lymphocytosis Hypoglycemia

Hyponatremia Hyperkalemia Hypercalcemia Azotemia Eosinophilia Anemia Low cortisol unresponsive to exogenous ACTH High ACTH Adrenal antibodies if autoimmune etiology

NO hyperkalemia Hyponatremia oiten present Low cortisol, low ACTH Hypoglycemia is mOre common

• acute condition - can be life-threatening • IV NS or D5WINS in large volumes (2-3 L) • hydrocortisone 100 mg IV q6-8h for 24h, then gradual tapering • identify and correct precipitating factors • maintenance • hydrocortisone 15-20 mg PO qam and 5-10 mg qpm • FlorinefTM (synthetic mineralocorticoid, i.e. fludrocortisone) 0.05-0.2 mg PO daily if mineralocorticoid deficient • increase dose of steroid 2- to 3- fold for a few days during illness or for surgery • medical alert bracelet for patient

E36 Endocrinology

Adrenal Medulla

Toronto Notes 2008

Adrenal Medulla
ABC of Adrenaline Adrenaline activates ~receptors, increases Cyclic AMP

Catecholamine Metabolism
• catecholamines are synthesized from tyrosine in postganglionic sympathetic nerves and chromaffin cells of adrenal medulla • predominant adrenal catecholamine = epinephrine (adrenaline) • predominant peripheral catecholamine =norepinephrine (noradrenaline)


• rare catecholamine secreting tumour derived from chromaffin cells of the sympathetic system

• most commonly a single tumour of adrenal medulla • 10% extra-adrenal (95% of which are intra-abdominal), 10% multiple tumours, 10% malignant, 10% familial • rare cause of hypertension «0.2% of all hypertensives) • curable if recognized and properly treated, but fatal if not

Etiology and Pathophysiology
• most cases sporadic • familial: associated with multiple endocrine neoplasia II (MEN II) (50%), von Hippel-Lindau (10-20%), paraganglioma (20%), or neurofibromatosis type 1 (NF l) (0.1-5.7%) • tumours, via unknown mechanism, able to synthesize and release catecholamines • signs and symptoms caused by hypersecretion of catecholamines

Clinical Features
• 50% suffer from paroxysmal HTN, and the rest have sustained HTN • classic triad: episodic "pounding" headache, palpitations/tachycardia, diaphoresis • other symptoms: tremor, anxiety, chest or abdominal pain, nausea/vomiting, visual blurring, wt loss, polyuria, polydipsia • other signs: orthostatic hypotension, papilledema, increased ESR, hyperglycemia, dilated cardiomyopathy • symptoms may be triggered by stress, exertion, anesthesia, abdominal pressure, certain foods (especially tyramine containing foods)

ClassicTriad of PHEochromocytoma
Palpitations Headache Episo~ic sweating.

• urine catecholamines • increased catecholamine metabolites (vanillylmandelic acid + metanephrines) and free catecholamines • total metanephrines: most sensitive test; >6.5 umol/day or 1.2 mg/day • plasma catecholamines • >2000 pg/ml (11.8 mmol/L) diagnostic; >950 pg/ml (5.6 mmol/L) suggestive -, proceed to clonidine suppression test (rarely done) • elevated plasma epinephrine unsuppressed by clonidine (central a-adrenergiC) diagnostic • CT scan • if CT is negative, meta-iodo-benzoguanidine (MffiC) scintigraphy, Octreoscan, or MRI might help

• adequate pre-operative preparation • a-blockade for BP control- phenoxybenzamine (14-21 days pre-op), IV phentolamine (peri-operative) • ~-blockade for HR control - propranolol (initiate only after adequate a-blockade) • metryosine (catecholamine synthesis inhibitor) + phenoxybenzamine or prazosin also used • volume restoration with vigorous salt-loading • surgical removal of tumour with careful pre-operative and post-operative lCU monitoring • rescreen urine one month post-operatively

Toronto Notes 2008

Adrenal Medulla

Endocrinology £37

Multiple Endocrine Neoplasm (MEN)
• • • • neoplastic syndromes involving multiple endocrine glands tumours of neuroectodermal origin autosomal dominant inheritance with variable penetrance genetic screening for RET proto-oncogene on chromosome 10 has long term benefit as to early cure and prevention of medullary thyroid cancer


Table 27. MEN Classification
Type Chromosome Implicated Tissues Involved Clinical Manifestations Ant. pituitary adenomas, often non-secreting but may secrete GH and PRL Primary hyperparathyroidism from hyperplasia Pancreatic islet cell tumours Gastrinoma (peptic ulcers) Insulinomas (hypoglycemia) VIPomas (secretory diarrhea)

Wenner's syndrome

11 IPYGM genel

• Pituitary

• Parathyroid • Entero-pancreatic endocrine

MeN I •Wermer'a Syndrome effecta the 3 Pa Pituitary Parathyroid Pancreas

MEN II 10 3 distinct syndromes (RET proto-oncogene) autosomal dominant lIa Sipple's syndrome

.Thyroid •Adrenal medulla • Parathyroid • Skin 'Thyroid

Medullary thyroid cancer (MTCI (>90%) Pheochromocytoma (40-50%1 1° parathyroid hyperplasia 110-20%) Cutaneous lichen amyloidosis Medullary thyroid ca without other clinical manifestations of MEN lIa or lib

Familial Medullary Thyroid Ca. (a variant of lIa)



• Adrenal medulla • Neurons 'MSK 'GI

Medullary thyroid ca: most common component, more aggressive and earlier onset than MEN lIa Pheochromocytoma Mucosal neuroma, intestinal ganglioneuromas Marfanoid habitus Ino aortic abnormalities) Parathyroid hyperplasia-NOT afeature Chronic constipation Megacolon

• MENI • symptoms of hyperparathyroidism, gastrinoma (abdominal pain, diarrhea, peptic ulcer diseases), and insulinoma • MEN II • family history of MEN syndromes • symptoms related to MTC, hyperparathyroidism, or pheochromocytoma • scaly skin rash (cutaneous lichen amyloidosis in MEN IIa)

• clinical picture depends on the endocrine organs involved and the hormones secreted • MENI • hyperparathyroidism - nephrolithiasis, bone abnormalities, MSK complaints, generalized weakness, and alterations of mental status in severe hypercalcemia • gastrinoma - upper abdominal pain due to peptic ulcers and esophagitis • glucagonoma - rash, anorexia, anemia, diarrhea, glossitis • pituitary tumor - headache, visual-field defects, prolactinoma (erectile dysfunction, decreased libido, amenorrhea, galactorrhea), acromegaly • carcinoid syndrome - flushing, diarrhea, bronchospasm

E38 Endocrinology

Adrenal Medulla

Toronto Notes 2008

• MEN II - physical signs are very variable and often subtle • MTC - neck mass or thyroid nodule; non-tender, anterior neck lymph nodes • pheochromocytoma - elevated BP and HR

• MENI laboratory • gastrinoma - elevated serum gastrin level (>200 nglmL) after an IV injection of secretin at 2 IU/kg of body weight • insulinoma - fasting blood glucose (hypoglycemia) • glucagonoma - elevated blood glucose and glucagon levels • pituitary tumours - assess GH and prolactin levels • hyperparathyroidism - PTH levels; bone density scan (DEXA) imaging • Mill for pituitary tumors, gastrinoma, insulinoma • MENII • laboratory • genetic screening for RET mutations in all index patients; if a mutation is identified, screen family members who are at risk • calcitonin levels, urine catecholamines, vanillylmandelic acid and metanephrine screen (pheochromocytoma); serum Ca and PTH levels (hyperparathyroidism) • pentagastrin +/- Ca stimulation test if calcitonin level is within reference ranges • imaging • CT or Mill for imaging of the adrenals • metaiodobenzylguanidine (MIBG) scan for pheochromocytoma • radionuclide scanning for determining the extent of metastasis • octreoscan for examining the spread of MTC • FNA (fine-needle aspiration)

• MENI • surgery is indicated for hyperparathyroidism, insulinoma, glucagonoma, pituitary tumours (transsphenoidal surgery with external radiation when medical treatment fails) • PPI for acid hypersecretion in gastrinoma • bromocriptine or other dopamine agonists to suppress prolactin secretion • somatostatin for symptomatic carcinoid tumors • MEN II • surgery for MEN IIa • pre-op treatment: • PG inhibitors to alleviate diarrhea associated with thyroid cancer • a-blocker for at least 2 weeks for pheochromocytoma • hypercalcemia - hydration; if remains severely hypercalcemic, consider calcitonin or bisphosphonates • post-op treatment: • hormone replacement following total thyroidectomy and bilateral adrenalectomy • calcium supplement and/or vitamin 0 for post-op hypoparathyroidism

Toronto Notes 2008

Calcium Homeostasis

Endocrinology E39

Calcium Homeostasis
• • • • • normal total serum Ca: 2.25-2.62 mmol/L; 9.0-10.5 mg/dL ionic/free Ca levels: 1.15-1.31 mmol/L; 4.6-5.25 mgldL serum Ca is about 50% protein bound (mostly albumin) regulated mainly by two factors: parathyroid hormone (PTH) and vitamin D actions mainly on three organs: GI tract, bone, and kidney

Parathyroid Hormone (PTH)
• secretion increased by low serum Ca and inhibited by low serum Mg (chronic) • not influenced directly by P04 (except by P04 effect on the ionic calcium levels)

UV light


~/ cholecalciferol
Bone 1'osteoclast activity Kidney ...... - - - - - 25 (OH) vit D (liver) 1




Release of Ca and PO.


1'Ca and Mg reabsorption 1'PO' excretion in urine and -J.-renal tubular reabsorption of PO.



Calcitriol formation

1'bone resorption

bone osteoclast

1'GI Ca and HPO. absorption



24, 25 (OH 2 ) vit D (inert)


kidney -J.-Ca and PO. excretion

1'Ca and HPO. release Net Effect

• l' ECF Co, Vit D
• -J.- ECF phosphate

Figure 13. Parathyroid Hormone (PTH) Regulation

Vitamin D
• necessary for Ca and P04 absorption from GI tract • cholecalciferol formed in the skin by the action of UV light

• polypeptide secreted by thyroid C cells • secretion enhanced by Ca, GI hormones, pentagastrin • major actions • decreased osteoclastic bone resorption (pharmacological effect) • increased renal P04 and Na clearance • acute net effect: decreased serum Ca when given in pharmacologic doses

• major intracellular divalent cation • Ca is reabsorbed from the kidney with Mg, and thus Ca balance is difficult to maintain in Mg deficiency

• intracellular cation • found in all tissues and necessary for most biochemical processes as well as bone formation

E40 Endocrinology

Calcium Homeostasis

Toronto Notes 2008

Table 28. Summary of Effects Hormone
Parathyroid Hormone IPTH)

Net Effect
l' Ca 1'Vit D


Vitamin D

l' Ca l' PO.
-J, Ca

Calcitonin (in pharmacologic doses)


• total corrected serum Ca >2.62 mmol/L (10.5 mg/dL) OR ionized Ca >1.35 mmol/L (5.4 mg/dL) • corrected Ca (mmol/L) = measured Ca + 0.25 (40 - albumin) 10 • for every -.l-- in albumin by 10, l' in Ca by 0.25
High or Normal PTH
Primary Hyperparathyroidism Imajor cause of hypercalcemial . Solitary adenoma 81 % - Hyperplasia 15% - Carcinoma 4% - MEN I and lIa Suspect if: -positive FHx -Hx of MENlllla -Hx of childhood H+N radiation -postmenopausal woman -normal physical exam - Presentation: 50% asymptomatic, renal calculi, neuromuscular disease, decreased bone density and associated consequences -asymptomatic with prolonged hyperparathyroidism -Investigations: serum Ca, PO., PTH, diagnostic imaging for renal calculi and osteopenia -Treatment: continued surveillance vs. surgery

benign (less likely malignant): <2.75 mmolll III mgldLI pathologic (more likely malignant!: >3.25 mmolll (13 mgldL)

Secondary Hyperparathyroidism

Suspect if: - chronic renal failure due to decreased Vit Dsynthesis Suspect if: -chronic renal failure -renal transplant patient Suspect if: -asymptomatic patient -hypocalciuric - Persistent increase in PTH after correction of secondary hyperparathyroidism

watch Out For: • volume depletion via diuresis

Tertiary Hyperparathyroidism

• arrhythmias
Familial hypocalciuric hypercalcemia IFHHI -Autosomal dominant -positive FHx

- Mutation in calcium sensing receptor gene leads to inappropriate secretion of PTH and excessive tubal reabsorption of calcium -DDx of hypocalciuria: FHH, milk alkali syndrome, thiazide, primary hyperparathyroidism if concomitant Vit Ddeficiency - Increase in set point where PTH secretion will be suppressed

Drug induced - Lithium



or nonnal p osphate


VIt o related .._ ~


ea lCldiol or VitD




~ phosphate (related 10 t PTHrP)
Ree, Pheochromocytoma)



Mfla b) lies 0

--...... t


1- Hypervitaminosis vit 0 I 0: excessive intake of or its metabolites 1


-Granulomatous disease i.e. TB, sarcoid, lymphoma tesp Hodgkins) which causes extra renal produdion of calcitriol by macrophages in the lung and lymph nodes ·Excessive caJcjtriol intake

... - Immobilization - Milk alkali syndrome (hypercalcemia with alkalosis and renal failure) - Drugs: thiazide diuretics, CaC0 3 , theophylline, estrogenftamoxifen - Metastatic bone disease i.e. breast Ca which is mediated by Osteoclast Activating Factor (OAF) and various cytokines • High bone turnover i.e. hypervitaminosis A, thyrotoxicosis, Pagel's Disease

Figure 14. Etiology and Clinical Approach to Hypercalcemia

Toronto Notes 2008

Calcium Homeostasis

Endocrinology E41

Clinical Features • symptoms dependent on the absolute Ca value and the rate of its rise (may be asymptomatic)
Table 29. Symptoms of Hypercalcemia
Cardiovascular Hypertension Arrhythmia Short OT Deposition of Ca on valves, coronary arteries, myocardial fibres GI Constipation Anorexia Nausea Vomiting Igroansl PUD pancreatitis Renal Rheumatological MSK Weakness Bone pain (bonesl Psychiatric Neurologic

Polyuria Gout Polydipsia Pseudogout Nephrogenic 01 Chondrocalcinosis Nephrolithiasis Istonesl Renal failure (irreversiblel

talertness } Hypotonia Anxiety Hyporeflexia Depression Myopathy Cognitive >3 mmollL Paresis dysfunction 112 mgJdLI Organic brain syndromes . Psychosis >4 mmollL 1'6 mg/dLI

The symptoms and signs of hypercalcemia include: 'Sones, stones, psychosisbased moans, and abdominal groans'

Treatment • treatment depends on the Ca level and the symptoms • treat acute, symptomatic hypercalcemia aggressively
Table 30. Treatment of Hypercalcemia
Increase urinary Ca excretion Diminish bone resorption Isotonic saline (4-5 L) ± loop diuretic (i.e. furosemide) but only if hypervolemic Sisphosphonates (Txof choice) • inhibit osteoclast activity • indicated in malignancy-related hypercalcemia IV pamidronate is most commonly used several days 12-4 days) until full effect but effect is long-lasting 12-4 weeks) Calcitonin -. additive effect with bisphosphonates • inhibits osteoclastic bone resorption and promotes renal excretion of calcium • acts rapidly but often transient response 1-1- by 0.3-0.5 mmollL (1.2 mg/dL - 2.0 mg/dL) beginning within 4-6 hours) • combination of calcitonin and steroids may prolong reduction in calcium • tachyphylaxis may occur Mithramycin (rarely used)- effective when patient cannot tolerate large fluid load (dangerous - hematotoxic and hepatotoxic) Corticosteroids in hypervitaminosis 0 and hematologic malignancies • anti-tumour effects'" -I- calcitriol production by the activated mononuclear cells in lung and lymph node • slow to act (5-10 days); need high dose

Decrease GI Ca absorption

Dialysis Chelation EDTA or IV phosphate (rarely usedl Oral phosphate in chronic hypercalcemia

Others • prostaglandin inhibitors • surgical treatment if indicated • avoid immobilization

ill Endocrinology

Calcium Homeostasis

Toronto Notes 200S


ocalcemia .....-£.-_._------_......_ - - - - - - - - - - - - - '
• total corrected serum Ca <2.25 mmol/L (9.0 mg/dL)
Iatrogenic hypoparathyroidism Primary hypoparathyroidism - post-thyroidectomy, 1'31 ablation, post surgical correction of primary hyperparathyroidism · Idiopathic/autoimmune hypoparathyroidism: DiGeorge syndrome, polyglandular autoimmune disease (acquired hypoparathyroidism ± adrenal insufficiency +/- gonadal failure ± hypothyroidism and rarely hypopituitarism, diabetes insipidus,Type I DMI -Infiltrative diseases of parathyroid gland · HIV - Under normal circumstances, low Mg level stimulate PTH secretion. However, chronic hypomagnesemia is paradoxically associated with impaired PTH secretion - Low Mg levels also impair peripheral responsiveness to PTH · Drugs: antineoplastic agents (cisplatin, mithramycinl -Alcoholism - Hemochromatosis - In pregnancy, there is alow total Ca due to hypoalbuminemia, but normal ionized level

Low magnesium

Liver dysfunction Pregnancy

High PTH

H phosphate

Vit D related


nonnal Ph1Phate

- Pseudohypoparathyroidism: PTH resistance secondary to Gs protein deficiency

- Decreased Gl absorption (intake, liverlbil1iary)
- Phenytoin

- Chronil.: Renal Failure


. Acute Pancreatitis: release of pancreatic caldecrin decreases bone resorption
- Drugs: Calcitonin, loop diuretics

i Calcitriol

- Vi! 0 dependent rickets type I

- Hereditary Vii D resistant rickets type D (receptor derect)

- Nephrotic Syndrome (lost: Vit D binding protein)

(renal I-alpha-hydroxylase ddiciency)

Figure 15. Etiology and Clinical Approach to Hypocalcemia

Clinical Features
• most characteristic symptom is tetany

Differential Diagnosis ofTetany
• metabolic alkalosis (with hyperventilation) • hypokalemia • hypomagnesemia
Table 31. Clinical Features of Hypocalcemia
Acute Hypocalcemia Laryngospasm (with stridorl Paresthesia Hyperreflexia Tetany Psychiatric Sx: emotional instability, anxiety and depression Chvostek's sign (tap CNVII) Trousseau's sign (carpal spasm) Chronic Hypocalcemia CNS: lethargy, seizures, psychosis, basal ganglia calcification, Parkinson's, dystonia, hemiballismus, papilledema, pseudotumour cerebri CVS: prolonged or interval GI: steatorrhea ENDO: impaired insulin release SKIN: dry, scaling, alopecia, brittle and transversely fissured nails, moniliasis, abnormal dentition OCULAR: cataracts MSK: generalized muscle weakness and wasting

Toronto Notes 2008

Calcium Homeostasis

Endocrinology E43

Treatment • correct underlying disorder • mild/asymptomatic (ionized Ca >0.8 mmol/L, 3.2 mg/dL) • treat by increasing dietary Ca by 1000 mg/day • acute/symptomatic hypocalcemia (ionized Ca <0.7 mmol/L, 2.8 mg/dL) • immediate treatment required • IV calcium gluconate 1-2 g in 10-20 mins followed by slow infusion if necessary • goal is to raise Ca to low normal range (2.0-2.1 mmol/L, 8.0-8.4 mg/dL) to prevent symptoms but allow maximum stimulation of PTH • if PTH recovery not expected, requires long-term therapy with vitamin D and calcium • do not correct hypocalcemia if it is suspected to be a transient response

1·'Signs and Sympotma of
Acute Hypocalcemia
• Paresthesias: perioral, hands and feet • Chvostek's sign: percussion of the facial nerve just anterior to the extemal auditory meatus elicits unilateral spasm of the orbicularis oculi or orbicularis oris muscle • Trousseau's sign: inflation of a blood pressure cuff above systolic pressure for 3minutes elicits carpal spasm and paresthesia

• pathophysiology: 2 general mechanisms

Etiology • increased intake • GI intake (rectal enema, GI bleeding) • IV phosphate load (K-Phos, blood transfusion) • endogenous phosphate (tumour lysis syndrome, rhabdomyolysis, hemolysis) • reduced renal clearance • ARF/CRF • hypoparathyroidism • acromegaly tumour calcinosis (ability of kidney to specifically clear phosphate is defective) Clinical Features • non-specific Treatment • low P04 diet, phosphate binders (e.g. CaC03 )



• pathophysiology: 4 general mechanisms


Etiology • inadequate intake • starvation • malabsorption (diarrhea, steatorrhea) • antacid use • alcoholism • renal losses • hyperparathyroidism • diuretics • x-linked or AD hypophosphatemic rickets • Fanconi syndrome • excessive skeletal mineralization • osteoblastic metastases • I?ost parathyroidectomy (referred to as 'hungry bone syndrome') • P0 4 shift into ICF • recovery from metabolic acidosis • respiratory alkalosis • starvation refeeding (stimulated by insulin) Clinical Features • non-specific (CHF, coma, hypotension, weakness) Treatment • treat underlying cause, supplement with oral P04 : 2-4 g/d divided bid-qid (start at 1000 mg/d to minimize diarrhea)



• pathophysiology: 2 general mechanisms

E44 Endocrinology

Calcium HomeostasislMetabolic Bone Disease

Toronto Notes 2008


Review: BiIp/loIphonIl8IlIld OIteonecrosis of the J-. IAmlnrem Med2006; 144:75~111 SIUdy. Review of the I~erature on osteonecrosis of the jaws 1368 reported cases) w~h discussion of risk factors, prevalence, clinical manifestations and treatment strategies. Main Rlltults. Risk factors include the type, dose and duration of treatment w~ bisphosphonate, and history of trauma or dental surgeryfinfection. 94% of described cases received IV pamidronate or zoledronic acid, and most cases 185%1 had either multiple myeloma or metastatic breast can· cer, although cases have been reported in patients taking oral bisphosphonates lalendronate, etc.1for osteoporosis or Paget disease of bone. 60% of described cases had recent dentoalveolar surgery. Prevalence has been reported between 7·10% and 3·10% for patients treated with IV bisphosphonates for mu~iple myeloma and breast cancer, respectively. Involvement of the mandible alone (65%1 was more common than involvement of the maxilla or both sites. One third of cases were painless and there was a3:2 female to male ratio. In general, treatment consists of pain control, con· servative debridement, antibiotics, antimicrobial mouth rinses, and withdrawal of bisphosphonate therapy. Conclusion: Patients receiving IV nitrogen-con· taining bisphosphonates for multiple myeloma or metastatic breast cancer are at greatest risk for osteonecrosis of the jaws. Future research is needed to clarify risk factors and optimize current treatment practices.

• Mg-containing antacids given to those with severe renal failure • IV administration of large doses of MgS04 (e.g. for pre-eclampsia - see Obstetrics, OB14)

Clinical Features
• drowsiness, hyporeflexia, respiratory depression, decreased deep tendon reflexes

• stop Mg-containing products

• pathophysiology: 2 general mechanisms

• GI
• starvation • malabsorption • vomiting • alcoholism • acute pancreatitis • excess renal loss • 2° hyperaldosteronism due to cirrhosis and CHF • hyperglycemia • hypokalemia • hypercalcemia

Clinical Features
• seizures, paresthesia, Chvostek and Trousseau signs

• Mg IM/IV (note: cellular uptake of Mg is slow therefore repletion requires sustained correction)

o Bisp/loIpIlon8I in OIl8oporosis INEJM 1995;333:1437-431 Study. Randomized, blinded, placebo-controlled trial 13 year follow-up). p,IienIJ: 994 post-menopausal women Imean 64 yrs, 87% white) with low BMD 1~.5). Exclusions included hx of glucocorticoid use, other disorders of bone, active PUD, and renal or hepatic insufficiency. /ntemntion: alendronate 5mg, 10 mg, 20 mg, or placebo, each once daily. All received calcium 500 mglday. In the 3'" year, women in the 20 mg group were blindly switched to 5mg. MIin oull:omel: Change in BMD, new vertebral fractures, and height IIBtuIlr: Women in all 3alendronate groups had sig· nificant increases in BMD, while those in the placebo group had significant decreases, Women taking alendronate had fewer new vertebral fractures IRRR 52%, NNT 34, 95% CI16 to 518), and alower mean loss of height (p:lI,005I. There were no significant differences between groups for non-vertebral fractures, adverse effects, or discontinuation rates. Conclusion: In post-menopausal women with osteoporosis, alendronate increased BMD, and reduced the risk of new vertebral fractures.

Metabolic Bone Disease
• a condition characterized by decreased bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to bone fracture

Etiology and Pathophysiology Primary Osteoporosis
Table 32. Etiology and Pathphysiology of Primary Osteoporosis
Type I Main Causes Pathophysiology Bones involved Commonlv seen fracture Type II

Postmenopausal decline in estrogen

Increasing age

High turnover: net increase in osteoclastic Low turnover: net decrease in osteoblastic activity activity Trabecular bone Wrist, vertebral crush fractures Trabecular + Cortical Hip, proximal humerus pelvis, vertebral bodies

Secondary Osteoporosis • gastrointestinal diseases • gastrectomy • malabsorption • chronic liver disease • bone marrow disorders • multiple myeloma • lymphoma • leukemia • endocrinopathies • Cushing's syndrome hyperparathyroidism hyperthyroidism

Toronto Notes 2008

Metabolic Bone Disease

Endocrinology E45

• premature menopause • diabetes • malignancy • multiple myeloma • breast cancer • prostate cancer • drugs • corticosteroid therapy ---+ 2nd most common cause of osteoporosis • mechanism: increased resorption + decreased formation • phenytoin • chronic heparin therapy • androgen deprivation therapy aromatase inhibitors • others • rheumatologic disorders • rheumatoid arthritis • SLE • ankylosing spondylitis renal disease • poor nutrition Immobilization

SEIlMs in osteoporosis - MORE trial

(JAMA 1999;282:63745) Study. Randomized, blinded, placelxH:ontrolied
trial (36 month follow-up). PatilInls: 7705 post-menopausal women (mean 67 yrs, 96% white) with low BMD It<l.5}, stratified according to presence or absence of vertebral fractures at baseline. Exclusions included abnonmal uterine bleeding, hx of breast or endometrial ca, hx of thromboembolism, and post-menopausal symptoms. InteIWntioo: raloxifene 60 mg, raloxifene 120 mg, or placebo, each once daily. All received calcium 500 mglday, and cholecalciferol 400-600 IU/day. lllain outcomes: Incident vertebral fractures, and change in BMD. I/esuIls: In both study groups, the rate of vertebral fractures was lower for women taking either 60 mg or 120 mg of raloxifene (RRR 35% and 46%, NNT 22 and 29, respectively). The treatment effect was greater for women with previous fractures INNT 10 with 120mgldl. Both raloxifene groups showed significant increase in BMD {p<O.OO1I. The incidence of venous thromboembolism was significantly higher in the treatment groups (RR 3.1). Conclusion: In post-menopausal women with osteoporosis, raloxifene reduced the incidence of vertebral, but not non-vertebral fractures.

Risk Factors
• low peak bone mass • small Caucasian or Asian females • family history • estrogen-related bone mass • early menopause (before age 45) • oophorectomy • amenorrhea • advanced age (>65) • secondary to medical disease (rheumatoid arthritis, thyroid disease, malabsorption) • lifestyle (diet, smoking, alcohol, caffeine) • minimal weight-bearing physical activity • drugs (glucocorticoids, heparin)


Key Risk of Osteoporosis • advanced age (>651 • history of fragility fracture >age 40 'Iow bone mass • family history of osteoporotic fracture

Clinical Features
• • • • commonly asymptomatic pain, especially backache collapsed vertebrae ---+ height loss fractures • hip, vertebrae, humerus, and wrist most common • Dowager's hump = collapse fracture of vertebral bodies in mid-dorsal region X-ray: vertebral compression and crush fractures, wedge fractures, "codfishing" sign (weakening of subchondral plates and expansion of intervertebral discs)



9)--------------, Calcium ContlInt in Common Foods Standard Porlion CalcilJm

11ft and Milk products Cheese - Brk*, Cheddar,

1.75 0I8J 9 112 cull'125 ml

353 mg 87 mg

Colby, Edam, Gouda
Cheese-cottage, creamed, 2%,1% Cheese - Mozzarella Cheese- SlIiss, Gruyere k:ecream Milk-powde!,dry Milk -whole, 2%, 1%, skim Yogourt

• usually normal serum Ca, PO-v alkaline phosphatase • also measure 25(OH)-vit D, TSH, serum and urine protein electrophoresis, celiac workup and 24 hr urinary Ca excretion to rio secondary causes • Densitometry • dual-energy x-ray absorptiometry (DEXA) - the gold standard in diagnosis of osteoporosis, (quantitative CT, ultrasonography) lumbar spine and femur compared with gender and ethnicity-matched controls • bone mineral density 1.0-2.5 SD below mean= osteopenia; >2.5 SD below mean = osteoporosis

1.75 oz.'j() 9 1.75oz.'j() 9 112 cull'115ml 3tbsp145ml 1glass250 ml
175 9

269 m9 493 mg 93mg 159m9 315 m9 320 mg

Screening: Who should we screen?
• good evidence to recommend screening postmenopausal women to prevent fragility fractures; screening is effective at identifying postmenopausal women at risk and treatment reduces the risk of fractures (grade A recommendation) • screening for postmenopausal women: age 2:65 years OR previous fragility fracture OR weight <60 kg OR SCORE questionnaire 2:6 OR ORAl score ~9, if YES should have DEXA performed, if NO should be reassessed in 1-2 years time. note: SCORE and ORAl are risk assessment tools for osteoporosis (available online)
See: Cheung, A et al. Prevention of osteoporosis and osteoporotic fractures in post-menopausal women: recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ. May 25,2004: 170 (111. Physician's guide to prevention and treatment of osteoporosis. National Osteoporosis Foundation. 2003.

Meat, fish, poultry IIld IItematMs ,lJmonds 112cupl115ml 2oom9 Beans-cooked 1cupl250 ml 90mg Sardines, llith bones 8small 153mg Sesame seeds 112 cupl125ml 100mg Soybeans -cooked 1cupl250ml 175mg Tofu -with calcium sulfate 112cupl115ml 130mg Breads and cereals Bread -whnelwhea1 1~K:eI3Og 15mg Muffin-bran 50mg 11359 Fruits and vegetables Broccoli - raw 112 cupl125ml 38mg Rgs-dried 10 270m9 Orange 1mediuml100 9 52m9 Combination dishes Baked beans -canned lcupl250ml 163mg lasagna - homemade 1cupl25Oml 286mg Soup made with milk 1cupl250 ml 189mg
Adapted from Health Canada: Canadian Nutrient RIe, 1991.

E46 Endocrinology

Metabolic Bone Disease

Toronto Notes 2008


.....'.}------------, ,
Bisphosphonates are considered 1st - line treatment in women with established osteoporosis.

Prevention and Lifestyle Modification: All postmenopausal women • diet: adequate intake of calories, elemental calcium (1000-1500 mg/day), vit 0 400-800 IV/day • exercise: recommended 3x30 min weight-bearing exercises per week • cessation of smokin~, reduce daily caffeine intake • discontinuation/avOldance of osteoporosis-inducing drugs Drug Therapy: Postmenopausal women, positive screen for osteoporosis • bisphosphonates: inhibitors of osteoclast binding; alendronate or risedronate • selective estrogen-receptor modulator (SERM): agonistic effect on bone but antagonistic effect on uterus and breast; raloxifene prevents osteoporotic fractures (grade A to B recommendation), improves lipid profile, decreases breast cancer rIsks, but can increase the risk of DVT/PE, stroke mortality, hot flashes and leg cramps Drug Therapy: Postmenopausal women, positive screen for osteoporosis + fragility fracture • bisphosphonates (aledronate, etidronate, oral pamidronate) or SERM (raloxifene) or parathyroid hormone (18-24 mos duration) • if above not tolerated, calcitonin or HRT can be considered • calcitonin (2nd-line treatment) - osteoclast receptor binding; 200 IV/day administered nasally; calcitriol 0.25 ug bid • HRT - for most women the risks may outweigh benefits (grade 0 recommendation), combined estrogen-progestin therapy prevents number ofhip, vertebral and total fractures (risks of bone health vs. breast cancer risk/cardiovascular risk) • combination therapy (synergistic): estrogen + bisphosphonate Potential New Treatments • strontium • growth factors


Osteomalacia a_n_d_R_i_ck_e_ts _~ _


• rickets - osteopenia with disordered calcification leading to higher proportion of osteoid (unmineralized) tissue prior to epiphyseal closure (in childhood) • osteomalacia - osteopenia with disordered calcification leading to higher proportion of osteoid (unmineralized) tissue after epiphyseal closure (in adulthood)

Etiology and Pathophysiology
Vitamin D Deficiency • leads to secondary hyperparathyroidism and hypophosphatemia • deficient uptake or absorption • nutritional deficiency • malabsorption: post-gastrectomy, small bowel disease (e.g. Celiac sprue), pancreatic insufficiency • defective 25-hydroxylation • liver disease • anticonvulsant therapy • loss of vit 0 binding protein • nephrotic syndrome • defective l-a-25 hydroxylation • hypoparathyroidism • renal failure Mineralization Defect • abnormal matrix • osteogenesis imperfecta • fibrogenesis imperfecta • axial osteomalacia • enzyme deficiency • hypophosphatasia (inadequate ALP bioactivity) • presence of calcification inhibitors • bisphosphonates, aluminum, high dose fluoride, anticonvulsants Phosphate Deficiency • decreased intake • antacids • impaired renal reabsorption • primary defect: Wilson's syndrome, Fanconi syndrome, multiple myeloma • secondary defect: primary hyperparathyroidism, oncogenic osteomalacia

Toronto Notes 2008

Metabolic Bone Disease

Endocrinology £47

Table 33. Clinical Presentations of Rickets and Osteomalacia
Rickets Osteomalacia

• skeletal pain and deformities, bowlegs • fracture susceptibililty • weakness and hypotonia • disturbed growth • ricketic rosary (prominent costochondral junctionsl • Harrison's groove (indentation of lower ribsl • hypocalcemia

• not as dramatic • diffuse skeletal pain • bone tenderness • fractures • gait disturbances (waddling) • proximal muscle weakness • hypotonia

Investigations Table 34. Laboratory Findings in Osteomalacia and Rickets
Disorder Serum phosphate Serum calcium Serum ALP Other features

Vit 0 deficiency Hypophosphatemia Proximal RTA Conditions assoc with abnormal matrix formation

-It -It -It

-It to Normal Normal
Normal Normal

t -It to Normal
Normal Normal

-It calcitriol
Assoc with hyperohloremic metabolic acidosis

• radiologic findings • pseudofractures, fissures, narrow radiolucent lines - thought to be healed stress fractures or the result of erosion by arterial pulsation loss of radiologic distinctness of vertebral body trabecula, concavity of the vertebral bodies • changes due to secondary hyperparathyroidism: subperiosteal resorption of the phalanges, bone cysts, resorption of the distal ends of long bones others: bowing of tibia, coxa profundus hip deformity • bone biopsy • usually not necessary but considered the gold standard for diagnosis

• • • • • depends on the underlying cause vitamin D supplementation P04 supplements if low serum P04 is present Ca supplements for isolated calcium deficiency HC03 if chronic acidosis

_.zRenal Osteodystrophy


• represents a mixture of four types of bone disease • low tum-over osteomalacia - from acidosis and retention of toxic metabolites • osteoporosis - metabolic acidosis dissolution of bone buffers • osteitis fibrosa cystica - from increased P1H • osteosclerosis - from increased P1H • metastatic calcification secondary to hyperphosphatemia may occur

• metabolic bone disease secondary to chronic renal failure • combination of hyperphosphatemia (inhibits 1,25(OH)z-vit D synthesis) and loss of renal mass (reduced l-a-hydroxylase)

Clinical Features
• • • • • soft tissue calcifications .~ necrotic skin lesions if vessels involved osteodystrophy --+ generalized bone pain and fractures pruritus neuromuscular irritability and tetany may occur radiologic features of osteitis fibrosa cystica, osteomalacia, osteosclerosis, osteoporosis

• prevention • maintenance of normal serum Ca and 1'04 by restricting P04 intake to 1 glday • Ca supplements • P04 binding agents

E48 Endocrinology

Metabolic Bone Disease

Toronto Notes 2008

• prophylactic use of vitamin D with close monitoring to avoid hypercalcemia and metastatic calcification


Paget's Disease of Bone
• a metabolic disease characterized by excessive bone destruction and repair

• a common disease: 5% of the population, 10% of population >80 years old

• postulated to be related to a slow progressing viral infection of osteoclasts, possibly paramyxovirus • strong familial incidence

• initiated by increased osteoclastic activity leading to increased bone resorption; osteoblastic activity increases in response to produce new bone that is structurally abnormal and fragile

Differential Diagnosis
• primary bone lesions • osteogenic sarcoma • multiple myeloma • fibrous dysplasia • secondary bone lesions • osteitis fibrosa cystica • metastases

Clinical Features
• • • • • usually asymptomatic (routine x-ray finding or elevated alkaline phosphatase) severe bone pain (e.g. pelvis, femur, tibia) is often the presenting complaint skeletal deformities - bowed tibias, kyphosis, frequent fractures skull involvement - headaches, increased hat size, deafness increased warmth over involved bones due to increased vascularity

• laboratory • serum alkaline phosphatase is usually very high (unless burnt out) • normal or increased serum Ca • normal serum PO,. • increased urinary hydroxyproline (indicates resorption) • imaging • evaluate the extent of disease with bone scan • initial lesion may be destructive and radiolucent • involved bones are expanded with cortical thickening and denser than normal • multiple fissure fractures in long bones

• local fractures osteoarthritis cranial nerve compression and palsies, e.g. deafness spinal cord compression osteosarcoma/sarcomatous change • 1 to 3% • indicated by marked bone pain, new lytic lesions and sudden increased alkaline phosphatase • systemic • hypercalcemia and nephrolithiasis • high output congestive heart failure due to increased vascularity • • • • •

• symptomatic therapy • treat if ALP >3x normal • bisphosphonates, e.g. alendronate 40 mg PO OD or risedronate 30 mg PO OD for 3-6 months • calcitonin 50-100 U/day subcutaneous injection • adequate calcium and vitamin D intake to prevent development of secondary hyperparathyroidism

Toronto Notes 2008

Male Reproductive Endocrinology

Endocrinology E49

Male Reproductive Endocrinology
• both positive and negative feedback may occur by androgens directly or after conversion to estrogen • testosterone (from the Leydig cell) primarily involved in negative feedback on LH, whereas inhibin (from the Sertoli cell) suppresses FSH secretion

Tests of Testicular Function
• testicular size (lower limit = 4 cm x 2.5 cm) • LH, FSH, testosterone • human chorionic gonadotropin (hCG) stimulation test • assesses ability of Leydig cell to respond to gonadotropin • semen analysis • semen volume, sperm count, morphology and motility • testicular biopsy • indicated in the context of normal FSH and azoospermia/oligospermia

• deficiency in gametogenesis or testosterone production


• causes include primary (testicular failure) and secondary (hypothalamic-pituitary failure) • primary hypogonadism is more common than secondary


L o

• primary testicular failure; characterized by increased LH and FSH, increased FSHLH, decreased level of serum testosterone and sperm count

• congenital • chromosomal defects, i.e. Klinefelter syndrome, Noonan syndrome • cryptorchidism • male pseudohermaphroditism • bilateral anorchia • myotonic dystrophy • mutation in the FSH or LH receptor gene • varicocele • disorders of androgen synthesis • germ cell defects • Sertoli cell only syndrome (arrest of sperm development) • Leydig cell aplasia/failure • infection/inflammation • orchitis - mumps, tuberculosis, lymphoma, leprosy • genital tract infection • physical factors • trauma, heat, irradiation, testicular torsion • drugs • marijuana, alcohol, chemotherapeutic agents, ketoconazole, glucocorticoid • autoimmune • chronic systemic disease • acquired immunodeficiency syndrome (AIDS) • idiopathic



Two distinct features of primary hypogonadism 1. The decrease in sperm count is affected to agreater extent than the decrease in serum testosterone level 2. Likely to be associated with gynecomastia


• hypothalamic-pituitary failure; characterized by decreased or normal LH, subnormal level of testosterone and sperm count

E50 Endocrinology

Male Reproductive Endocrinology

Toronto Notes 2008

. . . .!.../

• congenital • Kallman's syndrome, Prader-Willi syndrome, abnormal subunit of LH or FSH • infection • tuberculosis, meningitis (rare) • endocrine • Cushing's syndrome • hypothyroidism • hypopituitarism (pituitary tumours, pituitary apoplexy, hypothalamic lesions) • estrogen-secreting tumours (testicular, adrenal) • drugs • alcohol, marijuana, spironolactone, ketoconazole, GnRH agonists, prior androgen use, chronic narcotic administration • chronic illness • cirrhosis, CRF, AIDS • sarcoidosis, Langerhans cell histiocytosis, hemochromatosis • critical illness • surgery, MI, head trauma • idiopathic

• laboratory - FSH, LH, prolactin, testosterone, TSH • semen analysis

• medications - testosterone replacement or pulsatile GnRH/hCG • surgery - only if testicular tissues are not functioning


• complete androgen insensitivity (testicular feminization) • incomplete androgen insensitivity • 5-a-reductase deficiency • mixed gonadal dysgenesis • defects in testosterone synthesis • infertile male syndrome • undervirilized fertile male syndrome

Clinical Features
• depends on age of onset • fetal life • ambiguous genitalia and male pseudohermaphroditism • prepubertal • poor secondary sexual development, poor muscle development • eunuchoid skeletal proportions (upper/lower segment ratio <1; arm span/height ra tio >1) • postpubertal • decreased libido, erectile dysfunction, infertility • decreased facial and body hair if very significant androgen deficiency (very low levels required to maintain sexual hair) • fine wrinkles in the corners of mouth and eyes • osteoporosis with longstanding hypogonadism

• • • • • appropriate gender assignment in the newborn hormone replacement or supplementation psychological support gonadectomy for crytochidism reduction mammoplasty for gynecomastia

(see Urology, U33)


Erectile Dysfunction
(see Urology, U30)

_ _ _~ ~ _ ~ _ _~


Toronto Notes 2008

Male Reproductive Endocrinology

Endocrinology E51


• True gynecomastia refers to benign proliferation of the glandular component of the male breast, resulting in the formation of a concentric, rubbery, firm mass extending from the nipple(s) • pseudogynecomastia or lipomastia refers to enlargement of soft adipose tissue, especially seen in obese individuals and does not warrant further evaluation

Physiologic • puberty • elderly • neonatal (maternal hormone) Pathologic • endocrinopathies - primary hypogonadism, hyperthyroidism, extreme hyperprolactinemia, adrenal disease • tumours - pituitary, adrenal, testicular, breast • chronic diseases - liver, renal, malnutrition • drugs - spironolactone, cimetidine, digoxin, chemotherapy, marijuana • congenital/genetic - Klinefelter's syndrome • other - idiopathic, familial



..),- - - - - - - - - - - - - ,

Causes of Gynecomastia DOC TECH: Drugs Other Congenital Tumour Endocrine CHronic disease

• decreased androgen production + increased estrogen production • increased availability of estrogen precursors for peripheral conversion to estrogen • androgen receptor blockage + binding of androgen to sex hormone binding globulin (SHBG)

Table 35. Occurence of Gynecomastia
3 peaks % affected

infancy puberty ages 50-80

60-90 4-69 24-65

• • • • • • • • • • recent change in breast characteristics history of trauma to testicles history of mumps alcohol and/or drug use family history sexual dysfunction signs of feminization breast GU stigmata of liver or thyroid disease

Physical Exam

• laboratory - serum TSH, PRL, LH, FSH, free testosterone, estradiol, LFTs, (if ~hCG is elevated, need to locate the primary tumour) • CXR and CT of chest/abdomen/pelvis • testicular U/S to rule out testicular mass

• medical • correct the underlying disorder, discontinue responsible drug • androgens for hypogonadism • anti-estrogens - tamoxifen, clomiphene • surgical • usually required if have macromastia; gynecomastia present for > 1 year; or failed medical treatment and for cosmetic purposes

m ~



Drug Class Biguanide Medlanism of Action •increases sensitivity to insulin in the peripheral tissues; t glucose utilization and ,j, hepatic glucose production •stimulates Insulin release from ~ cells by causing Kchannel closure' depolarization; Ca mediated i~sulin release •use in nonobese Tyoe 2OM Generic Drug Neme Canada Neme mertormin Glucophage® Glumetta® US Nama (if different) Dosing 500 mg 00 titrated to 1000 mg bid maximum Indications •useful in obese Type 2OM •improves both fasting and postprandial hyperglycemia 'alsoHG Contreindications ABSOLUTE: •moderate to severe liver dysfunction • mild renal dysfunction • cardiac dysfunction Side Effects • GI upset labdo discomfort, bloating, diarrheal • lactic acidosis Commants
,j, HbA1C 1.0·1.5%


Insulin secretagogue

sulfonylureas: glyburide

Diabeta®, Euglucon® Mlcronase® Glynase PreTab<!'

2,5·5,0 mg/day titrated to >5 mg bid Max: 20 mg/day 40-160 mg bid 3()'120mg 00


Olamicron@1 Oiamicron MR

glimepiride non·sulfonylureas: repaglinide nateglinide


1-8 mg 00

ABSOLUTE: .~ •moderate to severe liver dysfunction • weight gain RELATIVE' •adjust dose in patients with severe kidney dysfunction land avoid glyburide in these patients) • avoid glyburide in the elderly INTERACTIONS: Do not combine with anon·sulfonylurea or preprandial insulin •Short t,. of I hour causes brief but rapid t in insulin, therefore effective for post prandial control ABSOLUTE: •hypoglycemia •weight gain •severe liver dysfunction •severe renal dysfunction INTERACTIONS: Do not combine with anon·sulfonylurea or preprandial insulin ABSOLUTE: 'peripheral edema •severe liver dysfunction •pulmonary edema •NYHA >class II CHF 'CHF •anemia INTERACTIONS: •weight gain Do not combine with insulin •fractures ABSOLUTE: • Inflammatory bowel syndrome •severe liver dysfunction •flatulence •abdominal cramps •diarrhea

J HbA1C 1,0·1.5%


S S 0






HbAIC lMS% for repaglinide and 0,5·1.0% for nateglinide

GlucoNorm® Starlix®

0,5-4 mg tid 60·120 mg tid

Insulin sensitizers Ithiazolidinedionel

• sensitizes peripheral tissues to insulin ;,j, FFA, ,j, hepatic glucose production • binds to nuclear receptor

rosiglitazone rioglitazone


2·8 mg 00 154SmgOO


HbA IC 1.().1.S%

a·glucosidase inhibitor

.,j, carbohydrate GI absorption by


Prandase Jll

inhibiting brush border a-glucosidase For insulin formulations, please refer to E5-E6

25 mg 00 titrated to 100 mg tid

• ,j, postprandial hyperglycemia

,j, HbA1C 0,S·1.0%


a ::s



<:> <:>



Drug Class-HMG CoA reductase inhibitor Mechanism of Action Generic Drug Name Canada Name lipitor lescol Mevacor Pravachol Crestor locor Bezalip lipidil lopid Niaspan Niacor US Name lif differentl Dosing 10-80 mg/day 20·80mg/day 20·80 mg/day 10·40 mg/day 10·40 mg/day 10·80 mglday 400 mg/day 67-200 mglday 600·1200 mglday 1.5·3 g/day Indications • used for 1'TG, l' LDl, secondary prevention of MI Contraindications • active liver disease • persistent l' in AST, AlT Side Effects •GI symptoms •rash, pruritus '1' liver enzymes • inhibits cholesterol biosynthesis, ,j, lDl atoNastatin synthesis, l' LDl clearance, modest l' fluvastatin lovastatin HDl, limited ,j, VLDl pravastatin rosuvastatin dimvastatin • ,j, lipolysis in adipose tissue, ,j, VlDl,,j, TG, modest,j, lDl, modest l' HDl •inhibits secretion of hepatic VlDl via lPl pathway ~ ~ VlDl and lDl ,j,; ~ clearance of HDl bezafibrate fenofibrate gemfibrozil nicotinic acid





<=> <=>

'" N


• myositis


•used for 1'TG, hyperchylomicronemia

• hepatic disease • renal disease •hypersensitivity •hepatic dysfunction • active PUD 'overtDM •hyperuricemia • complete biliary obstruction • pregnancy • lactation • hypersensitivity • hepatic dysfunction

'GI upset

•l' risk of gallstone formation
• generalized flushing • abnormal liver enzymes •pruritus 'IGT •severe hypertension •constipation


•used for l' lDl, 1'VlDl

Bile acid sequestrants

•resins that bind bile acids in intestinal lumen and prevent absorption thereby HDl • inhibits cholesterol absorption at the small intestine brush border


Questran Prevalite Colestid letia EZelrol

2·24 glday

• used for l' lDL

• flatulence • bloating • fatigue •pharyngitis • sinusitis • abdominal pain • diarrhea • arthralgia
0 0

colestipol Cholesterol absorption inhibitors ezetimibe

5·30g/day 10 mg/day •used for l' lDl, Apo B


:: '" e: ,.., ...
;:T. 0


Drug Class Antithyroid Agent Mechanism of Action • decreases thyroid hormone production by inhibiting iodine and peroxidase from interacting with thyroglobulin to form T4 andT3 • also interteres with conversion of T4toT3 Generic Drug Name propylthiouracil!PTUI Canada Name Propyl·Thyracil US Name (if differentl Dosing Indications Contraindications •hypersensitivity • relative: renal failure, liver disease Side Effects •nausea, vomiting •rash • drug·induced hepatitis • agranulocytosis

Start 100 mg PO tid, •hyperthyroidism then adjust accordingly Thyroid storm: start 200·300 PO qid, then adjust accordingly Start 5·20 mg PO OD, then adjust accordingly levoxyl 0.05-2.0 mglday, in elderly patients start at 0.025 mglday • hypothyroidism

methimazole !MMII Thyroid hormone • synthetic form of thyroxine IT41 levothyroxine I·thyroxine

Tapazole Synthroid levothroid Unithroid

•pregnancy, lactation • recent MI, thyrotoxicosis

• hepatitis • symptoms of hyperthyroidism • tachycardia

'weightloss •hyperthermia • diarrhea • insomnia • tremors • muscle weakness



"'" g.



Drug Class

US Name (if different) Dosing
5mg 00 10 mg 00 or 70 mg once weekly 5·10 mg 00 40 mg 00 for 6months

Med1anism of Action
•inhibits osteoclast·mediated bone resorption

Generic Drug Name

Canada Nama


• esophageal stricture or achalasia lorall •unable to stand or sit upright for >30 min lorall • hypersensitivity • hypocalcemia • renal insufficiency

Side Effacts
'GI • MSK pain • headache •osteonetrosis of the jaw




•prevention of postmenopausal osteoporosIs
•treatment of osteoporosis •glucocorticoid·induced osteoporosis •Paget's disease



5mg 00 or 35 mg once •treatment and prevention of weekly postmenopausal osteoporosis 5mgOD •treatment and prevention of glucocorticoid·induced osteoporosis 30 mg 00 for 2months •Paget's disease 400 mg 00 x14 days q3months with calcium PO •osteoporosis •symptomatic Paget's disease •prevention and treatment of heterotopic ossification after total hip replacement or spinal cord injury •treatment and prevention of postmenopausal osteoporosis IUS onlyl • hypercalcemia of malignancy • Paget's disease •osteolytic bone metastases of breast cancer •csteolytic lesions of mult;ple myeloma •hypercalcemia of maligna,cy •treatment and prevention of skeletal complications related to cancer •treatment and prevention of postmenopausal • lactation osteoporosis (2nd Iinel • pregnancy •active or past history of DVT, PE or retinal vein thrombosis •clinical allergy to calcitonin-salmon 'hotflashes 'Ieg cramps •increased risk of fatal stroke, venous thromboembolism •rhinitis •epistaxis •sinusitis • nasal dryness 'orthostatic hypotension , hypercalcemia •dizziness • leg cramps




Boniva ~

2.5 mg 00 or 150 mg once monthly IV












Selective Estrogen Receptor Modulators

•detreases resorption of bone through binding to estroge' receptors •Inhibits osteoclast·mediated bone resorption



60mg 00




One spray 1200 lUI per •treatment of postmenopausal osteoporosis, day, alternating nostrils greater than 5years postmenopause


•stimulates new bone formation by preferential stimulation of osteoblastic activity over osteoclastic activity



20 ~g SC 00

•treatment of postmenopausal women with osteoporosis who are at high risk for fracture •treatment of men with primary or hypogonadal osteoporosis who are at high risk for fracture

• Paget's disease •prior externai beam or implant radiation therapy involving the skeleton • bone metastases •metabolic bone diseases other than osteoporosis





Drug Class Mechanism of Action Generic Drug Name Canada Name US Name lif differentl Dosing Indications Contraindications Side Effects




~ Z


•Inhibits PTH secretion

1500 mglday (including dietl Divide in 3doses cholecalciferol Ivitamin D31 800lU/day

'osteopenia •osteoporosis •prevention of metabolic bone disease 'osteopenia •osteoporosis •prevention of metabolic bone disease

•caution with renal stones

'vomifing •constipation 'dry mouth •hypercalcemia •headache •nausea, vomiting •constipation




•Regulation of calcium and phosphate homeostasis

•caution in patients on digoxin (risk of hypercalcemia may precipitate arrhythmia)

ergocalciferol IviiaminD21

Osteoforte Deltalin®


•osteoporosis in patients with liver dysfunction, •hypercalcemia refractory rickets, hypoparathyroidism •malabsorption syndrome •decreased renal function •hypocalcemia and osteodystrophy in patients •hypercalcemia with chronic renal failure on dialysis •vitamin Dtoxicity

calcitriol (1,2510HI,·D)

Rocaltrol® CalcijeX®

Start 0.25 vglday Titrate up by 0.25 Vglday at 4-8 week intervals to 0.5-1 Vg1day Start 0.25 vglday Titrate up by 0.25 vg/dayat 2-4 week intervals to 0.5-2 vglday



~ ::s







E56 Endocrinology

Summary Key Questions

Toronto Notes 2008

Summary Key Questions
Questions Answers Polyuria, polydipsia, weight loss, polyphagia, blurry vision, nocturia Autoimmune Impaired insulin secretion, peripheral insulin resistance, and excess hepatic glucose production Biguanlde (e.g. metformin), insulin sensitizer (eg. TZD). insulin secretogogue (e.g. su~onylurea). alpha-glucosidase inhibitor (e.g. acarbosel 0.5-0.7 units/kg


What are the classic symptoms of diabetes?


What is the etiology of Type 10M? What is the pathophysiology of Type 2 OM?


What are the common classes of oral antihyperglycemic agents used in the treatment of Type 2OM? How do you estimate total daily Insulin requirements? What are the microvascular complications of diabetes? What lab test is used to indicate long-term glycemic control? What lab test is used in the diagnosis of diabetic nephropathy? What is Whipple's Triad?



Retinopathy, nephropathy, and neuropathy



Albumin to creatinine ratio


1) Serum glucose below 2.5 mmol/l (45 mg/dl) in males and 2.2 mmolll (40 mg/dl) in females 21 Neuroglycopenic symptoms or adrenergic symptoms 3) Relief provided by glucose administration C-peptide

10. What single lab test is the most useful when investigating the cause of hyperinsulinemic hypoglycemia?

11. What are the classic clinical signs of familial hypercholesterolemia?
12. What is the most common primary hype rc hoi este ro lemia? 13. How do you determine target lipid levels in the treatment of dyslipidemia?

Tendinous xanthomatosis, arcus corneae, xanthelasma

Polygenic hypercholesterolemia

Framingham risk assessment defines patients as High, Moderate, and low risk with corresponding target lDl and TC/HDllevels BMI

14. What defines obesity? 15. What test can differentiate central 01 from nephrogenic DI?

Response to exogenous ADH

16. What is the best test for assessing thyroid function? 17. How do you interpret thyroid function tests?


1° hyperthyroidism: ~ TSH, l'TfT. 2° hyperthyroidism: l'TSH, 1'TfT. 10 hypothyroidism: l'TSH, .J,TfT. 2° hypothyroidism: .J,TSH, .J,TfT. Thyroid U/S (gland size, solid vs. cystic nodule) FNA for cytology (benign vs. malignant) Thyroid scan (functioning vs. non-functioning nodules, high-uptake hyperthyroidism) Dual-energy x-ray absorptiometry (DEXA)

18. What other tests are available for athyroid work up?

19. What is the gold standard for diagnosing osteoporosis? 20. How are DEXA results interpreted?

Normal = T score ~-1.0
Osteopenia = Tscore <-1.0 and >-2.5 Osteporosis = Tscore ~-2.5

Toronto Notes 2llO8

Summary Key Questions

Endocrinology E57

21. Who should be screened for osteoporosis?

Postmenopausal women If age ~65 OR previous fragility fracture OR weight <60 kg OR SCORE questionnaire ~6 OR ORAl score ~9, then perform OEXA Adequate intake of elemental calcium (1000-1500 mg/dl and vitamin 0 (400-800 IU/d); weight bearing exercise, cessation of smoking; reduce daily intake of caffeine Bisphosphonates or SERMs

22. What lifestyle modifications can be made to prevent osteoporosis?

23. What is the first-line therapy of postmenopausal osteoporosis? 24. What are the three layers of the adrenal cortex and what do they produce?

G- granulosa (aldosteronel F- fasciculata (cortisoll R- reticularis (sex steroids) An aldosterone producing adrenal adenoma Long-term use of exogenous steroids

25. What is Conn's syndrome? 26. What is the most common cause of Cushing's syndrome? 27. List 7clinical features of Cushing's syndrome

Dorsal fat pad, acne, moon face, truncal obesity, purple striae, easy bruising, osteoporosis Autoimmune (70-90%)

28. What is the most common etiology of
Addison's disease in developed countries? 29. What is the most common cause of Addison's disease worldwide? 30. What are the laboratory findings of an acute adrenal crisis? 3l. What is the" classic triad" of pheochromocytoma? 32. What are the three tissue types affected by MEN I (i.e. Wermer's syndrome)?


Hypoglycemia, hyponatremia, hyperkalemia, hypercalcemia

Palpitations, headache, episodic sweating

Pituitary (often non-secreting) Parathyroid (hyperparathyroidismI Pancreas (gastrinoma, insulinoma, VIPomal Primary hyperparathyroidism

33. What is the most common cause of
hypercalcemia? 34. What are the main signs and symptoms of hypercalcemia? 35. What are the two main signs used to diagnose hypocalcemia? 36. What are 2distinct features of primary hypogonadism?

Bone pain, kidney stones, psychosis (moans), abdominal pain (groansl Chvostek's sign (tap CNVIlI Trousseau's sign (carpal spasml 1) Decrease in sperm count is more affected than decrease in sperm testosterone 2) Associated with gynecomastia

£58 Endocrinology


Toronto Notes 2008

Agus AZ Etiology of hypercalcemia. 2002 Uptodate online version 10.2. Agus AZ. Overview of metabolic bone disease. 2002 Uptodate online version 10.2. American Diabetes Association. 120021. Management of dyslipidemia in adults with diabetes IPosition Statement). Diabetes Care 25(Sl): S74-77. Arnold A. Classification and pathogenesis of the multiple endocrine neoplasila syndromes. 2002 Uptodate online version 10.2. Blood glucose control in type 2 D.M-UK PDS33 on page E5 reprinted from the Lancet. 352, United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes IUKPDS 331. 837-53, 1998. With permission from Elsevier. Burman KD. Overview of thyroiditis. 2002 Uptodate online version 10.2. Canadian Diabetes Association Clinical Practice Guidelines. Expert Committee. Canadian Diabetes Association 2003. Clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2003; 27IsuppI2). Canadian Journal of Diabetes. Dec 2003; 27 IS2) Canadian Task Force on Preventive Health Care. CMAJ. May 25, 2004: 170 (11). Cheng A et al. Oral antihyperglycemic therapy for type 2 diabetes mellitus. CMAJ. 18 January 2005; 172121: 213-226. Cheung, A et al. Prevention of osteoporosis and osteoporotic fractures in post-menopausal womem: recommendation statement from the Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Dayan CM. 120011. Interpretation of thyroid function tests. Lancet 357: 619-624. Fodor JG et al. 2000). Recommendations for the management and treatment of dyslipidemia. CMAJ 162110): 1441-1447. Genest J et al. Recommendations of the management of dyslipidemia and the prevention of cardiovascular disease: 2003 update. CMAJ Oct 28, 203: 169 (9) Greenspan FS. Garber DG. 2001. Basic and clinical endocrinology. New York: Lange Medical Books! McGraw Hill. p. 100-163, 201272,623-761. Hirsch IB et al. (1995). Inpatient management of adults with diabetes. Diabetes Care 18(6): 870-878. Kitabachi AE et al. (20011. Management of hyperglycemic crises in patients with diabetes. Diabetes Care 24 (1): 131-152. Kronenberg HM, Larsen PR et al. Williams Textbook of Endocrinology. 9th edition. 1998. W.B. Saunders Company Metlzer S et a1.119981. Clinical practice guidelines for the management of diabetes in Canada. CMAJ 15918 suppl). NIH Consensus Conference. (2001). Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785-795. Orth ON. Evaluation of the response to ACTH in adrenal insufficiency. 2002 Uptodate online version 10.2. www Powers AC. 120011. Diabetes Mellitus. In Harrisons's Principles of Internal Medicine. Braunwald E, Fauci A, Kasper 0, Hauser S, Longo 0, Jameson. J, Eds. New York. p. 2109-2135. Rosen HN and Rosenblatt M. Overview of the management of osteoporosis in women. 2002 Uptodate online version 10.2. Ross OS. Disorders that cause hypothyroidism. 2002 Uptodate online version 10.2. Ryan EA. (1998). Pregnancy in diabetes. Med Clin of N Amer 82(2): 823-845. Simvastatin to lower CAD risk - The Heart Protection Study on page E15 reprinted from Lancet, 360, Heart Protection Study Collaborative Group, Heart Protection Study of Cholesterol lowering with Simvastatin in 20,536 high risk individuals: a randomized placebo-controlled trial. 7-22, 2002, with permission from Elsevier. Statins and CHD in Dyslipidemia - 45Trial on page E15 reprinted from the Lancet. 344. Randomized trial of cholesterol lowering in 4,444 patients with coronary heart disease:The Scandinavian Simvastatin Survival Study 1451:1283-89, 1994, with permission from Elsevier. Tsui Eet al. (20011. Intensive insulin therapy with insulin lispro. Diabetes Care 24110): 1722-1727. Young WF and Kaplan NM. Diagnoss and treatment of pheochromocytoma in adults. 2002 Uptodate online version 10.2.